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Pu Xi,1,&ast; Guizhong Huang,1,&ast; Kewei Huang,2,&ast; Dailei Qin,1 Zehui Yao,1 Lingmin Jiang,1 Qi Zhu,1 Chaobin He1 1Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Department of Clinical Laboratory, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaobin He, Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, 651 Dongfeng Road E, Guangzhou, Guangdong, 510060, People’s Republic of China, Email hechb@sysucc.org.cnBackground: As a novel inflammatory-nutritional biomarker, the C-reactive protein–albumin–lymphocyte (CALLY) index has demonstrated significant prognostic value in various malignancies. However, research on its association with the prognosis of ampullary carcinoma (AC) is rare. This study aims to investigate the relationship between the CALLY index and the prognosis of patients with AC.Methods: We retrospectively analyzed data from 201 patients with AC at Sun Yat-sen University Cancer Center. Several clinicopathological factors and biomarkers were included in the study. Univariate and multivariate Cox regression analyses, along with competing risk analysis, were performed to identify prognostic factors for AC after pancreaticoduodenectomy (PD). Only factors with significant results in univariate analysis were included in multivariate analysis. To ensure the robustness of our findings, propensity score matching (PSM) analyses were conducted to assess survival differences according to the CALLY index.Results: The univariate and multivariate Cox regression analyses revealed that pathological type, N stage, T stage, postoperative chemotherapy regimen, and the CALLY index were all statistically significant prognostic factors for patients with AC after PD (all P values < 0.05). Taking into account non-cancer-related mortality as competing hazards, these factors remained significant predictors (all P values < 0.05). After PSM, the survival advantage observed between the low and high CALLY groups remained discernible and consistent.Conclusion: This study indicated that a reduced CALLY index correlates with a poorer cancer-specific survival in AC patients after PD, highlighting its utility as a prognostic marker for this condition.Keywords: ampullary carcinoma, prognosis, inflammation-nutritional-index, competing risk analysis, propensity matching analysis

Li Zhao,1 Yuanyuan Ren,1 Donghui Qin,2 Xue Yang,1 Zhuo Chen,1 Na Zhang1 1Department of Cardiology, The Third Affiliated Hospital of Qiqihar Medical College, Qiqihar, 161000, People’s Republic of China; 2General Hospital, Qiqihar City Second Hospital, Qiqihar, People’s Republic of ChinaCorrespondence: Na Zhang, Email 13904523506@163.comObjective: To retrospectively compare the efficacy of Sacubitril/Valsartan and Benazepril in the treatment of heart failure in patients following acute myocardial infarction.Methods: A retrospective analysis of clinical data was conducted for 103 patients with heart failure following acute myocardial infarction admitted to our hospital from January 2021 to January 2024. All patients met complete inclusion and exclusion criteria. Based on the treatment interventions received, they were divided into a control group (n=51) and an observation group (n=52). All patients received percutaneous coronary intervention (PCI) and conventional drug treatment upon admission. The control group received additional treatment with benazepril, while the observation group received Sacubitril/Valsartan on top of the baseline treatment. A comparison was made between the two groups in terms of clinical treatment outcomes, cardiac function indicators [left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDD), left ventricular ejection fraction (LVEF)], levels of inflammatory markers [high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6)], N-terminal pro-B-type natriuretic peptide (NT-proBNP), incidence of adverse reactions, major adverse cardiac events (MACEs), and 6-minute walking distance (6MWD).Results: No patients were lost to follow-up. After six months of treatment, the observation group demonstrated significantly greater improvements in left ventricular function parameters (LVESV, LVEDD, and LVEF) and reductions in inflammatory markers (hs-CRP, IL-6) and NT-proBNP levels compared to the control group (P < 0.05). The observation group also had a significantly lower incidence of major adverse cardiac events (MACEs) (11.54% vs 31.37%, P < 0.05) and a greater improvement in 6-minute walking distance (P < 0.05). The incidence of adverse reactions was comparable between the two groups (P > 0.05).Conclusion: Sacubitril/Valsartan is a safe and effective treatment for heart failure post-AMI, offering significant improvements in cardiac function, inflammatory response, exercise capacity, and a reduction in MACE risk.Keywords: sacubitril/valsartan, heart failure following acute myocardial infarction, efficacy, cardiac function

Xianjun Xiao,1,&ast; Peiwen Xue,1,&ast; Xiangyun Yan,2,&ast; Yanqiu Li,2,&ast; Yunzhou Shi,2 Haiyan Qin,2 Di Qin,2 Wei Cao,2 Zihao Zou,2 Lu Wang,2 Rongjiang Jin,1 Ying Li,2 Junpeng Yao,2 Juan Li1,3 1School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 3Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Chengdu, Sichuan, 611135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Yao; Juan Li, Email yjp@cdutcm.edu.cn; 785939016@qq.comBackground: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research.Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness.Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of − 22%, − 24.9%, and − 24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of − 21.7% and − 23.7%, respectively.Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs’ potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.Keywords: urticaria, short-chain fatty acids, gut microbiota, gut-skin axis, Mendelian randomization

Dongyuan Qin,1 Lin Wang,2 Yahui Ni,1 Zhangtao Shan,1 Lifang Yang1 1Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Lin Wang, Department of Pathology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China, Email 13613411069@139.comBackground: Chronic gastritis affects more than half of the global population to varying extents.Objectives: This study aimed to investigate the knowledge, attitude, and practice (KAP) of patients admitted to the gastroenterology department in the Shanxi region concerning chronic gastritis.Methods: This study was conducted in Shanxi between April and July 2023. The participants were enrolled when they consulted at the clinic. Demographic characteristics and KAP scores were collected through a self-administered questionnaire. KAP scores > 60% were considered good. Structural equation modeling (SEM) was utilized to examine the relationships among the dimensions of knowledge, attitude, and practice.Results: A total of 416 valid questionnaires were collected. The median knowledge score was 28 (0– 60) (with possible values of 0– 60), the median attitude score was 60 (28– 77) (with possible values of 16– 80), and the median practice score was 45 (12– 60) (with possible values of 12– 60). Hence, 133, 379, and 343 participants had knowledge, attitude, and practice scores, respectively, above the 60% threshold. Significant positive correlations were found between knowledge and attitude (r=0.300, P< 0.001), knowledge and practice (r = 0.297, P< 0.001), and attitude and practice (r=0.353, P=0.004) through correlation analysis. Structural Equation Modeling (SEM) revealed that knowledge directly and significantly influenced attitude (β=0.643, P< 0.001), as well as practice (β=0.095, P=0.034), and attitude had a direct effect on practice (β=0.094, P=0.009).Conclusion: Insufficient knowledge, positive attitudes, and proactive practices concerning chronic gastritis were observed in patients in the gastroenterology department. Prioritizing patient education and addressing patient attitudes during clinical consultations can enhance healthcare practices and improve the management of chronic gastritis.Keywords: knowledge, attitude, practice, Helicobacter pylori, chronic gastritis, cross-sectional study

Manjiao Zhuang,1,&ast; Lei Rao,2,3,&ast; Yadi Chen,1 Shangying Xiao,1 Haishan Xia,1 Jiangyong Yang,2 Xiaohua Lv,1 Dongyun Qin,1 Chunjie Zhu1 1Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Medical College, Shaoguan University, Shaoguan, 512026, People’s Republic of China; 3Department of Biomedicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Manjiao Zhuang, Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email manjiao@163.com Chunjie Zhu, School of Basic Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email zhuchunjie718@163.comIntroduction: Quercetin has an ideal therapeutic effect on islet function improvement in type 2 diabetes mellitus (T2DM). However, the therapeutic benefit of quercetin is hindered by its poor bioavailability and limited concentration in pancreatic islets. In this study, superparamagnetic iron oxide nanoparticle (SPION)-modified exosomes were prepared to load quercetin, hoping to endow quercetin with enhanced water solubility and active targeting capacity with the help of magnetic force (MF).Methods: Transferrin-modified SPIONs (Tf-SPIONs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry, and quercetin-loaded exosomes (Qu-exosomes) were acquired by electroporation. Tf-SPION-modified quercetin-loaded exosomes (Qu-exosome-SPIONs) were generated by the self-assembly of transferrin (Tf) and the transferrin receptor (TfR). The solubility of quercetin was determined by high-performance liquid chromatography (HPLC) analysis. The pancreatic islet targeting capacity and insulin secretagogue and antiapoptotic activities of Qu-exosome-SPIONs/MF were evaluated both in vitro and in vivo.Results: The Qu-exosome-SPIONs were well constructed and harvested by magnetic separation with a uniform size and shape in a diameter of approximately 86.2 nm. The water solubility of quercetin increased 1.97-fold when loaded into the SPION-modified exosomes. The application of SPIONs/MF endowed the Qu-exosomes with favorable targeting capacity. In vitro studies showed that Qu-exosome-SPIONs/MF more effectively inhibited or attenuated β cell apoptosis and promoted insulin secretion in response to elevated glucose (GLC) compared with quercetin or Qu-exosome-SPIONs. In vivo studies demonstrated that Qu-exosome-SPIONs/MF displayed an ideal pancreatic islet targeting capacity, thereby leading to the restoration of islet function.Conclusion: The Qu-exosome-SPIONs/MF nano-delivery system significantly enhanced the quercetin concentration in pancreatic islets and thereby improved pancreatic islet protection.Keywords: quercetin, exosome, SPION, solubility, targeted delivery, islet function

Danya Zhao,1 Danping Qin,2 Liming Yin,3 Qiang Yang4 1The First School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Institute of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Gastroenterology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Danping Qin, Email qindp19841@sina.comBackground: Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated.Methods: Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo.Results: A total of 36 DEGs were identified. AQP8, HMGCS2, and VNN1 were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. AQP8, HMGCS2, and VNN1 were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of AQP8 and HMGCS2 decreased, whereas that of VNN1 increased. Azathioprine treatment improved all the indicators to different degrees.Conclusion: AQP8, HMGCS2, and VNN1 are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.Keywords: ulcerative colitis, bioinformatics analysis, core genes, immune cells

Bingtong Wang,&ast; Wenlin Fang,&ast; Dingjiang Qin,&ast; Qiuming He, Chaoting Lan Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoting Lan, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China, Email 415879043@qq.comIntroduction: Hirschsprung’s disease (HSCR) is a developmental defect of the enteric nervous system (ENS), which is caused by abnormal development of enteric neural crest cells. Its occurrence is caused by genetic factors and environmental factors. It has been reported that single nucleotide polymorphisms (SNPs) of proprotein convertase subtilisin/kexin type 2 (PCSK2) gene are associated with HSCR. However, the correlation of HSCR in southern Chinese population is still unclear.Methods: We assessed the association of rs16998727 with HSCR susceptibility in southern Chinese children using TaqMan SNP genotyping analysis of 2943 samples, including 1470 HSCR patients and 1473 controls. The association test between rs16998727 and phenotypes was performed using multivariable logistic regression analysis.Results: We got an unexpected result, PCSK2 SNP rs16998727 was not significantly different from HSCR and its HSCR subtypes: S-HSCR (OR = 1.08, 95% IC: 0.93~1.27, P_adj = 0.3208), L-HSCR (OR = 1.07, 95% IC: 0.84~1.36, P_adj = 0.5958) and TCA (OR = 0.94, 95% IC: 0.61~1.47, P_adj = 0.8001).Conclusion: In summary, we report that rs16998727 (PCSK2 and OTOR) is not associated with the risk of HSCR in southern Chinese population.Keywords: Hirschsprung’s disease, HSCR, single nucleotide polymorphism, SNP, proprotein convertase subtilisin/kexin type 2, PCSK2, genetic susceptibility

Honglu Ding,1,&ast; Qiuxia Yang,2,&ast; Yize Mao,1,&ast; Dailei Qin,1 Zehui Yao,1 Ruiqi Wang,1 Tao Qin,3 Shengping Li1 1Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Medical Imaging, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengping Li, Department of Pancreatobiliary Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road E, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86- 020-87341843, Email lishengp@mail.sysu.edu.cnPurpose: There is an urgent need to discover a predictive biomarker to help patients with advanced pancreatic cancer (APC) choose appropriate chemotherapy regimens. This study aimed to determine whether baseline serum amyloid A (SAA) levels were associated with overall survival (OS), progression-free survival (PFS), and treatment response in patients with APC received chemotherapy.Patients and Methods: This retrospective study included 268 patients with APC who received first-line chemotherapy at the Sun Yat-Sen University Cancer Center between January 2017 and December 2021. We examined the effect of baseline SAA on OS, PFS and chemotherapy response. The X-Tile program was used to determine the critical value for optimizing the significance of segmentation between Kaplan-Meier survival curves. The Kaplan-Meier curves and Cox regression analyses were used to analyze OS and PFS.Results: The best cut-off value of baseline SAA levels for OS stratification was 8.2 mg/L. Multivariate analyses showed that SAA was an independent predictor of OS (Hazard Ratio (HR) = 1.694, 95% Confidence Interval (CI) = 1.247– 2.301, p = 0.001) and PFS (HR = 1.555, 95% CI = 1.152– 2.098, p = 0.004). Low SAA was associated with longer OS (median, 15.7 months vs 10.0 months, p < 0.001) and PFS (median, 7.6 months vs 4.8 months, p < 0.001). The patients with a low SAA who received mFOLFIRINOX had longer OS (median, 28.5 months vs 15.1 months, p = 0.019) and PFS (median, 12.0 months vs 7.4 months, p = 0.035) than those who received nab-paclitaxel plus gemcitabine (AG) or SOXIRI, whereas there was no significant difference among the three chemotherapy regimens in patients with a high SAA.Conclusion: Owing to the rapid and simple analysis of peripheral blood, baseline SAA might be a useful clinical biomarker, not only as a prognostic biomarker for patients with APC, but also as a guide for the selection of chemotherapy regimens.Keywords: advanced pancreatic cancer, serum amyloid A, chemotherapy, prognosis, biomarker

Liya Fu,1,2,&ast; Wanlong Zhu,1,2,&ast; Dongmei Tian,1,2 Yong Tang,2,3 Yun Ye,1 Qiming Wei,1 Chengbin Zhang,1 Wenqiao Qiu,2 Dalian Qin,2 Xuping Yang,1,2 Yilan Huang1,2 1Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2School of Pharmacy, Southwest Medical University, Luzhou, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuping Yang; Yilan Huang, Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China, Email yangxuping6552@163.com; lzyxyyxp123@163.comPurpose: Anoectochilus roxburghii (Wall.) Lindl. polysaccharides (ARPs) have been reported to exhibit multiple pharmacological activities including anti-inflammatory and anti-hyperglycemia. This study aims to investigate the effect of ARPs on cognitive dysfunction induced by high fat diet (HFD).Methods: Six-week-old male mice were treated with ARPs by dietary supplementation for 14 weeks. The effect of ARPs on cognitive function was determined by assessing the changes in spatial learning and memory ability, neurotrophic factors in hippocampus, inflammatory parameters, intestinal barrier integrity, and gut microbiota.Results: ARPs supplementation can effectively ameliorate cognitive dysfunction, decrease the phosphorylation levels of Tau protein in hippocampus. Meanwhile, the increased body weight, plasma glucose, total cholesterol, inflammatory factors induced by HFD were abolished by ARPs treatment. Furthermore, ARPs treatment restored the intestinal epithelial barrier as evidenced by upregulation of intestinal tight junction proteins. Additionally, ARPs supplementation significantly decreased the relative abundance of several bacteria genus such as Parabacteroides, which may play regulatory roles in cognitive function.Conclusion: These results suggest that ARPs might be a promising strategy for the treatment of cognitive dysfunction induced by HFD. Mechanistically, alleviation of cognitive dysfunction by ARPs might be associated with the “gut-brain” axis.Graphical Abstract: Keywords: Anoectochilus roxburghii (Wall.) Lindl. polysaccharides, diet-induced-obesity, cognitive dysfunction, gut microbiota, “gut-brain” axis

Yu Zhang,1– 3,&ast; Li Cui,2,&ast; Yizeng Lu,4 Jixiang He,5 Hidayat Hussain,6 Lei Xie,4 Xuan Sun,2 Zhaoqing Meng,7 Guiyun Cao,7 Dawei Qin,1 Daijie Wang2,3 1School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China; 2School of Pharmaceutical Sciences and Key Laboratory for Applied Technology of Sophisticated Analytical Instruments of Shandong Province, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, People’s Republic of China; 3Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, 274000, People’s Republic of China; 4Shandong Provincial Center of Forest and Grass Germplasm Resources, Jinan, 250102, People’s Republic of China; 5School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250353, People’s Republic of China; 6Department of Bioorganic Chemistry, Leibniz Institute of Plant BioChemistry, Halle, D-06120, Germany; 7Shandong Hongjitang Pharmaceutical Group Co., Ltd., Jinan, 250103, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dawei Qin, School of Chemistry and Chemical Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China, Tel/Fax +86 53189631208, Email qdw@qlu.edu.cn Daijie Wang, Biological Engineering Technology Innovation Center of Shandong Province, Heze Branch of Qilu University of Technology (Shandong Academy of Sciences), Heze, 274000, People’s Republic of China, Tel +86 53182605319, Fax +86 53182964889, Email wangdaijie@qlu.edu.cnBackground: The leaves of L. japonica (LLJ) are widely used as medicine in China. It is rich in caffeoylquinic acids, flavonoids and iridoid glycosides and has strong reducing capacities. Therefore, it can be used as a green material to synthesize silver nanoparticles.Methods: LLJ was used as a reducing agent to produce the LLJ-mediated silver nanoparticles (LLJ-AgNPs). The structure and physicochemical properties of LLJ-AgNPs were characterized by ultraviolet spectroscopy (UV-Vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and x-ray powder diffraction (XRD). Antioxidant activity of LLJ-AgNPs was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging. Antibacterial activity was determined by 96 well plates (AGAR) gradient dilution, while the anticancer potential was determined by MTT assay.Results: The results showed LLJ-AgNPs had a spherical structure with the maximum UV-Vis absorption at 400 nm. In addition, LLJ-AgNPs exhibited excellent antioxidant properties, where the free radical scavenging rate of LLJ-AgNPs was increased from 39% to 92% at concentrations from 0.25 to 1.0 mg/mL. Moreover, LLJ-AgNPs displayed excellent antibacterial properties against E. coli and Salmonella at room temperature, with minimum inhibitory values of 10− 6 and 10− 5 g/L, respectively. In addition, the synthetic LLJ-AgNPs exhibited a better inhibition effect in the proliferation of cancer cells (HepG2, MDA-MB − 231, and Hela cells).Conclusion: The present study provides a green approach to synthesize LLJ-AgNPs. All those findings illustrated that the produced LLJ-AgNPs can be used as an economical and efficient functional material for further applications in food and pharmaceutical fields.Keywords: leaves of Lonicera japonica Thunb, LLJ-AgNO3-NPs, green approach, antioxidant, antibacterial, anticancer

Dui Qin,1,2,* Lei Zhang,1,* Hongrui Zhu,1 Junjie Chen,1 Daocheng Wu,1 Ayache Bouakaz,3 Mingxi Wan,1 Yi Feng1 1The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Biomedical Engineering, School of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing, People’s Republic of China; 3UMR 1253, iBrain, Université de Tours, Inserm, Tours, F-37032, France*These authors contributed equally to this workCorrespondence: Mingxi Wan; Yi FengThe Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’ an Jiaotong University, Xi’ An, 710049, People’s Republic of ChinaTel +86 29 82667924Fax +86 29 82668668Email mxwan@mail.xjtu.edu.cn; fengyi@mail.xjtu.edu.cnBackground: Photothermal therapy (PTT) has attracted considerable attention for cancer treatment as it is highly controllable and minimally invasive. Various multifunctional nanosystems have been fabricated in an “all-in-one” form to guide and enhance PTT by integrating imaging and therapeutic functions. However, the complex fabrication of nanosystems and their high cost limit its clinical translation.Materials and Methods: Herein, a high efficient “one-for-all” nanodroplet with a simple composition but owning multiple capabilities was developed to achieve ultrasound (US) imaging-guided and cavitation-enhanced PTT. Perfluoropentane (PFP) nanodroplet with a polypyrrole (PPy) shell (PFP@PPy nanodroplet) was synthesized via ultrasonic emulsification and in situ oxidative polymerization. After characterization of the morphology, its photothermal effect, phase transition performance, as well as its capabilities of enhancing US imaging and acoustic cavitation were examined. Moreover, the antitumor efficacy of the combined therapy with PTT and acoustic cavitation via the PFP@PPy nanodroplets was studied both in vitro and in vivo.Results: The nanodroplets exhibited good stability, high biocompatibility, broad optical absorption over the visible and near-infrared (NIR) range, excellent photothermal conversion with an efficiency of 60.1% and activatable liquid-gas phase transition performance. Upon NIR laser and US irradiation, the phase transition of PFP cores into microbubbles significantly enhanced US imaging and acoustic cavitation both in vitro and in vivo. More importantly, the acoustic cavitation enhanced significantly the antitumor efficacy of PTT as compared to PTT alone thanks to the cavitation-mediated cell destruction, which demonstrated a substantial increase in cell detachment, 81.1% cell death in vitro and 99.5% tumor inhibition in vivo.Conclusion: The PFP@PPy nanodroplet as a “one-for-all” theranostic agent achieved highly efficient US imaging-guided and cavitation-enhanced cancer therapy, and has considerable potential to provide cancer theranostics in the future.Keywords: one-for-all nanodroplet, theranostics, photothermal therapy, acoustic cavitation, ultrasound imaging

Tongyi Sun,1 Bo Zhan,2,3 Weifen Zhang,2 Di Qin,1 Guixue Xia,2 Huijie Zhang,1,3 Meiyu Peng,4 Sheng-An Li,3 Yun Zhang,3 Yuanyuan Gao,2 Wen-Hui Lee1,3 1Department of Bioengineering, School of Bioscience and Technology, Weifang Medical University, Weifang 261053, Shandong, China; 2Department of Pharmaceutics, School of Pharmacy, Weifang Medical University, Weifang 261053, Shandong, China; 3Key Laboratory of Bioactive Peptide of Yunnan Province/Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China; 4Department of Immunology, School of Clinical Medicine, Weifang Medical University, Weifang 261053, Shandong, China Background: Nonscar wound healing is a desirable treatment for cutaneous wounds worldwide. Peptide OH-CATH30 (OH30) from king cobra can selectively regulate the innate immunity and create an anti-inflammatory micro-environment which might benefit nonscar wound healing.Purpose: To overcome the enzymatic digestion and control release of OH30, OH30 encapsulated in carboxymethyl chitosan nanoparticles (CMCS-OH30 NP) were prepared and their effects on wound healing were evaluated.Methods: CMCS-OH30 NP were prepared by mild ionic gelation method and properties of the prepared CMCS-OH30 NP were determined by dynamic light scattering. Encapsulation efficiency, stability and release profile of OH30 from prepared CMCS-OH30 NP were determined by HPLC. Cytotoxicity, cell migration and cellular uptake of CMCS-OH30 NP were determined by conventional methods. The effects of prepared CMCS-OH30 NP on the wound healing was investigated by full-thickness excision animal models.Results: The release of encapsulated OH30 from prepared CMCS-OH30 NP was maintained for at least 24 h in a controlled manner. CMCSOH30 NP enhanced the cell migration but had no effects on the metabolism and proliferation of keratinocytes. In the full-thickness excision animal models, the CMCS-OH30 NP treatment significantly accelerated the wound healing compared with CMCS or OH30 administration alone. Histopathological examination suggested that CMCS-OH30 NP promoted wound healing by enhancing the granulation tissue formation through the re-epithelialized and neovascularized composition. CMCS-OH30 NP induced a steady anti-inflammatory cytokine IL10 expression but downregulated the expressions of several pro-inflammatory cytokines.Conclusion: The prepared biodegradable drug delivery system accelerates the healing and shows better prognosis because of the combined effects of OH30 released from the nanoparticles. Keywords: wound healing, antimicrobial peptide, OH-CATH30, nanoparticles, skin destruction

Jianfei Liang,1,* Shanshan Xu,1,* Mingming Shen,2,* Bingkun Cheng,3 Yongfeng Li,4 Xiangwei Liu,1 Dongze Qin,1 Anuj Bellare,5 Liang Kong1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Disease & Shaanxi Key Laboratory of Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, Xi’an, 2Department of Stomatology, Xinhua Hospital of Beijing, Beijing, 3Department of Oral and Maxillofacial Surgery, School of Stomatology, The Second Hospital of Hebei Medical University, Shijiazhuang, 4Department of Stomatology, Chinese PLA 532 Hospital, Huangshan, People’s Republic of China; 5Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA *These authors contributed equally to this work Abstract: An easier method for constructing the hierarchical micro-/nano-structures on the surface of dental implants in the clinic is needed. In this study, three different titanium surfaces with microscale grooves (width 0.5–1, 1–1.5, and 1.5–2 µm) and nanoscale nanoparticles (diameter 20–30, 30–50, and 50–100 nm, respectively) were obtained by treatment with different concentrations of hydrofluoric acid (HF) and at different etching times (1%, 3 min; 0.5%, 12 min; and 1.5%, 12 min, respectively; denoted as groups HF1, HF2, and HF3). The biological response to the three different titanium surfaces was evaluated by in vitro human bone marrow-derived mesenchymal stem cell (hBMMSC) experiments and in vivo animal experiments. The results showed that cell adhesion, proliferation, alkaline phosphatase activity, and mineralization of hBMMSCs were increased in the HF3 group. After the different surface implants were inserted into the distal femurs of 40 rats, the bone–implant contact in groups HF1, HF2, and HF3 was 33.17%±2.2%, 33.82%±3.42%, and 41.04%±3.08%, respectively. Moreover, the maximal pullout force in groups HF1, HF2, and HF3 was 57.92±2.88, 57.83±4.09, and 67.44±6.14 N, respectively. The results showed that group HF3 with large micron grooves (1.5–2.0 µm) and large nanoparticles (50–100 nm) showed the best bio-functionality for the hBMMSC response and osseointegration in animal experiments compared with other groups. Keywords: hydrofluoric acid etching, surface modification, micro-/nano-structures, osteogenic activity, titanium implant

Since the first assessment report (FAR) of Inter-Governmental Panel on Climate Change (IPCC) in 1990, the international scientific community has made substantial progresses in climate change sciences. Changes in components of climate system, including the atmosphere, oceans and cryosphere, indicate that global warming is unequivocal. Instrumental records demonstrate that the global mean temperature has a significant increasing trend during the 20th century and in the latest 50 years the warming become faster. In the meantime, the global sea level has a strong increasing trend, as well as the snow coverage of Northern Hemisphere showed an obvious downward trend. Moreover, the global warming plays a key role in significantly affecting the climate system and social-economy on both global and regional scales, such as sea level rise, melting of mountain glaciers and ice sheets, desertification, deforestation, increase of weather extremes (typhoon, hurricane and rainstorm) and so on. The state of the art understanding of IPCC Fourth Assessment Report (AR4) was most of the observed increase in global average temperatures since the mid-20th century is very likely due to the observed increase in the concentrations of anthropogenic greenhouse gases. Climate change issues, as a grave challenge to the sustainable development of the human society, have received ever greater attention from the international community. Deeply cognizant of the complexity and extensive influence of these issues and fully aware of the arduousness and urgency of the task of addressing climate change, the Chinese government is determined to address climate change in the process of pursuing sustainable development. The facts of climate change in China and its impacts, and China’s policies and actions for addressing climate change are introduced in this paper.

Major outcomes of Working Group I, IPCC AR4 (2007), as well as the recent understandings from our regional climatic assessments in China were summarized. Changes of cryosphere in China, one of the major components in regional climate system, is specifically reviewed. Under the global/regional warming, all components of cryosphere in China (Tibetan Plateau and surroundings) including glaciers, frozen ground (including permafrost) and snow cover show rapid decay in the last decades. These changes have big socioeconomic impacts in west China, thus encourages both government and scientists pay more and more attention to this field.

Traffic safety situation refers to the current traffic operation safety situation and future evolution trend of one or more related highways. Accurate traffic safety situation assessment is of great significance for promoting traffic safety. This paper proposes a new urban traffic safety situation evaluation method based on Internet of Vehicles data. First, based on vehicle data, traffic condition data is collected as sample data for urban traffic safety assessment. Secondly, from the perspective of traffic environment, traffic characteristics, road traffic accidents and road conditions, a traffic safety evaluation index system is constructed and quantified. Finally, the weight of each index is calculated by using the analytic hierarchy process, and the evaluation score of urban traffic safety is calculated to judge the safety level. The experimental results show that, compared with the traditional traffic safety situation assessment method, the evaluation accuracy and efficiency of this method have been greatly improved, and the evaluation accuracy rate is more than 95%. [ABSTRACT FROM AUTHOR]

In this paper, based on the 24 scenes Sentinel-1A images covering the Beibu Gulf region from 2018 to 2020, we used the PSInSAR technique to obtain the surface subsidence information in the study area and analyzed the surface subsidence spatial-temporal characteristics. The results showed that (1) The subsidence rate of most subsidence areas in Beibu Gulf is from −10.0 mm/year to −1.1 mm/year. And most of the subsidence areas are located in the coastal areas in the south of the study area. The distribution was obvious, and the maximum subsidence rate can reach −17.2 mm/a. However, the subsidence areas of villages and towns located in Qinzhou in the north and inland of the study area are relatively stable. (2) Subsidence was mainly concentrated in Yinhai District, Haicheng District, Tieshan Port District and Fangcheng District of Fangchenggang in Beihai City. The annual average Subsidence range from −10.0 mm/year to −1.1 mm/year. Among them, the Tieshan Port area and Fangcheng District had obvious subsidence trends, with the maximum cumulative subsidence reaching −35.9 mm. (3) The spatial-temporal characteristics of wide-area surface subsidence and the relationship between surface subsidence and influencing factors in the Beibu Gulf region were determined. [ABSTRACT FROM AUTHOR]

Vulvovaginal candidiasis (VVC) is an infectious disease caused mainly by Candida albicans. Kangfuxin (KFX) is a traditional Chinese medicine preparation made from Periplaneta americana extracts, which promotes wound healing and enhances body immunity and also acts as an antifungal agent. Here, we evaluated the effect of KFX in the treatment of VVC in vitro and in vivo. The minimum inhibitory concentration (MIC50) of KFX against C. albicans ranged from 7·65 to 20·57%. In addition, KFX was more efficient than fluconazole (FLC) in inhibiting the drug‐resistant C. albicans, and the effect was more intense after 8 h. The KFX treatment also exhibited good activity in vivo. It restored the body weight and reduced the vulvovaginal symptoms in mice induced with VVC. It downregulated the expression of the hyphae‐related gene, HWP1, thus inhibiting the growth and development of C. albicans hyphae. It also increased the number of neutrophils and promoted the secretion of interleukin‐17A (IL‐17A); however, the levels of interleukin‐8 (IL‐8) and interleukin‐1β (IL‐1β) decreased in mice with VVC. We deduce that KFX effectively treats vaginal candidiasis in two ways: by inhibiting the growth and development of mycelia to reduce colonization of C. albicans and by promoting the secretion and release of IL‐17A and neutrophils in high numbers to fight C. albicans infection. This study provides a theoretical basis for the use of KFX for the clinical treatment of VVC. [ABSTRACT FROM AUTHOR]

In the wind tunnel test of trains, the scale size changes the Reynolds numbers of trains, which may affect the aerodynamic characteristics of the train. Based on computational fluid dynamics (CFD), numerical models of train aerodynamics with five different scale sizes are established. The five different scale sizes are λ=1/1, 1/2, 1/8, 1/16 and 1/25, respectively, and the aerodynamic characteristics of trains running in the open-air operating condition and crosswind operating condition with different scale sizes are numerically simulated. The results show that the pressure drag coefficients and pressure lift coefficients of the train tend to decrease with the decrease of the scale size. In the open-air operating condition, compared with the full-size train, the pressure drag coefficient of the 1/25th scaled train is less by 14.4%, and the pressure lift coefficients of the head car, middle car and tail car change 16.1%, 46.6% and 12.3%, respectively. The scale size affects the velocity gradient near the train surface and the position of flow separation changes. The decrease of the scale size leads to the decrease of Reynolds numbers and the increase of viscous drag coefficient. When the scale size is 1/25, the viscous drag coefficient of the train is 0.186, which is 48.6% larger than the one of the full-size train. Compared with the open-air operating condition, the trend of the pressure drag coefficients and viscous drag coefficients is consistent except for the head car in crosswind operating condition when the scale size decreases. In the range of scale size λ between 1/1 and 1/25, the aerodynamic drag coefficient of the head car, middle car and tail car increase with the decrease of scale size, and the difference in the aerodynamic drag coefficient of the train is 12.9%. In addition, the train's aerodynamic lift coefficient shows an increasing trend with the decrease of scale size. [ABSTRACT FROM AUTHOR]

The strictest ever Clean Air Action has been implemented since 2013 at nationwide scale in China. Nevertheless, PM2.5 (particulate matter with aerodynamic diameter smaller than 2.5 μm) mass and number of ultrafine particles (UFPs, the particles with diameters smaller than 100 nm) exhibited contrasting response to the emission mitigation policies. Unlike reduction of PM2.5 and number of accumulation mode particles, UFPs number decreased from 2012 to 2015, and then has begun to increase sharply since 2016, and annual change of number in nucleation mode particles can reach 40% at noontime during 2017–2019. We examined inter‐annual trends of mode diameter, frequency of new particle formation (NPF) events, formation and growth rates, and particles were found to be much finer and NPF events have been more frequent since 2017. The much higher temperature and stronger solar radiation induced by PM2.5 reduction could promote the formation of secondary aerosol particles at noon. Plain Language Summary: Since 2013, China has implemented the strictest ever air pollution control policies, which resulted in substantial reductions in PM2.5 mass concentrations. However, it is still unclear how the recent stringent control measures influence number concentration of ultrafine particles, part of them from secondary formation. Furthermore, it remained a critical challenge to study the effect of PM2.5 reduction on formation of secondary pollutants. Using long‐term particle number size distribution (PNSD) data, we found a dramatic increasing trend in UFPs number after 2016 in urban Lanzhou of west China with maximum increase in nucleation mode particles at noon. Further, we checked the inter‐annual variations of mode diameter of PNSDs, NPF frequency, formation and growth rates, and then frequent new particle formation (NPF) events were found to dominate the variation in UFPs number during the observation period. The high temperature and strong solar radiation induced by PM2.5 reduction in response to emission mitigation policies could promote occurrence of NPF events, and thus resulted in increase in UFPs. This study is important for revising future emission control measures to reduce number concentrations of ultrafine particles. Key Points: Annual change of N13–25 at noon time increased by 40% during 2017–2019Increases in ultrafine particles were mainly induced by more frequent NPF eventsNPF is increasingly frequent due to reduction in Coagulation sink in response to Clean Air Action in China [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess the reporting quality and methodological quality of split-mouth trials (SMTs) published during the past 2 decades and to determine whether there has been an improvement in their quality over time. We searched the MEDLINE database via PubMed to identify SMTs published in 1998, 2008, and 2018. For each included SMT, we used the CONsolidated Standards Of Reporting Trials (CONSORT) 2010 guideline, CONSORT for within-person trial (WPT) extension, and a new 3-item checklist to assess its trial reporting quality (TRQ), WPT-specific reporting quality (WRQ), and SMT-specific methodological quality (SMQ), respectively. Multivariable generalized linear models were performed to analyze the quality of SMTs over time, adjusting for potential confounding factors. A total of 119 SMTs were included. The mean overall score for the TRQ (score range, 0 to 32), WRQ (0 to 15), and SMQ (0 to 3) was 15.77 (SD 4.51), 6.06 (2.06), and 1.12 (0.70), respectively. The primary outcome was clearly defined in only 28 SMTs (23.5%), and only 27 (22.7%) presented a replicable sample size calculation. Only 45 SMTs (37.8%) provided the rationale for using a split-mouth design. The correlation between body sites was reported in only 5 studies (4.2%) for sample size calculation and 4 studies (3.4%) for statistical results. Only 2 studies (1.7%) performed an appropriate sample size calculation, and 46 (38.7%) chose appropriate statistical methods, both accounting for the correlation among treatment groups and the clustering/multiplicity of measurements within an individual. Results of regression analyses suggested that the TRQ of SMTs improved significantly with time (P < 0.001), while there was no evidence of improvement in WRQ or SMQ. Both the reporting quality and methodological quality of SMTs still have much room for improvement. Concerted efforts are needed to improve the execution and reporting of SMTs. [ABSTRACT FROM AUTHOR]

0.5-mm-thick 7075-T6 aluminum alloy sheets were butt joined successfully by high-speed micro friction stir welding (μFSW) as well as conventional μFSW using a pinless tool. The influences of welding parameters on the axial force, residual stresses, and deformations were studied through experiments. Good surface morphology and defect-free joints were obtained by high-speed μFSW as well as conventional μFSW in a fixed rotational speed/welding speed of 6.67 rad/mm. The axial force during μFSW increased with the increment in welding speed and decreased with the increment in rotational speed. When the ratio of rotational speed/welding speed was 6.67 rad/mm, compared with conventional μFSW (2000/300), the lower axial force of 1460 N was obtained by using high-speed μFSW (10,000/1500). Longitudinal tensile residual stress and transverse compressive residual stress occurred around the weld zone for all μFSW joints. The residual stresses of joint fabricated by a parameter of 10,000/1500 were slightly less than that fabricated by 2000/300. Both longitudinal maximum bending deformation Zmax and transverse angular deformation α increased with the increment in rotational speed and decreased with the increment in welding speed. As a comparison to 2000/300, the welded sheet with a parameter of 10,000/1500 exhibited slightly lower Zmax and α. [ABSTRACT FROM AUTHOR]

Scenic ecotourism spots, as major attractors of tourists, boast great economic values and development potentials. Many local governments have developed a series of tourism resources with the aim to fully utilize resources and promote regional economy. However, the tourism development has exerted negative environmental impacts on scenic ecotourism spots. Targeting Xixi Wetland Park, Hangzhou, southeastern China’s Zhejiang Province, this paper explores the effects of tourism development and tourist activities on the soil and water environments in scenic ecotourism spots, and draws the following conclusions: The environment in the ecotourism scenic spot is influenced in varied degrees by both tourism development and tourist activities; soil porosity can characterize how tourism development and tourist activities affect the environment of scenic ecotourism spots; the impacts of tourism development or tourist activities on scenic ecotourism spots can be demonstrated by the pH, chemical oxygen demand (COD), total ammonia nitrogen (TAN) and turbidity of water bodies. [ABSTRACT FROM AUTHOR]