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Ting-Yu Wang, Zi-Qing Ye, Weiguo Xie Department of Burns, Tongren Hospital of WuHan University & WuHan Third Hospital, WuHan, People’s Republic of ChinaCorrespondence: Zi-Qing Ye; Weiguo Xie, Department of Burns, Tongren Hosptial of WuHan Unversity & WuHan Third Hospital, 241 Pengliuyang Road, Wuchang District, WuHan, 430074, People’s Republic of China, Tel +86 13277933698 ; +86 18071085225, Email 71737700@qq.com; wgxie@hotmail.comObjective: To investigate the clinical effectiveness of laser and secure wound-closure system (Tension reducer) in the treatment of postoperative scarring after tension incision.Methods: A retrospectively observational study was conducted. Twenty-six patients who underwent surgical treatment in our department between June 2017 and December 2021 were selected, and those treated with laser and tension reducer were treated as a combined treatment group, and those treated with laser were treated as a conventional treatment group. Fifteen patients in the conventional group were treated with the pulsed dye laser and CO2 fractional laser at 1– 2 month intervals. Eleven people in the combined treatment group were treated with the laser in addition to a tension reducer for 3– 6 months. The scar width, scar thickness, scar hardness, pruritus score, modified Vancouver scar scale and complication rates between the two treatment modalities were compared between the two groups at 6 months postoperatively.Results: The scar thickness, scar hardness and modified Vancouver scar scale of 1.25 (0.14, 1.90) mm, 31.80 (21.00, 37.20) HA, (6.00 ± 2.17) in patients in the combined treatment group were less than those of patients in the conventional treatment group of 5.50 (4.00, 11.50) mm, 42.60 (32.50, 47.00) HA, (8.25± 1.91), (Z=2.883, 2.718, t=2.904, p< 0.05). The scar width and pruritus score in the combined treatment group, were 8.00 (5.00, 18.00) mm and 0 (0, 1) respectively, while the scar score and pruritus score in the conventional treatment group, were 5.50 (4.00, 11.50) mm respectively, with no statistically significant difference between the two groups. The complication rate was 55% in the combined treatment group and no adverse reactions occurred in the control group.Conclusion: Sequential laser combined with tension reducer treatment can effectively inhibit the proliferation of postoperative tension incision scar.Keywords: tension reducer, tension surgical incision, scar, CO2 LASER, pulsed dye laser

Si Yang Dong,* Hao Chen,* Li Zhi Lin, Lingli Jin, Dan Xiang Chen, Ou Chen Wang, Zhi Qiang Ye Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhi Qiang Ye; Ou Chen WangDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000 People’s Republic of ChinaTel/Fax +86 13867705524Email yezhiqiang1982@126.com woc@wmu.edu.cnBackground: Microfibril-associated protein 2 (MFAP2) is a protein coding gene that exerts important phenotypic effects on cell motility, and increasing research has indicated that MFAP2 was correlated with many cancers. However, the functional and potential clinical role of MFAP2 in papillary thyroid cancer (PTC) has not yet been verified.Materials and Methods: We performed whole transcriptome sequencing on 78 paired PTC tissues and corresponding adjacent normal tissues and found that MFAP2 was highly expressed in PTC tissues. Then, we analyzed the expression of MFAP2 and its relation with the clinicopathological features of PTC in The Cancer Genome Atlas (TCGA) PTC genomic dataset. We detected MFAP2 expression in 40 paired PTC tissues and corresponding adjacent normal tissues through RT-qPCR (real time-quantitative polymerase chain reaction) to validate the sequencing data and TCGA cohort. Cell functional assays were performed to elucidate the function of MFAP2 in PTC cells, Western blot assay was performed to explore the correlation between MFAP2 and EMT (epithelial-mesenchymal transition)-related proteins.Results: Statistical analysis showed that MFAP2 was obviously upregulated in PTC tissues compared to matched normal tissues, and the expression levels of MFAP2 in PTC tissues were strongly related with lymph node metastasis (p=0.016). The results of RT-qPCR of our own tissue specimens showed the same conclusions as that in TCGA dataset. The results of functional assays in PTC cell lines showed that MFAP2 could promote proliferation, colony formation, migration and invasion abilities and decrease the apoptotic rate in PTC cells. Western Blot assay showed that MFAP2 could regulate the expression of EMT-related proteins.Conclusion: MFAP2 increases the proliferation, motility and decreases the apoptosis of PTC cells, and might be a potential therapeutic target for papillary thyroid cancer.Keywords: biomarker, proliferation, migration, epithelial-mesenchymal transition, EMT, apoptosis

Kuey teow is one of the delicacies of Guangdong, China and is a gluten-free noodle dish made from rice. It has a short storage period and extending the shelf life by quick freezing induces quality deterioration due to temperature fluctuations. To improve its freeze-thaw frozen storage quality, this paper examined the effects of hydroxypropyl corn starch (HCS), guar gum (GG), and compound phosphates (CP) on the quality of quick-frozen kuey teow during freeze-thaw cycles. The mechanism was investigated by identifying changes in the moisture status, aging degree of the starch, and textural and cooking characteristics. The results showed that all three additions improved the toughness, chewiness and steaming characteristics of the kuey teow, with CP significantly enhancing chewiness. XRD and FTIR results revealed that GG more significantly inhibited the decrease of starch crystallinity, while HCS inhibited starch aging. GG, HCS and CP all improved the hydration characteristics and water holding capacity of rice starch. GG enhances the ability of starch to bind more tightly with water, resulting in a more uniform water distribution and a more continuous and tight structure of the kuey teow. This study will provide a theoretical basis for compounding and optimizing the quick-freezing of kuey teow., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Microplastic (MP) contamination in soil severely impairs plant growth. However, mechanisms underlying the effects of MPs on plant nutrient uptake remain largely unknown. In this study, we revealed that NO 3 - content was significantly decreased in shoots and roots of wheat plants exposed to high concentrations (50-100 mg L -1 ) of MPs (1 μm and 0.1 μm; type: polystyrene) in the hydroponic solution. Isotope labeling experiments demonstrated that MP exposure led to a significant inhibition of NO 3 - uptake in wheat roots. Further analysis indicated that the presence of MPs markedly inhibited root growth and caused oxidative damage to the roots. Additionally, superoxide dismutase and peroxidase activities in wheat roots decreased under all MP treatments, whereas catalase and ascorbate peroxidase activities significantly increased under the 100 mg L -1 MP treatment. The transcription levels of most nitrate transporters (NRTs) in roots were significantly downregulated by MP exposure. Furthermore, exposure to MPs distinctly suppressed the activity of nitrate reductase (NR) and nitrite reductase (NiR), as well as the expression levels of their coding genes in wheat shoots. These findings indicate that a decline in root uptake area and root vitality, as well as in the expression of NRTs, NR, and NiR genes caused by MP exposure may have adverse effects on NO 3 - uptake and assimilation, consequently impairing normal growth of plants., 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 Ltd. All rights reserved.)

Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts' experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes., (© 2024. The Author(s).)

Background: Pediatric asthma is a significant public health issue that impacts the quality of life of children globally. Traditional management approaches focus on symptom control and medication adherence but often overlook the comprehensive educational needs of patients and their families. A multifaceted health education approach may offer a more holistic strategy in managing pediatric asthma, especially in outpatient settings., Aim: To evaluate the efficacy of a comprehensive health education strategy in improving disease management, medication adherence, and quality of life among children with asthma in outpatient settings., Methods: In total, 100 pediatric patients with severe asthma were enrolled from January 2021 to November 2022 and randomly allocated to a control group ( n = 50) or an observation group ( n = 50). The control group received standard nursing care, including basic nursing interventions and health education upon admission. In contrast, the observation group was exposed to a broad spectrum of health education methodologies, including internet-based hospital systems, social media channels, one-on-one verbal education, informational brochures, slide presentations, telephone check-ins, animated videos, and illustrated health education manuals. Data on asthma management knowledge, symptom control, quality of life [St. George's Respiratory Questionnaire (SGRQ)], treatment adherence, and nursing satisfaction were collected and analyzed., Results: The scores of the observation group in knowledge areas, such as medication, home care, disease understanding, symptom management, prevention strategies, and nutritional guidance, were significantly higher than those of the control group ( P < 0.05). In addition, the observation group exhibited greater symptom control, improved quality of life based on their SGRQ scores, and higher treatment adherence post-intervention ( P < 0.05). Nursing satisfaction was also rated higher in the observation group across all evaluated areas ( P < 0.05)., Conclusion: Implementing a diversified health education approach in pediatric asthma management significantly enhances disease understanding, symptom management, and treatment adherence, leading to improved quality of life for affected children. These findings underscore the importance of multifaceted clinical health education in augmenting disease awareness and facilitating continuous improvements in asthma control rates, highlighting the potential benefits of incorporating comprehensive educational strategies into pediatric asthma care protocols., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest involved in this study., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Background: Eurycomanone (EN) is a diterpenoid compound isolated from the roots of Eurycoma longifolia ( E. longifolia ). Previous studies have confirmed that E. longifolia can enhance bone regeneration and bone strength. We previously isolated and identified ten quassinoids from E. longifolia , and the result displayed that five aqueous extracts have the effects on promotion of bone formation, among whom EN showed the strongest activity. However, the molecular mechanism of EN on bone formation was unknown, and we further investigated in this study., Methods: After the verification of purity of extracted EN, following experiments were conducted. Firstly, the pharmacologic action of EN on normal bone mineralization and the therapeutic effect of EN on Dex-induced bone loss using zebrafish larvae. The mineralization area and integral optical density (IOD) were evaluated using alizarin red staining. Then the vital signaling pathways of EN relevant to OP was identified through network pharmacology analysis. Eventually in vitro, the effect of EN on cell viability, osteogenesis activities were investigated in human bone marrow mesenchymal stem cells (hMSCs) and C3H10 cells, and the molecular mechanisms by which applying AKT inhibitor A-443654 in hMSCs., Results: In zebrafish larvae, the administration in medium of EN (0.2, 1, and 5 μM) dramatically enhanced the skull mineralization area and integral optical density (IOD), and increased mRNA expressions of osteoblast formation genes (ALP, RUNX2a, SP7, OCN). Meanwhile, exposure of EN remarkably alleviated the inhibition of bone formation induced by dexamethasone (Dex), prominently improved the mineralization, up-regulated osteoblast-specific genes and down-regulated osteoclast-related genes (CTSK, RANKL, NFATc1, TRAF6) in Dex-treated bone loss zebrafish larvae. Network pharmacology outcomes showed the MAPK and PI3K-AKT signaling pathways are closely associated with 10 hub genes (especially AKT1), and AKT/GSK-3β/β-catenin was selected as the candidate analysis pathway. In hMSCs and C3H10 cells, results showed that EN at appropriate concentrations of 0.008-5 μM effectively increased the cell proliferation. In addition, EN (0.04, 0.2, and 1 μM) significantly stimulated osteogenic differentiation and mineralization as well as significantly increased the protein phosphorylation of AKT and GSK-3β, and expression of β-catenin, evidencing by the results of ALP and ARS staining, qPCR and western blotting. Whereas opposite results were presented in hMSCs when treated with AKT inhibitor A-443654, which effectively inhibited the pro-osteogenesis effect induced by EN, suggesting EN represent powerful potential in promoting osteogenesis of hMSCs, which may be closely related to the AKT/GSK-3β/β-catenin signaling pathway., Conclusions: Altogether, our findings indicate that EN possesses remarkable effect on bone formation via activating AKT/GSK-3β/β-catenin signaling pathway in most tested concentrations., The Translational Potential of This Article: This study demonstrates EN is a new effective monomer in promoting bone formation, which may be a promising anabolic agent for osteoporosis (OP) treatment., Competing Interests: All authors disclosed no relevant relationship, and no potential conflict of interest was reported by the authors., (© 2023 Published by Elsevier B.V. on behalf of Chinese Speaking Orthopaedic Society.)

Fungal residue is a unique abundant organic material undervalued in agricultural production. The application of chemical fertilizer combined with fungal residue can not only improve soil quality but also regulate the microbial community. However, it is unclear whether the response of soil bacteria and fungi to the combined application of fungal residue and chemical fertilizer is consistent. Therefore, a long-term positioning experiment in a rice field was conducted with a total of nine treatments. Chemical fertilizer (C) and fungal residue (F) were applied at 0, 50%, and 100% to evaluate 1 the change in soil fertility properties and microbial community structure and 2 the main driving factors of soil microbial diversity and species composition. The results showed that soil total nitrogen (TN) was highest after treatment C 0 F 100 (55.56% higher than in the control), and the carbon to nitrogen ratio (C/N), total phosphorus (TP), dissolved organic carbon (DOC), and available phosphorus (AP) contents were highest after treatment with C 100 F 100 (26.18%, 26.46%, 17.13%, and 279.54% higher than in the control, respectively). The amounts of soil organic carbon (SOC), available nitrogen (AN), available potassium (AK), and pH were highest after treatment with C 50 F 100 (85.57%, 41.61%, 29.33%, and 4.62% higher than in the control, respectively). Following the application of fungal residue with chemical fertilizer, there were significant changes in the α -diversity of bacteria and fungi in each treatment. Compared with that of the control (C 0 F 0 ), different long-term applications of fungal residue with chemical fertilizer did not significantly change soil bacterial β -diversity but resulted in significant differences in fungal β -diversity, and the relative abundance of soil fungal Ascomycota and Sordariomycetes significantly decreased after the application of C 50 F 100 . The random forest prediction model indicated that AP and C/N were the main driving factors of bacterial and fungal α -diversity, respectively, and AN, pH, SOC, and DOC were the main driving factors of bacterial β -diversity, whereas AP and DOC were the main driving factors of fungal β -diversity. Correlation analysis suggested that the relative abundance of soil fungal Ascomycota and Sordariomycetes had a significantly negative correlation with SOC, TN, TP, AN, AP, AK, and C/N. PERMANOVA showed that variation in soil fertility properties, dominant species of soil bacteria at the phylum and class level, and dominant species of soil fungi at the phylum and class level were all best explained by fungal residue (46.35%, 18.47%, and 41.57%, respectively), and variation in bacterial diversity was best explained by fungal residue (23.84%) and to a lesser extent by the interaction between fungal residue and chemical fertilizer (9.90%). In contrast, the variation in fungal diversity was best explained by the interaction between fungal residue and chemical fertilizer (35.00%) and to a lesser extent by fungal residue (10.42%). In conclusion, the application of fungal residue has more advantages than chemical fertilizer in influencing soil fertility properties and microbial community structure changes.

Background: It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage., Methods: The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively., Results: 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (r s  = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization., Conclusions: We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression., Competing Interests: Conflict of interest There are no other potential conflicts of interest relevant to this article., (Copyright © 2022. Published by Elsevier B.V.)

Copper is a trace element necessary for the normal functioning of organisms, but excessive copper contents may be toxic to the heart. The goal of this study was to investigate the role of excessive copper accumulation in mitochondrial damage and cell apoptosis inhibition. In vivo, the heart copper concentration and cardiac troponin I (c-TnI) and N-terminal forebrain natriuretic peptide (NT-pro-BNP) levels increased in the copper-laden model group compared to those of the control group. Histopathological and ultrastructural observations revealed that the myocardial collagen volume fraction (CVF), perivascular collagen area (PVCA) and cardiomyocyte cross-sectional area (CSA) were markedly elevated in the copper-laden model group compared with the control group. Furthermore, transmission electron microscopy (TEM) showed that the mitochondrial double-layer membrane was incomplete in the copper-laden model groups. Furthermore, cytochrome C (Cyt-C) expression was downregulated in mitochondria but upregulated in the cytoplasm in response to copper accumulation. In addition, Bcl-2 expression decreased, while Bax and cleaved caspase-3 levels increased. These results indicate that copper accumulation in cardiomyocyte mitochondria induces mitochondrial injury, and Cyt-C exposure and induces apoptosis, further resulting in heart damage., (Copyright © 2022. Published by Elsevier Inc.)

A Fe-Mn oxide-microbe combined biochar (FM-DB) was prepared to simultaneously remove Cd(Ⅱ) and As(Ⅲ) contamination in an aqueous system. In the FM-DB, the best ratio of Fe-Mn oxide (FMBO) and carya cathayensis shell biochar (CCSB) was 3%+3%. The material had good acid resistance, mechanical strength, and mass transfer performance, and the maximum removal rates for Cd(Ⅱ) and As(Ⅲ) in the binary system were 77.29% and 99.94%, respectively. Characterization confirmed that the FM-DB was successfully prepared and had a rich functional group structure. The single-factor adsorption test results for Cd(Ⅱ) and As(Ⅲ) showed that the composite material had a certain adsorption capacity affected by initial pH, equilibration time, and initial concentration for Cd(Ⅱ) and As(Ⅲ) under different conditions. The adsorption isotherm and kinetic data indicated the adsorption equilibrium time for Cd(Ⅱ) and As(Ⅲ) was 3.5 h and 8 h, and the maximum capacity was 59.27 mg·g -1 and 84.73 mg·g -1 , respectively. The adsorption of Cd(Ⅱ) and As(Ⅲ) was mainly affected by the electron exchange, electron sharing, and complexation on the surface of the material. The whole adsorption process was a combination of single-layer adsorption and multi-layer adsorption on an uneven surface. The adsorption process was a multi-step process, including outer surface diffusion and inner particle diffusion. In addition, comparing the removal rate of composite materials in the single-component system and the binary system, a mutual promotion of adsorption between Cd(Ⅱ) and As(Ⅲ) was found under the binary system. In conclusion, oxide-microbe combined biochar could be an efficient adsorption material and was suitable for the remediation of aqueous system pollution caused by Cd(Ⅱ) and As(Ⅲ).

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results., Competing Interests: None

Atmospheric Particulate Matter (PM) is one of the leading environmental risk factors for the global burden of disease. Increasing epidemiological studies demonstrated that PM plays a significant role in CNS demyelinating disorders; however, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. Using multiple in vivo and in vitro strategies, in the present study we demonstrate that PM exposure aggravates neuroinflammation, myelin injury, and dysfunction of movement coordination ability via boosting microglial pro-inflammatory activities, in both the pathological demyelination and physiological myelinogenesis animal models. Indeed, pharmacological disturbance combined with RNA-seq and ChIP-seq suggests that TLR-4/NF-kB signaling mediated a core network of genes that control PM-triggered microglia pathogenicity. In summary, our study defines a novel atmospheric environmental mechanism that mediates PM-aggravated microglia pathogenic activities, and establishes a systematic approach for the investigation of the effects of environmental exposure in neurologic disorders., Competing Interests: BH, XL, RA, SD, ZY, XD, WM, SX, JW, LW, CX, YZ, YX, YZ No competing interests declared, (© 2022, Han et al.)

Background: Epidemiologic studies have produced conflicting results on the effects of metformin on pancreatic cancer. This study aimed to observe and analyze whether metformin use is associated with better prognosis in pancreatic cancer. Materials and Methods: In this retrospective cohort study, all baseline data were retrieved from The Chinese Medicine Information Retrieval System (https://dc.wzhospital.cn/vpn/index.html) of The First Affiliated Hospital of Wenzhou Medical University. Survival data were collected by follow-up visits and medical records. Overall survival was the primary endpoint, while progression-free survival and disease-free survival were secondary endpoints. Progression or recurrence was assessed with radiologic images. Results: Seventy-six metformin users and 92 metformin nonusers diagnosed with pancreatic cancer from 2012 to 2020 in this hospital were enrolled. The adjusted hazard ratio for overall survival for metformin users was 0.50 (95% confidence interval = 0.33-0.76), where median overall survival was 16.0 months for metformin users versus 11.5 months for metformin nonusers. The protective effect was also found by analyzing progression-free survival (adjusted hazard ratio = 0.39, 95% confidence interval = 0.18-0.86) and disease-free survival (adjusted hazard ratio = 0.30, 95% confidence interval = 0.14-0.68). In the subgroup analysis, metformin use had a statistically significant association with prolongation of survival in stage I to II pancreatic cancer patients (hazard ratio = 0.47, 95% confidence interval = 0.25-0.91), but not for advanced tumor stage (hazard ratio for IV stage = 0.62, 95% confidence interval = 0.33-1.19), after adjustment for other risk factors. Conclusion: Metformin use is related to favorable survival outcomes of pancreatic cancer, especially in early tumor stage.

Background: The wide application of gene sequencing has accumulated numerous amino acid substitutions (AAS) with unknown significance, posing significant challenges to predicting and understanding their pathogenicity. While various prediction methods have been proposed, most are sequence-based and lack insights for molecular mechanisms from the perspective of protein structures. Moreover, prediction performance must be improved., Methods: Herein, we trained a random forest (RF) prediction model, namely AAS3D-RF, underscoring sequence and three-dimensional (3D) structure-based features to explore the relationship between diseases and AASs., Results: AAS3D-RF was trained on more than 14,000 AASs with 21 selected features, and obtained accuracy (ACC) between 0.811 and 0.839 and Matthews correlation coefficient (MCC) between 0.591 and 0.684 on two independent testing datasets, superior to seven existing tools. In addition, AAS3D-RF possesses unique structure-based features, context-dependent substitution score (CDSS) and environment-dependent residue contact energy (ERCE), which could be applied to interpret whether pathogenic AASs would introduce incompatibilities to the protein structural microenvironments., Conclusion: AAS3D-RF serves as a valuable tool for both predicting and understanding pathogenic AASs., (© 2021 The Author(s). Published by BRI.)

Background: Heterogeneous nuclear ribonucleoprotein K (HnRNPK) is a nucleic acid-binding protein that regulates diverse biological events. Pathologically, HnRNPK proteins are frequently overexpressed and clinically correlated with poor prognosis in various types of human cancers and are therefore pursued as attractive therapeutic targets for select patients. However, both the transcriptional regulation and degradation of HnRNPK in prostate cancer remain poorly understood., Methods: qRT-PCR was used to detect the expression of HnRNPK mRNA and miRNA; Immunoblots and immunohistochemical assays were used to determine the levels of HnRNPK and other proteins. Flow cytometry was used to investigate cell cycle stage. MTS and clonogenic assays were used to investigate cell proliferation. Immunoprecipitation was used to analyse the interaction between SPOP and HnRNPK. A prostate carcinoma xenograft mouse model was used to detect the in vivo effects of HnRNPK and miRNA., Results: In the present study, we noted that HnRNPK emerged as an important player in the carcinogenesis process of prostate cancer. miR-206 and miR-613 suppressed HnRNPK expression by targeting its 3'-UTR in PrCa cell lines in which HnRNPK is overexpressed. To explore the potential biological function, proliferation and colony formation of PrCa cells in vitro and tumor growth in vivo were also dramatically suppressed upon reintroduction of miR-206/miR-613. We have further provided evidence that Cullin 3 SPOP is a novel upstream E3 ubiquitin ligase complex that governs HnRNPK protein stability and oncogenic functions by promoting the degradation of HnRNPK in polyubiquitination-dependent proteolysis in the prostate cancer setting. Moreover, prostate cancer-associated SPOP mutants fail to interact with and promote the destruction of HnRNPK proteins., Conclusion: Our findings reveal new posttranscriptional and posttranslational modification mechanisms of HnRNPK regulation via miR-206/miR-613 and SPOP, respectively. More importantly, given the critical oncogenic role of HnRNPK and the high frequency of SPOP mutations in prostate cancer, our results provide a molecular rationale for the clinical investigation of novel strategies to combat prostate cancer based on SPOP genetic status., (© 2021. The Author(s).)

Motility is finely regulated and is crucial to bacterial processes including colonization and biofilm formation. There is a trade-off between motility and growth in bacteria with molecular mechanisms not fully understood. Hypermotile Escherichia coli could be isolated by evolving non-motile cells on soft agar plates. Most of the isolates carried mutations located upstream of the flhDC promoter region, which upregulate the transcriptional expression of the master regulator of the flagellum biosynthesis, FlhDC. Here, we identified that spontaneous mutations in clpX boosted the motility of E. coli largely, inducing several folds of changes in swimming speed. Among the mutations identified, we further elucidated the molecular mechanism underlying the ClpX V78F mutation on the regulation of E. coli motility. We found that the V78F mutation affected ATP binding to ClpX, resulting in the inability of the mutated ClpXP protease to degrade FlhD as indicated by both structure modeling and in vitro protein degradation assays. Moreover, our proteomic data indicated that the ClpX V78F mutation elevated the stability of known ClpXP targets to various degrees with FlhD as one of the most affected. In addition, the specific tag at the C-terminus of FlhD being recognized for ClpXP degradation was identified. Finally, our transcriptome data characterized that the enhanced expression of the motility genes in the ClpX V78F mutations was intrinsically accompanied by the reduced expression of stress resistance genes relating to the reduced fitness of the hypermotile strains. A similar pattern was observed for previously isolated hypermotile E. coli strains showing high expression of flhDC at the transcriptional level. Hence, clpX appears to be a hot locus comparable to the upstream of the flhDC promoter region evolved to boost bacterial motility, and our finding provides insight into the reduced fitness of the hypermotile bacteria., 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 Li, Hou, Ju, Feng, Ye, Xiao, Gu, Fu, Wei and You.)

Although minimally invasive diagnosis and treatment technology for urinary stones has been widely developed, with continuous progress and cross integration of imaging, laser technology, endoscopic technology, and materials science, new diagnosis and treatment equipment emerge in endlessly, which promotes the continuous progress and innovation in diagnosis and treatment technology for urinary stones. By introducing the advances in imaging, lithotripsy tools, new endoscopes and ureteral stents, and analyzing their application prospects, it helps us understand the development trend of diagnosis and treatment of urinary stones in the future.

Objective: To observe the changes in the related indicators of bone formation and bone resorption in severely burned rats. Methods: The experimental research method was adopted. Thirty female Sprague-Dawley rats aged 6 to 8 weeks were divided into sham injury group, 12% total body surface area (TBSA) full-thickness burn group, and 24%TBSA full-thickness burn group according to the random number table, with 10 rats in each group. The rats were treated on the back correspondingly, after which, the burned rats were rehydrated by intraperitoneal injection according to the Parkland formula, and the wound was coated with 20 g/L iodophor until wound healing. On post injury day (PID) 28, the tibia tissue of rats in each group was collected. The new bone tissue and the number of osteoclasts were observed after staining with Masson and tartrate-resistant acid phosphatase, respectively. The abdominal aortic blood of rats in each group was harvested for serum preparation. The bone metabolism indexes of serum calcium ion and phosphorus ion concentration were determined by the methyl thymol blue colorimetric method and phosphomolybdic acid method, respectively. The serum levels of bone formation marker of aminoterminal propeptide of type 1 procollagen (P1NP) and bone resorption marker of beta-carboxy-terminated peptide of type Ⅰ collagen (β-CTX) were determined by enzyme-linked immunosorbent assay. The first lumbar spine tissue of rats in each group was collected, and the mRNA expression levels of osteoprotegerin, receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor receptor-associated factor 6 (TRAF-6), nuclear factor of activated T cell 1 (NFATC1), c-Fos, and c-Src were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with one-way analysis of variance, Bonferroni method, Welch test, Games-Howell test, Kruskal-Wallis test, Mann-Whitney U test, and Bonferroni correction. Results: On PID 28, compared with that in sham injury group, the formation of new bone tissue in the tibia tissue of rats in the two burn groups was decreased, and the larger the burn area, the more obvious the decrease. The numbers of osteoclasts in the tibia tissue of rats in the two burn groups were similar, both significantly more than the number in sham injury group. On PID 28, the serum calcium ion concentration and serum level of β-CTX of rats in the three groups were similar ( P >0.05). The serum phosphorus ion concentration of rats in 24%TBSA full-thickness burn group was significantly higher than that in 12%TBSA full-thickness burn group ( P <0.05), and the serum phosphorus ion concentrations in the two burn groups were significantly higher than the concentration in sham injury group ( P <0.01). The serum level of P1NP of rats in 24%TBSA full-thickness burn group was significantly lower than that in sham injury group ( P <0.01). On PID 28, the mRNA expression levels of osteoprotegerin in the first lumbar spine tissue of rats in sham injury group, 12%TBSA full-thickness burn group, and 24%TBSA full-thickness burn group were 1.01±0.20, 1.71±0.83, and 2.24±0.51, respectively, and that in 24%TBSA full-thickness burn group was significantly higher than that in sham injury group ( P <0.01). The mRNA expression level of RANKL in the first lumbar spine tissue of rats in 24%TBSA full-thickness burn group was 1.31±0.17, which was significantly higher than 1.00±0.14 in sham injury group and 0.97±0.10 in 12%TBSA full-thickness burn group ( P <0.01). The mRNA expression levels of TRAF-6, NFATC1 ( Z =3.141, 3.782), and c-Src in the first lumbar tissue of rats in 12%TBSA full-thickness burn group and 24%TBSA full-thickness burn group and the mRNA expression level of c-Fos in the first lumbar tissue of rats in 12%TBSA full-thickness burn group were significantly higher than those in sham injury group ( P <0.05 or P <0.01). The mRNA expression levels of c-Fos and c-Src in the first lumbar spine tissue of rats in 12%TBSA full-thickness burn group were significantly higher than those in 24%TBSA full-thickness burn group ( P <0.01). Conclusions: Severe burns can cause a decrease in the generation of new bone tissue, an increase in the number of osteoclasts and the serum phosphorus ion concentration, and a decrease in the serum level of P1NP in rats. The level of osteoprotegerin, RANKL, TRAF-6, NFATC1, c-Fos, and c-Src in bone tissue showed an increasing trend while the level of NFATC1, c-Fos, and c-Src showed a decreasing trend with the increase of burn area.

Background: Genomic instability (GI) is among the top ten characteristics of malignancy. Long non-coding RNAs (lncRNAs) are promising cancer biomarkers that are reportedly involved in GI. So far, the clinical value of GI-related lncRNAs (GIlncs) in papillary thyroid cancer (PTC) has not been clarified., Methods: Integrative analysis of lncRNA expression and somatic mutation profiles was performed to identify GIlncs. Analysis of differentially expressed lncRNAs in the group with high- and low- cumulative number of somatic mutations revealed significant GIlncs in PTC. Univariate and multivariate Cox proportional hazard regression analyses were performed to identify hub-GIlncs., Results: A computational model based on four lncRNAs ( FOXD2-AS1 , LINC01614 , AC073257.2 , and AC005082.1 ) was identified as a quantitative index using an in-silicon discovery cohort. GILS score was significantly associated with poor prognosis, as validated in the TCGA dataset and further tested in our local RNA-Seq cohort. Moreover, a combination of clinical characteristics and the composite GILS-clinical prognostic nomogram demonstrates satisfactory discrimination and calibration. Furthermore, the GILS score and FOXD2-AS1 , LINC01614 , AC073257.2 , and AC005082.1 were also associated with driver mutations and multiple clinical-pathological variables, respectively. Moreover, RNA-Seq confirmed the expression patterns of FOXD2-AS1 , LINC01614 , AC073257.2 , and AC005082.1 in PTC and normal thyroid tissues. Biological experiments demonstrated that downregulated or overexpressed LINC01614 affect PTC cell proliferation, migration, and invasion in vitro . Activation of the stromal and immune cell infiltration was also observed in the high LINC01614 group in the PTC microenvironment., Conclusion: In summary, we identified a signature for clinical outcome prediction in PTC comprising four lncRNAs associated with GI. A better understanding of the GI providing an alternative evaluation of the progression risk of PTC. Our study also demonstrated LINC01614 as a novel oncogenic lncRNA and verified its phenotype in PTC., 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 Dong, Jin, Chen, Chen, Ye, Zhang, Huang, Zhang and Gu.)

NRT1.1 is the first nitrate transport protein cloned in plants and has both high- and low-affinity functions. It imports and senses nitrate, which is modulated by the phosphorylation on Thr101 (T101). Structural studies have revealed that the phosphorylation of T101 either induces dimer decoupling or increases structural flexibility within the membrane, thereby switching the NRT1.1 protein from a low- to high-affinity state. Further studies on the adaptive regulation of NRT1.1 in fluctuating nitrate conditions have shown that, at low nitrate concentrations, nitrate binding only at the high-affinity monomer initiates NRT1.1 dimer decoupling and priming of the T101 site for phosphorylation activated by CIPK23, which functions as a high-affinity nitrate transceptor. However, nitrate binding in both monomers retains the unmodified NRT1.1, maintaining the low-affinity mode. This NRT1.1-mediated nitrate signalling and transport may provide a key to improving the efficiency of plant nitrogen use. However, recent studies have revealed that NRT1.1 is extensively involved in plant tolerance of several adverse environmental conditions. In this context, we summarise the recent progress in the molecular mechanisms of NRT1.1 dual-affinity nitrate transport/signalling and focus on its expected and unexpected roles in plant abiotic stress resistance and their regulation processes., 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 Fang, Fang, Ye, Liu, Zhao and Jin.)

Background: Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent genotype-phenotype correlation, and patients carrying the same mutations may have different phenotypes. Therefore, it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation (HSCT) for LRBA-deficient patients. We hypothesized that there may be a protein-phenotype correlation to indicate HSCT for LRBA-deficient patients., Aim: To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes ., Methods: Clinical data of three Chinese LRBA-deficient patients were collected, and protein levels were detected by Western blot analysis. In addition, LRBA mutation information of another 83 previously reported patients was summarized., Results: All the major clinical findings indicated enteropathy, but patients 1 and 3 presented with more severe symptoms than patient 2. Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2. Compound heterozygous mutations in LRBA were found in patient 1, and homozygous mutations in LRBA were found in patient 2 and patient 3. Only patient 2 responded well to traditional immunosuppressive treatment. Residual expression of the LRBA protein in patients 1 and 3 was very low, but in patient 2, a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control. After HSCT, patient 1 had increased LRBA protein expression. We summarized the genetic information of 86 patients, and the mutations in patients 1 and 3 were novel mutations., Conclusion: We described three Chinese LRBA-deficient patients, two of whom carried novel mutations. These patients had no genotype-phenotype correlations, but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two iron-based materials, Fe-Ca composite (FeCa) and Fe-Mn binary oxide (FMBO), were applied to immobilize As, Pb, and Cd in heavy metal contaminated paddy soils. Seven kinds of paddy soil (tidal soil) contaminated by arsenic, lead and cadmium were collected from Shangyu, Shaoxing (SY), Foshan, Guangdong (FS), Shaoguan, Guangdong (SG), LiuYang, Hunan (LY), Ganzhou, Jiangxi (GZ), Dushan, Guizhou (DS), and Ma'anshan, Anhui (MAS). The effects of iron-based materials on the dynamic changes of As, Pb, and Cd concentration in soil solution, the stabilization efficacy of available As, Pb, and Cd in soil, and the effects of soil types and properties on stabilization efficacy were studied through soil incubation experiment. The results showed that the content of soil dissolved As, Pb, and Cd were lower in iron-based material treatments than in control throughout the incubation. The addition of two iron-based materials significantly reduced the availability of Cd, Pb, and As. Moreover, the stabilization efficiency of FeCa for As was higher than FMBO, but no significant difference was found in the stabilization efficiency of Pb and Cd between two materials. The stabilization efficiency of As, Pb, and Cd in FeCa treatments could be ordered as GZ > SG > DS and MAS; FS>SY, LY, and SG>MAS; SY, GZ, and DS>MAS, respectively. While the stabilization efficiency for As, Pb, and Cd in FMBO could be ordered as SY, LY, and GZ > DS > FS; FS > GZ > SY; DS > LY > MAS, respectively. In addition, the statistical results showed that the stabilization efficiencies of various soils under the treatment of iron-based materials were significantly correlated with sand content (negatively correlated for As), soil pH (positively correlated for Pb), and clay content (negatively correlated for Cd). In conclusion, the two iron-based materials evaluated in this study may be effective stabilization agents for remediating different types of arsenic-, lead-, and cadmium-contaminated soils.

Gouty arthritis is a common inflammatory disease characterized by monosodium urate (MSU) crystal-induced nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation with upregulated caspase 1 protease and IL-1β in macrophages. Cucurbitacin B (CuB) is a tetracyclic triterpene that possesses a potential anti-inflammatory activity. However, the immunomodulatory and anti-inflammatory effects of CuB on gout have not been well characterized. Therefore, the purpose of the present study was to determine whether CuB exhibits anti-inflammatory effects on gout and to analyze the underlying molecular mechanism. We examined the effects of CuB on various stimuli-activated bone marrow-derived macrophages (BMDMs) and in a mouse model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB effectively suppressed multiple stimuli-activated IL-1β secretion by interrupting NLRP3 inflammasome complex formation, inhibiting NLRP3 inflammasome activation and suppressing key enzymes of glycolysis in macrophages. Consistent with this, CuB pretreatment also ameliorated MSU-induced arthritis in vivo models of gout arthritis, manifested by reduced foot swelling and inflammatory cell infiltration. Taken together, our data provide the evidence that CuB is an NLRP3 inflammasome inhibitor with therapeutic potential for treating NLRP3 inflammasome-mediated diseases, especially gouty arthritis.

Montelukast is a leukotriene receptor antagonist that is known to prevent allergic rhinitis and asthma. Blocking the Cysteinyl leukotriene receptor (CysLTR1), one of the primary receptors of leukotrienes, has been demonstrated to be efficacious in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through disrupting chemotaxis of infiltrating T cells. However, the role of CysLTR1 in the pathogenesis of MS is not well understood. Here, we show that MS patients had higher expression of CysLTR1 in the circulation and central nervous system (CNS). The majority of CD4 + T cells expressed CysLTR1 in MS lesions. Among T-cell subsets, Th17 cells had the highest expression of CysLTR1, and blocking CysLTR1 signalling abrogated their development in vitro. Inhibition of CysLTR1 by montelukast suppressed EAE development in both a prophylactic and therapeutic manner and inhibited myelin loss in EAE mice. Similarly, the in vivo results showed that montelukast inhibited Th17 response in EAE mice and that Th17 cells treated with montelukast had reduced encephalitogenic in adoptive EAE. Our findings strongly suggest that targeting Th17 response by inhibiting CysLTR1 signalling could be a promising therapeutic strategy for the treatment of MS and CNS inflammatory diseases., (© 2021 John Wiley & Sons Ltd.)

Diamond-Blackfan Anemia (DBA) is an inherited rare disease characterized with severe pure red cell aplasia, and it is caused by the defective ribosome biogenesis stemming from the impairment of ribosomal proteins. Among all DBA-associated ribosomal proteins, RPS19 affects most patients and carries most DBA mutations. Revealing how these mutations lead to the impairment of RPS19 is highly demanded for understanding the pathogenesis of DBA, but a systematic study is currently lacking. In this work, based on the complex structure of human ribosome, we comprehensively studied the structural basis of DBA mutations of RPS19 by using computational methods. Main structure elements and five conserved surface patches involved in RPS19-18S rRNA interaction were identified. We further revealed that DBA mutations would destabilize RPS19 through disrupting the hydrophobic core or breaking the helix, or perturb the RPS19-18S rRNA interaction through destroying hydrogen bonds, introducing steric hindrance effect, or altering surface electrostatic property at the interface. Moreover, we trained a machine-learning model to predict the pathogenicity of all possible RPS19 mutations. Our work has laid a foundation for revealing the pathogenesis of DBA from the structural perspective., 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 An, Zhou, Xiong, Han, Wang, Ye and Wu.)

Senescence is activated in response to gemcitabine to prevent the propagation of cancer cells. However, there is little evidence on whether senescence is involved in gemcitabine resistance in pancreatic cancer. Increasing evidence has demonstrated that microRNAs (miRs) are potential regulators of cellular senescence. The present study aimed to investigate whether aberrant miR-7 expression modulated senescence to influence pancreatic cancer resistance to chemotherapy. In the present study, cell senescence assay, ALDEFLUOR™ assay, luciferase reporter assay, flow cytometry, quantitative PCR, immunohistochemistry and western blot analysis were performed to explore the association between senescence and gemcitabine therapy response, and to clarify the underlying mechanisms. The present study revealed that gemcitabine-induced chronically existing senescent pancreatic cells possessed stemness markers. Therapy-induced senescence led to gemcitabine resistance. Additionally, it was found that miR-7 expression was decreased in gemcitabine-resistant pancreatic cancer cells, and that miR-7 acted as an important regulator of cellular senescence by targeting poly (ADP-ribose) polymerase 1 (PARP1)/NF-κB signaling. When miR-7 expression was restored, it was able to sensitize pancreatic cancer cells to gemcitabine. In conclusion, the present study demonstrated that miR-7 regulated cellular senescence and relieved gemcitabine resistance by targeting the PARP1/NF-κB axis in pancreatic cancer cells., (Copyright: © Ye et al.)

Purpose: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality., Methods: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality., Results: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19., Conclusions: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist.

Background: Aberrant DNA methylation is significantly associated with breast cancer., Methods: In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis., Results: In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994-1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976-1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival., Conclusions: Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

Motivation: Despite of the lack of folded structure, intrinsically disordered regions (IDRs) of proteins play versatile roles in various biological processes, and many nonsynonymous single nucleotide variants (nsSNVs) in IDRs are associated with human diseases. The continuous accumulation of nsSNVs resulted from the wide application of NGS has driven the development of disease-association prediction methods for decades. However, their performance on nsSNVs in IDRs remains inferior, possibly due to the domination of nsSNVs from structured regions in training data. Therefore, it is highly demanding to build a disease-association predictor specifically for nsSNVs in IDRs with better performance., Results: We present IDRMutPred, a machine learning-based tool specifically for predicting disease-associated germline nsSNVs in IDRs. Based on 17 selected optimal features that are extracted from sequence alignments, protein annotations, hydrophobicity indices and disorder scores, IDRMutPred was trained using three ensemble learning algorithms on the training dataset containing only IDR nsSNVs. The evaluation on the two testing datasets shows that all the three prediction models outperform 17 other popular general predictors significantly, achieving the ACC between 0.856 and 0.868 and MCC between 0.713 and 0.737. IDRMutPred will prioritize disease-associated IDR germline nsSNVs more reliably than general predictors., Availability and Implementation: The software is freely available at http://www.wdspdb.com/IDRMutPred., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press.)

Objective: To investigate the early changes in serum osteoprotegerin/receptor activator of nuclear factor-κB ligand (RANKL) and related indexes of calcium and phosphorus in severe burn patients. Methods: Thirty severe burn patients who met the inclusion criteria and were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital within 8 hours post injury from June 2017 to December 2018 were recruited into severe burn group (24 males and 6 females, aged (38±13) years). Ten healthy volunteers with normal physical examination results in the Physical Examination Center of the same hospital in the same period of time were recruited into healthy control group (7 males and 3 females, aged (37±8) years). A prospective controlled study was conducted. The fasting venous blood of 5 mL was taken from each patient in severe burn group on post injury day (PID) 1, 7, 14, 21, and 28, respectively, and the fasting venous blood of 5 mL was taken from each volunteer in healthy control group. The serum osteoprotegerin, RANKL, 25 hydroxyvitamin D, and parathyroid hormone (PTH) levels were determined by enzyme-linked immunosorbent assay, and the RANKL/osteoprotegerin ratio was calculated. Serum albumin, serum calcium, and serum phosphorus levels were determined by bromocresol green method, methylthymol blue method, and phosphomolybdic acid method, respectively. Data were statistically analyzed with Fisher's exact probability test, analysis of variance for repeated measurement, Mann-Whitney U test, independent sample t test, and Bonferroni correction. Results: (1) The serum osteoprotegerin levels of patients in severe burn group on PID 1, 7, 14, 21, and 28 were 155.11 (102.91, 187.02), 170.07 (84.60, 196.86), 174.95 (59.09, 208.35), 190.01 (47.08, 214.52), and 188.85 (58.73, 223.13) pg/mL, respectively, which were significantly higher than 33.34 (28.59, 45.68) pg/mL of volunteers in healthy control group, Z =-3.436, -4.311, -3.248, -2.811, -4.217, P <0.01. The serum levels of RANKL of patients in severe burn group on PID 1, 7, 14, 21, and 28 were (1 869±791), (1 746±857), (1 781±713), (2 015±825), and (2 272±583) pg/mL, respectively, significantly higher than (49±16) pg/mL of volunteers in healthy control group, t =12.600, 10.844, 13.294, 13.041, 20.880, P <0.01. The ratios of RANKL/osteoprotegerin of patients in severe burn group on PID 1, 7, 14, 21, and 28 were 12.23 (8.10, 24.73), 11.40 (8.25, 16.96), 11.15 (6.91, 38.32), 12.98 (9.22, 49.68), and 13.91 (10.29, 40.68), respectively, which were significantly higher than 1.17 (0.91, 1.74) of volunteers in healthy control group, Z =-4.560, -4.529, -4.529, -4.560, -4.623, P <0.01. (2) The serum level of 25 hydroxyvitamin D of patients in severe burn group on PID 1 was significantly lower than that of volunteers in healthy control group ( Z =-2.749, P <0.01). Compared with those of volunteers in healthy control group, the serum levels of albumin of patients in severe burn group on PID 1, 7, 14, 21, and 28 were significantly lower ( t =-4.374, -7.689, -8.257, -7.651, -6.259, P <0.01), the serum levels of PTH were significantly elevated ( Z =-4.685, -4.685, -4.685, -4.654, -4.685, P <0.01), and the serum levels of phosphorus were not changed significantly. The serum levels of calcium of patients in severe burn group on PID 1, 7, 14, and 21 were significantly lower than the level of volunteers in healthy control group ( Z =-2.375, -3.455, -2.442, -2.016, P <0.05 or P <0.01). Conclusions: The serum osteoprotegerin, RANKL, RANKL/osteoprotegerin ratio, and PTH are increased, and the serum 25 hydroxyvitamin D, albumin, and calcium are decreased in the early stage of severe burn patients, which may be the mechanism leading to bone loss in patients.

Background: Herpes simplex virus type 1 (HSV-1)-mediated oncolytic therapy is a promising cancer treatment modality. However, viral tropism is considered to be one of the major stumbling blocks to the development of HSV-1 as an anticancer agent., Methods: The surface of oncolytic HSV-1 G207 was covalently modified with folate-poly (ethylene glycol) conjugate (FA-PEG). The specificities and tumor targeting efficiencies of modified or unmodified G207 particles were analyzed by a real-time polymerase chain reaction at the level of cell attachment and entry. Immune responses were assessed by an interleukin-6 release assay from RAW264.7 macrophages. Biodistribution and in vivo antitumoral activity after intravenous delivery was evaluated in BALB/c nude mice bearing subcutaneous KB xenograft tumors., Results: FA-PEG-HSV exhibited enhanced targeting specificity for folate receptor over-expressing tumor cells and had lower immunogenicity than the unmodified HSV. In vivo, the FA-PEG-HSV group revealed an increased anti-tumor efficiency and tumor targeting specificity compared to the naked HSV., Conclusions: These results indicate that folate-conjugated HSV G207 presents a folate receptor-targeted oncolytic virus with a potential therapeutic value via retargeting to tumor cells., (© 2020 John Wiley & Sons, Ltd.)

Objective: To investigate the causes of death and etiological characteristics of skin tissue donors, and to provide reference for allogeneic skin transplantation. Methods: From October 2008 to October 2018, 49 skin tissue donors accepted by the Burn Department of Wuhan Third Hospital met the inclusion criteria of this study, and a cross-sectional study was conducted. According to the cause of death, the donors were divided into accidental death group (19 cases) and non-accidental death group (30 cases). The sex and death age of 49 donors were recorded, and the death age between different sex donors and that of donors between accidental death group and non-accidental death group were compared. Diseases or circumstances that caused the death of donors, hepatitis B, hepatitis C, acquired immunodeficiency syndrome, syphilis virus carrying status, and peripheral blood microbial culture results of 49 donors were recorded, and the detection of blood-borne infectious risk factors of donors between accidental death group and non-accidental death group was compared. Abnormal skin tissue was also selected during allogenic skin graft preparing for pathological examination. Data were statistically analyzed with Mann-Whitney U test and continuity correction chi-square test. Results: (1) Out of the 49 donors in this group, 38 were male (77.55%) and 11 were female (22.45%). The death age was 42.00 (24.00, 55.00) years, and the death age of male donors was similar to that of female donors ( Z =0.120, P >0.05). The death age of donors in accidental death group was lower than that in non-accidental death group, but the difference was not statistically significant ( Z =-1.581, P >0.05). (2) Among the causes and circumstances of the 49 donors in this group, there were 19 cases (38.78%) of injury, poisoning, and some other consequences of external causes, 11 cases (22.45%) of circulatory system diseases, 9 cases (18.37%) of tumors, 3 cases (6.12%) of nervous system diseases, 2 cases (4.08%) of respiratory system diseases, and 2 cases (4.08%) of congenital malformation, deformation, and chromosome abnormality, 1 case (2.04%) of blood and hematopoietic organ diseases and some diseases related to immune mechanism, 1 case (2.04%) of digestive system disease, and 1 case (2.04%) of genitourinary system disease. (3) There were 9 donors (18.37%) with blood-borne infectious risk factors among the 49 donors in this group, including 8 cases (16.33%) of blood-borne infectious diseases, which were 5 cases (10.20%) of hepatitis B, 2 cases (4.08%) of syphilis, and 1 case (2.04%) of hepatitis C, respectively. Blood microorganism culture was positive in 1 case (2.04%), in which multi-drug resistant Pseudomonas aeruginosa was detected. Risk factors of blood-borne infection were detected in 2 donors in accidental death group, with detection ratio lower than that in non-accidental death group (7 cases), but the difference was not statistically significant ( χ (2)=0.562, P >0.05). (4) A total of 8 donors' abnormal skin tissue were selected, including 4 cases of intradermal pigmented nevus, 1 case of scar, 1 case of pseudoepithelioma hyperplasia, 1 case of epidermal verrucous hyperplasia, and 1 case of large amount of pigment granules in dermis. Conclusions: Non-accidental death caused by diseases is the main cause of death of skin tissue donors, and the risk of donor-derived infection of non-accidentally dead donors is slightly higher than that of accidentally dead donors. Before the allogeneic skin is obtained and transplanted, the cause of death of the donor should be carefully investigated, and the health status should be evaluated, so as to avoid the occurrence of donor-derived infection.

Background: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome., Aim: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity., Methods: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data., Results: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group ( P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD., Conclusion: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

MicroRNAs play critical roles in tumor progression. Our recent study has indicated that microRNA-7 (miR-7) impairs autophagy-derived pools of glucose to suppress the glycolysis in pancreatic cancer progression. However, the roles of miR-7 in clinical significance and chemoresistance of pancreatic cancer remain unexplored. The aim of this study was to assess the expression of miR-7 in patients with pancreatic cancer and to evaluate the possibility of its usage as a prognostic molecular biomarker. MicroRNA array-based quantification analysis of 372 miRNAs was compared in serum between pancreatic cancer and healthy individuals, gemcitabine-sensitive and gemcitabine-resistance patients. We identified miR-7 showed the potential predictive power for gemcitabine-sensitive patients with pancreatic cancer. Then, the results were validated in pancreatic tissue microarray and The Cancer Genome Atlas (TCGA) dataset, demonstrating that lower miR-7 expression was correlated with more advanced tumor stages and worse prognosis in pancreatic cancer. The Cox proportional-hazards model analysis identified miR-7 to be an independent variable for prediction of the survival. Furthermore, the mechanistic exploration suggested the clinical significance of miR-7 involved its interference effect on autophagy and glycolysis in pancreatic cancer using pancreatic cancer tissue microarrays and TCGA data. Therefore, the results of the present study provide evidences that low microRNA-7 expression may contribute to tumor progression and poor prognosis in pancreatic cancer., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Zhi-qiang Ye et al.)

Summary: The WD40-repeat proteins are a large family of scaffold molecules that assemble complexes in various cellular processes. Obtaining their structures is the key to understanding their interaction details. We present WDSPdb 2.0, a significantly updated resource providing accurately predicted secondary and tertiary structures and featured sites annotations. Based on an optimized pipeline, WDSPdb 2.0 contains about 600 thousand entries, an increase of 10-fold, and integrates more than 37 000 variants from sources of ClinVar, Cosmic, 1000 Genomes, ExAC, IntOGen, cBioPortal and IntAct. In addition, the web site is largely improved for visualization, exploring and data downloading., Availability and Implementation: http://www.wdspdb.com/wdsp/ or http://wu.scbb.pkusz.edu.cn/wdsp/., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)

Bevacizumab (BEV) is widely used for the treatment of patients with recurrent glioblastoma (GBM), but recent evidence demonstrated that BEV induced cytoprotective autophagy, which allows tumor cells to survive. Hydroxychloroquine (HCQ) inhibits lysosomal acidification and blocks autophagy via influencing autophagosome fusion and degradation. HCQ is often used to enhance the efficacy of chemoradiotherapy. However, whether HCQ sensitizes GBM cells to BEV and the molecular mechanism of this effect are not clear. We showed that high concentrations of BEV increased the LC3-II/LC3-I ratio and caused the degradation of Beclin1 in the LN18 and LN229 cell lines, indicating that high concentrations of BEV induced the autophagy of the LN18 and LN229 cells. However, BEV (100 μg/ml) did not influence the autophagy of the LN18 and LN229 cells, and HCQ at less than 5 μg/ml significantly accumulated LC3B-II and p62 proteins and blocked the autophagy process. Importantly, we found that HCQ (5 μg/ml) potentiated the anti-cancer effect of BEV (100 μg/ml). Therefore, HCQ is a novel strategy that may augment the efficacy of BEV for GBM via the inhibition of autophagy., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Scope: Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder, with increasing incidence worldwide but unknown etiology. 6-Gingerol (6-GIN), a major dietary compound found in ginger rhizome, has immunomodulatory activity. However, its role in autoimmune diseases, as well as the underlying mechanisms, are unclear. In this study, it is evaluated if 6-GIN can effectively ameliorate the clinical disease severity of experimental autoimmune encephalomyelitis, an animal model of MS., Methods and Results: Clinical scores of experimental autoimmune encephalomyelitis (EAE) mice are recorded daily. Inflammation of periphery and neuroinflammation of EAE mice are determined by flow cytometry analysis, ELISA, and histopathological analysis, and results show that 6-GIN significantly inhibits inflammatory cell infiltration from the periphery into the central nervous system and reduces neuroinflammation and demyelination. Flow cytometry analysis, ELISA, and quantitative PCR show that 6-GIN could suppress lipolysaccharide-induced dendritic cell (DC) activation and induce the tolerogenic DCs. Immunoblot analysis reveals that the phosphorylation of nuclear factor-κB and mitogen-activated protein kinase, two critical regulators of inflammatory signaling, are significantly inhibited in 6-GIN-treated DCs., Conclusion: The results of this study demonstrate that 6-GIN has significant potential as a novel anti-inflammatory agent for the treatment of autoimmune diseases such as MS via direct modulatory effects on DCs., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Scopoletin, a phenolic coumarin derived from many medical or edible plants, is involved in various pharmacological functions. In the present study, we showed that Scopoletin effectively ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through novel regulatory mechanisms involving inhibition of NF-κB activity in dendritic cells (DCs). Scopoletin treatment significantly improved the severity of the disease and prominently decreased inflammation and demyelination of central nervous system (CNS) in EAE mice. Disease alleviation correlated with the downregulation of major histocompatibility complex (MHC) class II, CD80 and CD86, expressed on DCs of CNS or spleens, and the infiltration and polarization of encephalitogenic Th1/Th17 cells. Consistent with the in vivo data, Scopoletin-treated, bone marrow-derived dendritic cells (BM-DCs) exhibited reduced expression of MHC class II and costimulatory molecules (e.g., CD80 and CD86) and reduced NF-κB phosphorylation. These findings, for the first time, demonstrated the ability of Scopoletin to impair DC activation, downregulating pathogenic Th1/Th17 inflammatory cell responses and, eventually, reducing EAE severity. Our study demonstrates new evidence that natural products derived from medical or edible plants, such as Scopoletin, will be valuable in developing a novel therapeutic agent for MS in the future.

Breast milk is recognized and strongly recommended by the World Health Organization (WHO) as the optimal feeding for all babies. Breastfeeding is associated with better nutritional and non-nutritional outcomes when compared to formula feeding, and has proven health benefits to both infants and their mothers. This clinical research is to examine the feasibility and efficacy of Acupoint-Tuina therapy in treating postpartum women who underwent C-sections and suffered from insufficient milk production.The patients in the control group received standard medical care, while the patients in the Tuina group received Tuina therapy during the next 48 hours in addition to standard care, given once daily for 2 days. To evaluate the efficacy of Tuina therapy, patients of both groups were assessed for surface temperature of breasts, volume of breasts, volume of breast milk production, serum PRL level, and uterus recovery at various time points.Tuina therapy significantly increased the milk production when compared to the control group, for as much as 13-fold and 10-fold of that in the control group on the third and fourth postpartum days. In addition, Tuina therapy also significantly increased the full breast enlargement and the serum PRL level change, and decreased the breast surface temperature rise. Last but not the least, Tuina therapy also accelerated the post-surgery recovery of uterus.During the early postpartum days, Tuina therapy increases the milk production and promotes other physiological changes supporting lactation for postpartum women with C-section delivery and insufficient breast milk production. The novel intervention is warranted for further investigation and validation.

Oligodendrocyte progenitor cells (OPCs) are a subtype of glial cells responsible for myelin regeneration. Oligodendrocytes (OLGs) originate from OPCs and are the myelinating cells in the central nervous system (CNS). OLGs play an important role in the context of lesions in which myelin loss occurs. Even though many protocols for isolating OPCs have been published, their cellular yield remains a limit for clinical application. The protocol proposed here is novel and has practical value; in fact, OPCs can be generated from a source of autologous cells without gene manipulation. Our method represents a rapid, and high-efficiency differentiation protocol for generating mouse OLGs from bone marrow-derived cells using growth-factor defined media. With this protocol, it is possible to obtain mature OLGs in 7-8 weeks. Within 2-3 weeks from bone marrow (BM) isolation, after neurospheres formed, the cells differentiate into Nestin + Sox2 + neural stem cells (NSCs), around 30 days. OPCs specific markers start to be expressed around day 38, followed by RIP + O4 + around day 42. CNPase + mature OLGs are finally obtained around 7-8 weeks. Further, bone marrow-derived OPCs exhibited therapeutic effect in shiverer (Shi) mice, promoting myelin regeneration and reducing the tremor. Here, we propose a method by which OLGs can be generated starting from BM cells and have similar abilities to subventricular zone (SVZ)-derived cells. This protocol significantly decreases the timing and costs of the OLGs differentiation within 2 months of culture.

Introduction: Standard bi-level non-invasive ventilation with fixed-level pressure support (PS) delivery may not maintain ventilation during the changes in pulmonary mechanics that occur throughout day and night, so average volume-assured pressure support (AVAPS) modes that target a preset volume by adjustment of PS may be effective., Objective: Our meta-analysis wants to compare AVAPS and pressure support non-invasive ventilation (PS-NIV) regarding arterial blood gases (ABGs), sleep efficiency and compliance., Method: Relevant publications indexed in PubMed, Cochrane Library, Embase, Web of Science, Wanfang Data, China National Knowledge Infrastructure and VIPI were identified. Appropriate articles identified from the reference lists of the above searches were also reviewed. We included randomized controlled trials involved the use of AVAPS and PS-NIV ventilation for chronic respiratory failure. Each included study weighted mean differences, and 95% confidence intervals (CI) were calculated for continuous outcomes. Statistical heterogeneity was assessed using the I 2 value ≤ 50% were considered as no statistical heterogeneity and used fixed effects model. Otherwise, a random effects model was used., Results: Eight trials were eligible. No significant difference was observed between AVAPS and PS-NIV groups to compare PaCO 2 (OR -0.97, CI-2.54-0.61, P = 0.23) and PaO 2 (OR -1.81, CI-4.29-0.67, P = 0.15) in ABGs. There was no significant difference between the two groups with sleep efficiency (OR -3.31, CI-7.58-0.95, P = 0.13) and visual analog scale (OR 0.32, CI-6.97-7.61, P = 0.93)., Conclusions: The evidence shows there is no significant difference in clinical outcomes when comparing AVAPS and PS-NIV used for chronic respiratory failure patients., (© 2019 John Wiley & Sons Ltd.)