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Ling Jin,1,2,&ast; Kai Fan,1,2,&ast; Chunyan Yao,1,&ast; Yongjun Chang,1 Yang Wang,1 Jiawei Lu,1 Shaoqing Yu1,2 1Department of Otolaryngology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China; 2Department of Allergy,Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqing Yu, Department of Otolaryngology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of China, Tel/Fax +8602166111042, Email yu_shaoqing@163.comPurpose: The treatment of chronic rhinosinusitis (CRS) is often a difficult and long-term behavior, so it is necessary to seek a local treatment method that can be used for a long time, and is safe and effective. Nasal saline irrigation after functional endoscopic sinus surgery (FESS) is currently recognized as a local treatment method, but it has no anti-inflammatory, anti-damage, and healing-promoting functions. To investigate the efficacy and safety of hydrogen-rich saline (HRS) for nasal irrigation after CRS surgery.Patients and Methods: A total of 61 patients after CRS completed the study. Subjects were randomly assigned to rinse the nasal cavity with HRS or normal saline (NS) after CRS. Participants were followed up once a week for 12 times, and were evaluated with visual analogue score (VAS), 22-item Sinonasal Outcomes Test (SNOT-22), and Lund-Kennedy endoscopy scores (LKES). The primary outcome was the VAS score of patients.Results: After 12 weeks of follow-up, the VAS scores of both groups decreased, and the HRS group (0.52± 0.85) was lower than the NS group (1.47± 1.55), P=0.005. The total number of cases with complete control (clinical cure) in the short-term efficacy evaluation was more in the HRS group (20/31) than in the NS group (11/30), P=0.03< 0.05. No obvious adverse reactions occurred in the two groups during the follow-up.Conclusion: This study found that HRS was more effective than NS alone in nasal irrigation after CRS surgery, and could shorten the time of nasal mucosal healing and epithelialization, with a higher rate of recent complete control.Keywords: physiological saline, hydrogen -rich saline, nasal irrigation, chronic rhinosinusitis, endoscopic sinus surgery

Wen-Jia Li,1,&ast; Chen Yao,2,&ast; Lu Han,1 Ji-Hong Zhou,1 Rui-Ming Pang2 1Department of Pulmonary and Critical Care Medicine, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China; 2Department of Orthopedics and Traumatology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ji-Hong Zhou, Department of Pulmonary and Critical Care Medicine, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China, Email zjh14569@163.com Rui-Ming Pang, Department of Orthopedics and Traumatology, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen City, People’s Republic of China, Email prm1757607@163.comBackground: The associations between gut microbiota and chronic obstructive pulmonary disease (COPD) have gained increasing attention and research interest among scholars. However, it remains unclear whether gut microbiota serves as a causal factor for COPD or if it is a consequence of the disease. Therefore, we investigated the causal relationship between COPD and gut microbiota, with intention of providing novel insights and references for clinical diagnosis and treatment.Methods: Based on the genome-wide association study (GWAS) data, we employed MR-Egger regression, random-effects inverse variance-weighted (IVW) method, and weighted median method for bidirectional Mendelian randomization (MR) analysis. We conducted Cochran’s Q test for heterogeneity assessment and performed multivariable analysis, sensitivity analysis, and heterogeneity testing to validate the reliability and stability of results.Results: Utilizing MR analysis, mainly employing the IVW method, we detected a collective of 11 gut microbiota species that exhibited associations with COPD. Among them, Bacteroidia, family XIII, Clostridium innocuum group, Barnesiella, Collinsella, Lachnospiraceae NK4A136 group, Lachnospiraceae UCG004, Lachnospiraceae UCG010, and Bacteroidales were found to be protective factors for COPD. On the other hand, Holdemanella and Marvinbryantia were identified as risk factors for COPD. Individuals with elevated levels of Holdemanella exhibited a 1.141-fold higher risk of developing COPD compared to their healthy counterparts, and those with increased levels of Marvinbryantia had a 1.154-fold higher risk. Reverse MR analysis yielded no evidence indicating a causal relationship between gut microbiota and COPD occurrence.Conclusion: Our study established a causal link between 11 specific gut microbiota species and COPD, offering novel insights and valuable references for targeted therapies in the clinical management of COPD. However, our results were mainly based on the analysis of database, and further clinical studies are needed to clarify the effects of gut microbiota on COPD and its specific protective mechanism.Keywords: gut microbiota, COPD, bidirectional MR, causal, association

Jiong Li,1 Dongqin Lei,1 Yanbing Cao,2,3 Fuli Xin,2,3 Zhenxi Zhang,1 Xiaolong Liu,2,3 Ming Wu,2,3 Cuiping Yao1 1Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 3Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People’s Republic of ChinaCorrespondence: Ming Wu, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xi Hong Road, Fuzhou, 350025, People’s Republic of China, Email wmmj0419@163.com Cuiping Yao, School of Life Science and Technology, Xi’an Jiaotong University, 28 Xian Ning West Road, Xi’an, 710049, People’s Republic of China, Email zsycp@xjtu.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy.Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.Keywords: 2D porphyrin MOF, hypoxic relief, Pt nanozyme, photodynamic therapy

1. Biodiversity is an important component of natural ecosystems, with higher species richness often correlating with an increase in ecosystem productivity. Yet, this relationship varies substantially across environments, typically becoming less pronounced at high levels of species richness. However, species richness alone cannot reflect all important properties of a community, including community evenness, which may mediate the relationship between biodiversity and productivity. If the evenness of a community correlates negatively with richness across forests globally, then a greater number of species may not always increase overall diversity and productivity of the system. Theoretical work and local empirical studies have shown that the effect of evenness on ecosystem functioning may be especially strong at high richness levels, yet the consistency of this remains untested at a global scale. 2. Here, we used a dataset of forests from across the globe, which includes composition, biomass accumulation and net primary productivity, to explore whether productivity correlates with community evenness and richness in a way that evenness appears to buffer the effect of richness. Specifically, we evaluated whether low levels of evenness in speciose communities correlate with the attenuation of the richness–productivity relationship. 3. We found that tree species richness and evenness are negatively correlated across forests globally, with highly speciose forests typically comprising a few dominant and many rare species. Furthermore, we found that the correlation between diversity and productivity changes with evenness: at low richness, uneven communities are more productive, while at high richness, even communities are more productive. 4. Synthesis. Collectively, these results demonstrate that evenness is an integral component of the relationship between biodiversity and productivity, and that the attenuating effect of richness on forest productivity might be partly explained by low evenness in speciose communities. Productivity generally increases with species richness, until reduced evenness limits the overall increases in community diversity. Our research suggests that evenness is a fundamental component of biodiversity–ecosystem function relationships, and is of critical importance for guiding conservation and sustainable ecosystem management decisions.

Lu Zhang,1– 3,&ast; Fei Teng,1,2,&ast; Huajie Xin,1,2 Wei Xu,1,2 Wei Wu,4 Chenguo Yao,3 Zhiqiang Wang1,2 1Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Center of Thoracic Cancer, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3The State Key Laboratory of Power Transmission Equipment and System Security and New Technology, College of Electrical Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China; 4College of Biological Engineering, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Zhang; Zhiqiang Wang, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Email luzhang_524@aliyun.com; zhiqiangwang@21cn.comAbstract: Patients diagnosed with glioma typically face a limited life expectancy (around 15 months on average), a bleak prognosis, and a high likelihood of recurrence. As such, glioma is recognized as a significant form of malignancy. Presently, the treatment options for glioma include traditional approaches such as surgery, chemotherapy, and radiotherapy. Regrettably, the efficacy of these treatments has been less than optimal. Nevertheless, a promising development in glioma treatment lies in the use of hydrogel nano-systems as sophisticated delivery systems. These nano-systems have demonstrated exceptional therapeutic effects in the treatment of glioma by various responsive ways, including temperature-response, pH-response, liposome-response, ROS-response, light-response, and enzyme-response. This study seeks to provide a comprehensive summary of both the therapeutic application of hydrogel nano-systems in managing glioma and the underlying immune action mechanisms. Keywords: glioma, hydrogel nano-system, immunotherapy, tumor immune microenvironment

Yueda Jihu,1,2,&ast; Ruobing Leng,1,&ast; Mengchang Liu,1,2 Hongjing Ren,1,2 Defu Xie,1,2 Chong Yao,1,2 Hong Yan1,2 1Clinical College of Medicine, Southwest Medical University, Lu zhou, People’s Republic of China; 2Department of Plastic and Burn Surgery, the Affiliated Hospital of Southwest Medical University, Lu zhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Yan, Email zxsswk@163.comIntroduction: Angiotensin (1– 7) (Ang-(1-7)) is an emerging component of the renin-angiotensin system (RAS) with effective anti-fibrosis properties and has been shown to interfere with epithelial-mesenchymal transition (EMT) by numerous studies. In recent years, EMT has been proposed as a new therapeutic target for skin fibrotic diseases such as keloids. However, the effect of Ang-(1-7) on EMT in skin is still unclear. Hence, the purpose of this study was to explore the effect of Ang-(1-7) on Transforming growth factor-β 1(TGF-β 1)–induced EMT of human immortalized keratinocytes HaCaT in vitro.Methods: The study involved the use of the human immortalized keratinocyte cell line (HaCaT). The cells were cultured in high-glucose DMEM medium with 10% fetal bovine serum and 1% penicillin-streptomycin. Four groups were created for experimentation: control group (Group C), TGF-β 1-treated group (Group T), Ang-(1-7)-treated group (Group A), and a group treated with both TGF-β 1 and Ang-(1-7) (Group A + T). Various assays were conducted, including a cell proliferation assay using CCK-8 solution, a scratch wound healing assay to evaluate cell migration, and Western blotting to detect protein expressions related to cell characteristics. Additionally, quantitative real-time polymerase chain reaction (PCR) was performed to analyze epithelial-mesenchymal transition (EMT) related gene expression levels. The study aimed to investigate the effects of TGF-β 1 and Ang-(1-7) on HaCaT cells.Results: We found that Ang-(1-7) not only reduced the migration of HaCaT cells induced by TGF-β 1 in vitro but also reduced the expression of α-SMA and vimentin, and restored the protein expression of E-cadherin and claudin-1. Mechanistically, Ang-(1-7) inhibits the phosphorylation levels of Smad2 and Smad3 in the TGF-β 1 canonical pathway, and suppresses the expression of EMT-related transcription factors (EMT-TFs) such as SNAI2, TWIST1, and ZEB1.Discussion: Taken together, our findings suggest that Ang-(1-7) inhibits TGF-β 1–induced EMT in HaCaT cells in vitro by disrupting the TGF-β 1-Smad canonical signaling pathway. These results may be helpful in the treatment of EMT in skin fibrotic diseases such as keloids.Keywords: angiotensin (1-7), epithelial-mesenchymal transition, transforming growth factor-β, keratinocytes

Guiyun Zhang,1 Yufeng Lu,2 Lin Qi,1 Chunli Yao1 1Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Thoracic Surgery, Sino-Japanese Friendship Hospital of Jilin University, Changchun, 130012, People’s Republic of ChinaCorrespondence: Chunli Yao, Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China, Tel +86-431-81136244, Email ycl@jlu.edu.cnIntroduction: Rare studies have reported pilomatricoma in twins, and extremely rare cases showed lesions in the same part of the body position. We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper extremity.Case Presentation: Seven-year-old monozygotic twins presented to our department with a palpable, painless, and solid mass in the subcutaneous tissue of the right upper limb. A 1.5-cm diameter nodule was seen on the anterolateral aspect of the right upper extremity of the twins. The node was irregular in shape, and upon palpation, the patients reported no noticeable tenderness. Following the administration of local anesthesia, the twins underwent surgical procedure to excise the solid mass. Finally, they were diagnosed with pilomatricoma based on the clinical and histopathological features. Complete surgical resection followed by primary closure was performed. During a follow-up period of three years, there has been no recurrence observed in the twins.Conclusion: We reported a case of monozygotic twins with pilomatricoma in the same location on the skin of the right upper arm. Our findings underscore the requirement of considering genetic factors in the diagnosis and treatment of the rare conditions.Keywords: pilomatricoma, pilomatrixoma, calcifying epithelioma of malherbe, case report

Changyu Yao,&ast; Jian Kong,&ast; Fei Xu, Shaohong Wang, Shilun Wu, Wenbing Sun, Jun Gao Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbing Sun; Jun Gao, Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital, Capital Medical University, No. 5 Jingyuan Road, Shijingshan District, Beijing, 100043, People’s Republic of China, Tel +86-010-51718382, Fax +86-010-51718372, Email sunwenbing@bjcyh.com; gaojun8430@163.comPurpose: Systemic inflammatory response syndrome (SIRS) is a common complication of radiofrequency ablation (RFA) for hepatic hemangiomas. RFA can cause hemolytic reactions during hepatic hemangioma ablation. However, the mechanisms underlying RFA-induced SIRS remain unclear.Methods: We established an orthotopic liver hemangioma model and performed radiofrequency ablation. The levels of interleukin (IL)-1β and IL-18 and the production of ROS were measured. The wet-to-dry lung ratio, inflammation score, and in vivo endothelial cell permeability were examined. GSDMD−/− mice were used to investigate the effect of heme-inducing SIRS. RNA sequencing (RNA-seq) was performed to identify the main pathways underlying heme-induced SIRS. Western blotting and immunoprecipitation were used to determine the changes and interactions of associated proteins.Results: The levels of heme, IL-1β, and IL-18 were significantly increased after RFA. The wet-to-dry lung ratio increased in hepatic hemangiomas after RFA, indicating that SIRS occurred. Heme induced increased levels of IL-1β and IL-18, cell death, wet-to-dry lung radio, and inflammation score in vitro and in vivo, indicating that heme induced SIRS and pyroptosis. Furthermore, GSDMD participates in heme-induced SIRS in mice, and GSDMD deletion in mice reverses the effect of heme. Heme regulates NLRP3 activation through the NOX4/ROS/TXNIP-TRX pathway, and an N-acetyl-L-cysteine (NAC) or NOX4 inhibitor (GLX351322) reverses heme-induced SIRS.Conclusion: Our findings suggest that heme induces endothelial cell pyroptosis and SIRS in mice and decreasing heme levels and ROS scavengers may prevent SIRS in hepatic hemangioma after RFA. Keywords: hemangioma, radiofrequency ablation, systemic inflammatory response syndrome, pyroptosis, endothelial cells

Yu Zhou,1,&ast; Huoying Cai,1,&ast; Lin Huang,1,&ast; Mingshan Wang,1 Ruiming Liu,2 Siwen Wang,1 Yuansen Qin,1 Chen Yao,1 Zuojun Hu1 1Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Laboratory of Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuojun Hu; Chen Yao, Email huzuojun@mail.sysu.edu.cn; yaochen@mail.sysu.edu.cnBackground: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct.Methods and Results: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥ 200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO.Conclusion: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.Keywords: arteriosclerosis obliterans, circular RNA, gene ontology analysis, pathway analysis, circRNA-miRNA-mRNA interaction network

Tianhui Gao,1,&ast; Cong Yao,1,&ast; Yuanyuan Shang,1 Renchun Su,1 Xuxia Zhang,1 Weicong Ren,1 Shanshan Li,1 Wei Shu,2 Yu Pang,1 Qi Li2 1Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Clinical Center on Tuberculosis Control, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Li; Yu Pang, Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel/Fax +86 010 6954 6690 ; +86 10 8950 9366, Email lq0703@hotmail.com; pangyupound@163.comPurpose: Unsatisfactory efficacies of currently recommended anti-Mycobacterium abscessus complex (MABC) treatment regimens have led to development of novel drugs to combat MABC infections. In this study, we evaluated in vitro antimicrobial activities of bedaquiline (BDQ) and four oxazolidinones against MABC isolates.Methods: The resazurin microplate assay was performed to determine minimum inhibitory concentrations (MICs) of BDQ and four oxazolidinones, including tedizolid (TZD), sutezolid (SZD), delpazolid (DZD), and linezolid (LZD), against 65 MABC isolates. A checkerboard method was used to investigate efficacies of various antimicrobial drug combinations.Results: BDQ MICs for MABC isolates ranged from < 0.031 to 1 μg/mL, while MIC50 and MIC90 values were 0.125 μg/mL and 0.25 μg/mL, respectively. TZD MIC50 and MIC90 values for MABC isolates were 1 μg/mL and 4 μg/mL, respectively, which were fourfold lower than corresponding LZD values (P < 0.001). DZD MIC90 values for MABC isolates was 8 μg/mL, which were 0.5-fold lower than corresponding LZD values (P < 0.01). MICs of BDQ, SZD, and LZD for M. abscessus subspecies massiliense isolates were significantly lower than corresponding MICs for M. abscessus subspecies abscessus isolates (P < 0.05). Notably, use of oxazolidinones (DZD, SZD, LZD, or TZD) with BDQ against MABC isolates led to reduction of the oxazolidinone median MIC range from 4 to 0.125 μg/mL to 1– 0.031 μg/mL.Conclusion: These results demonstrated excellent BDQ inhibitory activity against MABC isolates. TZD exhibited stronger antimicrobial efficacy against MABC isolates as compared to efficacies of DZD, SZD, and LZD. Importantly, MICs of oxazolidinones were markedly decreased when they were combined with BDQ, thus suggesting that combinations of BDQ and oxazolidinones may be effective treatments for MABC infections.Keywords: bedaquiline, tedizolid, oxazolidinones, susceptibility testing, Mycobacterium abscessus complex, delpazolid

Brandon Tejada,1,2 Roby Joehanes,1,2 Shih-Jen Hwang,1,2 Tianxiao Huan,1– 3 Chen Yao,1,2 Jennifer E Ho,4 Daniel Levy1,2,5 1Framingham Heart Study, Framingham, MA, USA; 2Population Sciences Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA; 3Ophthalmology and Visual Sciences, University of Massachusetts Medical School, Worcester, MA, USA; 4CardioVascular Institute and Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, Unites States; 5Boston University School of Medicine, Boston, MA, USACorrespondence: Daniel Levy, Framingham Heart Study, 73 Mt. Wayte Avenue, Suite 2, Framingham, MA, 01702, USA, Email Levyd@nih.govPurpose: Assessing an individual’s systemic inflammatory state is vital to understand inflammation’s role in cardiometabolic diseases and identify those at the greatest risk of disease. We generated global inflammation scores and investigated their associations with cardiometabolic risk factors and adverse outcomes.Patients and Methods: Aggregate Inflammation Scores (AIS) and Principal Component Analysis (PCA) scores were generated for 7287 Framingham Heart Study participants using up to 26 inflammation-related proteins, with higher scores reflecting a pro-inflammatory milieu. Multivariable regression and proportional hazards analyses were conducted to investigate the associations of inflammation with cardiometabolic risk factors and outcomes. The primary outcomes for cross-sectional analyses included age, cigarette smoking, fasting lipid and glucose levels, blood pressure, body mass index (BMI), and hypertension, diabetes, and obesity. For prospective analyses, new-onset hypertension, diabetes, obesity, cardiovascular disease and all-cause mortality were investigated.Results: Higher inflammation scores were associated with smoking and older age, higher BMI, systolic blood pressure, lipids, and glucose levels, and with greater odds of hypertension and diabetes after adjusting for age, sex, cohort, and BMI (all p < 0.001). Higher baseline scores were associated with greater odds of new-onset hypertension after adjusting for traditional risk factors (OR [95% CI] per one standard deviation [1-SD] increase, AIS: 1.33 [1.21– 1.47], PCA score: 1.26 [1.12– 1.42], p < 0.001). The AIS also was associated with new-onset diabetes (1.32 [1.14– 1.52], p < 0.001). Proportional hazards analyses revealed greater risk of new-onset cardiovascular disease events and all-cause mortality (HR [95% CI] per 1-SD, AIS: 1.25 [1.14– 1.37] and 1.32 [1.23– 1.42], PCA score: 1.22 [1.13– 1.33] and 1.40 [1.31– 1.49], p < 0.001).Conclusion: Global inflammation scores encompassing an array of pro- and anti-inflammatory proteins and pathways may enhance risk assessment for cardiometabolic diseases. The AIS and PCA scores provide further opportunities to investigate the mechanisms of inflammation-related risk of disease.Keywords: inflammation scores, cardiovascular disease, heart failure, pathways

Summary: While commonly treated as a uniform state in practice, rapid eye movement sleep contains two distinct microstructures—phasic (presence of rapid eye movement) and tonic (no rapid eye movement). This study aims to identify technical challenges during rapid eye movement sleep microstructure visual classification in patients with rapid eye movement sleep behaviour disorder, and to propose solutions to enhance reliability between scorers. Fifty‐seven sleep recordings were randomly allocated into three subsequent batches (n = 10, 13 and 34) for scoring. To reduce single‐centre bias, we recruited three raters/scorers, with each trained from a different institution. Two raters independently scored each 30‐s rapid eye movement sleep into 10 × fSEM3‐s phasic/tonic microstructures based on the AASM guidelines. The third rater acted as an "arbitrator" to resolve opposite opinions persisting during the revision between batches. Besides interrater differences in artefact rejection rate, interrater variance frequently occurred due to transitioning between microstructures and moderate‐to‐severe muscular/electrode artefact interference. To enhance interrater agreement, a rapid eye movement scoring schematic graph was developed, incorporating proxy electrode use, filters and cut‐offs for microstructure transitioning. To assess potential effectiveness of the schematic graph proposed, raters were instructed to systematically apply it in scoring for the third batch. Of the 34 recordings, 27 reached a Cohen's kappa score above 0.8 (i.e. almost perfect agreement between raters), significantly improved from the prior batches (p = 0.0003, Kruskal–Wallis test). Our study illustrated potential solutions and guidance for challenges that may be encountered during rapid eye movement sleep microstructure classification. [ABSTRACT FROM AUTHOR]

We propose an SPH‐based method for simulating viscoelastic non‐Newtonian fluids within a multiphase framework. For this, we use mixture models to handle component transport and conformation tensor methods to handle the fluid's viscoelastic stresses. In addition, we consider a bonding effects network to handle the impact of microscopic chemical bonds on phase transport. Our method supports the simulation of both steady‐state viscoelastic fluids and discontinuous shear behavior. Compared to previous work on single‐phase viscous non‐Newtonian fluids, our method can capture more complex behavior, including material mixing processes that generate non‐Newtonian fluids. We adopt a uniform set of variables to describe shear thinning, shear thickening, and ordinary Newtonian fluids while automatically calculating local rheology in inhomogeneous solutions. In addition, our method can simulate large viscosity ranges under explicit integration schemes, which typically requires implicit viscosity solvers under earlier single‐phase frameworks. [ABSTRACT FROM AUTHOR]

Microgrids have become increasingly popular in the United States. Supported by favorable federal and local policies, microgrid projects can provide greater energy stability and resilience within a project site or community. This paper reviews major federal, state, and utility-level policies driving microgrid development in the United States. Representative U.S. demonstration projects are selected and their technical characteristics and non-technical features are introduced. The paper discusses trends in the technology development of microgrid systems as well as microgrid control methods and interactions within the electricity market. Software tools for microgrid design, planning, and performance analysis are illustrated with each tool's core capability. Finally, the paper summarizes the successes and lessons learned during the recent expansion of the U.S. microgrid industry that may serve as a reference for other countries developing their own microgrid industries.

Wei Fang,1,&ast; Yu Zhang,1,&ast; Sinian Li,1,&ast; Aiming Liu,2,&ast; Yin Jiang,2 Dandan Chen,1 Binbin Li,3 Can Yao,3 Rongchang Chen,1 Fei Shi3 1Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen National Climate Observatory, Meteorological Bureau of Shenzhen Municipality, Shenzhen Key Laboratory of Severe Weather in South China, Shenzhen, Guangdong, People’s Republic of China; 3Emergency Department, Institute of Shenzhen Respiratory Diseases, Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongchang Chen; Fei Shi Email chenrc@vip.163.com; shi.fei@szhospital.comBackground: Reversible airflow obstruction (RO) and fixed airflow obstruction (FO) are two important clinical phenotypes of asthma. However, the relationship between air pollutant exposure and exacerbation of the two phenotypes is unknown.Objective: To study the effects of air pollutant exposure on exacerbation severity in asthma patients with or without FO.Methods: A total of 197 severe asthma patients were enrolled, and divided into two groups: the FO group (n=81) and the RO group (n=116). We collected the demographic data, laboratory parameters, pulmonary function test parameters, and the daily average concentrations of different air particles in Shenzhen on the different lag days of each subject. The receiver operating characteristic (ROC) curve was used to identify the effects of major air pollutants on the severity of asthma patients with RO.Results: Compared with the RO group, the FO group had fewer women, lower body mass index (BMI), longer disease duration, higher smoking history rate, allergic family history rate, FeNO level, and lower levels of large airway parameters. The median exposure levels of PM10 and PM2.5 in the severe RO subgroup were both higher than those in the mild-to-moderate RO subgroup on Lag0, 1 and 3, and the median exposure level of PM1 on Lag0 in the severe RO subgroup was significantly higher than that in the mild-to-moderate RO subgroup. Logistic regression modeling indicated exposure to PM2.5 and PM1.0 on Lag0, and PM10 on Lag0-2 were the independent risk factors for hospital admissions for asthma patients with RO. By performing an ROC curve analysis, PM2.5 on Lag0 (AUC = 0.645, p = 0.027) provided a best performance to predict severe asthma exacerbations with RO, with a sensitivity of 36.0% and a specificity of 91.2%.Conclusion: Short-term exposure to PM10, PM2.5 and PM1 may play a role in exacerbation severity among asthma patients with RO.Keywords: air particles, asthma, reversible airflow obstruction, fixed airflow obstruction

Jidong Guo,1,2,&ast; Qiang Li,1,&ast; Xuxia Zhang,2 Cong Yao,2 Rongmei Liu,1 Yu Pang,2 Mengqiu Gao1 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: : Yu PangDepartment of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9162Email pangyupound@163.comMengqiu GaoDepartment of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of ChinaTel/Fax +86-10-8950 9322Email gaomqwdm@aliyun.comIntroduction: Interferon-γ release assays (IGRAs) can have high false-negative rates for active tuberculosis (TB) cases. Here we investigated factors, including potential anti-inflammatory mechanisms, that contributed to false-negative IGRA results.Methods: We established two cohorts. In the first cohort, we reviewed IGRA results for confirmed TB cases diagnosed in our hospital in 2018. Cases with false-negative IGRA results were analysed to identify factors contributing to false-negative results. In the second cohort, we prospectively studied IL-10 expression levels in peripheral blood mononuclear cells (PBMCs) of IGRAs-positive and IGRAs-negative TB cases after antigenic stimulation to correlate IL-10 expression with IGRAs results.Results: Of 1232 culture-confirmed TB cases, 1124 produced true-positive IGRA results and 108 had false-negative IGRA results. Multivariate logistic regression analysis identified glucocorticoid use and extrapulmonary TB as independent risk factors for false-negative IGRA results. Notably, IL-10 expression of the IGRA-negative group was significantly up-regulated as compared to that of the IGRA-positive group. The average cell supernatant IL-10 concentration of the IGRA-negative group was 4.77 pg/mL, a value that was statistically greater than the IGRA-positive group concentration (1.47 pg/mL, P = 0.007). After PBMCs pretreatment with BRD6989 (to enhance IL-10 secretion), average IFN-γ concentrations in cell supernatants from the IGRA-positive group significantly decreased from 59.73 pg/mL to 33.79 pg/mL (P = 0.011). By contrast, addition of AS101 (to inhibit IL-10 secretion) to false-negative group PBMCs led to an increase of average IFN-γ concentration in cell supernatants from 19.01 pg/mL to 45.10 pg/mL (P = 0.030), a result that was inversely correlated with IL-10 concentration.Conclusion: Our data demonstrate that increased IL-10 secretion by PBMCs is inversely correlated with IGRA assay results in culture-confirmed TB patients. Glucocorticoids use and extrapulmonary TB are significantly associated with false-negative IGRA results. Combination testing to measure IL-10 secretion and IFN-γ release is recommended to improve IGRAs specificity.Keywords: tuberculosis, interferon-γ release assay, interleukin 10

Si Sun,1,* Weipu Mao,1– 3,* Shuchun Tao,1,* Xiangyu Zou,4 Shengwei Tian,1 Siwei Qian,1 Chi Yao,1 Guangyuan Zhang,1,2 Ming Chen1– 3 1Department of Urology, Zhongda Hospital, Southeast University, Nanjing, 210009, People’s Republic of China; 2Surgical Research Center, Institute of Urology, Southeast University Medical School, Nanjing, 210009, People’s Republic of China; 3Department of Urology, Nanjing Lishui District People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, 211200, People’s Republic of China; 4Department of Urology, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Chen; Guangyuan ZhangDepartment of Urology, Zhongda Hospital, Southeast University, No. 87 Dingjiaqiao, Hunan Road, Gulou District, Nanjing, 210009, People’s Republic of ChinaTel +86-139 13009977; +86-139 51658634Fax +86-139 13009977; +86-139 51658634Email mingchenseu@126.com; zgy0879@qq.comBackground: Polycyclic aromatic hydrocarbons (PAHs) exposure may cause various diseases. However, the association between PAHs exposure and kidney stones remains unclear. The purpose of this study was to examine the relationship between PAHs and the risk of kidney stones in the US population.Methods: The study included a total of 30,442 individuals (≥ 20 years) from the 2007– 2012 National Health and Nutrition Examination Survey (NHANES). Nine urinary PAHs were included in this study. Logistic regression and dose–response curves were used to evaluate the association between PAHs and the risk of kidney stones.Results: We selected 4385 participants. The dose–response curves showed a significant positive association between total PAHs, 2-hydroxynaphthalene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 9-hydroxyfluorene and the risk of kidney stones after adjusting for confounding factors. Compared with the low group, an increased risk of kidney stones was observed in the high group of total PAHs [OR (95% CI), 1.32 (1.06– 1.64), P=0.013], 2-hydroxynaphthalene [OR (95% CI), 1.37 (1.10– 1.71), P=0.005], 1-hydroxyphenanthrene [OR (95% CI), 1.24 (1.00– 1.54), P=0.046] and 9-hydroxyfluorene [OR (95% CI), 1.36 (1.09– 1.70), P=0.007].Conclusion: High levels of PAHs were positively associated with the risk of kidney stones in the US population.Keywords: polycyclic aromatic hydrocarbons, kidney stones, NHANES, cross-sectional survey

Summary: Background: Dietary management of patients with inflammatory bowel disease (IBD) involves more than defining a therapeutic diet. The profusion of 'expert advice' is not necessarily built on evidence. Aims: To provide evidence‐based guidance on all clinically relevant aspects of nutritional and dietary management of patients with IBD. Methods: A comprehensive review of the published literature was made. Results: Four pillars of management should be considered in all patients. First, nutritional status should be optimised, since myopenia and visceral obesity are associated with poorer outcomes, which can be improved with attention to their correction. Accurate point‐of‐care measurement of body composition is advocated to identify problems, guide interventions and monitor outcomes. Second, exclusive enteral nutrition and the Crohn's Disease Exclusion Diet with partial enteral nutrition in reducing intestinal inflammation in patients with Crohn's disease have sufficient evidence to be advocated. Multiple other dietary approaches, while promising, have insufficient evidence to be recommended. Third, dietary approaches are important in symptomatic control in many non‐inflammatory scenarios. Finally, guidance on following a healthy diet is fundamental to the general health of patients. Multiple approaches are advocated, but the optimal strategy is unclear. The precarious nutritional status of patients with IBD together with the risks of nutritional inadequacy and maladaptive eating behaviours associated with restrictive diets dictate involvement of expert dietitians in assessment and personalised delivery of dietary interventions. Conclusions: Four pillars of nutritional management require specific assessment and interventional strategies that should be chosen by evidence. Optimal delivery requires the skills of a specialised dietitian. [ABSTRACT FROM AUTHOR]

Zhenrui Xue,1– 3,* Minli You,2,3,* Ping Peng,1– 3,* Haoyang Tong,2,3 Wanghong He,2– 4 Ang Li,4 Ping Mao,1– 3 Ting Xu,1 Feng Xu,2,3 Chunyan Yao1 1Department of Transfusion Medicine, Southwest Hospital, Third Military Medical University, Army Medical University, Chongqing, 400038, People’s Republic of China; 2The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 3Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 4Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chunyan Yao; Feng XuDepartment of Transfusion Medicine, Southwest Hospital, Third Military Medical University, Army Medical University, Chongqing, 400038, People’s Republic of ChinaTel +64 389 619 2922Email yao_yao24@yahoo.com; fengxu@mail.xjtu.edu.cnPurpose: Detection of single-base mutations is important for real-time monitoring of tumor progression, therapeutic effects, and drug resistance. However, the specific detection of single-base mutations from excessive wild-type background sequences with routine PCR technology remains challenging. Our objective is to develop a simple and highly specific qPCR-based single-base mutation detection method.Methods: Using EGRF T790M as a model, gold nanoparticles at different concentrations were separately added into the Taqman-MGB qPCR system to test specificity improvement, leading to the development of the optimal Taqman-MGB nanoPCR system. Then, these optimal conditions were used to test the range of improvement in the specificity of mutant-type and wild-type templates and the detection limit of mutation abundances in a spiked sample.Results: The Taqman-MGB nanoPCR was established based on the traditional qPCR, with significantly suppressed background noise and improved specificity for single-base mutation detection. With EGFR T790M as a template, we demonstrated that our Taqman-MGB nanoPCR system could improve specificity across a wide concentration range from 10− 9 μM to 10 μM and detect as low as 0.95% mutation abundance in spiked samples, which is lower than what the traditional Taqman-MGB qPCR and existing PCR methods can detect. Moreover, we also proposed an experimentally validated barrier hypothesis for the mechanism of improved specificity.Conclusion: The developed Taqman-MGB nanoPCR system could be a powerful tool for clinical single-base mutation detection.Keywords: nanoparticle-assisted PCR, point mutation, gold nanoparticle, specificity

Ling Huo,1,* Yao Tan,2,* Shu Wang,3 Cuizhi Geng,4 Yi Li,5 XiangJun Ma,6 Bin Wang,2 YingJian He,1 Chen Yao,2,7 Tao Ouyang1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 2Department of Biostatistics, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Breast Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 4The Fourth Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Shunyi District Health Care Hospital for Women and Children of Beijing, Beijing, People’s Republic of China; 6Haidian Maternal and Child Health Hospital, Beijing, People’s Republic of China; 7Peking University Clinical Research Institute, Peking University Health Science Center, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen YaoPeking University First Hospital, Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86 18610640562Email yaochen@hsc.pku.edu.cnTao OuyangPeking University Cancer Hospital & Institute, Haidian District, Beijing, 100142, People’s Republic of ChinaTel +86 010 88121122Email ouyanghongtao@263.netPurpose: This study aimed to establish and evaluate the usefulness of a simple, practical, and easy-to-promote machine learning model based on ultrasound imaging features for diagnosing breast cancer (BC).Materials and Methods: Logistic regression, random forest, extra trees, support vector, multilayer perceptron, and XG Boost models were developed. The modeling data set of 1345 cases was from a tertiary class A hospital in China. The external validation data set of 1965 cases were from 3 tertiary class A hospitals and 2 primary hospitals. The area under the receiver operating characteristic curve (AUC) was used as the main evaluation index, and pathological biopsy was used as the gold standard for evaluating each model. Diagnostic capability was also compared with that of clinicians.Results: Among the six models, the logistic model showed superior diagnostic efficiency, with an AUC of 0.771 and 0.906 and Brier scores of 0.181 and 0.165 in the test and validation sets, respectively. The AUCs of the clinician diagnosis and the logistic model were 0.913 and 0.906. Their AUCs in the tertiary class A hospitals were 0.915 and 0.915, respectively, and were 0.894 and 0.873 in primary hospitals, respectively.Conclusion: The externally validated logical model can be used to distinguish between malignant and benign breast lesions in ultrasound images. Compared with clinician diagnosis, the logistic model has better diagnostic efficiency, making it potentially useful to assist in screening, particularly in lower level medical institutions.Trial Registration: http://www.clinicaltrials.gov. ClinicalTrials.gov ID: NCT03080623.Keywords: breast cancer, machine learning, diagnostic accuracy, patient stratification, screening modalities, ultrasound imaging

Min Xu,1,2,* Chong Yao,3,* Wei Zhang,1 Shen Gao,1 Hao Zou,1 Jing Gao1,4 1School of Pharmacy, Second Military Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Shanghai, 200003, People’s Republic of China; 3Clinical Pharmacy Center, Department of Pharmacy, Chinese PLA General Hospital, Beijing, 100850, People’s Republic of China; 4State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Gao; Hao ZouSchool of Pharmacy, Second Military Medical University, No. 325 Guohe Road, Yangpu District, Shanghai, People’s Republic of ChinaTel +86-10-6687-4665Email gjsmmu@126.com; haozou@smmu.edu.cnPurpose: Nanocarriers, with a high drug loading content and good safety, to achieve desirable therapeutic effect are always the goals for industry and research.Methods and Results: In the present study, we developed a docetaxel loaded poly-2-oxazoline polymer micellar system which employed poly-2-butyl-2 oxazoline and poly-2-methyl-2 oxazoline as the hydrophobic chain and hydrophilic chain, respectively. This micellar system achieves a high load up to 25% against the docetaxel, and further demonstrates an IC50 as low as 40% of the commercialized docetaxel injection in vitro and a double maximum tolerated dose in MCF-7 cells in vivo.Conclusion: The high drug loading content, superior safety, and considerable anti-cancer activity make this newly developed docetaxel loaded poly(2-oxazoline) micelle go further in future clinical research.Keywords: poly(2-oxazoline)s, micelle, docetaxel, high loading, anti-cancer activity

Qinchang Chen,1,2,* Qingui Chen,3,* Yanchen Ye,1,2 Ridong Wu,1,2 Shenming Wang,1,2 Chen Yao1,2 1Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shenming Wang; Chen YaoDepartment of Vascular Surgery; National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of ChinaEmail shenmingwang@hotmail.com; yaochen@mail.sysu.edu.cnObjective: To investigate the characteristics and prognosis of abdominal or thoracic aortic aneurysm (AAA or TAA) patients admitted to intensive care unit (ICU) postoperatively.Methods: Patients admitted to ICU postoperatively with a primary diagnosis of AAA or TAA were screened in the eICU Collaborative Research Database, which contained data from multiple ICUs throughout the continental United States in 2014 and 2015. Baseline characteristics and comorbidities and were investigated and factors associated with ICU mortality were explored using univariable logistic regression. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the prognosis predictive performance of the widely used severity scoring system APACHE IVa.Results: A total of 974 patients including 677 AAA and 297 TAA patients admitted to ICU postoperatively were included. Compared with TAA, AAA patients had a significantly higher median age (72 versus 64 years, P< 0.001). 89.07% AAA and 84.51% TAA patients underwent elective surgery (P=0.046), 8.71% AAA and 31.99% TAA patients were with aortic dissection (P< 0.001), and 10.19% AAA and 2.36% TAA patients suffered from rupture of aortic aneurysm (P< 0.001). Hypertension requiring treatment was the most common comorbidity (57.31% for AAA and 61.95% for TAA). TAA patients had significantly higher ICU mortality (9.43% versus 2.36%, P< 0.001) than AAA. Several factors were found to be significantly associated with ICU mortality, including urgent surgery, with aortic dissection, rupture of aortic aneurysm, TAA, and a higher APACHE IVa score on ICU admission. APACHE IVa showed a good predictive performance for ICU mortality with an area under the ROC curve of 0.9176 (95% CI 0.8789– 0.9390).Conclusion: The prognosis of aortic aneurysm patients admitted to ICU postoperatively is yet to improve, and factors associated with prognosis are mainly related to the condition itself. APACHE IVa can be used for prognosis prediction.Keywords: vascular surgery, intensive critical care, epidemiology

Bin Wang,1 Junkai Lai,1 Xiaoyan Yan,2 Feifei Jin,1 Bin Yi,3 Caixia An,3 Yuanxiao Li,4 Chen Yao1,2 1Department of Biostatistics, Peking University First Hospital, Beijing, People’s Republic of China; 2Peking University Clinical Research Institute, Beijing, People’s Republic of China; 3Children’s Emergency Center, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, People’s Republic of China; 4Department of Pediatric Gastroenterology, Second Hospital of Lanzhou University, Lanzhou, People’s Republic of ChinaCorrespondence: Chen YaoPeking University First Hospital, Xicheng District, Beijing 100034, People’s Republic of ChinaTel +86 18610640562Email yaochen@hsc.pku.edu.cnObjective: This study aims to comprehensively evaluate the characteristics of clinical drug trials to facilitate the collection of evidence for COVID-19 drug treatments.Methods: A retrospective analysis of 910 trials retrieved on August 7, 2020.Results: A total of 910 registered clinical trials with at least one drug intervention were evaluated. The number of registrations (32.4%, 295) from the United States accounted for nearly one-third of the total and far exceeded that of other countries individually. Furthermore, the peak number of trials were registered in April (34.3%, 312). Over half of the trials (51.2%, 466) are in the recruitment phase, and only 4.2% (38) of the trials have been completed. The median (interquartile range) estimated enrollment is 127 (59, 365). In 39% (355) of trials, the estimated enrollment is less than 100 participants. A total of 94.5% (790) of the trials use randomization in the allocation, 82.7% (753) use a parallel intervention mode, and 52.2% (475) use masking. A total of 287 drug names have been standardized and mapped. “Hydroxychloroquine” is the leading drug among the registered trials (7.47%, 68). Among the main countries contributing to investigations on “hydroxychloroquine”, the United States ranks first with 36.76% (25) of the trials.Conclusion: The designs of COVID-19 clinical drug trials have greatly improved in terms of the implementation of randomization and, particularly, blinding methods. In terms of drug reuse, the number of drug types has greatly increased, and hundreds of drugs have been used for efficacy screening. The emergence of large-sample registration trials is expected to address the uncertainty regarding the current clinical efficacy of some drugs.Keywords: COVID-19, clinical trials, investigation, intervention, drug, treatment

Hui Yang,1 Wei Sun,2 Pei Ma,1 Chunsuo Yao,1 Yannan Fan,1 Shuyi Li,1 Jiqiao Yuan,1 Ziqian Zhang,1 Xuyu Li,1 Mingbao Lin,1 Qi Hou1 1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Mingbao Lin; Qi Hou Tel +86-10-63165192; +86-10-63165191Email mingbaolin@imm.cams.cn; houq@imm.ac.cnBackground: Perilla frutescens (L.) Britt., a classic medicinal plant, has been demonstrated to have anti-inflammatory and anti-allergic effects in asthma. Perilla leaves extract (PLE) exerted significant therapeutic effect against allergic asthma inflammation through Syk inhibition. But the active chemical ingredients from PLE are complex and unclear, it is difficult to fully elucidate its pharmacological mechanisms.Methods: A method was established for rapid screening and characterization of active ingredients from PLE that targeted Syk, with which three potential active ingredients were identified. By using OVA-induced allergic asthma mouse model in vivo, OVA-induced human PBMCs inflammation model and DNP-IgE/BSA-induced RBL-2H3 cells model in vitro, the effects and mechanisms of PLE and its active components were evaluated.Results: Using Syk-affinity screening method, roseoside (RosS), vicenin-2 (Vic-2) and rosmarinic acid (RosA) were identified from PLE. In vitro, PLE and its ingredients showed significant inhibitory activities against Syk, with their mixture (Mix, prepared by RosS, Vic-2 and RosA in accordance with their ratio in Syk-conjugated beads bound fraction) showing a stronger inhibitory activity. RosS, Vic-2 and RosA also showed significant effects on allergic asthma, and a synergistic effect of Mix was observed. Moreover, treatment with PLE, RosS, Vic-2, RosA, and Mix significantly inhibited the expression and phosphorylation of Syk, PKC, NF-κB p65, and cPLA2 in allergic mice lung tissue and in RBL-2H3 cells.Conclusion: PLE may alleviate allergic airway inflammation partly through the multiple components synergistic targeting on Syk and its downstream inflammatory pathway.Keywords: allergic airway inflammation, multi-component, PLE, Syk, synergistic effect

Lingxia Niu,1,* Chunlin Yao,1,* Yu Wang,1 Yan Sun,1 Juan Xu,2 Yun Lin,1 Shanglong Yao1 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, People’s Republic of China; 2School of Medicine and Health Management, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430022, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun Lin; Shanglong YaoDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277# Jiefang Avenue, Wuhan 430022, Hubei, People’s Republic of ChinaTel +86 13986288403; +86 13886128437Fax +86 27 85726970Email franklinyun@hust.edu.cn; yaoshanglong@hust.edu.cnPurpose: This study examined whether different neuromuscular-blocking agents (NMBAs) work differently on the short-term outcomes of gastric cancer patients in terms of laboratory test results and severity of postoperative illness, and whether the effect is dose-related.Patients and Methods: Data of 1643 adult patients receiving gastric cancer surgery were analyzed by employing generalized linear models (GLMs), to explore the effects of different NMBAs on neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR) at postoperative day 1 (POD1), POD3, POD7, and return to intended oncologic therapy (RIOT), among others. We adjusted multiple covariants, including patient-, anesthesia-, and surgical complexity-related risk factors.Results: Without adjusting dosage of NMBAs, POD1NLR, POD1PLR (P < 0.05), POD3NLR, POD7NLR, POD3 lymphocytes, POD7LMR (P < 0.01) in gastric cancer patients administered with benzylisoquinoline NMBAs worsened, and the administration of aminosteroidal NMBAs was associated with less risk of transfer to ICU (P < 0.01); without adjusting the types of NMBAs, the highest dose of NMBAs postponed the RIOT (P < 0.05) and was negatively associated with POD3NLR, POD7NLR and POD7LMR (P < 0.01), and increased risk of postoperative transfer to ICU (P < 0.01). When patients given benzylisoquinolines were re-divided in terms of five equal quintiles, from low to high dose, RIOT was delayed and POD7LMR decreased significantly in the fourth and fifth quintile groups as compared to the first quintile group. A higher risk for postoperative transfer to ICU was found in the fifth quintile group as compared to the first quintile group.Conclusion: Patients with gastric cancer given benzylisoquinoline NMBAs had more unfavorable short-term outcomes, such as more severe inflammation and increased risk of transfer to ICU than their counterparts administered aminosteroidal NMBAs, and the effect of benzylisoquinolines was dose-related. The effect of aminosteroids on short-term outcomes was not dose-related in the dosage range we used.Keywords: neuromuscular-blocking agents, benzylisoquinoline, aminosteroid, short-term postoperative outcomes, gastric cancer surgery