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Yu Zhang,1,2 Fan Liu,2,3,* Chuntao Shao,2,* Jun Huang,3 Guoping Yan1 1College of Chemical and Material Engineering, Quzhou University, Quzhou, Zhejiang Province, 324000, People’s Republic of China; 2School of Materials Science and Engineering, Wuhan Institute of Technology, Wuhan, 430205, People’s Republic of China; 3School of Chemical and Biomolecular Engineering, University of Sydney, NSW, 2006, Australia*These authors contributed equally to this workCorrespondence: Guoping Yan, Tel +86 570 8028560, Email guopingyan@qzc.edu.cnBackground: Precise intraoperative tumor delineation is essential for successful surgical outcomes. However, conventional methods are often incompetent to provide intraoperative guidance due to lack specificity and sensitivity. Recently fluorescence-guided surgery for tumors to delineate between cancerous and healthy tissues has attracted widespread attention. The contrast-enhanced fluorescent imaging has been applied for non-invasive diagnosis of cancers using tumor-targeting fluorescent probes.Methods: The carbonic anhydrase IX targeted polyaspartamide fluorescent compounds (SD-PHEA-NI) were synthesized by incorporating a tumor-targeting group of sulfadiazine (SD) and N-butyl-4-ethyldiamino-1,8-naphthalimide (NI) into water-soluble carriersof poly-α,β-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA). These derivatives were also characterized by Fourier transform infrared spectroscopy, gel permeation chromatography, ultraviolet-visible spectroscopy, nuclear magnetic resonance spectroscopy and fluorescence assays. The cellular uptake, cytotoxicity, and fluorescence imaging ability were evaluated.Results: Experiment results indicated that SD-PHEA-NI has low cytotoxic to Henrietta Lacks (HeLa) cells. Moreover, B16F10 melanoma cells can take up SD-PHEA-NI and show good green fluorescent images. However, SD-PHEA-NI displayed a low-intensity green fluorescence signal in healthy human embryonic kidney (293T) cells.Conclusion: SD-PHEA-NI can be considered a potential fluorescent probe for the detection of tumors. This study has the potential to enhance tumor diagnosis and image-guided surgical interventions by providing real-time information and robust decision support, thereby reducing recurrence and complication rates and ultimately improving patient outcomes.Keywords: fluorescent imaging, polyaspartamide, sulfadiazine, naphthalimide, fluorescent probes

Mohammad Abdullah Taher,1,2 Hasin Hasnat,3 Safaet Alam,1,4 Suriya Akter Shompa,3 Mirola Afroze,2 Mala Khan,2 Chuxiao Shao,5 Shuanghu Wang,5 Peiwu Geng,5 Abdullah Al Mamun5 1Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka, 1000 Bangladesh; 2Bangladesh Reference Institute for Chemical Measurements (BRiCM), Dhaka, 1205 Bangladesh; 3Department of Pharmacy, State University of Bangladesh, Dhaka, 1207 Bangladesh; 4Chemical Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, 1205, Bangladesh; 5Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Abdullah Al Mamun, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Tel +86-19715780050, Email pharmaalmamun@yahoo.comBackground: Throughout history, plants have played a crucial role in advancing medicinal treatments by providing a diverse range of compounds for the development of innovative therapies. Canna indica L. a tropical herb of the Cannaceae family, also known as Indian shot, has a rich history of traditional use in treating ailments like inflammation, malaria, dysentery, fever, dropsy, and diarrhea.Objective: This comprehensive research invesigates the extract preparation of C. indica leaves using multidisciplinary analytical approaches for this extract in order to shed light on its therapeutic potentials.Methods: The research, an international collaboration involving researchers from Bangladesh and China, utilized GC-MS/MS analysis to identify bioactive compounds across different C. indica extracts. Biological assays were conducted to assess antimicrobial activity using the disc diffusion method (in vitro), cytotoxicity through the brine shrimp lethality assay (in vitro), analgesic effects via the acetic acid-induced writhing test (in vivo), and antidiarrheal activity with the castor oil-induced diarrhea model (in vivo). Molecular docking studies were performed to determine binding affinities with Epidermal Growth Factor Receptor (EGFR), Dihydrofolate Reductase (DHFR), Delta Opioid Receptor (DOR), Tumor Necrosis Factor-alpha (TNF-α), and Cyclooxygenase-2 (COX-2) receptors.Results: The GC-MS/MS analysis identified 35, 43, 27, and 20 compounds in dichloromethane, aqueous, petroleum ether, and ethyl acetate extracts, respectively. The aqueous (AQSF) and dichloromethane (DCMSF) extracts showed notable antimicrobial activity, particularly against gram-negative bacteria. Cytotoxicity tests indicated that ethyl acetate (EASF) and dichloromethane (DCMSF) fractions were potent. Analgesic activity was highest in DCMSF, and antidiarrheal effects were dose-dependent, with DCMSF showing the greatest efficacy. Molecular docking revealed strong affinities of Ergostane-3,5,6,12,25-pentol, 25-acetate, (3.beta.,5.alpha.,6.beta.,12.beta).- for EGFR and Norgestrel for COX-2.Conclusion: This research provides valuable insights into the bioactivity evaluation of C. indica, bridging the gap between its chemical composition and diverse biological effects. The findings contribute to the growing body of knowledge in natural product-based drug discovery and underscore the significance of C. indica as a potential source of novel therapeutic agents to treat inflammation and other disease states.Keywords: Canna indica, GC-MS/MS, cytotoxicity, antimicrobial, antidiarrheal, analgesic, molecular docking

Abdullah Al Mamun,1,2 Peiwu Geng,1 Shuanghu Wang,1 Chuxiao Shao1 1Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Chuxiao Shao; Shuanghu Wang, Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, the Lishui Hospital of Wenzhou Medical University, the First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Email scx1818@126.com; wangshuanghu@lsu.edu.cnAbstract: Pyroptosis is an inflammatory cell death induced by inflammasomes that release several pro-inflammatory mediators such as interleukin-18 (IL-18) and interleukin-1β (IL-1β). Pyroptosis, a type of programmed cell death, has recently received increased interest both as a therapeutic and immunological mechanism. Numerous studies have provided substantial evidence supporting the involvement of inflammasomes and pyroptosis in a variety of pathological conditions including cancers, nerve damage, inflammatory diseases and metabolic conditions. Researchers have demonstrated that dysregulation of pyroptosis and inflammasomes contribute to the progression of endometriosis and gynecological malignancies. Current research also indicates that inflammasome and pyroptosis-dependent signaling pathways may further induce the progression of endometrial cancer (EC). More specifically, dysregulation of NLR family pyrin domain 3 (NLRP3) and caspase-1-dependent pyroptosis play a contributory role in the pathogenesis and development of EC. Therefore, pyroptosis-regulated protein gasdermin D (GSDMD) may be an independent prognostic biomarker for the detection of EC. This review presents the molecular mechanisms of pyroptosis-dependent signaling pathways and their contributory role and function in advancing EC. Moreover, this review offers new insights into potential future applications and innovative approaches in utilizing pyroptosis to develop effective anti-cancer therapies. Keywords: endometrial cancer, pyroptosis, NLRP3, caspase-1, GSDMD, IL-1β, IL-18

Pair Ahmed Jiko,1 Mahathir Mohammad,1 Fahmida Tasnim Richi,2 Md. Anisul Islam,3 Safaet Alam,2,4 Mohammad Abdullah Taher,2,5 Chuxiao Shao,6 Shuanghu Wang,6 Peiwu Geng,6 Abdullah Al Mamun6 1Department of Chemistry, Chittagong University of Engineering & Technology, Chittagong, 4349, Bangladesh; 2Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh; 3Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, 4202, Bangladesh; 4Chemical Research Division, BCSIR Dhaka Laboratories, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, 1205, Bangladesh; 5Bangladesh Reference Institute for Chemical Measurements (BRiCM), Laboratory Road, Dhaka, 1205, Bangladesh; 6Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of ChinaCorrespondence: Abdullah Al Mamun, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Tel +86-19715780050, Email pharmaalmamun@yahoo.comBackground: Shirakiopsis indica (Willd)., commonly known as Sa-Mor-Ta-Lay in Thailand, is a mangrove plant belonging to the Euphorbiaceae family. As mangrove plants’ medicinal potentials are less explored, this study sought to qualitatively and quantitatively verify the bioactive components of Shirakiopsis indica fruits methanolic extract (SIF-ME) at the side of its analgesic, anti-inflammatory and anti-oxidant effects followed by in-silico studies.Methods: The in-vivo assessments of analgesic activity involved the hot plate test, acetic acid-induced writhing test, and formalin-induced licking test. The anti-inflammatory efficacy was assessed through the human RBC membrane stabilization assay (HRBC), protein denaturation assay, and xylene-induced ear edema methods. Antioxidant potential was implemented by the DPPH scavenging method.Results: The SIF-ME consistently displayed significant anti-nociceptive activity in a dose-dependent pattern (p < 0.05). The maximum analgesic activity was found in the highest dose (200 mg/kg; p < 0.001) in a hot plate, acetic acid-induced writhing test 43.47%, and in formalin-induced licking test in both early phase (43.3%; p < 0.01) and late phase (61.84%; p < 0.001%). The extract provided optimal protection against hemolysis (83.41% decrease) at 1000 μg/mL and significantly inhibited protein denaturation (67.34– 26.05%) at doses of 1000– 62.5 μg/mL. At 200 mg/kg, the extract showed dose-dependent and substantial inhibition (54.07%; p < 0.01) of xylene-induced ear edema. The in-vitro DPPH (IC50 = 469.5 μg/mL) results showed remarkable scavenging activity and concentration-dependent reducing power. The extract demonstrates no acute oral toxicity, as indicated by an LD50 value exceeding 1000 mg/kg body weight. Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS) analysis was performed which yielded sixty bioactive compounds. In-silico and molecular docking studies revealed favorable pharmacological properties, including good binding affinities and ADME/T profiles.Conclusion: These results support the medicinal use of the plant, which makes it a potential source of analgesic, anti-inflammatory, and antioxidant candidates.Keywords: natural products, medicinal plants, shirakiopsis indica, acute oral toxicity, analgesic, anti-inflammatory, antioxidant, GC-MS/MS, molecular docking

Fangyuan Kuang,1,2 Yang Gao,3 Qingyun Zhou,4 Chenying Lu,3 Qiaomei Lin,4 Abdullah Al Mamun,5 Junle Pan,6 Shuibo Shi,7 Chaoyong Tu,4,&ast; Chuxiao Shao2,&ast; 1School of Medicine, Shaoxing University, Shaoxing, Zhejiang, 312000, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, People Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui, Zhejiang, 323000, People’s Republic of China; 3Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China; 5Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 6First Academy of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 7The First Clinical Medical College of Nanchang University, Nanchang City, Jiangxi, 330000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoyong Tu, Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China, Email tcy7409@163.comBackground: A limited number of studies have examined the use of radiomics to predict 3-year overall survival (OS) after hepatectomy in patients with hepatocellular carcinoma (HCC). This study develops 3-year OS prediction models for HCC patients after liver resection using MRI radiomics and clinicopathological factors.Materials and Methods: A retrospective analysis of 141 patients who underwent surgical resection of HCC was performed. Patients were randomized into two set: the training set (n=98) and the validation set (n=43) including the survival groups (n=111) and non-survival groups (n=30) based on 3-year survival after hepatectomy. Furthermore, x2 or Fisher’s exact test, univariate and multivariate logistic regression analyses were conducted to determine independent clinicopathological risk factors associated with 3-year OS. 1688 quantitative imaging features were extracted from preoperative T2-weighted imaging (T2WI) and contrast-enhanced magnetic resonance imaging (CE-MRI) of arterial phase (AP), portal venous phases (PVP)and delay period (DP). The features were selected using the variance threshold method, the select K best method and the least absolute shrinkage and selection operator (LASSO) algorithm. By using Bernoulli Naive Bayes (BernoulliNB) and Multinomial Naive Bayes (MultinomialNB) classifiers, we constructed models based on the independent clinicopathological factors and Rad-scores. To determine the best model, receiver operating characteristics (ROC) and Delong’s test were used. Moreover, calibration curves were used to determine the calibration ability of the model, while decision curve analysis (DCA) was implemented to evaluate its clinical benefit.Results: The fusion model showed excellent prediction precision with AUC of 0.910 and 0.846 in training and validation set and revealed significant diagnostic accuracy and value in the calibration curve and DCA analysis.Conclusion: Nomograms based on MRI radiomics and clinicopathological factors have significant predictive value for 3-year OS after hepatectomy and can be used for risk classification.Keywords: hepatocellular carcinoma, hepatectomy, MRI radiomics

Abdullah Al Mamun,1,2 Chuxiao Shao,1 Peiwu Geng,1 Shuanghu Wang,1 Jian Xiao1– 3 1Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Wound Healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaCorrespondence: Jian Xiao, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Email xfxj2000@126.com Shuanghu Wang, Central Laboratory of The Lishui Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China, Email wangshuanghu@lsu.edu.cnAbstract: Pyroptosis is a pro-inflammatory form of cell death resulting from the activation of gasdermins (GSDMs) pore-forming proteins and the release of several pro-inflammatory factors. However, inflammasomes are the intracellular protein complexes that cleave gasdermin D (GSDMD), leading to the formation of robust cell membrane pores and the initiation of pyroptosis. Inflammasome activation and gasdermin-mediated membrane pore formation are the important intrinsic processes in the classical pyroptotic signaling pathway. Overactivation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome triggers pyroptosis and amplifies inflammation. Current evidence suggests that the overactivation of inflammasomes and pyroptosis may further induce the progression of cancers, nerve injury, inflammatory disorders and metabolic dysfunctions. Current evidence also indicates that pyroptosis-dependent cell death accelerates the progression of diabetes and its frequent consequences including diabetic peripheral neuropathy (DPN). Pyroptosis-mediated inflammatory reaction further exacerbates DPN-mediated CNS injury. Accumulating evidence shows that several molecular signaling mechanisms trigger pyroptosis in insulin-producing cells, further leading to the development of DPN. Numerous studies have suggested that certain natural compounds or drugs may possess promising pharmacological properties by modulating inflammasomes and pyroptosis, thereby offering potential preventive and practical therapeutic approaches for the treatment and management of DPN. This review elaborates on the underlying molecular mechanisms of pyroptosis and explores possible therapeutic strategies for regulating pyroptosis-regulated cell death in the pharmacological treatment of DPN. Keywords: Diabetes mellitus, Diabetic peripheral neuropathy, Inflammation, Pyroptosis, NLRP3, Caspase-1, GSDMD, IL-1β and IL-18

Cuixiang Shao,1,2 Qi Chen,3 Siwen Tang,4 Chaowen Wang,1 Renjuan Sun5 1Department of Obstetrics, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 3Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of China; 4Department of Intensive Care Unit, First People ‘s Hospital of Pinghu, Pinghu, Zhejiang, 314299, People’s Republic of China; 5Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214000, People’s Republic of ChinaCorrespondence: Renjuan Sun, Department of Nutrition, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Tel +86 13813479833, Email sunrj2023rj@163.comPurpose: This study aimed to create, verify and assess the clinical utility of a prediction model for maternal and neonatal adverse outcomes in pregnant women with hypothyroidism.Methods: A prediction model was developed, and its accuracy was tested using data from a retrospective cohort. The study focused exclusively on female patients diagnosed with hypothyroidism who were admitted to a tertiary hospital. The development and validation cohort comprised individuals who gave birth between 1 October 2020 and 31 December 2022. The primary outcome was a combination of crucial maternal and newborn problems (eg premature births, abortions and neonatal asphyxia). The prediction model was developed using logistic regression. Evaluation of the model’s performance was conducted based on its ability to discriminate, calibrate and provide clinical value.Results: In total, nine variables were chosen to develop the predictive model for adverse maternal and neonatal outcomes during pregnancy with hypothyroidism. The area under the curve of the model for predicting maternal adverse outcomes was 0.845, and that for predicting neonatal adverse outcomes was 0.685. The calibration plots showed good agreement between the nomogram predictions and the actual observations in both the training and validation cohorts. Furthermore, decision curve analysis suggested that the nomograms were clinically useful and had good discriminative power to identify high-risk mother–infant cases.Conclusion: Two models to predict the risk probability of maternal and neonatal adverse outcomes in pregnant women with hypothyroidism were developed and verified to assist physicians in evaluating maternal and neonatal adverse outcomes throughout pregnancy with hypothyroidism and to facilitate decision-making regarding therapy.Keywords: pregnancy with hypothyroidism, maternal and neonatal adverse outcomes, nomogram, forecasting model

Zheng Yang, Cuixiang Shao, Chen Tang Department of Obstetrics, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of ChinaCorrespondence: Chen Tang, Department of Obstetrics, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214122, People’s Republic of China, Email 15852766902@163.comBackground: Maternal anxiety or depression in the perinatal period has a high prevalence. The negative emotion during the puerpera is unfavorable to the process of childbirth and also affects the recovery and the quality of life in postpartum patients significantly. The present study aimed to elucidate the risk factors of negative emotion in perinatal women and its influence on prognosis to provide a reference for improving maternal prognosis.Methods: Initially, 350 expectant mothers were randomly enrolled in the present study between August 2021 and August 2022. Among these, after applying the established inclusion and exclusion criteria, 314 patients were eventually selected. The independent risk factors of negative emotion and poor prognosis were analyzed through binary logistics regression and multiple linear regression. Follow-up was conducted via telephone, email, and a follow-up visit one month after discharge.Results: Among the included patients, 18 (5.7%) had prenatal anxiety, 16 (5.1%) had prenatal depression, 31 (9.9%) had postnatal anxiety, and 28 (8.9%) had postnatal depression. Perinatal negative emotional risk factors include age, marital relationship, regular prenatal examination, E2 level, 5-HT level before and after delivery, family monthly income, neonatal health, breastfeeding time, intrapartum hemorrhage, constipation and other complications. The development of postpartum negative emotions is a risk factor for maternal prognosis.Conclusion: The results showed that the risk factors of perinatal depression and anxiety were complex. In order to improve the quality of life of pregnant women, maintain their long-term emotional stability, and promote their postpartum recovery, it may be considered to promote the use of screening tools to identify women at risk of anxiety and depression before and after delivery, and timely psychological counseling for patients with high risk factors to promote their mental health.Keywords: anxiety, depression, puerpera, perinatal period, negative emotions

Abdullah Al Mamun,1,2 Chuxiao Shao,1 Peiwu Geng,1 Shuanghu Wang,1 Jian Xiao2,3 1Central Laboratory of the Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui City, Zhejiang, 323000, People’s Republic of China; 2Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Wound Healing, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Jian Xiao, Email xfxj2000@126.comAbstract: Pyroptosis defines a form of pro-inflammatory-dependent programmed cell death triggered by gasdermin proteins, which creates cytoplasmic pores and promotes the activation and accumulation of immune cells by releasing several pro-inflammatory mediators and immunogenic substances upon cell rupture. Pyroptosis comprises canonical (mediated by Caspase-1) and non-canonical (mediated by Caspase-4/5/11) molecular signaling pathways. Numerous studies have explored the contributory roles of inflammasome and pyroptosis in the progression of multiple pathological conditions such as tumors, nerve injury, inflammatory diseases and metabolic disorders. Accumulating evidence indicates that the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome results in the activation of pyroptosis and inflammation. Current evidence suggests that pyroptosis-dependent cell death plays a progressive role in the development of diabetic complications including diabetic wound healing (DWH) and diabetic foot ulcers (DFUs). This review presents a brief overview of the molecular mechanisms underlying pyroptosis and addresses the current research on pyroptosis-dependent signaling pathways in the context of DWH. In this review, we also present some prospective therapeutic compounds/agents that can target pyroptotic signaling pathways, which may serve as new strategies for the effective treatment and management of diabetic wounds.Keywords: diabetes mellitus, diabetic wound healing, pyroptosis, NLRP3, caspase-1, GSDMD, inflammation, inflammasome

Shujie Wang,1,2 Chunyan Shao,2 Xingkai Zhao,1 Yizhe Guo,1 Houhui Song,2 Lida Shen,3 Zhenlei Zhou,1 Zhen Li4,5 1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China; 2College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3College of Mechanical and Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, 210016, People’s Republic of China; 4College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China; 5State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, Jiangsu, 210008, People’s Republic of ChinaCorrespondence: Zhenlei Zhou, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China, Tel +86 (25) 84395505, Email zhouzl@njau.edu.cn Zhen Li, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China, Tel/Fax +86 (25) 84399827, Email lizhen@njau.edu.cnIntroduction: Hydroxylapatite (HAp) is a biodegradable bone graft material with high biocompatibility. However, the clinical application of HAp has been limited due to the poor absorption rate in vivo.Methods: In this study, carbonated hydroxylapatite (CHAp) with a chemical composition similar to natural bone was synthesized. HAp and CHAp scaffolds were fabricated by 3D printing. Each material was designed by two types of scaffold model with a maximum width of 8 mm and a thickness of 2 mm, ie, structure I (round shape) and structure II (grid shape). Then, the HAp scaffolds were loaded with lutein. These scaffolds were implanted into the 8 mm bone defect on the top of the rabbit skull within 3 hours in the morning. The curative effects of the scaffolds were assessed two months after implantation.Results: The 3D printed scaffolds did not cause severe inflammation or rejection after implantation. It showed that the porous structures allow bone cells to enter into the scaffolds. Furthermore, CHAp scaffolds were more biocompatible than HAp scaffolds, and showed a higher level of degradation and new bone formation after implantation. Structure II scaffolds with a smaller mineral content degraded faster than structure I, while structure I had better osteoconductive properties than structure II. Besides, the addition of lutein significantly enhanced the rate of new bone formation.Discussion: The uniqueness of this study lies in the synthesis of 3D printed CHAp scaffolds and the implantation of CHAp in rabbit bone defects. The incorporation of suitable carbonate and lutein into HAp can enhance the osteoinductivity of the graft, and CHAp has a faster degradation rate in vivo, all of which provide a new reference for the research and application of apatite-based composites.Keywords: bone, 3D printing, hydroxylapatite, lutein, repair

Shao C, Cheng C, Shao Q, Chen B. Int J Gen Med. 2021;14:3497–3509. We, the Editor and Publisher of the journal International Journal of General Medicine have retracted the published article. Following publication of the article, concerns were raised that the images used in Figure 3 were not taken from stomach adenocarcinoma (STAD) tissue or cancer cell lines as described. Specifically, The two immunohistochemical images of stomach adenocarcinoma (STAD) tissue for Figure 3A are not STAD tissues but are labelled as thyroid cancer tissues on the website (https://www.proteinatlas.org/ENSG00000182492-BGN/pathology/thyroid+cancer#img). The image used for Figure 3C does not show a cancer cell line, as stated in the figure legend, but an image from a normal human foreskin fibroblast cell line (BJ) as described on the website (https://www.proteinatlas.org/ENSG00000182492-BGN/subcellular#img). The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be incorrectly used or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Jinpeng Li,1,&ast; Yuntao Jia,1,&ast; Changdong Shao,2,&ast; Yuanming Li,3 Jinlong Song1 1Intervention Ward 1, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Qixia Hospital of Traditional Chinese Medicine Hospital, Qixia, Shandong, People’s Republic of China; 3Laizhou Hospital of Traditional Chinese Medicine, Laizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinpeng Li, Intervention Ward 1, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86 531 67626412, Fax +86 531 67626411, Email Ljpxxx308@126.comPurpose: This study aimed to evaluate the safety and efficacy of a combination of programmed death-1 (PD-1) inhibitor and regorafenib as second-line treatment for advanced hepatocellular carcinoma (HCC).Patients and Methods: We retrospectively analyzed the data of 38 patients with unresectable HCC who were treated with PD-1 inhibitor in combination with regorafenib as a second⁃line therapy as well as the data of 32 patients treated with regorafenib only therapy as a control. The clinical data, previous treatment strategies, follow-up imaging results, and adverse events during follow-ups were recorded. The mRECIST Criteria were used to evaluate the treatment outcome of intrahepatic lesions, and the Kaplan–Meier method was used to evaluate survival time.Results: Up to the last follow-up, the rego-PD-1 group had higher objective response rate (39.5% vs 15.6%, P = 0.028), longer progression-free survival (median 5.9 vs 4.6 months; P = 0.044), and better overall survival (OS) (median 14.5 vs 9.5 months; P = 0.041) than the regorafenib only group. Among the 38 patients in rego-PD-1 group, 1 patient (2.7%) achieved complete response, 14 patients (36.8%) achieved partial response, 14 patients (36.8%) achieved stable disease, and 9 patients (23.7%) achieved progressive disease. Among the 32 patients in regorafenib alone, 5 (15.6%) achieved partial response, 12 (37.5%) achieved stable disease, and 15 (46.9%) achieved progressive disease. Regorafenib alone, Child–Pugh B, and tumors > 3 were independent prognostic factors for poor OS. The difference in the incidence of grade 3/4 adverse events between the two groups was not statistically significant (36.8% vs 28.1%; P = 0.439). Grade ≥ 3 treatment-related adverse events included hypertension and diarrhea.Conclusion: PD-1 inhibitor combined with regorafenib is a promising regimen in treating patients with unresectable HCC owing to its safety and effectiveness as well as low incidence of serious adverse events with its use.Keywords: hepatocellular carcinoma, immune checkpoint inhibitor, regorafenib, anti-PD-1 antibody, second-line treatment, overall survival

Jianyi Li,1,&ast; Keke Li,2,&ast; Yukun Du,1,&ast; Xiaojie Tang,3,&ast; Chenjing Liu,1 Shannan Cao,3 Baomeng Zhao,2 Hai Huang,3 Hongri Zhao,3 Weiqing Kong,1 Tongshuai Xu,3 Cheng Shao,1 Jiale Shao,1 Guodong Zhang,4 Hongbo Lan,5 Yongming Xi1 1Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Yantai Campus of Binzhou Medical University, Yantai, People’s Republic of China; 3Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People’s Republic of China; 4Tengzhou Central People’s Hospital, Tengzhou, People’s Republic of China; 5Shandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Xi, Department of Orthopaedic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, 266071, People’s Republic of China, Email xym700118@163.com Hongbo Lan, Shandong Engineering Research Center for Additive Manufacturing Qingdao University of Technology, Qingdao, 266520, People’s Republic of China, Email hblan99@126.comBackground: Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects.Methods: Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation.Results: The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 μg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration.Conclusion: Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.Graphical Abstract: Keywords: osteogenesis, dual-nozzle 3D printing technology, drug-loaded microspheres, vancomycin, nano-hydroxyapatite

Cui Shao,1,&ast; Mengxue Sun,2,&ast; Wanwen Liu,2 Shaoyang Zhao,1 Yang Liu,2 Yuna Chen,1 Shu-Nung Liang,2 Haoyu Yuan,2 Huacheng Sui,2 Baohua Wang,1 Saimei Li1 1Department of Endocrinology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baohua Wang; Saimei Li, Department of Endocrinology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China, Tel +8613580515855 ; +8615818159018, Fax +86 20-36588726, Email wangbaohua@gzucm.edu.cn; lsm@gzucm.edu.cnPurpose: We aimed to assess the efficacy of the Jiang Tang San Huang (JTSH) tablet for the treatment of patients with type 2 diabetes mellitus (T2DM).Methods: All data for this retrospective cohort study were acquired from the outpatient clinic database of our institution, and all enrolled patients received JTSH tablet for at least two months. Overall, 147 patients were included in the analysis. The primary outcome was patient-reported outcomes on the efficacy of the JTSH tablets using a questionnaire survey. Correlation analysis evaluated the duration of JTSH tablet administration and glycemic control in patients with T2DM. The secondary outcome measures included: changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial blood glucose, homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) after 2 months of treatment with JTSH tablets.Results: Overall,120 patients (81.63%) reported a JTSH tablet treatment satisfaction score of ≥ 60 points, and believed that JTSH tablets had satisfactory hypoglycemic effects and could improve symptoms. The average duration of JTSH tablet treatment was 2.57± 1.45 years. Overall, 111 patients achieved good blood glucose control, while 36 patients had poor glycemic control. Multivariate logistic regression model analysis showed that taking JTSH tablets for 1 year might reduce the risk of poor hypoglycemic effect by 17.00% (Risk ratio=0.830, 95% confidence interval:0.578, 1.021, P=0.066). Compared with the baseline data, the levels of HbA1c, FPG and HOMA-IR decreased significantly and HOMA-β levels increased significantly (P< 0.05).Conclusion: Good blood glucose control may be positively correlated with the duration of JTSH tablets administration. Patients with T2DM were satisfied with the anti-diabetic effects of JTSH tablets, which can significantly reduce blood glucose and insulin resistance, and improve the function of islet cells.Keywords: type 2 diabetes mellitus, Jiang Tang San Huang tablet, patient-reported outcomes, blood glucose control, multiple logistic regression

Ting Yan,1,&ast; Chengming Shao,1,&ast; Minjie Zhang,1 Yongxing Ge,1 Tingting Chen,1 Dayang Chai2 1Department of Dermatology, The First People’s Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, People’s Republic of China; 2Department of Cardiology, The First People’s Hospital of Taicang, The Affiliated Taicang Hospital of Soochow University, Taicang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dayang Chai, Department of Cardiology, The First People’s Hospital of Taicang, The Affiliated Taicang Hospital of Suzhou University, No. 58 Changsheng Road, Taicang, 215400, People’s Republic of China, Tel/Fax +86-512-53101356, Email dayangchai@outlook.comBackground: The COVID-19 pandemic has considerable impact on health care system in the world directly. Although the pandemic has been effectively controlled, people’s lifestyle, stress of job, economic status and health conditions have all changed. Therefore, it is unclear whether the COVID-19 pandemic has affected the distribution of diseases in dermatology outpatient department, especially in the post-pandemic era and how we should respond to these changes.Objective: We aimed to assess the impact of the COVID-19 pandemic on diagnosis of dermatology outpatient department in eastern China.Methods: A pre-post study design was a retrospective study to assess the changes of diseases diagnoses from the outpatient department of Dermatology, Taicang first people’s hospital, Suzhou University, Suzhou, China in the 2021 (Post-COVID-19 pandemic) compared to the 2019 (Pre-COVID-19 pandemic). Statistical analysis was performed using the SPSS 23.0 and Excel 2010. The data were analysed by methods independent t-test and Pearson’s chi-square test. A two-sided p-value of < 0.05 was considered statistically significant.Results: A total of 67,994 patients in 2019 and 67,288 patients in 2021 were included in the study. During the pre-pandemic year, the most common diagnoses in the outpatient department were urticaria, fungal dermatitis, acne, herpes zoster, seborrheic dermatitis. Urticaria, acne, allergic dermatitis, fungal dermatitis, herpes zoster, were statistically more common in the post-pandemic period. Acne, animal-related diseases, allergic dermatitis, insect dermatitis, alopecia, and verruca vulgaris diagnoses were found to increase statistically during the post-pandemic period when compared with the pre-pandemic period.Conclusion: The COVID-19 pandemic had a minimal effect on the average yearly dermatology outpatients department visits, but the distribution of dermatology diagnoses was affected. As a result, governments and health departments may introduce innovative ways and training of medical teams according to the impact of the pandemic to ensure normal medical care.Keywords: COVID-19 pandemic, dermatology outpatient, dermatologic diseases, diagnostic distribution, pre-post study

Haipeng Yao,1 Zhen Sun,1 Wei Yuan,1 Chen Shao,1 Honghua Cai,2 Lihua Li,3 Yongjiang Qian,1 Zhongqun Wang1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Zhongqun Wang, Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212000, People’s Republic of China, Email wangtsmc@126.comPurpose: The research explores the relationship between the triglyceride-glucose index (TyG index) and the macroangiopathy risk in single-center hospitalized type 2 diabetes mellitus (T2DM) patients and develops a risk prediction nomogram model.Patients and Methods: A total of 858 patients with T2DM were studied retrospectively. Lasso regression was used to eliminate unimportant factors, and multivariate logistic regression analysis was used to investigate the association between the TyG index and macrovascular disease in T2DM. A nomogram model was constructed to predict macrovascular disease in T2DM and tested using the bootstrap technique, and the efficacy of the nomogram model was investigated using ROC curves. The multivariate Cox proportional hazards model estimated the association between the TyG index and all-cause mortality.Results: TyG index, high-density lipoprotein, red blood cell count, hypertension, history of taking ACEI/ARB drugs, and aortic calcification were closely related to macrovascular complications. In Cox proportional hazard model, the HRs of TyG index were 1.89 (95% confidence interval (CI) 1.29– 2.76, p < 0.001) after adjusting for covariates. The risk of all-cause mortality in T2DM with macrovascular complications was significantly higher than in diabetic patients without vascular disease. In the ROC curve analysis, the cut-off value of the TyG index for macrovascular complications of T2DM was 9.31 (AUC: 0.702, 95% CI 0.67– 0.74, p < 0.001).Conclusion: TyG index predicts future macrovascular disease in diabetic patients independently of known cardiovascular risk factors, suggesting that TyG index may be a useful marker for prognosis in diabetic patients.Keywords: diabetes, cardiovascular events, vascular complications, risk factors, triglyceride-glucose index

Yitian Zheng,1– 3,&ast; Yu Qi,1,&ast; Samuel Seery,4,5 Jie Yang,2,3 Chen Li,2,3 Wenyao Wang,1 Jun Gao,1 Xiangbin Meng,1 Chunli Shao,1 Yi-Da Tang1 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, People’s Republic of China; 2Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4School of Humanities and Social Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 5Faculty of Health and Medicine, Division of Health Research, Lancaster University, Lancaster, UK&ast;These authors contributed equally to this workCorrespondence: Yi-Da Tang, Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People’s Republic of China, Email tangyida@bjmu.edu.cnObjective: Anti-inflammatory therapies are reported to have additional benefits beyond lipid control for patients with cardiovascular disease. However, no study has focused on the relationship between inflammation status and long-term outcomes for chronic obstructive pulmonary disease (COPD) patients, after percutaneous coronary intervention (PCI).Methods: 277 COPD-PCI patients were divided into two groups according to hsCRP status upon admission. Major adverse cardiac events (MACE) in high hsCRP patients were compared to patients with low hsCRP. Restricted cubic spline (RCS) analysis was performed using MACE hazard ratios (HR) to investigate interrelations with hsCRP, as a continuous variable.Results: Patients in the high hsCRP group incurred more inflammation activation, in terms of higher white blood cell counts, neutrophil, lymphocytes, and had higher smoking rates, compared to those with lower hsCRPs. A significant increase in MACEs was observed in hsCRP high group, compared to the low hsCRP group (HR: 2.47, 95% CI: 1.22– 5.00; p = 0.012). RCS curves suggest that HRs rise beyond 1.0, after the 0.24 juncture for Lg HsCRP (base 10 logarithm with hsCRP), HR per SD: 1.19 (95% CI: 0.96– 1.48). Further subgroup analysis implies that elevated hsCRP is associated with a higher risk of MACEs across the sub-groups tested.Conclusion: HsCRP could be a useful indicator for COPD-CAD patient prognosis, after PCI. This is because hsCRP highlights inflammation activation. More multi-center research, designed for COPD-CAD patients should be conducted to more accurately determine the cut-off value for hsCRP.Keywords: HsCRP, chronic obstructive pulmonary disease, coronary artery disease, percutaneous coronary intervention, outcomes

Cancan Shao,1,&ast; Haojie Wang,2,&ast; Feng Sang,3,4 Liran Xu1,3,4 1Department of First Clinical School of Medicine of Henan University of Chinese Medicine, Zhengzhou, Henan, 450000, People’s Republic of China; 2Department of Tuberculosis of Henan Provincial Chest Hospital, Zhengzhou, Henan, 450000, People’s Republic of China; 3Key Laboratory of Viral Diseases Prevention and Treatment with TCM of Henan Province, Zhengzhou, Henan, 450000, People’s Republic of China; 4Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liran Xu, Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of CM, No. 19 Renmin Road, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86-371-13633818030, Email xuliran@hactcm.edu.cnPurpose: This study was the first to screen the active compounds of Jian Aikang Concentrated Pill (JAKCP) with network pharmacology, predict its potential targets, screen the signaling pathways, and combine with cellular experimental validation to explore the potential mechanism of JAKCP for the treatment of acquired immunodeficiency syndrome (AIDS).Methods: The main compounds and targets of Chinese herbs in JAKCP were identified by TCMSP; the targets of AIDS were collected from Genecards, Online Mendelian Inheritance in Man (OMIM), Disgenet, Therapeutic Target Database (TTD) and Drugbank; the network of “Chinese herbs-active compounds-targets” for JAKCP was constructed by Cytoscape, and protein–protein interaction (PPI) network was constructed using STRING to generate the intersection targets, Metascape was conducted to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the network of “main active compounds-core targets-pathways” was constructed by Cytoscape. Finally, the effect of JAKCP on the survival rate of HIV pseudovirus-infected MT-4 cells was investigated by CCK-8 assay, and the predicted targets were verified by ELISA, qPCR and Western blot.Results: A total of 147 active compounds of JAKCP were screened covering 351 targets and 416 AIDS disease targets were obtained, besides 140 intersection targets and 321 KEGG pathways were collected. Ultimately, quercetin, kaempferol, stigmasterol, beta-sitosterol, epigallocatechin gallate were identified as the important compounds, the core targets are HSP90AA1, IL-10, IL-6, TNF, IL-1β, TP53, and IL-1ɑ, and the biological pathways and processes mainly include T cell activation, regulation of DNA-binding transcription factor activity and apoptotic signaling pathway. Experiments on the targets of “T cell activation” demonstrated that JAKCP promotes the survival of HIV pseudovirus-infected MT-4 cells. Also, JAKCP down-regulated mRNA and protein levels of IL-1ɑ, IL-1β, and IL-6 while up-regulated mRNA and protein levels of IL-2, IL-6ST, and IL-10 in vitro.Conclusion: JAKCP exerted regulatory immune functions through multi-component, multi-target and multi-pathway, thereby providing novel ideas and clues for the treatment of AIDS.Keywords: Jian Aikang Concentrated Pill, network pharmacology, HIV/AIDS, multi-pathway, mechanism

Yao Yao,1,&ast; Chunlai Shao,2,&ast; Xiaoye Li,1 Zi Wang,1 Chengchun Zuo,1 Yan Yan,3 Qianzhou Lv1 1Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Yan; Qianzhou Lv, Zhongshan Hospital, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86 13916088938, Fax +86 021-64041990, Email yan.yan@zs-hospital.sh.cn; 13916088938@163.comPurpose: The Global Registry of Acute Coronary Events (GRACE) score has proven value in predicting short-term prognosis in non-ST-elevation myocardial infarction (NSTEMI), but it has only moderate discrimination for long-term outcomes. The purpose of this study is to develop and test a multi-biomarker score for better risk stratification and indication of 2-year risk in patients with NSTEMI.Patients and Methods: A total of 6076 consecutive patients with NSTEMI (66 [59– 73] years, 73.1% males) admitted at Zhongshan Hospital, Fudan University were collected in this observational, prospective study between 2012 and 2018 with a 24-month follow-up. The primary endpoint was all-cause death and non-fatal major adverse cardiac events (MACE). A biomarker score ranged from 0 to 12 was constructed. The predictive power of the biomarker score was evaluated alone or combined with the GRACE score by C-statistic, net reclassification index (NRI) and integrated discrimination index (IDI).Results: During a 2-year follow-up, all-cause death occurred in 159 patients (2.6%), and non-fatal MACEs were presented in 709 patients (11.7%). When added to the GRACE score, the biomarker score demonstrated better prognostic accuracy, patient reclassification and risk discrimination for both mortality and non-fatal MACEs at 2 years by improving the C-statistic from 0.714 (0.671– 0.756) and 0.623 (0.600– 0.646) to 0.851 (0.820– 0.882) and 0.721 (0.702– 0.741) with NRI > 25% (P< 0.001) and IDI > 0.30 (P< 0.001).Conclusion: The single use of biomarker score could markedly enhance the prognostic value of concurrent risk stratification tools for 2-year mortality and non-fatal MACEs in NSTEMI. The GRACE score with incorporation of the biomarker score led to more accurate risk reclassification and warrants more consideration in further NSTEMI management.Keywords: risk stratification, prognosis, net reclassification improvement, integrated discrimination improvement

Chunyan Shao,1– 5,&ast; Ziwei Yu,1– 5,&ast; Tongwang Luo,1– 5,&ast; Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

Xianhua Liao,1 Qianqian Ma,1 Tingfeng Wu,1 Congxiang Shao,1 Yansong Lin,1 Yanhong Sun,2 Shiting Feng,3 Wei Wang,4 Junzhao Ye,1 Bihui Zhong1 1Department of Gastroenterology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Laboratory of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Radiology of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Medical Ultrasonics of The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Bihui Zhong; Junzhao Ye, Department of Gastroenterology of the First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan II Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Tel +86 135 0307 9262 ; +86 135 0151 9252, Email zhongbh@mail.sysu.edu.cn; yejzh@mail2.sysu.edu.cnPurpose: Effective treatment of dyslipidemia with lipid-lowering agents is pivotal in the management of metabolic-associated fatty liver disease (MAFLD) for preventing cardiovascular complications. We explored the associations between improvements in liver injuries indicated by changes in transaminases and a reduction in lipid levels in MAFLD patients with dyslipidemia and elevated transaminases during lipid-lowering therapies.Methods: This prospective, cohort study enrolled consecutive MAFLD patients with hyperlipidemia and elevated transaminases. Patients were divided into a group receiving lipid-lowering agents and an age-, sex- and baseline lipid level-matched control group without receiving lipid-lowering agents. Clinical visits were performed at the 1st month and then every 3 months for 1 year.Results: This study included 541 MAFLD patients (lipid-lowering group: 325 patients; control group: 216 patients). Compared with controls, there was a substantially greater reduction in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) in the lipid-lowering group after 12 months (all P < 0.05). The decrease in ALT was positively correlated with the decrease in TC (r = 0.332), TG (r = 0.180), LDL-c (r = 0.253) and apolipoprotein E (ApoE) (r = 0.119), while the decrease in AST was positively correlated with the decrease in TC (r = 0.228) and LDL-c (r = 0.192) (all P< 0.05). The greater range of reduction in blood lipids (TC/TG/LDL-c), the higher the transaminase and GGT normalization rate (all P< 0.05). Multivariate analysis confirmed that a TG decrease of over 50% remained an independent predictor of transaminase and GGT normalization (OR 2.07, 95% CI 1.12– 3.84, P=0.020).Conclusion: Lipid-lowering to target levels might be beneficial to liver injury improvements in MAFLD patients with dyslipidemia when receiving lipid-lowering agents.Keywords: dyslipidemia, metabolic dysfunction-associated fatty liver disease, alanine aminotransferase, triglyceride, gamma glutamyl transpeptidase, statins

Peiying Wei,1,2,&ast; Chang Shao,3,&ast; Min Tian,4 Mengwei Wu,5 Haibin Wang,2 Zhijiang Han,2 Hongjie Hu1 1Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Pathology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4The Fourth Clinical Medical College, Zhejiang Traditional Chinese Medicine University, Hangzhou, People’s Republic of China; 5Department of Radiology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijiang HanDepartment of Radiology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, 310006, People’s Republic of ChinaEmail hzjsyy@126.comHongjie HuDepartment of Radiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of ChinaEmail hongjiehu@zju.edu.cnObjective: To investigate the value of the signal intensity on T2-weighted magnetic resonance (MR) imaging using quantitative analysis in the differentiation of parotid tumors.Materials and Methods: MR data of 80 pleomorphic adenomas (PAs), 68 Warthin tumors (WTs), and 34 malignant tumors (MTs) confirmed by surgery and histology were retrospectively analyzed. The signal intensities of tumor, normal parotid gland, spinal cord, and buccal subcutaneous fat were measured, and the signal intensity ratios (SIRs) between the tumor and the three references were calculated. Receiver operating characteristic curve was used to determine the optimal threshold and diagnostic efficiency of SIR for differentiating PAs, WTs, and MTs.Results: The area under the curve (AUC) of tumor to parotid gland SIR (SIRP), tumor to spinal cord SIR (SIRC), and tumor to buccal subcutaneous fat SIR (SIRF) for differentiating PAs and WTs was 0.922, 0.918, and 0.934, respectively. The sensitivity and specificity at an optimal SIR threshold were 86.3% and 91.2%, 80.0% and 97.1%, and 85.0% and 94.1%, respectively. The AUC of SIRP, SIRC, and SIRF for distinguishing PAs from MTs was 0.793, 0.802, and 0.774, respectively. The sensitivity and specificity at an optimal SIR threshold was 86.3% and 61.8%, 80.0% and 73.5%, and 82.5% and 73.5%, respectively. The AUC of SIRP, SIRC, and SIRF for distinguishing WTs from MTs was 0.716, 0.709, and 0.759, respectively. The sensitivity and specificity at an optimal SIR threshold were 61.8% and 82.4%, 55.9% and 82.4%, and 64.7% and 86.8%, respectively.Conclusion: SIRP, SIRC, and SIRF on T2-weighted MR images had high diagnostic efficiency for differentiating between PAs and WTs, while SIRP and SIRC for differentiating between PAs and MTs, and SIRF for differentiating between WTs and MTs had relatively high diagnostic efficiency.Keywords: parotid tumor, signal intensity ratio, pathology, magnetic resonance imaging, T2-weighted imaging

Guanghui Zheng,1– 3,&ast; Chenxi Zhang,1– 3,&ast; Guojun Zhang,1– 3 Chunqing Shao1– 3 1Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital and Capital Medical University, Beijing, People’s Republic of China; 2NMPA Key Laboratory for Quality Control of in vitro Diagnostics, National Medical Products Administration, Beijing, People’s Republic of China; 3Beijing Engineering Research Center of Immunological Reagents Clinical Research, Beijing Municipal Science and Technology Commission, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunqing Shao; Guojun Zhang Tel +86 18600148997; +86 15811219411Email shaocq0210@163.com; zgjlunwen@163.comAim: To evaluate the diagnostic and prognostic value of CSF presepsin levels in patients with postneurosurgical ventriculitis/meningitis (PNVM).Methods: We conducted a case-control study to achieve our aims. First, we prospectively enrolled patients who had undergone neurosurgery in Beijing Tiantan Hospital from June to November 2020 and measured the CSF levels of 8 biomarkers, including presepsin and other meningitis biomarkers. The diagnostic and prognostic accuracies of presepsin levels were evaluated by determining the values for the area under the receiver operating characteristic curve (AUC).Results: Two hundred thirty-nine patients were enrolled in this study; 34 were diagnosed with confirmed ventriculitis/meningitis (cVM), 138 were classified as probable ventriculitis/meningitis (pVM), and the others were rejected ventriculitis/meningitis (rVM). Presepsin levels effectively diagnose cVM and predict the outcomes of patients with PNVM, with thresholds of 1257.4 pg/mL and 1276.2 pg/mL and AUCs of 0.746 and 0.825, respectively. Furthermore, a joint analysis with CSF lactate (C-Lac) levels shows that the AUCs of the two markers increased to 0.856 and 0.872, respectively.Conclusion: The rapid diagnosis and prediction of the clinical outcome is important in neurosurgery. CSF presepsin levels are an impressive diagnostic and prognostic biomarker for meningitis, and when combined with C-Lac, they indeed improve the diagnostic and predictive efficiency of PNVM.Keywords: presepsin, cerebrospinal fluid, postneurosurgical ventriculitis/meningitis

Changming Shao,1,&ast; Chunfa Cheng,2,&ast; Qinshu Shao,3 Bing Chen1 1Department of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, People’s Republic of China; 2Department of Vascular Surgery, The First People’s Hospital of Yuhang District, Hangzhou, 311100, Zhejiang, People’s Republic of China; 3Department of General Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, 310009, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing ChenDepartment of Vascular Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 1511 Jianghong Road, Binjiang District, Hangzhou, 310000, Zhejiang, People’s Republic of ChinaEmail 2114008@zju.edu.cnQinshu ShaoDepartment of General Surgery, Zhejiang Provincial People’s Hospital, 158 Shangtang Road, Xiacheng District, Hangzhou, 310009, Zhejiang, People’s Republic of ChinaEmail chmshao@126.comObjective: Previous studies have confirmed the biglycan (BGN) as a core gene in stomach adenocarcinoma (STAD). Present study aimed at conducting further investigations to reveal the potential function of BGN in STAD.Methods: The mRNA and protein expressions of BGN in STAD were firstly evaluated, followed by immune infiltration analyses. The influence of BGN expression on the overall survival of STAD patients was subsequently analyzed, and a restrict survival analysis was performed as well. The protein–protein interaction (PPI) network analysis on the co-expressed genes with BGN was finally adopted to obtain the most important module in the whole network, and significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway associated with hub genes within the main module was further predicted.Results: (1) We verified the mRNA high expression of BGN in STAD (all P< 0.05), and higher expression was observed in patients with stage 4 (P< 0.001) and grade 3 (P< 0.001). The BGN protein was mainly localized to the golgi apparatus, and protein expression displayed an individual difference. (2) Immune infiltration analysis showed the strongest correlation between BGN expression and abundance of natural killer cell (P< 0.001), Transforming Growth Factor beta 1 (TGFB1) (P< 0.001), TNF Receptor Superfamily Member 4 (TNFRSF4) (P< 0.001) and C-X-C Motif Chemokine Ligand 12 (CXCL12) (P< 0.001) in STAD. BGN expression was also correlated to immune subtypes (P=0.0347) and molecular subtypes (P=0.0263) in STAD. (3) High expression of BGN shortened the overall survival time of STAD patients (all P< 0.01). The influence of BGN expression on the prognosis was statistically affected by several clinical phenotypes and cohorts of patients. Cox regression showed that BGN can be considered as a prognostic predictor of STAD (P< 0.05). (4) Pathway analysis indicated that BGN possibly participated in ECM–receptor interaction, focal adhesion, human papillomavirus infection and PI3K-Akt signaling pathway (all P< 0.001).Conclusion: BGN was highly expressed in STAD, implying a poor prognosis of patients. Relevant signal pathways associated with BGN were distinguished as well. BGN could be used as a potential therapeutic biomarker for STAD.Keywords: biglycan, stomach adenocarcinoma, high expression, immune infiltration, prognosis

Xiaofei Yu,1,* Zhengwei Dong,2,* Wanying Wang,1 Shiqi Mao,1 Yingying Pan,1 Yiwei Liu,1 Shuo Yang,1 Bin Chen,1 Chunyan Wang,1 Xuefei Li,3 Chao Zhao,3 Keyi Jia,1 Chuchu Shao,1 Chunyan Wu,2 Shengxiang Ren,1 Caicun Zhou1 1Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China; 2Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China; 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengxiang RenDepartment of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of ChinaTel +86-21-65115006Fax +86-21-65111298Email harry_ren@126.comChunyan WuDepartment of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507, Zheng Min Road, Shanghai, 200433, People’s Republic of ChinaFax +86-21-65111298Email wuchunyan581@163.comPurpose: High-grade patterns (micropapillary/solid/complex gland) are associated with a higher recurrence rate and shorter disease-free survival. Thus far, it remains unclear whether the efficacy of first-line anticancer therapy is different from that of the other adenocarcinoma subgroups for patients with high-grade patterns. The study aimed to investigate the association between an adenocarcinoma with high-grade patterns with the outcomes of first-line treatment in patients with lung cancer.Patients and Methods: Patients with a high-grade pattern adenocarcinoma (more than 20% of micropapillary/solid components/complex glandular patterns) were retrospectively analyzed between June 2015 and June 2017. Patients’ clinical characteristics and treatment outcomes were compared with those of the remaining control adenocarcinoma subgroups.Results: In total, 239 patients with adenocarcinoma, including 115 (48.1%) high-grade patterns and 124 (51.9%) control groups, were enrolled. Patients’ clinical characteristics such as age, sex, smoking status, and stage were similar between the two groups. Among them, 108 patients received first-line chemotherapy, and 131 received epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs). In the chemotherapy group, adenocarcinoma of high-grade patterns had a significantly lower objective response rate (ORR; 15.6% vs 36.4%, P=0.045), shorter progression-free survival (PFS; median 4.1 vs 5.4 months, P=0.007) and overall survival (OS, median 19.6 vs 23.8 months, P=0.048) compared with the control group. As for these treated with EGFR-TKIs, a similar ORR (70.7% vs 72.1%, P=0.703), PFS (median 11.3 vs 13.9 months, P=0.065) and OS (median 34.1 vs 29.6%, p=0.575) were observed between these two groups.Conclusion: An adenocarcinoma with high-grade patterns is associated with inferior outcomes to first-line chemotherapy in relapsed lung cancer. Patients who received chemotherapy had a significantly shorter PFS and OS and lower ORR than control subjects, while there was no difference in the EGFR-TKI cohort. This study is the first to report the distribution of adenocarcinoma with high-grade patterns.Keywords: adenocarcinoma, micropapillary, solid, chemotherapy, EGFR-TKIs

Lele Jing,1 Lihua Li,2 Xiaomei Ren,3 Zhen Sun,1 Zhengyang Bao,4 Guoyue Yuan,5 Honghua Cai,6 Lin Wang,1 Chen Shao,1 Zhongqun Wang1 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s Republic of China; 3Department of Geriatrics, Zhongda Hospital Affiliated of Southeast University, Nanjing, People’s Republic of China; 4Department of Internal Medicine, Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi 214000, People’s Republic of China; 5Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s Republic of China; 6Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, People’s Republic of ChinaCorrespondence: Zhongqun WangDepartment of Cardiology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang 212001, People’s Republic of ChinaTel +86 511 85030586Email wangtsmc@126.comBackground and Aims: To investigate the role of Sortilin and matrix vesicles (MVs) in Nϵ-Carboxymethyl-lysine (CML)-induced diabetic atherosclerotic calcification (AC).Methods: At human level, the correlation between Sortilin and CD9 (marker proteins of MVs) in serum MVs and CML in serum was explored by enzyme-linked immunosorbent assay (ELISA) detection and Pearson correlation analysis. After a diabetic apoE-/- mouse model was constructed, the calcification of aorta and the expressions of related proteins under CML and MVs injection were observed by calcification staining, immunofluorescence staining, and Western blot. MVs levels released by smooth muscle cells (SMCs) under different treatments was detected by nanometer tracking analysis (NTA). After treating SMCs with MVs and Anti-Sortilin, cell calcification was observed by Alizarin red staining.Results: Serological analysis of patients showed that the concentrations of Sortilin and CD9 in serum MVs were positively correlated with the concentration of CML in serum. Animal experiments showed that CML could promote the progression of diabetic AC and the high expression of Sortilin in plaques. Diabetic apoE-/- mouse tail vein injection of CML-induced SMCs-derived MVs obviously aggravated AC. Cell experiment results showed that a high concentration of CML significantly promoted the release of MVs from SMCs. MVs from this source could markedly worsen cell calcification, while the administration of GW4869 (a widely used extracellular vesicles biogenesis inhibitor) significantly reduced cell calcification. Finally, treatment of high concentrations of CML could also promote the recruitment of Sortilin to MVs, and administration of Anti-Sortilin could markedly reduce cell calcification caused by MVs.Conclusion: We proved that CML not only affects the release of MVs from SMCs but also affects the recruitment of Sortilin to MVs, thereby promoting diabetic AC. This discovery may provide a new strategy for targeted prevention of vascular calcification in diabetes.Keywords: Nϵ-Carboxymethyl-lysine, sortilin, matrix vesicles, plaque calcification, diabetes

Chunhai Shao,1,* Jiwei Wang,2,* Jingfang Liu,1 Fang Tian,1 Hua Li3 1Department of Nutrition, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: We aimed to investigate the effect of a Health Belief Model (HBM)-based education program on the perception scores of 5 HBM domains, physical activity, and serum uric acid (SUA) among asymptomatic hyperuricemia (AHU) patients in a randomized controlled trial. Methods: One hundred and ninety-three AHU patients were involved in this prospective experimental interventional study in Shanghai, China. Subjects were randomly divided into interventional or control group. The educational program was designed based on HBM component for the improvement of knowledge and promotion of lifestyle adherence in terms of low-purine diet and physical activity among AHU patients. This program included educational booklets and educational classes. Data were collected from interventional and control group members both before and after the intervention, using a questionnaire covering sociodemographic characteristics, HBM variables, physical activity from the Health-Promoting Lifestyle Profile II, and a check list for recording the subject’s SUA values, as well as the body mass index, waist–hip ratio, systolic blood pressure, and diastolic blood pressure. Results: In the interventional group, the mean scores of the HBM variables (perceived susceptibility, perceived severity, perceived benefit, perceived barriers, and self-efficacy), SUA values, physical activity, body mass index, and waist–hip ratio were improved significantly after the intervention (p

Chen Shao, Kun Shang, Huaibao Xu, Yu Zhang, Zhichao Pei, Yuxin Pei Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, China Background: Photodynamic therapy is a safe, noninvasive modality for cancer therapy, in which the photosensitizer (PS) is a crucial component. Hypericin (Hy) is a promising PS; however, its clinical application is significantly limited by its poor hydrophilicity. Materials and methods: To overcome the clinical application limitation of Hy, a novel strategy is developed here by entrapping Hy into polydopamine (PDA) film formed on the surface of magnetic iron oxide nanoparticles (MNPs) through the self-polymerization of dopamine under alkaline condition. The amount of Hy in the Hy-entrapped PDA–MNP composite nanoparticles (denoted as PHMs) was measured by spectrophotometry. Furthermore, lactose, as the targeting ligand to asialoglycoprotein receptors, was conjugated to the surface of the PHMs by taking advantage of the spontaneous reaction of PDA with amino groups. Results: Spectrophotometry analysis revealed that the amount of Hy in the PHMs was 72 µmol g-1 PHMs. The fabricated Hy-entrapped glyconanoparticle (Lac-PHM) exhibited excellent water dispersibility, stability, and selectivity for asialoglycoprotein receptors overexpressing HepG2 cells. Atomic absorption spectroscopy analysis showed that the amount of the Lac-PHMs taken in HepG2 cells was 2.1-fold higher than that of the triethylene glycol-modified PHMs. The results of intracellular reactive oxygen species generation detection, cytotoxicity study, and apoptosis detection indicated that the Lac-PHMs had a satisfying photodynamic effect to HepG2 cells. Conclusion: The strategy developed in this work offers great potential for delivery of a variety of hydrophobic PSs. Keywords: hypericin, photodynamic therapy, glyconanoparticles, targeted drug delivery

Xin Huang,1,* Chengqi Fan,2,* Huanhuan Zhu,1 Wenjun Le,1 Shaobin Cui,1 Xin Chen,3 Wei Li,4 Fulei Zhang,4 Yong Huang,4 Donglu Shi,1,5 Zheng Cui,1,6 Chengwei Shao,2 Bingdi Chen1 1The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China; 2Radiology Department of Changhai Hospital, The Second Military Medical University, Shanghai, China; 3Department of Thyroid Surgery, The First Bethune Hospital of Jilin University, Jilin, China; 4International Joint Cancer Institute, The Second Military Medical University, Shanghai, China; 5The Materials Science & Engineering Program, Department of Mechanical & Materials Engineering, College of Engineering & Applied Science, University of Cincinnati, OH, USA; 6Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA *These authors contributed equally to this work Introduction: Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods: In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd–Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Results: Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s−1 mM−1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s−1 mM−1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Conclusion: Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC. Keywords: pancreatic cancer, Glypican-1, fluorescence imaging, magnetic resonance imaging, Gd–Au NCs

Jialie Fang,1,* Ji-Wei Wang,2,* Jiang Li,3 Hua Li,4 Chunhai Shao5 1Shanghai Jing’an District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 2Key Lab of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Faculty of Health, University of Canberra, Canberra, Australian Capital Territory, Australia; 4Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 5Department of Nutrition, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: To investigate the correlates of social capital and adherence to healthy lifestyle in patients with coronary heart disease (CHD).Methods: This register-based, cross-sectional study consisted of individuals diagnosed with CHD at four community health service centers, Shanghai, China, between April and July 2016 (n=609). The sociodemographic characteristics, social capital, adherence to physical activity, and nutrition data were obtained through face-to-face interviews. Social capital was assessed by social participation, social networking, social support, social trust, and sense of belonging. Physical activity and nutrition were measured with the Health-Promoting Lifestyle Profile II. The independent two-sample t-test and Pearson’s correlations were used to analyze associations among variables. Hierarchical multiple regression models were used to evaluate effects of social capital on adherence to physical activity and nutrition.Results: The average age of the sample was 60.87 (standard deviation [SD] =6.91), with 54.4% being male and 45.6% female. The average score of physical activity and nutrition were 2.38 (SD =0.59) and 2.78 (SD =0.50), respectively. The final model significantly explained 28.9% of variance in physical activity (F=34.96, P

Non-typeable Haemophilus influenzae (NTHi) is a frequent cause of lower respiratory tract infection in people with chronic obstructive pulmonary disease (COPD). Pellino proteins are a family of E3 ubiquitin ligases that are critical regulators of TLR signaling and inflammation. The aim of this study was to identify a role for Pellino-1 in airway defense against NTHi in the context of COPD. Pellino-1 is rapidly upregulated by LPS and NTHi in monocyte-derived macrophages (MDMs) isolated from individuals with COPD and healthy control subjects, in a TLR4 dependent manner. C57BL/6 Peli1−/− and wild-type (WT) mice were subjected to acute (single LPS challenge) or chronic (repeated LPS and elastase challenge) airway inflammation followed by NTHi infection. Both WT and Peli1−/− mice develop airway inflammation in acute and chronic airway inflammation models. Peli1−/− animals recruit significantly more neutrophils to the airway following NTHi infection which is associated with an increase in the neutrophil chemokine, KC, in bronchoalveolar lavage fluid as well as enhanced clearance of NTHi from the lung. These data suggest that therapeutic inhibition of Pellino-1 may augment immune responses in the airway and enhance bacterial clearance in individuals with COPD.

Zhiwang Song,1 Chuan Shao,2 Chan Feng,1 Yonglin Lu,1 Yong Gao,1 Chunyan Dong1 1Department of Oncology, Shanghai East Hospital, Tongji University, Shanghai, 2Department of Neurosurgery, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China Background: Several case–control studies investigating the relationship between genetic polymorphisms of glutathione S-transferase (GST) M1, GSTT1, and GSTP1 (rs1695) and the risk of breast cancer have reported contradictory results. We therefore performed a meta-analysis to clarify this issue.Materials and methods: An updated meta-analysis using PubMed and Web of Knowledge databases for the eligible case–control studies was performed. Random- or fixed-effects model was used.Results: A total of 10,067 cancer cases and 12,276 controls in 41 independent case–control studies from 19 articles were included in this meta-analysis. Significant increase in risk of breast cancer for Asians was found in GSTM1-null genotype (P=0.012, odds ratio [OR] =1.17, 95% confidence interval [CI] =1.04–1.32) and GSTT1-null genotype (P=0.039, OR =1.19, 95% CI =1.01–1.41). In addition, our results showed that the GSTP1 (rs1695) polymorphisms can significantly increase the risk among Caucasians (P=0.042, OR =1.16, 95% CI =1.01–1.34). Sensitivity analysis and publication bias further confirmed the dependability of the results in this meta-analysis.Conclusion: Our results demonstrate that both GSTM1- and GSTT1-null polymorphisms are associated with an increased risk of breast cancer in Asians and that GSTP1 Val105Ile (rs1695) polymorphism is associated with an increased breast cancer risk in Caucasians. Keywords: GSTM1, GSTT1, GSTP1, polymorphism, breast cancer, meta-analysis

Fang Liu,1,* Wenjun Le,2,* Tianxiao Mei,2 Tiegong Wang,1 Luguang Chen,1 Yi Lei,1 Shaobin Cui,2 Bingdi Chen,2 Zheng Cui,2,3 Chengwei Shao1 1Radiology Department of Changhai Hospital, Second Military Medical University, 2Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA *These authors contributed equally to this work Abstract: Pancreatic cancer is a highly malignant disease with a 5-year survival rate ,5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by -61.233±33.9 and -58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P

Yihua Peng,1,* Chunhong Shao,1,* Ye Gong,2 Xuehai Wu,2 Weijun Tang,3 Shenxun Shi1 1Psychiatry Department, 2Neurosurgery Department, 3Radiology Department, Huashan Hospital, Fudan University, People’s Republic of China *These authors contributed equally to this work Background: The purpose of this study is to assess the relationship between apathy and tumor location, size, and brain edema in patients with intracranial meningioma. Methods: We enrolled 65 consecutive patients with meningioma and 31 normal controls matched for age, gender, and education. The patients were divided into frontal or non-frontal (NF) meningioma groups based on magnetic resonance imaging; the frontal group was then subdivided to dorsolateral frontal (DLF), medial frontal (MF), and ventral frontal (VF) groups. Tumor size and brain edema were also recorded. Apathy was assessed by the Apathy Evaluation Scale (AES). Assessments were carried out 1 week before and 3 months after surgery, respectively. Logistic regression analysis was performed to identify the predictive effect of tumor size, location, and brain edema on apathy. Analysis of variance and chi-square analysis were applied to compare apathy scores and apathy rates among the frontal, NF, and normal control groups, and all subgroups within the frontal group. Results: Compared with the NF and control groups, the mean AES score was much higher in the frontal group (34.0±8.3 versus 28.63±6.0, P=0.008, and 26.8±4.2, P

Wei-kang Xing,1 Chuan Shao,2 Zhen-yu Qi,1 Chao Yang,1 Zhong Wang1 1Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 2Department of Neurosurgery, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China Background: Standard treatment for high-grade glioma (HGG) includes surgery followed by radiotherapy and/or chemotherapy. Insertion of carmustine wafers into the resection cavity as a treatment for malignant glioma is currently a controversial topic among neurosurgeons. Our meta-analysis focused on whether carmustine wafer treatment could significantly benefit the survival of patients with newly diagnosed glioblastoma multiforme (GBM).Method: We searched the PubMed and Web of Science databases without any restrictions on language using the keywords “Gliadel wafers”, “carmustine wafers”, “BCNU wafers”, or “interstitial chemotherapy” in newly diagnosed GBM for the period from January 1990 to March 2015. Randomized controlled trials (RCTs) and cohort studies/clinical trials that compared treatments designed with and without carmustine wafers and which reported overall survival or hazard ratio (HR) or survival curves were included in this study. Moreover, the statistical analysis was conducted by the STATA 12.0 software.Results: Six studies including two RCTs and four cohort studies, enrolling a total of 513 patients (223 with and 290 without carmustine wafers), matched the selection criteria. Carmustine wafers showed a strong advantage when pooling all the included studies (HR =0.63, 95% confidence interval (CI) =0.49–0.81; P=0.019). However, the two RCTs did not show a statistical increase in survival in the group with carmustine wafer compared to the group without it (HR =0.51, 95% CI =0.18–1.41; P=0.426), while the cohort studies demonstrated a significant survival increase (HR =0.59, 95% CI =0.44–0.79; P