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Zhiyuan Yu,1– 3,&ast; Haopeng Liu,4,&ast; Rui Li,1– 3,&ast; Liai Hu,3 Chun Xiao,5 Yunhe Gao,2 Peiyu Li,1– 3 Wenquan Liang,2 Sixin Zhou,2 Xudong Zhao2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin, People’s Republic of China; 4Department of Hepatobiliary Surgery, Zhangqiu District People’s Hospital, Jinan, Shandong Province, People’s Republic of China; 5Department of General Surgery, PLA Rocket Force Characteristic Medical Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xudong Zhao; Sixin Zhou, Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, People’s Republic of China, Email 601489554@qq.com; 35060555@qq.comBackground: The research on lymph node metastasis (LNM) in locally advanced gastric cancer (LAGC) infiltrating the subserous tissue and serous membrane (T3-4a) is significantly inadequate. This study aims to explore the clinicopathological factors related to LNM in stages T3 and T4a LAGC, while also developing predictive nomograms.Methods: After systematic searching and rigorous screening, 1995 T3 and 1244 T4a LAGC cases who underwent surgery without neoadjuvant or perioperative chemotherapy were selected. The risk factors associated with LNM were identified using both univariate and multivariate logistic regression analyses. Subsequently, the independent variables identified through the multivariate analyses were utilized to construct a nomogram.Results: The incidence of LNM in T3 and T4a LAGC was 77.1% (1539/1995) and 83.8% (1043/1244), respectively. The following factors were found to be independently associated with LNM in T3 LAGC: preoperative serum albumin < 41g/L (P=0.007), gastrointestinal obstruction (P< 0.001), tumor location (P=0.040), tumor size > 4cm (P=0.002), mixed (P=0.001) and undifferentiated histological types (P=0.002), presence of lymphovascular invasion (LVI) (P< 0.001) and nerve invasion (P< 0.001). Additionally, in T4a LAGC cases, serum albumin < 39g/L (P=0.004), tumor size > 6cm (P=0.020), mixed (P< 0.001) and undifferentiated histological types (P< 0.001), presence of gastrointestinal hemorrhage (P=0.016), neuroendocrine differentiation (P=0.024), and LVI (P< 0.001) independently influenced the occurrence of LNM.Conclusion: This study identified the risk factors associated with LNM in T3-4a LAGC cases and constructed nomograms, thereby providing valuable guidance for formulating and implementing a multidisciplinary perioperative treatment program.Keywords: locally advanced gastric cancer, lymph node metastasis, clinicopathological factors, nomogram

Shuang Lv,1 Yiming Li,2 Bojian Sun,1 Yu Jing,1 Xing Wang,3 Zhanqing Gu,1 Bailiang Wang,4 Cheng Xiao3 1Department of Rheumatology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Cardiovascular, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 4Department of Orthopaedic Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of ChinaCorrespondence: Bailiang Wang; Cheng Xiao, Email orthopaedic_wang@126.com; xc2002812@126.comObjects: Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease.Methods: We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity.Results: We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex).Conclusion: The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.keywords: receptor-interacting protein kinase, rheumatoid arthritis, polymorphism, single nucleotide, biochemical parameters

Yu Huang,&ast; Ying Huang,&ast; Chaoyong Xiao, Qingling Huang, Xue Chai Department of Radiology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Chai, Department of Radiology, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email 20600412@163.comObjective: This study aims to evaluate the effectiveness of Magnetic Resonance Virtual Endoscopy combined with 3D-FIESTA-c and 3D-TOF-MRA in preoperative assessment of MVD for PTN, with a focus on accurately detecting neuromuscular contact.Methods: We retrospectively analyzed clinical and imaging data from 240 patients with unilateral primary trigeminal neuralgia undergoing MVD surgery between April 2016 and July 2023. Preoperative scans with 3D-FIESTA-c and 3D-TOF-MRA were performed, and MRVE images were obtained to analyze the relationship between the trigeminal nerve and adjacent vessels. Using the findings during microvascular decompression (MVD) surgery as the gold standard, the diagnostic results of 3D-TOF-MRA + 3D-FIESTA-c were considered as group I, while the combined use of MRVE, 3D-TOF-MRA + 3D-FIESTA-c was considered as group II.Results: In 240 cases, group I had a positive rate of 96.25% and an accuracy rate of 86.25% for identifying responsible blood vessels, while group II had a positive rate of 98.3% and an accuracy rate of 94.17%. There were no statistically significant differences in positive rates between group I and group II, group I and MVD, or group II and MVD (P > 0.05). However, there were statistically significant differences in accuracy rates (P < 0.05). The accuracy for single and multiple arteries with group I was 99.38% and 80.0%, respectively, while with group II, it was 100% and 95.0%. No statistically significant difference was found in accuracy for single or multiple arteries (P> 0.05). The accuracy of evaluating responsibility veins with or without other vessels was 52.73% and 80.0%, respectively, with a statistically significant difference (P< 0.05).Conclusion: MRVE combined with 3D-TOF-MRA + 3D-FIESTA-c significantly improves the accuracy of identifying responsibility vessels, especially veins, in preoperative assessment for MVD. This has important clinical implications for preoperative decision-making and surgical planning. Keywords: primary trigeminal neuralgia, magnetic resonance imaging, magnetic resonance virtual endoscopy, microvascular decompression

Rong Huang,1,&ast; Jun Zeng,1,&ast; Xiaoze Yu,1 Yunke Shi,2 Na Song,1 Jie Zhang,1 Peng Wang,1 Min Luo,1 Yiming Ma,2 Chuang Xiao,1 Lueli Wang,1 Guanhua Du,3 Hongyan Cai,4 Weimin Yang1 1School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2The First Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 4The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimin Yang, School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, 650500, People’s Republic of China, Email ywmbessie@yeah.net Hongyan Cai, The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, People’s Republic of China, Email caihy@ydyy.cnPurpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN.Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified.Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-β, IL-1β, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPKα (Th172) while simultaneously down-regulated the protein expression of p-NF-&kgreen;B (p65), NLRP3, TGF-β 1, α-SMA, and Collagen I.Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-β signaling pathway.Keywords: diabetic nephropathy, network pharmacology, inflammation, TGF-β, fibrosis

Di Wang,1,2 Qiqi Li,1,2 Chunsheng Xiao,2 Hao Wang,2 Shujun Dong1 1The First Outpatient Department, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Hao Wang, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Chaoyang District, Changchun, 130022, People’s Republic of China, Tel +86-431-85262110, Email wangh@ciac.ac.cn Shujun Dong, The First Outpatient Department, Hospital of Stomatology, Jilin University, Room 101, Building G5, Phase 3, China Resources Ziyun Mansion, the Intersection of Jinhu Road and Nanhu Middle Street, Nanguan District, Changchun, 130021, People’s Republic of China, Tel +86-431-80621155, Email dsj@jlu.edu.cnAbstract: Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis. Keywords: anti-inflammatory, antibacterial, guided tissue regeneration, nanofibers, hydrogel, films

Yang Zhang,1,&ast; Chenggen Xiao,2,&ast; Guoqing Huang,2 Minxue Shen1,3 1Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha City, Hunan Province, People’s Republic of China; 2Department of Emergency, Xiangya Hospital, Central South University, Changsha City, Hunan Province, People’s Republic of China; 3Furong Laboratory, Central South University, Changsha City, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqing Huang; Minxue Shen, Email hgq97@126.com; shenmx1988@csu.edu.cnObjective: This study aims to evaluate the impact of COVID-19 prevention and control policies on the frequency of emergency department (ED) visits in a large tertiary hospital in central China, from January 2018 to September 2023.Methods: We conducted a multi-stage interrupted time series analysis to investigate the impact of various epidemic control policies on weekly ED visits at a tertiary hospital in Hunan Province, China. The study period ranged from January 1, 2018, to September 30, 2023, and was divided into four distinct periods: pre-epidemic, pandemic, normalized control, and end of control. Using a quasi-Poisson regression model, we examined the specific effects of these policies on emergency visits, with a particular focus on stratifying patients based on respiratory versus non-respiratory diseases.Results: Compared to the pre-pandemic period, the number of ED visits in a tertiary hospital decreased by 38.5% (95% CI: 25.1% to 49.8%) during the COVID-19 pandemic, of which the number of ED visits for respiratory diseases increased by 79.4% (95% CI: 13.2% to 177.2%) and the number of ED visits for non-respiratory diseases decreased by 45.9% (95% CI: − 55.7% to − 34.2%). After the end of the epidemic control, the total number of ED visits increased by 31.5% (95% CI: 19.1% to 45.0%), with the number of ED visits for respiratory diseases rising by 379.2% (95% CI: 275.9% to 511.8%), but with no significant change in the number of ED visits for non-respiratory emergencies.Conclusion: Control policies were associated with people avoiding emergency care for non-respiratory related reasons during the pandemic, while the end of control policies was associated with a sharp rise in emergency care for respiratory diseases. This study provides a scientific basis for the different changes in ED visits under the implementation of varying epidemic prevention and control policies.Keywords: COVID-19, health policy, emergency visit, respiratory disease, interrupted time series analysis

Kaiyang Xue,1 Xianzhu Wang,1 Caihong Xiao,2 Ning Zhang,1 Minghui Liu,3 Jing Fu,1 Jin Cui1 1College of Acupuncture and Massage, Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, People’s Republic of China; 2Department of Acupuncture and Moxibustion, No.1 Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, People’s Republic of China; 3Department of Acupuncture and Moxibustion, No.2 Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, People’s Republic of ChinaCorrespondence: Jin Cui, College of Acupuncture and Massage, Guizhou University of Traditional Chinese Medicine, No. 50 Shidong Road, Nanming District, Guiyang, 550002, People’s Republic of China, Email 516260179@qq.comObjective: Our pilot study shows that a modified moxibustion therapy called Ma’s bamboo-based medicinal moxibustion can alleviate the symptoms of low back pain in lumbar disc herniation (LDH), and has the potential to treat LDH. The aim of this study is to evaluate the efficacy and safety of Ma’s bamboo-based medicinal moxibustion for low back pain in LDH.Methods: A total of 312 LDH patients with low back pain were randomized to receive Ma’s bamboo-based medicinal moxibustion (MBMM) or acupuncture (AT). The primary efficacy measure was the change of Visual Analogue Scale (VAS) on the 14th day compared with that at baseline. The secondary efficacy measures included VAS score, Oswestry disability index (ODI), modified Japanese Orthopaedic Association (M-JOA) score, and the content of β-endorphin (β-EP) and substance-P (SP). The safety measures included the occurrence of adverse events and the changes in laboratory indicators.Results: In total, 304 patients were incorporated for the analysis of efficacy, including 96 males and 208 females, aged 21– 65 years. There was no statistically significant difference in the change of VAS score between the two groups on the 14th day [mean difference (95% CI) = − 2.31 (− 2.48, − 2.13) and − 2.28 (− 2.45, − 2.11), respectively; p = 0.819]. The VAS, ODI, and M-JOA scores changed after the intervention in both groups (p < 0.001), with increased β-EP content (p = 0.014, p = 0.032) and decreased SP content (p < 0.001, p = 0.048). The ODI score (p = 0.039) and M-JOA score (p = 0.032) of the MBMM group on the 28th day were lower than those of the AT group.Conclusion: The efficacy of Ma’s bamboo-based medicinal moxibustion therapy in relieving low back pain of LDH patients is comparable to that of acupuncture, and it has post-effect advantages in improving lumbar dysfunction and daily living ability, which can be used as a safe and effective alternative method for LDH treatment.Keywords: LDH, low back pain, Ma’s bamboo-based medicinal moxibustion, acupuncture, randomized controlled trial

Mengyang Li,1,&ast; Yuting Wang,2,&ast; He Liu,2 Xiaonan Huang,2 Huagang Peng,2 Yi Yang,2 Zhen Hu,2 Jianxiong Dou,2 Chuan Xiao,2 Juan Chen,3 Weilong Shang,2 Xiancai Rao1,2 1Department of Microbiology, School of Medicine, Chongqing University, Chongqing, 400044, People’s Republic of China; 2Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Key Laboratory of Microbial Engineering Under the Educational Committee in Chongqing, Chongqing, 400038, People’s Republic of China; 3Department of Pharmacy, The Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiancai Rao; Weilong Shang, Department of Microbiology, College of Basic Medical Sciences, Army Medical University, Key Laboratory of Microbial Engineering under the Educational Committee in Chongqing, Chongqing, 400038, People’s Republic of China, Email raoxiancai@126.com; shangwl0414@163.comIntroduction: Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated.Methods: MVs of Staphylococcus aureus USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2–MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor.Results: The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2–MVs (R2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10− 3 μg. Antares2–MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2–MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo.Conclusion: S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment. Keywords: Staphylococcus aureus, membrane vesicles, Antares2, cancer therapy, pyroptosis, caspase-1, GSDMD

Xue Ding,1 Qian Shi,2 Chao Xiao2 1School of Financial Technology, Shanghai Lixin University of Accounting and Finance, Shanghai, People’s Republic of China; 2School of Economics and Management, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Chao Xiao, School of Economics and Management, Tongji University, Building A, Tongji Mansion, No. 1500, Siping Road, Yangpu District, Shanghai, 200092, People’s Republic of China, Tel +86 18516393686, Email chaoxiao@tongji.edu.cnPurpose: Recent research has focused on the impact of communication networks on the performance of construction project teams, attempting empirical exploration from various social network analysis perspectives. However, there is still a significant gap in understanding the variations in performance and the mechanisms for teams using different communication networks. Drawing from organizational learning theory and social network theory, this study, based on the Input-Mediator-Output (IMO) model, explores the effects of the interaction between centralization and tie strength in communication networks on team performance, as well as the mediating mechanisms of knowledge sharing behavior and team resilience performance in engineering project teams.Methods: Drawing on classic group communication experiment, we design an online communication and collaboration platform to simulate the execution of a construction engineering project. Finally, data was collected through the communication experiment with 720 participants, and hypotheses were tested using ANOVA and PROCESS.Results: The results indicate that under conditions of weak tie strength, centralized communication networks yield higher performance. Conversely, under conditions of strong tie strength, decentralized communication networks demonstrate superior performance. Furthermore, this study also verifies the mediating role of knowledge sharing behavior and team resilience performance when tie strength is strong.Conclusion: This study focuses on engineering project team, exploring the evolutionary development of knowledge sharing behavior and team resilience performance from the perspective of the interaction of communication network structural characteristics, as well as the paths to enhancing team performance. Our research results highlight the interactive effects of structural indicators and relational indicators of communication networks, revealing the mechanism by which the structure of communication networks impacts team performance. Additionally, from the perspectives of forming and timely adjusting team communication models, and motivating and supporting employee communication behavior, our study provides practical insights for project managers and relevant administrators.Keywords: engineering project team, communication network, knowledge sharing behavior, team resilience performance, team performance

Yan Fang,1,2,&ast; Chuang Xiao,1,&ast; Lueli Wang,1,&ast; Youlan Wang,3 Jun Zeng,1 Yaping Liang,1 Rong Huang,1 Yunke Shi,2 Sha Wu,1 Xiaohua Du,2 Shibo Sun,2 Min Li,2 Yuanyuan Zheng,2 Hongxiang Wu,1 Qiuzhe Guo,4 Weimin Yang1 1School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, People’s Republic of China; 2The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Kunming Institute of Medical Sciences, Kunming, People’s Republic of China; 4Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuzhe Guo; Weimin Yang, Email drguoqz@163.com; ywmbessie@yeah.netBackground: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation.Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR.Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2.Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.Keywords: isoforskolin, sepsis, acute lung injury, pulmonary inflammation, glucocorticoids, regulator of G-protein signaling 2

Yinyi Chen,1 Chunlan Xiao,2 Yubin Liao,2 Liming Tan1 1Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of University of South China, Hengyang, Hunan, People’s Republic of ChinaCorrespondence: Liming Tan, Email ndefy84029@ncu.edu.cnObjective: The purpose of the research was to explore the possible risk factors for the development of hypocomplementemia (HC) in rheumatoid arthritis (RA) patients by analyzing their clinical and laboratory features.Methods: This retrospective research contained 501 RA patients, divided into RA patients with HC (n=78) and RA patients without HC (n=423). Demographic characteristics and laboratory test results of RA patients were collected and analyzed, such as age, sex, anti-mutated citrullinated vimentin antibody (Anti-MCV), serum complements (C3, C4), immunoglobulins (IgA, IgG, IgM), hemoglobin (Hb), platelets (PLT) and erythrocyte sedimentation rate (ESR), etc. Spearman correlation was served as assessing the correlations of the levels of serum C3 and C4 with each index. Receiver operating characteristic (ROC) curves were served as assessing the diagnostic efficacy of each index for RA patients with HC. Furthermore, risk factors for the occurrence of HC in RA patients were analyzed by employing binary logistic regression of single and multiple factors.Results: Compared RA patients with HC to without HC, the former were older and had a longer disease duration with increased levels of Anti-MCV, IgM and DAS28 and lower levels of Hb, PLT and ESR; Spearman correlation analysis verified the level of serum Anti-MCV was a negative correlation with C3 (r=− 0.156); the area under the ROC curve (AUC) of PLT in diagnosing RA patients with HC was the largest at 0.65 (95% CI: 0.60– 0.69); binary logistic regression analysis indicated that advanced age (> 66 years), long disease duration (> 62 months), high DAS28 value (> 6.13), the levels of Anti-MCV> 107.68IU/mL, IgM> 1.54g/L, ESR≤ 69.00mm/h, Hb≤ 99.00g/L and PLT≤ 305.00× 109/L were probable risk factors for the occurrence of HC in RA patients.Conclusion: Age and disease duration, DAS28, Anti-MCV, IgM, ESR, Hb, and PLT are closely related to the development of HC in RA patients. Timely monitoring of these indicators can help to evaluate disease activity of RA patients and further improve their prognosis.Keywords: rheumatoid arthritis, hypocomplementemia, risk factors, disease activity

Yunhao Zheng,1 Rui Zhu,2 Chuqiao Xiao,3 Qiaoyu Cheng,3 Yifei Long,3 Xueman Zhou,3 Shilong Zhang,4 Jun Wang,3 Xin Xiong1,3 1Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 4Department of Orthodontics, School and Hospital of Stomatology, Hebei Medical University & Hebei Key Laboratory of Stomatology, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xin Xiong, National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Temporomandibular Joint, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China, Tel/Fax +86-28-85503898, Email drxiongxin@scu.edu.cnPurpose: This study aims to explore the association of pressure pain thresholds (PPTs) with age, gender, and pain in patients with temporomandibular disorders (TMD).Patients and Methods: A total of 301 TMD patients (248 female and 53 male) were recruited and classified into the high and low age groups according to their median age of 26 years. Patients’ demographics, pain-related variables, TMD-related variables, and PPTs of both left and right temporomandibular joints (TMJs), masseter, and temporalis were collected.Results: Pain duration and visual analog scale of pain (VAS) showed no significant correlations with PPTs (P> 0.05). Multiple linear regression analysis revealed a significant positive association of PPTs of all six sites with males (β=0.41– 0.72 kg·cm− 2, 95% CI (0.19– 0.38, 0.74– 0.99), P< 0.001), as well as with the high age group [β=0.28– 0.36 kg·cm− 2, 95% CI (0.07– 0.20, 0.47– 0.53), P< 0.020]. Furthermore, PPTs of the left TMJ showed a significant negative association with left pain-related TMD (PT) [β=− 0.21 kg·cm− 2, 95% CI (− 0.38, − 0.04), P=0.026], but PPTs of the remaining sites did not show a significant association with PT (P> 0.05). Stratified analysis showed that PPTs in females were associated with the high age group [β=0.25– 0.37 kg·cm− 2, 95% CI (0.04– 0.20, 0.45– 0.56), P< 0.020] and that PPT of the left TMJ was associated with left PT [β=− 0.21 kg·cm− 2, 95% CI (− 0.39, − 0.03), P=0.043]. The remaining PPTs did not show a significant association with PT (P> 0.05). In males, PPTs did not show significant correlations with age, PT and VAS (P> 0.05).Conclusion: PPTs in the orofacial region are associated with gender and age in TMD patients. Pain duration and intensity show no significant correlations with PPTs in TMD patients. Researchers and dentists should take age and gender into account when using PPTs as auxiliary diagnostic indicators for PT.Keywords: pain sensitivity, temporomandibular disorders, pressure pain threshold, age, gender

Chao Xiao,1,2,&ast; Xiuen Chen,1,&ast; Lizhi Lu,3 Ziming Ye,2 Xiangren Chen,2 Meiyu Dong,4 Chao Qin2 1Department of Neurology, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Neurology, Forsea Life Insurance Nanning Hospital, Nanning, People’s Republic of China; 4The First Clinical Medical College of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Qin, Department of Neurology, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email mdqc2019@126.comObjective: This study aimed to investigate the feasibility and clinical efficacy of endovascular recanalization in patients with chronic internal carotid artery occlusion (CICAO) and explore the application value of computed tomography perfusion (CTP) in endovascular recanalization.Methods: This non-randomized controlled study included 41 patients with CICAO. All patients received active medical treatment. In this study, patients with successful endovascular recanalization and those who refused endovascular recanalization were included in the recanalization and medication groups, respectively. Before and 90 days after treatment, cognitive function was evaluated using the Montreal Cognitive Function Assessment, and neurological function was evaluated using the National Institutes of Health Stroke Scale and modified Rankin scale. For patients with successful endovascular recanalization, brain CTP imaging was performed to evaluate hemodynamic changes in patients with CICAO before and three days after treatment.Results: Overall, 41 symptomatic patients with CICAO were included, and 20 patients received endovascular recanalization therapy, with a success rate of 60% (12/20). The perioperative complication rate was 15% (3/20); there were no events such as hyperperfusion, distal embolism, vascular rupture, or cerebral hemorrhage, and no stroke-related or death-related events. Patients were divided into a medication group (n=21) and recanalization group (n=12). After 90 days of follow-up, patients in the recanalization group showed greater improvement in overall cognitive and neurological function. In addition, successful endovascular recanalization significantly improved cerebral blood perfusion on the occluded side of patients with CICAO.Conclusion: Successful recanalization can effectively improve the overall cognitive and neurological functions of patients in the short term. CTP can be used to quantitatively evaluate not only the cerebral hemodynamic changes after internal carotid artery occlusion but also the improvement of cerebral blood perfusion after successful endovascular recanalization, which provides a reliable method for postoperative follow-up.Keywords: hemodynamics, chronic internal carotid artery occlusion, endovascular recanalization, clinical effect

Zheng Y, Zhu R, Xiao C, et al. J Pain Res. 2023;16:2205–2216. The authors have advised that they neglected to include a funding statement on page 2215 of the published paper. The funding statement should read as follows. Funding This work was supported by the Technology Innovation Project of Science and Technology Bureau of Chengdu (2022-YF05-01691-SN) and Clinical Research Project of West China Hospital of Stomatology, Sichuan University (LCYJ-2023-YY-2). The authors apologize for this error.

The main component (CaO) in KR (Kambara reaction) desulfurization slag is a high value slag raw material for converter smelting, and attempts to utilize KR desulfurization slag in converter smelting are conducive to reducing the buildup of KR desulfurization slag and improving the economic efficiency of converter smelting. However, the removal of sulfur in the slag is a key issue. The influence of temperature on the sulfur oxidation behavior in KR slag in the form of synthetic slag was investigated. SEM-EDS, XRD, and an infrared carbon and sulfur analyzer were used to analyze and detect the oxidized slag samples at different temperatures. The results show that the desulfurization rate increases gradually with the increase in temperature at a flow rate of Ar-50%O2 of 2 L/min. Under the condition of low temperature (T ≤ 1220℃), the desulfurization rate of slag is less affected by temperature. When T > is 1220℃, the desulfurization rate of slag is greatly affected by temperature. When the reaction temperature reaches 1420℃, the desulfurization rate reaches 93.5%. Furthermore, the types of sulfur-containing phases in the oxidized slag samples gradually decrease with the increase of temperature, and the sulfur in the oxidized slag samples is mainly present in the silicate phase when the temperature is less than or equal to 1220℃.

Xu Jiang,1,&ast; Yang Pan,1,&ast; Sha Zhu,1 Yaxi Wang,1 Ruxin Gu,1 Yinyin Jiang,1 Bo Shen,1 Jun Zhu,1 Shulan Xu,1 Jun Yan,1 Jingde Dong,1 Wenbin Zhang,2 Chaoyong Xiao,3 Li Zhang1 1Department of Geriatrics, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Radiology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zhang, Department of Geriatrics, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China, Email jx13773958367@163.comObjective: Patients with rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson’s disease (PD-RBD) tend to have poor cognitive performance and faster cognitive deterioration, and the potential mechanism is still ambiguous. Therefore, this study aimed to detect the alterations in local brain function in PD-RBD.Methods: Fifty patients, including 23 patients with PD-RBD and 27 patients with PD without RBD (PD-nRBD), and 26 healthy controls were enrolled. All subjects were subjected to one-night polysomnography and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The fMRI images of the three groups were analyzed by regional homogeneity (ReHo) to observe the local neural activity. Correlations between altered ReHo values and chin electromyographic (EMG) density scores and cognitive scores in the PD subgroups were assessed.Results: Compared with the patients with PD-nRBD, the patients with PD-RBD had higher ReHo values in the frontal cortex (the right superior frontal gyrus, the right middle frontal gyrus and the left medial superior frontal gyrus), the right caudate nucleus and the right anterior cingulate gyrus, and compared with the HCs, the patients with PD-RBD had lower ReHo values in the bilateral cuneus, the bilateral precuneus, the left inferior temporal gyrus and the left inferior occipital gyrus. For the patients with PD-RBD, the phasic chin EMG density scores were positively correlated with the ReHo values in the left medial superior frontal gyrus, and the tonic chin EMG density scores were positively correlated with the ReHo values in the right anterior cingulate gyrus.Conclusion: This study indicates that increased ReHo in the frontal cortex, the caudate nucleus and the anterior cingulate gyrus may be linked with the abnormal motor behaviors during REM sleep and that decreased ReHo in the posterior regions may be related to the visuospatial–executive function in patients with PD-RBD.Keywords: Parkinson’s disease, rapid eye movement sleep behavior disorder, resting-state fMRI, regional homogeneity

Chenlu Xiao,1,2,&ast; Dan Qiao,1,&ast; Lijuan Xiong,3,&ast; Wenjie Tian,4 Dongjiang Wang,4 Shuwen Deng,5 Jian Guo4 1Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Clinical Microbiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Laboratory Medicine, Second Affiliated Hospital of Traditional Chinese Medicine of Guizhou University, Guizhou, People’s Republic of China; 4Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 5Department of Medical Microbiology, People’s Hospital of Suzhou New District, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Guo; Shuwen Deng, Email guojian1110@126.com; shuwen.deng@gmail.comBackground: Aspergillus spp. infection in immunocompromised patients results in increasing morbidity and mortality. This study investigated clinical and microbiological characteristics of aspergillosis in a Chinese tertiary teaching hospital.Methods: A total of 114 patients with aspergillosis were included over a 5-year period at Ruijin Hospital. In sum, 114 Aspergillus strains were isolated and identified at species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry, confirmed by ITS gene region and β-tubulin (BenA) gene sequencing. Sensititre YeastOne was used in vitro to test susceptibility to antifungal drugs: amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole, micafungin, anidulafungin, and caspofungin.Results: The median age of the patients was 61 (19) years, men accounted for 53.5% (n=61) of the sample, about 64% were immunocompromised, and 36% had underlying diseases. Pulmonary diseases accounted for 27.2%. Aspergillus isolates were mainly isolated from sputum (n=42, 36.8%). Antifungal therapy was administered to 106 (93.0%) patients and voriconazole (n=76, 66.7%) was the most frequently used as empirical therapy. Aspergillus fumigatus (n=69, 60.5%) was the most common species. There was a 73.7% concordance between MALDI-TOF MS and molecular identification. All Aspergillus isolates showed good susceptibility to anidulafungin and caspofungin.Conclusion: Immunocompromised patients are an at-risk population for aspergillosis, and voriconazole was used as empirical therapy in Ruijin Hospital, China. A. fumigatus was the predominant Aspergillus species causing aspergillosis, and A. flavus — as non–A. fumigatus species are increasing — the second-leading cause of aspergillosis. Anidulafungin and caspofungin were the most active in vitro against the Aspergillus isolates tested. The MALDI-TOF MS method showed good accuracy for identification of common Aspergillus spp. In vitro antifungal-susceptibility testing is crucially important for decisions on effective therapy with aspergillosis.Keywords: aspergillosis, epidemiology, Aspergillus spp., MALDI-TOF MS, molecular identification, antifungal susceptibility

Xiaofeng Zheng,1,&ast; Cong Xiao,1,&ast; Zhuocheng Xie,2 Lijuan Liu,1 Yinhua Chen1 1Department of Orthopedics, Third Hospital of Mianyang Sichuan Mental Health Center, Mianyang, Sichuan, 621000, People’s Republic of China; 2Department of Orthopedics, Sichuan Science City Hospital, Mianyang, Sichuan, 621000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinhua Chen, Department of Orthopedics, Third Hospital of Mianyang Sichuan Mental Health Center, 190 East Jiannan Road, Youxian, Mianyang, Sichuan, 621000, People’s Republic of China, Tel +86-139-9014-7729, Email yhcdoc@outlook.comPurpose: To establish prediction models for 6-month prognosis in femoral neck–fracture patients receiving total hip arthroplasty (THA).Patients and Methods: In total, 182 computed tomography image pairs from 85 patients were collected and divided into a training set (n=127) and testing set (n=55). Least absolute shrinkage–selection operator regression was used for selecting optimal predictors. A random-forest algorithm was used to establish the prediction models, which were evaluated for accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC).Results: The best model in this study was constructed based on demographic data, preoperative laboratory indicators, and three preoperative radiomic features. In the random-forest model, activated partial thromboplastin time, a preoperative radiomic feature (maximum diameter), and fibrinogen were important variables correlating with patient outcomes. The AUC, sensitivity, specificity, PPV, NPV, and accuracy in the training set were 0.986 (95% CI 0.971– 1), 0.925 (95% CI 0.862– 0.988), 0.983 (95% CI 0.951– 1.016), 0.984 (95% CI 0.953– 1.014), 0.922 (95% CI 0.856– 0.988), and 0.953 (95% CI 0.916– 0.990), respectively. The AUC, sensitivity, specificity, PPV, NPV, and accuracy in the testing set were 0.949 (95% CI 0.885– 1), 0.767 (95% CI 0.615– 0.918), 1 (95% CI 1– 1), 1 (95% CI 1– 1), 0.781 (95% CI 0.638– 0.924), and 0.873 (95% CI 0.785– 0.961), respectively.Conclusion: The model based on demographic, preoperative clinical, and preoperative radiomic data showed the best predictive ability for 6-month prognosis in the femoral neck–fracture patients receiving THA.Keywords: prediction model, total hip arthroplasty, computed tomography, prognosis, femoral neck fracture

Huocheng Liao, Qiuyue Chen, Lin Liu, Sigan Zhong, Chun Xiao Department of Cardiology, The Third People’s Hospital of Huizhou and the Affiliated Hospital of Guangzhou Medical University, Huizhou City, Guangdong Province, People’s Republic of ChinaCorrespondence: Chun Xiao, Department of Cardiology, The Third People Hospital of Huizhou, The Affiliated Hospital of Guangzhou Medical University, Huizhou City, Guangdong Province, People’s Republic of China, Email lhcdoctor@tom.comObjective: The current study was to design a cardiovascular risk score for the diagnosis of coronary heart disease (CHD) in the rural area of China and the sensitivity and specificity of this score would be assessed.Methods: A total of 520 patients were enrolled and based on the results from coronary artery angiography, patients were divided into three groups: CHD group (coronary artery ≥ 50% stenosis), atherosclerosis group (coronary artery < 50% stenosis) and normal groups (without stenosis). Between-group differences were evaluated and the sensitivity and specificity of cardiovascular risk score were evaluated.Results: Compared to the normal and atherosclerosis groups, patients in the CHD group were older, had higher body mass index, and more likely to be smoking and obese, and had dyslipidemia, hypertension and diabetes, and had higher cardiovascular risk score (4.05 ± 2.15 vs 2.94 ± 1.90 vs 2.54 ± 1.59). Patients in the CHD group were more likely to have cardiovascular risk scores ≥ 2 (90.2% CHD group vs 74.2% atherosclerosis group vs 76.1% normal group, P < 0.05). The area under the ROC was 0.673, with 95% confidence interval was 0.623– 0.722 (P < 0.001), and the sensitivity and specificity were highest when the cardiovascular risk score was 4, indicating that the value of cardiovascular risk score of 4 was a good cutoff point for CHD diagnosis.Conclusion: Using cardiovascular risk score can improve CHD diagnosis which may help to reduce health disparities between rural and urban area.Keywords: coronary heart disease, cardiovascular risk score, sensitivity, specificity

Chen Pan,1 Honghong Wang,2 Minzhen Chen,3 Yu Cai,1 Peihuan Li,4 Changgen Xiao,5 Qiuping Tang,1 Deborah Koniak-Griffin6 1Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Department of Fundamental Nursing, Xiangya School of Nursing, Central South University, Changsha, People’s Republic of China; 3Department of AIDS, The First Hospital of Changsha, Changsha, People’s Republic of China; 4College of Resources of Environment, Hunan Agricultural University, Changsha, People’s Republic of China; 5Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 6School of Nursing, University of California Los Angeles, Los Angeles, CA, USACorrespondence: Qiuping Tang, Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86 731 88618567, Email tt96@sina.comBackground/Purpose: Nurses engaged in the care of people living with HIV (PLWH) are commonly exposed to workplace stress. This study aimed to explore the stress experiences and coping strategies among nurses taking care of PLWH in China.Methods: Nurses were recruited from the AIDS department of a public, general, third-grade class-A hospital, which has the largest HIV care department in the Hunan Province of China. Thirty-three nurses working in the AIDS Department were recruited in this qualitative study. Eight nurses participated in a focus group and 25 nurses underwent in-depth individual interviews aimed at characterizing the nurse’s feelings and struggles with stress during caregiving for PLWH. The interviews were audio-recorded, transcribed verbatim, anonymized, and imported into NVivo 8.0 software. The data were coded and subjected to thematic analysis.Results: Concerns about occupational exposure, heavy workload, mental health problems and risk behaviors of patients, and discrimination towards nurses caring for PLWH were the four main sources of stress. The negative impact of stress included problems with emotion regulation, somatic health and sleep, and work performance. Some participants also reported a positive impact of work stress on their mental health. Using personality strengths, problem-solving, help-seeking, concealing and avoiding/suppression were common coping strategies employed by nurses caring for PLWH.Conclusion: Our findings help characterize the stress experienced by nurses caring for PLWH in the Chinese cultural context, and may inform specific interventions to help manage stress and promote mental health of nurses.Keywords: HIV, nurses, stress, job burnout, coping

Yee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of China, Email baoguolian@163.com; 35792191@qq.comPurpose: Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.Methods: The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.Results: The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higher Borderella bronchiseptica (Bb)-specific antibody production and lymphocyte proliferation. The splenic lymphocytes of mice immunized with GAN-OMVs displayed a higher ratio of CD4+/CD8+ T cells and CD19+ B cells and produced significantly higher levels of Th1/Th2/Th17 cytokines. GAN-OMV also effectively prevented Bb reinfection.Conclusion: In this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.Keywords: outer membrane vesicles, glycyrrhizic acid nanoparticle, macrophage, protective immune response, anti-bacterial infection

Junhui Ji,1,&ast; Xiafang Gu,2,&ast; Chengjiao Xiao1 1Anesthesiology Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Anesthesiology Department, The No.2 People’s Hospital of Suzhou Xiangcheng District, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjiao XiaoAnesthesiology Department, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Gusu District, Suzhou, 215000, Jiangsu, People’s Republic of ChinaTel +86-13962100544Email xiaocj1646@126.comBackground: Whether intraoperative temperature management can help patients recover quickly in the postanesthesia care unit (PACU) still remains to be investigated. This study aimed to investigate the effect of intraoperative temperature management on the quality of postoperative recovery of patients who underwent pulmonary lobectomy in the PACU.Methods: Totally, 98 patients aged 45– 60 years with a body mass index of 20– 25 kg/m2 who underwent elective thoracoscopic lobectomy were enrolled. Patients were categorized into two groups using a random number table: the conventional group received routine intervention to maintain normothermia (Group C, n = 49) and the aggressive group received integrated interventions (Group A, n = 49). In Group C, normothermic fluid was infused intravenously, the heating blanket was turned on when the intraoperative temperature was < 35.0 °C, and the warming was stopped when the temperature reached 36.5 °C. In Group A, the fluid heated to 37 °C was infused intravenously, and the heating blanket was used intraoperatively. When the body temperature was > 37 °C, the heating blanket was turned off, and when the body temperature was < 36.5 °C, the heating blanket was turned on to continue heating.Results: Steward awakening scores at 1 min and 5 min after extubation and PaO2 levels at 15 min after extubation were higher in Group A than in Group C (P < 0.05); incidence of chills, nausea, and vomiting in the PACU was lower in Group A than in Group C (P < 0.05); and length of stay in the PACU was shorter in Group A than in Group C (P < 0.05).Conclusion: Aggressive intraoperative temperature management of patients undergoing thoracoscopic lobectomy can improve the quality of postoperative recovery in the PACU through a safe and smooth transition compared with routine insulation measures.Keywords: hypothermia, recovery room, thoracoscopy, thoracic surgery

Feng Lin,1,2 Yixuan Liu,2,3 Wenqi Luo,1,2 Shuhan Liu,4 Yiming Wang,1,2 Rui Gu,1 Wanguo Liu,1 Chunsheng Xiao2,5 1Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China; 3School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, People’s Republic of China; 4Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 5Jilin Biomedical Polymers Engineering Laboratory, Changchun, 130022, People’s Republic of ChinaCorrespondence: Rui Gu; Wanguo Liu Tel +8613804371075; +8618186881807Fax +86431-89876939; +86431-89876921Email gurui@jlu.edu.cn; liuwanguo6016@jlu.edu.cnPurpose: Traumatic spinal cord injury (TSCI) induces a powerful inflammatory response that can significantly exacerbate the extent and severity of neural damage (termed as “secondary injury”). Thus, the suppression of inflammation is crucial for reducing neurological dysfunction following TSCI. However, the conventional anti-inflammatory drugs show limited efficacy because of poor penetration and release kinetics at the injury site. This study describes the design, synthesis, release kinetics, biosafety, and preclinical efficacy of minocycline (MC)-loaded poly(α-lipoic acid)–methylprednisolone (PαLA-MP) prodrug nanoparticles (NPs) for the combined anti-inflammatory treatment of TSCI.Methods: NPs were produced by conjugating MP to PαLA and then loading MC. The NP structure was confirmed through 1H nuclear magnetic resonance (1H NMR), Fourier transform infrared spectroscopy, ultraviolet–visible absorption spectroscopy, gel permeation chromatography, dynamic light scattering, and transmission electron microscopy. Drug-loading content and efficacy were measured using high-performance liquid chromatography (HPLC) or 1H NMR and release kinetics through HPLC. Biosafety was examined using the MTT assay, cell penetration efficiency using confocal microscopy, and flow cytometry using Cyanine5 (Cy5)-labeled MC-PαLA-MP NPs, effects on injury-induced pro-inflammatory cytokine release using enzyme-linked immunosorbent assays and immunofluorescence, and treatment efficacy by measuring motor recovery in a rat model of TSCI.Results: The MC-PαLA-MP NPs exhibited high biocompatibility and released 81% MC and 54% MP within 24 h under TSCI-like conditions, effectively reducing 40% of pro-inflammatory cytokine release both in cultures and injured rat spinal cord tissues. Systemic injection increased the Basso, Beattie, Bresnahan score of TSCI rats from 2.33 ± 0.52 to 8.83 ± 1.83 in 8 weeks, providing effective neuroprotection and enhanced exercise recovery in the TSCI rats.Conclusion: The MC-PαLA-MP NPs can mitigate secondary inflammation and preserve motor function following experimental TSCI, which suggests their potential for clinical application.Keywords: anti-inflammation, motor recovery, nanomedicine, neuroprotection, spinal cord injury

Hua Cao,1 Chungang Xiao,1 Zhangxiu He,2 Hong Huang,3,4 Huifang Tang1,4 1The First Affiliated Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 2The First Affiliated Hospital, Department of Nephrology, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 3The First Affiliated Hospital, Institute of Clinical Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China; 4The First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaCorrespondence: Hong Huang; Huifang TangThe First Affiliated Hospital, Institute of Cardiovascular Disease, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaEmail trave1@126.com; tanghuifang999@163.comAbstract: Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, and dysfunction, eventually leading to heart failure (HF). However, the molecular mechanisms involved in cardiac remodeling are complicated, especially the association with immune. Immunoglobulin E (IgE) is a class of immunoglobulins involved in immune response to specific allergens. Recently, Zhao et al characterized a novel specific role of IgE and its high affinity receptor (Fc&epsiv;R1) in directly promoting pathological myocardial remodeling and cardiac dysfunction. Additionally, upon blocking IgE-Fc&epsiv;R1 signaling using Fc&epsiv;R1 genetic depletion or by administrating the anti-IgE monoclonal antibody omalizumab (Oma) in mice, they observed that cardiac hypertrophy and cardiac interstitial fibrosis induced by angiotensin II (Ang II) or transverse aortic constriction (TAC) were significantly suppressed. In contrast, IgE administration alone can aggravate pathological cardiac remodeling and dysfunction. RNA-seq and downstream analysis indicated that TGF-β was the common pathway and the most pivotal mediator in IgE-Fc&epsiv;R1-induced cardiac remodeling and dysfunction. Furthermore, the administration of a TGF-β inhibitor could ameliorate cardiac remodeling and improve cardiac function. Therefore, these findings suggest that IgE-Fc&epsiv;R1 maybe promising therapeutic targets for cardiac remodeling and provide an experimental basis for the use of omalizumab for HF patients combined with high serum IgE levels or allergic diseases.Keywords: cardiac remodeling, IgE- Fc&epsiv;R1, immunoglobulins, TGF-&#x03B2

Pan He,1 Bingtong Tang,1 Yusheng Li,1 Yu Zhang,2 Xinming Liu,2 Xin Guo,1 Dong Wang,3 Peng She,3,4 Chunsheng Xiao2 1School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China; 3Department of Orthopaedics, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China; 4Joint Surgery Department, The First Hospital, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Pan He; Peng SheSchool of Materials Science and Engineering, Changchun University of Science and Technology, Changchun, 130022, People’s Republic of ChinaTel +86-431-85583188Fax +86-431-85583188Email hepan@cust.edu.cn; shep@mail.sysu.edu.cnBackground: High levels of oxidants, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), are typical characteristics of an inflammatory microenvironment and are closely associated with a various inflammatory pathologies, eg, cancer, diabetes, atherosclerosis, and neurodegenerative diseases. Therefore, the delivery of anti-inflammatory drugs by oxidation-responsive smart systems would be an efficient anti-inflammatory strategy that benefits from the selective drug release in an inflammatory site, a lower treatment dose, and minimizes side effects.Purpose: In this study, we present the feasibility of an oxidation-sensitive PEGylated alternating polyester, methoxyl poly(ethylene glycol)-block-poly(phthalic anhydride-alter-glycidyl propargyl ether) (mPEG-b-P(PA-alt-GPBAe)), as novel nanocarrier for curcumin (CUR), and explore the application in anti-inflammatory therapy.Methods: The copolymers used were obtained by combining a click reaction and a ring-opening-polymerization method. CUR was loaded by self-assembly. The in vitro drug release, cytotoxicity toward RAW 264.7 cells and cellular uptake were investigated. Furthermore, the anti-inflammatory effects of CUR-loaded polymeric nanoparticles (NPs-CUR) were investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and tested in a murine model of ankle inflammation.Results: Fast drug release from NPs-CUR was observed in trigger of 1 mM H2O2 in PBS. Compared with NPs and free drugs, the significant anti-inflammatory potential of NPs-CUR was proven in activated RAW 264.7 cells by inhibiting the production of TNF-α, IL-1β, and IL-6 and increasing the level of an anti-inflammatory cytokine IL-10. Finally, a local injection of NPs-CUR at a dose of 0.25 mg/kg suppressed the acute ankle inflammatory response in mice by histological observation and further reduced the expression of pro-inflammatory cytokines in the affected ankle joints compared to that of free CUR.Conclusion: Both the significant in vitro and in vivo anti-inflammatory results indicated that our oxidation responsive polymeric nanoparticles are promising drug delivery systems for anti-inflammatory therapy.Keywords: oxidation responsiveness, PEGylated polyesters, nanosized micelles, anti-inflammatory therapy, curcumin delivery

Zhixia Song,1,* Chao Xiao,2,* Xiaoli Jia,2 Chunhua Luo,3 Lang Shi,1 Rong Xia,1 Jiefu Zhu,4 Shizhong Zhang2 1Department of Nephrology, The First Clinical Medical College of Three Gorges University, Center People’s Hospital of Yichang, Yichang, 443000, People’s Republic of China; 2Three Gorges University College of Medical Science, Yichang, 443000, People’s Republic of China; 3Department of Clinical Laboratory, The First Clinical Medical College of Three Gorges University, Center People’s Hospital of Yichang, Yichang, 443000, People’s Republic of China; 4Center of Nephrology and Dialysis, Transplantation, Renmin Hospital of Wuhan University, Wuchang, Hubei, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiefu Zhu; Shizhong Zhang Email sojeff@163.com; zhangsz@ctgu.edu.cnObjective: The present study is to investigate the effect of vitamin D/Vitamin D Receptor (VDR) signaling on podocyte autophagy in diabetic nephropathy.Methods: Kidney tissue sections from patients with diabetic nephropathy and nontumor kidney were checked under electronic microscope and VDR immunohistochemistry. Diabetic rat models were induced by intraperitoneal injection of streptozotocin (STZ) (60 mg/kg). Calcitriol treatment was achieved by gavage at dose of 0.1μg/kg/d. Blood, urine and kidney tissue specimens were used for serum, urine biochemistry, histopathology and molecular biology testing. Podocyte cell line MPC-5 was cultured under hyperglycaemic conditions in the absence or presence of 100 nmol/L calcitriol to investigate podocyte injury and autophagy.Results: VDR and autophagosomes in podocytes were significantly decreased in renal biopsy from patients with diabetic nephropathy, compared to healthy kidney tissue. Rats with STZ treatment developed typical diabetic kidney disease with low VDR expression. Calcitriol, the active form of vitamin D, could activate VDR and attenuate diabetic nephropathy including proteinuria and glomerular sclerosis. Calcitriol treatment also alleviated the podocyte foot process fusion, reduced podocyte injury marker desmin and preserved slit diaphragms proteins in diabetic nephropathy. Reduced LC3II/I, Beclin-1 and elevated p62 in renal homogenate and reduced autophagosomes and LC3II in podocytes indicated podocytes autophagy impairment in diabetic nephropathy. Whereas calcitriol treatment restored podocyte autophagy activities. In cultured podocytes, the protective effect of calcitriol against high glucose induced podocyte injury could be abated by autophagy inhibitor chloroquine.Conclusion: Our study delivered the evidence that calcitriol/VDR signaling attenuated diabetic nephropathy and podocytes injury by restoring podocytes autophagy. This finding may have potential implication for exploring protective mechanisms of calcitriol/VDR in diabetic nephropathy.Keywords: vitamin D receptor, calcitriol, diabetic nephropathy, podocyte, autophagy

Shuai Bian,1 Hongfei Cai,1 Youbin Cui,1,* Wanguo Liu,2,* Chunsheng Xiao3 1Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of China; 3Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youbin CuiDepartment of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaEmail cuiyb@jlu.edu.cnWanguo LiuDepartment of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, People’s Republic of ChinaEmail liuwanguo6016@jlu.edu.cnAbstract: Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) may lead to a life-threatening form of respiratory failure, resulting in high mortality of up to 30– 40% in most studies. Although there have been decades of research since ALI was first described in 1967, the clinical therapeutic alternatives for ALI are still in a state of limited availability. Supportive treatment and mechanical ventilation still have priority. Despite some preclinical studies demonstrating the benefit of pharmacological interventions, none of these has been proved completely effective to date. Recent advances in nanotechnology may shed new light on the pharmacotherapy of ALI. Nanomedicine possesses targeting and synergistic therapeutic capability, thus boosting pharmaceutical efficacy and mitigating the side effects. Currently, a variety of nanomedicine with diverse frameworks and functional groups have been elaborately developed, in accordance with their lung targeting ability and the pathophysiology of ALI. The in-depth review of the current literature reveals that liposomes, polymers, inorganic materials, cell membranes, platelets, and other nanomedicine approaches have conferred attractive therapeutic benefits for ALI treatment. In this review, we explore the recent progress in the study of the nanomedicine-based therapy of ALI, presenting various nanomedical approaches, drug choices, therapeutic strategies, and outcomes, thereby providing insight into the trends.Keywords: acute lung injury, acute respiratory distress syndrome, drug delivery, nanoparticle, nanomedicine

Maojian Chen,1,* Chanchan Xiao,2,* Wei Jiang,3 Weiping Yang,4 Qinghong Qin,1 Qixing Tan,1 Bin Lian,1 Zhijie Liang,5 Changyuan Wei1 1Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 2Department of Microbiology and Immunology, School of Medicine and Public Health, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 3Department of Medical Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 4Department of Ultrasound Diagnosis, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of China; 5Department of Gland Surgery, The Fifth Affiliated Hospital of Guangxi Medical University & The First People’s Hospital of Nanning, Nanning, Guangxi 530022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changyuan WeiDepartment of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People’s Republic of ChinaTel/Fax +86 0771 5308593Email changyuanwei@gxmu.edu.cnBackground: As a natural compound extracted from a variety of hot peppers, capsaicin has drawn increasing attention to its anti-cancer effects against multiple human cancers including breast cancer. FBI-1 is a major proto-oncogene negatively regulating the transcription of many tumor suppressor genes, and plays a vital role in tumorigenesis and progression. However, whether FBI-1 is involved in capsaicin-induced breast cancer suppression has yet to be ascertained. This study aimed to investigate the effects of capsaicin on proliferation and apoptosis and its association with FBI-1 expression in breast cancer.Methods: CCK-8 and morphological observation assay were employed to detect cell proliferation. Flow cytometry and TUNEL assay were conducted to detect cell apoptosis. RNA interference technique was used to overexpress or silence FBI-1 expression. qRT-PCR and/or Western blot analysis were applied to detect the protein expression of FBI-1, Ki-67, Bcl-2, Bax, cleaved-Caspase 3, Survivin and NF-κB p65. Xenograft model in nude mice was established to assess the in vivo effects.Results: Capsaicin significantly inhibited proliferation and induced apoptosis in breast cancer in vitro and in vivo, along with decreased FBI-1, Ki-67, Bcl-2 and Survivin protein expression, increased Bax protein expression and activated Caspase 3. Furthermore, FBI-1 overexpression obviously attenuated the capsaicin-induced anti-proliferation and pro-apoptosis effect, accompanied with the above-mentioned proteins reversed, whereas FBI-1 silencing generated exactly the opposite response. In addition, as a target gene of FBI-1, NF-κB was inactivated by p65 nuclear translocation suppressed with capsaicin treatment, which was perceptibly weakened with FBI-1 overexpression or enhanced with FBI-1 silencing.Conclusion: This study reveals that FBI-1 is closely involved in capsaicin-induced anti-proliferation and pro-apoptosis of breast cancer. The underlying mechanism may be related to down-regulation of FBI-1-mediated NF-κB pathway. Targeting FBI-1 with capsaicin may be a promising therapeutic strategy in patients with breast cancer.Keywords: capsaicin, breast cancer, proliferation, apoptosis, FBI-1, NF-κB

Wenqi Luo,1,2 Yiming Wang,1,2 Feng Lin,1,2 Yixuan Liu,2,3 Rui Gu,1 Wanguo Liu,1 Chunsheng Xiao2,4 1Department of Orthopaedic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China; 3School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, 230026, People’s Republic of China; 4Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, People’s Republic of ChinaCorrespondence: Wanguo Liu; Rui Gu Email liuwanguo6016@jlu.edu.cn; gurui@jlu.edu.cnBackground: The excess production of reactive oxygen species (ROS) after traumatic spinal cord injury (TSCI) has been identified as a leading cause of secondary injury, which can significantly exacerbate acute damage in the injured spinal cord. Thus, scavenging of ROS has emerged as an effective route to ameliorate secondary spinal cord injury.Purpose: Selenium-doped carbon quantum dots (Se-CQDs) with the ability to scavenge reactive oxygen species were prepared and used for efficiently ameliorating secondary injury in TSCI.Methods: Water-soluble Se-CQDs were easily synthesized via hydrothermal treatment of l-selenocystine. The chemical structure, size, and morphology of the Se-CQDs were characterized in detail. The biocompatibility and protective effects of the Se-CQDs against H2O2-induced oxidative damage were investigated in vitro. Moreover, the behavioral test, bladder function, histological observation, Western blot were used to investigate the neuroprotective effect of Se-CQDs in a rat model of contusion TSCI.Results: The obtained Se-CQDs exhibited good biocompatibility and remarkable protective effect against H2O2-induced oxidative damage in astrocytes and PC12 cells. Moreover, Se-CQDs displayed marked anti-inflammatory and anti-apoptotic activities, which thereby reduced the formation of glial scars and increased the survival of neurons with unscathed myelin sheaths in vivo. As a result, Se-CQDs were capable of largely improving locomotor function of rats with TSCI.Conclusion: This study suggests that Se-CQDs can be used as a promising therapeutic platform for ameliorating secondary injury in TSCI.Keywords: carbon quantum dots, spinal cord injury, reactive oxygen species, antioxidant, inflammation

Xijiang Zhao,1,* Linna You,1,* Tao Wang,1 Xianjun Zhang,1 Zexi Li,2 Luguang Ding,2 Jiaying Li,2 Can Xiao,2 Fengxuan Han,2 Bin Li2 1Department of Orthopedics, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, People’s Republic of China; 2Departments of Orthopaedic Surgery and Stomatology, The First Affiliated Hospital, Orthopaedic Institute, Soochow University, Suzhou, Jiangsu 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin LiSoochow University (South Campus), 708 Renmin Road, Rm 308 Bldg 1, Suzhou, Jiangsu 215007, People’s Republic of ChinaTel/Fax (+86) 512-6778-1163Email binli@suda.edu.cnCan XiaoThe First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, People’s Republic of ChinaEmail canxiao0511@163.comIntroduction: Despite great progress made in developing orthopedic implants, the development of titanium (Ti) implants with ideal early osseointegration remains a big challenge. Our pilot study has demonstrated that Si-TiO2 nanotubes on the surface of Ti substrates could enhance their osteogenic activity. Hence, in this study, we aim to comprehensively evaluate the effects of silicon-doped titania (Si-TiO2) nanotubes on the osseointegration property of Ti implants.Materials and Methods: The Ti implants were surface modified with Si-TiO2 nanotubes through in situ anodization and Si plasma immersion ion implantation (PIII) method. Three groups were divided as Ti implants (Ti), Ti modified with TiO2 nanotubes (TiO2-NTs) and Ti modified with Si-TiO2 nanotubes (Si-TiO2-NTs). The morphology of Si-TiO2 nanotubes was observed by scanning electron microscope. The growth and osteogenic differentiation of MC3T3-E1 cells on the Ti implants were evaluated. Further, the pull-out tests and in vivo osseointegration ability evaluation were performed after implanting the screws in the femur of Sprague Dawley rats.Results: The Si-TiO2 nanotubes could be seen on the surface of Ti implants. The MC3T3-E1 cells could grow on the surface of Ti, TiO2-NTs and Si-TiO2-NTs, and showed fast proliferation rate on the Si-TiO2-NTs. Moreover, the production of some osteogenesis-related proteins (ALP and Runx2) at one week and calcium deposition at four week was also enhanced in Si-TiO2-NTs rather than other groups. In vivo osseointegration results showed that Si-TiO2 nanotube-modified Ti screws had higher pullout force at two and four weeks as well as enhanced new bone formation at six weeks compared to bare Ti screws and Ti screws modified with TiO2 nanotubes alone.Discussion: The modification of Si-TiO2-NTs on the Ti substrate could generate a nanostructured and hydrophilic surface, which can promote cell growth. Moreover, the existence of the TiO2 nanotubes and Si element also can improve the in vitro osteogenic differentiation of MC3T3-E1 cells and early bone formation around the implanted screws. Together, findings from this study show that surface modification of Ti implants with Si-TiO2 nanotubes could enhance early osseointegration and therefore has the potential for clinical applications.Keywords: osseointegration, implant, silicon, titanium dioxide, nanotubes

Guoqing Yang1 ,* Chenchang Xiao2 ,* Shiyue Li,3 Ningxi Yang1 1College of Humanities and Social Sciences, Harbin Engineering University, Harbin, People’s Republic of China; 2City College, Wuhan University of Science and Technology, Wuhan, People’s Republic of China; 3School of Health Sciences, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ningxi Yang College of Humanities and Social SciencesHarbin Engineering University, NO. 145 Nantong Road, Harbin, Heilongjiang, People’s Republic of ChinaTel +86 45182569608Email yangningxi@bjmu.edu.cnBackground and Aim: Coronavirus disease 2019 (COVID-19) is currently prevalent worldwide. This research aimed to explore the effect of adverse childhood experience (ACE) on suicide ideation in young cancer patients during the COVID-19 pandemic. Self-reported questionnaires analyzed the mediating effects of sleep quality, anxiety symptoms, and inflammatory conditions between ACE and suicide ideation.Materials and Methods: A total of 197 young cancer patients (age 18– 40) completed questionnaires and a blood test. Correlation analysis and structural equation model were used to explore the relationships between ACE, sleep quality, anxiety symptom, serum C-reactive protein (CRP) levels and suicide ideation. The mediating roles of sleep quality, anxiety symptoms, and CRP levels on the influence of ACE on suicide ideation were explored.Results: ACE was positively related to anxiety symptoms, CRP levels, and suicide ideation, and negatively related to sleep quality. Anxiety symptoms and CRP levels were positively related to suicide ideation, while sleep quality was negatively related to suicide ideation. Anxiety symptoms were positively related to CRP levels but negatively related to sleep quality. From these results, we found ACE affected suicide ideation directly and was mediated by roles sleep quality, anxiety symptom and CRP.Conclusion: ACE not only directly affected suicide ideation but also affected suicide ideation through sleep quality, anxiety symptoms, and inflammatory conditions in young cancer patients during the COVID-19 pandemic. Therefore, targeted intervention and help for cancer patients from the perspective of ACE should be put into practice.Keywords: coronavirus disease 2019, psychosocial oncology, adverse childhood experience, anxiety symptom, sleep quality, suicide ideation

Lei Wang,1,* Qiao Ke,2,* Kongying Lin,2,* Jingbo Chen,3 Ren Wang,4 Chunhong Xiao,5 Xiaolong Liu,6 Jingfeng Liu2,6 1Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, People’s Republic of China; 4Department of Pediatric Surgery, Huai’an Women and Children’s Hospital, Huaian, People’s Republic of China; 5Department of General Surgery, 900th Hospital of PLA, Fuzhou, People’s Republic of China; 6The United Innovation of Mengchao Hepatobiliary Technology Key of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingfeng Liu Tel +86 139 0502 9580Fax +86 591 8370 2529Email drjingfeng@126.comBackground: Prophylactic transarterial chemoembolization (p-TACE) is strongly recommended for hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI), but the potential beneficiaries remain controversial.Methods: Data of HCC patients with MVI who underwent R0 resection between December 2013 and December 2015 were identified through the primary liver cancer big data. Disease-free survival (DFS) and overall survival (OS) were compared between patients who received p-TACE or not using Kaplan–Meier survival curves before and after propensity scoring match (PSM).Results: A total of 695 patients were eligible for this study, including 199 patients (28.6%) receiving p-TACE and 496 patients (71.4%) receiving resection alone. In the crude cohort, median DFS and OS were longer in the p-TACE group than those in the non-TACE group without significant differences (25.0 months vs 24.2 months, P=0.100; 48.0 months vs 46.5 months, P=0.150; respectively), but significant differences were observed both in DFS and OS (both P< 0.05) after 1:1 PSM. p-TACE was identified as one of the independent risk factors of both DFS and OS using multivariate analysis in the matched cohort (HR=0.69, 95% CI=0.54– 0.88; HR=0.66, 95% CI=0.50– 0.88; respectively). Subgroup analysis showed that p-TACE could beneficiate patients if they were male, aged ≥ 50 years old, had HBV infection, preoperative AFP level ≥ 400 ng/mL, Child-Pugh grading A, no transfusion, single tumor, tumor diameter ≥ 5cm, Edmondson–Steiner grading I/II, capsule, or BCLC stage A, CNLC stage Ib, AJCC stage II both in DFS and OS (all P< 0.05).Conclusion: With the current data, we concluded that not all HCC patients with MVI would be benefited from p-TACE, and p-TACE could benefit patients with “middle risk” according to the current staging systems.Keywords: hepatocellular carcinoma, microvascular invasion, R0 resection, transarterial chemoembolization

Jinran Li,1 Yuxi Jia,1 Peng Zhang,2 Huailin Yang,2 Xianling Cong,1 Lin An,3 Chunsheng Xiao2,4 1Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun 130033, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People’s Republic of China; 3Department of Hand Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, People’s Republic of China; 4Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, People’s Republic of ChinaCorrespondence: Xianling Cong; Lin An Tel +86-431-89876626; +86-431-84995523Email congxl@jlu.edu.cn; anlin.changchun@163.comBackground: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL.Purpose: We proposed a facile “in situ drug conjugation-induced self-assembly” strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma.Methods: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)-b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model.Results: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL.Conclusion: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.Keywords: celastrol, self-assembly, self-stabilization, nanomedicine, melanoma

Abstract Background Diagnostic uncertainty occurs frequently in emergency medical care, with more than one-third of patients leaving the emergency department (ED) without a clear diagnosis. Despite this frequency, ED providers are not adequately trained on how to discuss diagnostic uncertainty with these patients, who often leave the ED confused and concerned. To address this training need, we developed the Uncertainty Communication Education Module (UCEM) to teach physicians how to discuss diagnostic uncertainty. The purpose of the study is to evaluate the effectiveness of the UCEM in improving physician communications. Methods The trial is a multicenter, two-arm randomized controlled trial designed to teach communication skills using simulation-based mastery learning (SBML). Resident emergency physicians from two training programs will be randomly assigned to immediate or delayed receipt of the two-part UCEM intervention after completing a baseline standardized patient encounter. The two UCEM components are: 1) a web-based interactive module, and 2) a smart-phone-based game. Both formats teach and reinforce communication skills for patient cases involving diagnostic uncertainty. Following baseline testing, participants in the immediate intervention arm will complete a remote deliberate practice session via a video platform and subsequently return for a second study visit to assess if they have achieved mastery. Participants in the delayed intervention arm will receive access to UCEM and remote deliberate practice after the second study visit. The primary outcome of interest is the proportion of residents in the immediate intervention arm who achieve mastery at the second study visit. Discussion Patients’ understanding of the care they received has implications for care quality, safety, and patient satisfaction, especially when they are discharged without a definitive diagnosis. Developing a patient-centered diagnostic uncertainty communication strategy will improve safety of acute care discharges. Although use of SBML is a resource intensive educational approach, this trial has been deliberately designed to have a low-resource, scalable intervention that would allow for widespread dissemination and uptake. Trial registration The trial was registered at clinicaltrials.gov (NCT04021771). Registration date: July 16, 2019.

Yee Huang,1 Li Nan,1,2 Chenwen Xiao,1 Quanan Ji,1 Ke Li,1 Qiang Wei,1 Yan Liu,1 Guolian Bao1 1Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou 310021, People’s Republic of China; 2Zhejiang Normal University, Jinhua 321000, People’s Republic of ChinaCorrespondence: Yan Liu; Guolian BaoInstitute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou 310021, People’s Republic of ChinaEmail 35792191@qq.com; baoguolian@163.comBackground: Rehmannia glutinosa polysaccharide is the main reason that contributes to the immunological function of R. glutinosa. Due to its disadvantages in clinical use, here we designed the PEGylation nano-RGP (pRL) to improve the drug-targeting effect and the immunological function. Our present work aims to establish the optimum condition of preparing the pRL and to investigate its immunological function on macrophages.Methods: pRL was prepared by thin film hydration method combined with ultra-sonication technique. And its preparation conditions were optimized with response surface methodology. Also, the lyophilization method was optimized. The characteristics of the pRL were evaluated, including particle size, drug loading, encapsulation efficiency and morphology. The immunological function of pRL on macrophage was investigated through CCK-8 test, ELISA and flow cytometry.Results: The lipid-to-cholesterol molar ratio of 8:1, the addition of DSPE-PEG2000 of 9% and the lipid-to-drug ratio of 5.4:1 were the optimum preparation technology for pRL. The encapsulation efficiency (EE) of pRL under this preparation technology was 95.81±1.58%, with a particle size of 31.98 ± 2.6 nm. The lactose-to-lipid ratio (2:1) was the optimal lyophilization method. pRL promoted macrophage proliferation, which is significantly better than that of nano-RGP without PEGylation (RL). pRL-stimulated RAW264.7 cells showed a high secretion of pro-inflammatory cytokines, which is the characteristic indicator of M1 polarization. Enhanced cellular uptake through macropinocytosis-dependent and caveolae-mediated endocytosis was observed in pRL-treated RAW264.7 cells.Conclusion: Our study concluded that PEGylation effectively overcame the poor targeting effect of Rehmannia glutinosa polysaccharide (RGP) and significantly improved the immunological profile of its nano-formulation, which suggested that pRL could serve as an immune adjuvant in clinical application.Keywords: Rehmannia glutinosa polysaccharide, PEGylation, preparation technology, lyophilization method, macrophages

Chen Pan,1 Honghong Wang,2 Minzhen Chen,3 Yu Cai,1 Changgen Xiao,4 Qiuping Tang,1 Deborah Koniak-Griffin5 1Department of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Department of Fundamental Nursing, Xiangya School of Nursing, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3AIDS Department of the First Hospital of Changsha, Hunan 410005, People’s Republic of China; 4Department of Applied Psychology, School of Humanities and Management, Hunan University of Chinese Medicine, Changsha, Hunan 410208, People’s Republic of China; 5School of Nursing of University of California Los Angeles, Los Angeles, CA 90095-1702, USACorrespondence: Qiuping TangDepartment of Clinical Psychology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, People’s Republic of ChinaTel +86 13787256418Fax +86 731 88618487Email tt96@sina.comBackground/purpose: Workplace stress among nurses providing care for people living with human immunodeficiency virus is a serious problem in China that may increase rates of job burnout and affect quality of care. Mindfulness-based intervention has been shown to be effective in relieving stress and burnout in nurses. Therefore, we designed a mixed-method pilot study to evaluate a mindfulness-based intervention for nurses providing care for people living with human immunodeficiency virus.Methods: Twenty nurses caring for people living with human immunodeficiency virus in the First Hospital of Changsha, China participated in a mindfulness-based intervention for 2 hr sessions weekly for 6 weeks. The Perceived Stress Scale, Maslach Burnout Inventory, Five Facets Mindfulness Questionnaire, State-Trait Anxiety Inventory, and the Beck Depression Inventory were used to collect data before and after the mindfulness-based intervention. Participants were invited to attend an in-depth interview 1 week after the end of the mindfulness-based intervention to give feedback.Results: The quantitative analyses revealed a significant change in Five Facets Mindfulness Questionnaire scores. There were no significant differences between pre- and post-intervention measures of any other variables. Qualitative results showed nurses experienced a decrease in work and daily life pressures; improvements in communications with patients, colleagues and families, with better regulation of negative emotions, and acceptance of other people and attention.Conclusion: This study supports the acceptability and potential benefits of the mindfulness-based intervention in helping nurses caring for people living with human immunodeficiency virus to manage stress and emotions, and improve their acceptance of others and attention. A larger study with a randomized controlled trial design is warranted to confirm the effectiveness of this mindfulness-based intervention.Keywords: human immunodeficiency virus, stress, emotions, job burnout, mindfulness-based intervention

Abstract Background Deep Learning (DL) has advanced the state-of-the-art capabilities in bioinformatics applications which has resulted in trends of increasingly sophisticated and computationally demanding models trained by larger and larger data sets. This vastly increased computational demand challenges the feasibility of conducting cutting-edge research. One solution is to distribute the vast computational workload across multiple computing cluster nodes with data parallelism algorithms. In this study, we used a High-Performance Computing environment and implemented the Downpour Stochastic Gradient Descent algorithm for data parallelism to train a Convolutional Neural Network (CNN) for the natural language processing task of information extraction from a massive dataset of cancer pathology reports. We evaluated the scalability improvements using data parallelism training and the Titan supercomputer at Oak Ridge Leadership Computing Facility. To evaluate scalability, we used different numbers of worker nodes and performed a set of experiments comparing the effects of different training batch sizes and optimizer functions. Results We found that Adadelta would consistently converge at a lower validation loss, though requiring over twice as many training epochs as the fastest converging optimizer, RMSProp. The Adam optimizer consistently achieved a close 2nd place minimum validation loss significantly faster; using a batch size of 16 and 32 allowed the network to converge in only 4.5 training epochs. Conclusions We demonstrated that the networked training process is scalable across multiple compute nodes communicating with message passing interface while achieving higher classification accuracy compared to a traditional machine learning algorithm.

Hongliang Li,1,* Xiaopeng Guo,1,* Qiutian Li,2,* Pengzhan Ran,1 Xudong Xiang,3 Yuncang Yuan,1 Tianqi Dong,1 Bei Zhu,1 Lei Wang,1 Fangfang Li,1 Chunyan Yang,1 Dengcai Mu,1 Dan Wang,4 Chunjie Xiao,1 Shangyong Zheng1 1School of Medicine, Yunnan University, Kunming, China; 2Department of Oncology, Kunming General Hospital of Chengdu Military Command, Teaching Hospital of Kunming Medical University, Kunming, China; 3Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, China; 4Department of Pharmacy, Kunming General Hospital of Chengdu Military Command, Teaching Hospital of Kunming Medical University, Kunming, China *These authors contributed equally to this work Purpose: Emerging evidence suggests that many differentially expressed long non-coding RNAs (lncRNAs) are involved in tumorigenesis. However, the functional roles of these transcripts and the mechanisms responsible for their deregulation in non-small-cell lung cancer (NSCLC) remain elusive. Here, we identified a novel lncRNA (lncRNA 1308), which was significantly upregulated in NSCLC tissues and investigated its biological function and potential molecular mechanism.Methods: Differences in the lncRNA expression profiles between NSCLC and tumor-adjacent normal tissues were assessed by lncRNA expression microarray analysis. The microRNA in vivo precipitation (miRIP) method was used to identify the targeting microRNAs (miRNAs) on lncRNA 1308, and luciferase reporter assays were performed. Loss-of-function studies were used to explore the effect of lncRNA 1308 on lung carcinogenesis in NSCLC cells.Results: The novel lncRNA 1308 was upregulated in NSCLC tissues and cell lines. By using biotin-labeled lncRNA 1308 for miRIP in NSCLC cells and dual-luciferase reporter assays, the results suggested that miRNA-124 was associated with lncRNA 1308. Furthermore, the expression of a disintegrin and a metalloproteinase 15 (ADAM 15) was downregulated in NSCLC cells when silencing of lncRNA 1308, the target of oncogenic miR-124, inhibits NSCLC cell proliferation and invasion. Conversely, the expression of ADAM 15 was significantly increased, when inhibiting the expression of miR-124, and alleviated cell invasion inhibition.Conclusion: The results suggested that lncRNA 1308 may function as a competing endogenous RNA (ceRNA) for miR-124 to regulate cell invasion through the miR-124/ADAM 15 signaling pathway, indicating that lncRNA 1308 plays an important role in the disease progression of NSCLC. Keywords: lung cancer, lncRNA 1308, miR-124, ADAM 15, competing endogenous RNA

Jiewei Chen,1,2,* Qingmei He,2,* Jun Liu,1,2,* Yongbo Xiao,1 Canhua Xiao,3 Keming Chen,1 Dan Xie,1,2 Xinke Zhang1,2 1Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China; 3Department of Pathology, Qingyuan People’s Hospital, Qingyuan, 511581, People’s Republic of China *These authors contributed equally to this work Purpose: The aim of this study was to investigate the degree of infiltration of CD8+ tumor-infiltrating lymphocytes (TILs) including high and low density in lung sarcomatoid carcinoma (LSC) and their clinicopathological significance.Patients and methods: The density of CD8+ TILs in paraffin-embedded tissue sections from 100 LSC patients was detected by immunohistochemical staining, and the relationship of CD8+ TILs with clinicopathological features and prognosis was analyzed.Results: The chi-squared test showed that the degree of infiltration of CD8+ TILs was significantly correlated with the clinicopathological stage and T stage of LSC (P

Xinyi Yuan, Fuhuan Fei, Huanmei Sun, Chaoni Xiao, Xinfeng Zhao, Yajun Zhang, Xiaohui Zheng Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, People’s Republic of China Background: Tanshinol borneol ester (DBZ) is a hybrid of danshensu (DSS) and borneol and has anti-ischemic activity in animals. However, its low water solubility and short half-life limit its clinical application. Methods: We prepared polyethylene glycol (PEG)-modified and DBZ-loaded nanostructured lipid carriers (DBZ-PEG-NLC) and DBZ-NLC, and examined their physical characteristics, such as particle size, zeta potential, entrapment efficiency and drug loading. The in vitro stability and pharmacokinetics in rats as well as antioxidant activity of DBZ-PEG-NLC and DBZ-NLC in a C57BL/6 mouse model of ischemia/reperfusion-related brain injury were investigated. The levels of DBZ and its hydrolyzed DSS in rat plasma and brain microdialysates were determined by liquid chromatography–mass spectroscopy/mass spectroscopy analysis. Results: We found that the mean particle size and entrapment efficacy of DBZ-PEG-NLC were similar to that of DBZ-NLC. The DBZ-PEG-NLC, like DBZ-NLC, released DBZ in a biphasic manner with initially burst release and then prolonged slow release in vitro. Intravenous injection of DBZ-PEG-NLC resulted in significantly higher levels and longer retention periods of DBZ and DSS in plasma and the brains than DBZ-NLC and DBZ in rats. Finally, treatment with DBZ-PEG-NLC achieved a better antioxidant activity than DBZ or DBZ-NLC in mouse model of ischemia/reperfusion by reducing the levels of brain malondialdehyde, but increasing the levels of brain superoxide dismutase and glutathione. Conclusion: DBZ-PEG-NLC is a preferable option to deliver DBZ for sustainable release of DSS and borneol in vivo, and may serve as a promising drug for effective therapy of ischemic cardiovascular and cerebrovascular diseases. Keywords: nanovesicles, pharmacokinetics, brain microdialysis, ischemic cerebrovascular diseases, polyethylene glycol, danshensu

Minxun Lu,* Li Min,* Cong Xiao, Yongjiang Li, Yi Luo, Yong Zhou, Wenli Zhang, Chongqi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Introduction: Currently, it is challenging to treat giant cell tumor (GCT) of distal radius. For Campanacci grade III or recurrent GCTs, en bloc resection has been accepted as a better treatment option. Although numerous methods are available for reconstruction, all of them have some limitations in joint function and complications. In this study, our aims were to treat the GCT of distal radius with uncemented three-dimensional (3D)-printed prosthesis and to present and evaluate the surgical techniques and short-term outcomes. Methods: Between September 2015 and March 2017, 11 patients with distal radius GCTs were treated with personalized uncemented 3D-printed prosthesis. The preoperative/postoperative pain, range of motion, and grip strengths of all patients were evaluated. Oncological results, complications, and degenerative changes in the wrist joint were evaluated. Functional outcomes were assessed according to the disabilities of the arm, shoulder, and hand (DASH) questionnaire and Mayo wrist scoring systems. Results: The average follow-up was 14.45 months (range, 8–18 months). There was a significant decrease in the mean postoperative visual analog scale score (2.33) compared with the preoperative score (5.22; p

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Xianxie Zhang,1 Yuguang Wang,2 Zengchun Ma,2 Qiande Liang,2 Xianglin Tang,2 Donghua Hu,2 Hongling Tan,2 Chengrong Xiao,2 Yue Gao2 1Air Force General Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China Abstract: Tanshinone IIA (Tan IIA) (C19H18O3) is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD). Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR). The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. Keywords: dashen, ulcerative colitis, Crohn’s disease, tanshinone IIA, pregnane X receptor, inflammatory bowel disease, dextran sodium sulfate

Hydrogen sulfide (H2S) plays a vital role in Al3+ stress resistance in plants, but the underlying mechanism is unclear. In the present study, pretreatment with 2 μM of the H2S donor NaHS significantly alleviated the inhibition of root elongation caused by Al toxicity in rice roots, which was accompanied by a decrease in Al contents in root tips under 50 μM Al3+ treatment. NaHS pretreatment decreased the negative charge in cell walls by reducing the activity of pectin methylesterase and decreasing the pectin and hemicellulose contents in rice roots. This treatment also masked Al-binding sites in the cell wall by upregulating the expression of OsSATR1 and OsSTAR2 in roots and reduced Al binding in the cell wall by stimulating the expression of the citrate acid exudation gene OsFRDL4 and increasing the secretion of citrate acid. In addition, NaHS pretreatment decreased the symplasmic Al content by downregulating the expression of OsNRAT1, and increasing the translocation of cytoplasmic Al to the vacuole via upregulating the expression of OsALS1. The increment of antioxidant enzyme [superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD)] activity with NaHS pretreatment significantly decreased the MDA and H2O2 content in rice roots, thereby reducing the damage of Al3+ toxicity on membrane integrity in rice. H2S exhibits crosstalk with nitric oxide (NO) in response to Al toxicity, and through reducing NO content in root tips to alleviate Al toxicity. Together, this study establishes that H2S alleviates Al toxicity by decreasing the Al content in the apoplast and symplast of rice roots.