Publications by authors named "Yitong Wang"

79 Publications

Clinical characteristics and clinicopathological correlations of bilateral breast cancer in China: A multicenter study from Chinese Society of Breast Surgery (CSBrS-006).

Chin J Cancer Res 2021 Feb;33(1):27-32

Department of Oncology & Breast Surgery, the Second Hospital of Dalian Medical University, Dalian 116023, China.

Objective: To investigate the clinical characteristics and clinicopathological correlations of bilateral breast cancer (BBC) in China.

Methods: Data of 440 patients diagnosed with BBC in 2018 were collected from 33 centers of the Chinese Society of Breast Surgery. Demographic characteristics, bilateral tumor characteristics, and comprehensive treatment data were obtained. Correlations between the clinicopathological characteristics of bilateral tumors were analyzed.

Results: The proportion of BBC was 0.22%-3.08%. A total of 33 (7.5%) patients had a family history of malignant tumors, 304 (69.1%) patients had synchronous BBC. Only 1 (0.2%) patient was male. More than half of all patients received concurrent or asynchronous endocrine/chemotherapy, 32.5% of all human epidermal growth factor receptor 2 (HER2)-positive patients received HER2-targeted therapy, and approximately 21.6% of all patients received radiotherapy. The most common pathological cancer type was invasive ductal cancer (>60%). Approximately 70% of all patients had bilateral hormone receptor (HR)-positive tumors and presented with a single breast mass. Significant correlations were found with pathological type, histological grade, locations of tumor, molecular subtype, Ki-67 index, tumor site and size of bilateral tumors. Results of the subgroup analysis showed more clinicopathological characteristics when synchronous BBC was compared with metachronous BBC.

Conclusions: In China, the clinicopathological characteristics of bilateral tumors showed significant correlations, and more significant clinicopathological correlations were observed when synchronous BBC was compared with metachronous BBC.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2021.01.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941691PMC
February 2021

Heat-killed Lactobacillus acidophilus mediates Fusobacterium nucleatum induced pro-inflammatory responses in epithelial cells.

FEMS Microbiol Lett 2021 Apr;368(5)

Center of Craniofacial Orthodontics, Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai 200011, China.

Probiotics is widespreadly used nowadays. However, the safety issue with the use of live probiotics is still a matter of contention. In recent years, an expanding body of evidence supports the beneficial role of heat-killed probiotics in the maintenance of systemic health, whereas the role of these heat-killed bacteria on periodontal health remains unclear. This study aimed to evaluate the effects of heat-killed probiotics on periodontal pathogen virulence and associated mechanisms. We demonstrated that heat-killed Lactobacillus acidophilus was able to coaggregate with Fusobacterium nucleatum, the bridging bacteria of oral biofilm, and inhibit the adhesion and invasion of F. nucleatum, leading to a subsequent elimination of pro-inflammatory cytokine production in oral epithelial cells. This coaggregation further caused a suppression of the virulence gene fap2 expression in F. nucleatum. Therefore, heat-killed L. acidophilus might downregulate the pro-inflammatory cytokine expression in epithelial cells via coaggregation with F. nucleatum and suppression of F. nucleatum fap2 expression, which was the first demonstration that heat-killed probiotics modulate periodontal disease pathogenesis via coaggregation. Collectively, this finding provides new evidence that heat-killed probiotics might exert beneficial effects to periodontal health by coaggregating with periodontal pathogens and modulating their virulence.
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http://dx.doi.org/10.1093/femsle/fnaa160DOI Listing
April 2021

Phenols in soils and agricultural products irrigated with reclaimed water.

Environ Pollut 2021 May 9;276:116690. Epub 2021 Feb 9.

College of Hydraulic Science and Engineering, Yangzhou University, Yangzhou, 225009, China. Electronic address:

The presence of phenols, such as nonylphenol (NP), bisphenol (BPA), and octylphenol (OP), in the environment have been receiving increased attention due to their potential risks to human health and environment. The use of reclaimed water for irrigation may be one of the sources of these phenols in the agricultural system. A field experiment was conducted to assess the effects of reclaimed water irrigation on phenol contamination of agricultural topsoil and products in the North China Plain between 2015 and 2016. Three irrigation treatments were applied to all crops: reclaimed water irrigation, groundwater irrigation and alternative irrigation with reclaimed water and groundwater (1:1, v/v). The results showed that the concentrations of NP, BPA, and OP in the topsoil were 0.02-0.54, 0.004-0.06, and ND-9.9 × 10 mg/kg, respectively; the corresponding values in agricultural products were 0.007-0.70, 0.004-0.24, and ND-1.08 mg/kg, respectively. The concentration of NP in the topsoil and agricultural products and that of BPA in the agricultural products were all less than the recommended limits. The yields of wheat, maize, vegetables were 4.35-7.08, 1.03-6.46, and 10.9-67.0 t/ha, respectively. The bioaccumulation factors (BCFs) of OP, NP, and BPA for cereals were 0.7-4.77, 0.16-4.59, and 1.3-23.9, respectively; the corresponding values in vegetables were 0.0-4.53 (except cucumber and eggplant), 0.38-12.6, and 0.57-24.3, respectively. No significant differences in phenol concentrations, BCFs, or yields of wheat and vegetables were observed among the three irrigation treatments. In conclusion, compared with groundwater irrigation, reclaimed water irrigation in this experiment did not significantly affect phenol concentrations in the topsoil and agricultural products as well as BCFs and yields of wheat and vegetables. However, because the quality of reclaimed water may vary across collected areas, additional experiments are warranted to analyze the effects of reclaimed water irrigation on the risk of phenol contamination.
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http://dx.doi.org/10.1016/j.envpol.2021.116690DOI Listing
May 2021

Enzymolysis-microwave assisted hydrodistillation for extraction of volatile oil from Atractylodes chinensis and its hypoglycemic activity in vitro.

J AOAC Int 2021 Jan 20. Epub 2021 Jan 20.

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.

Background: Atractylodes chinensis (family Asteraceae) is a perennial herb with many pharmacological effects.

Objective: Extraction of volatile oil from Atractylodes chinensis was optimized and its hypoglycemic activities were studied.

Methods: Enzymolysis-microwave assisted hydrodistillation (EMAHD) was adopted to extract the volatile oil, and the technology was optimized using a single-factor experiment that incorporated response surface methodology (RSM). The extraction rates of volatile oil by EMAHD, microwave assisted hydrodistillation (MAHD), and hydrodistillation (HD) methods were compared at different times. The ingredients of Atractylodes chinensis volatile oil were analyzed by gas chromatography-mass spectrometry (GC-MS). Scanning electron microscopy (SEM) were used to analyze the microstructural changes in Atractylodes chinensis residue before and after extraction. The inhibition of α-amylase activity was determined.

Results: The obtained optimal extraction conditions for EMAHD were as follows: enzyme concentration 1.6%, pH 7, enzymolysis time 20 min, enzymolysis temperature 50 °C, liquid-solid ratio 30:1, microwave power 455W and microwave time 40 min. The levels of the main ingredients and the in vitro inhibition of α-amylase activities were higher for Atractylodes chinensis volatile oil extracted by EMAHD than by HD or MAHD. The powder residue of Atractylodes chinensis remaining after EMAHD showed a ruptured and collapsed cell structure, indicating accelerated dissolution of the volatile oil.

Conclusions And Highlights: EMAHD is deemed a method with many advantages for extraction of volatile oil from Atractylodes chinensis. The volatile oil of Atractylodes chinensis is a promising component for treating hyperglycemia.
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http://dx.doi.org/10.1093/jaoacint/qsab008DOI Listing
January 2021

Which Criteria are Considered and How are They Evaluated in Health Technology Assessments? A Review of Methodological Guidelines Used in Western and Asian Countries.

Appl Health Econ Health Policy 2021 Jan 11. Epub 2021 Jan 11.

Public Health Department, Aix-Marseille University, 27 Boulevard Jean Moulin, 13385, Marseille, France.

Objectives: This study aimed to provide an exhaustive description of criteria and methodological recommendations for evaluating them in health technology assessment (HTA) in Western and Asian countries.

Methods: We conducted a system literature review of HTA-related guidelines by searching the websites of HTA agencies and related data sources. The guidelines, reports, or recommendations introducing the HTA evaluation methods, processes, decision-making frameworks, and criteria for priority setting were eligible to be included. The review was limited to guidelines from countries belonging to the European Network for Health Technology Assessment (EUnetHTA) and HTAsiaLink organisations and other countries with well-established available guidelines.

Results: A total of 52 guidelines from 24 countries were identified, including 13 countries from the EUnetHTA organisation, 9 countries from the HTAsiaLink organisation and 2 other countries (Canada and the USA). A strong consensus was observed among the HTA agencies on the core set of criteria including efficacy or effectiveness, cost-effectiveness, safety, and budget impact. More similarities were observed than differences in methodological recommendations for clinical and economic evaluations among the agencies.

Conclusions: Substantial convergence is seen in the criteria included in the HTA process, as well as the methods to evaluate and quantify them. Further efforts are needed to verify whether the criteria identified from the guidelines are incorporated in real HTA decisions, and how they are assessed and weighted in practice.
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http://dx.doi.org/10.1007/s40258-020-00634-0DOI Listing
January 2021

Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis.

Cancer Cell Int 2021 Jan 6;21(1):10. Epub 2021 Jan 6.

Department of Clinical Laboratory, The Second Hospital of Jilin University, No. 218ZiQiang Street, Changchun, 130001, Jilin, China.

Background: Circular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear.

Methods: The morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC.

Results: Circ_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells.

Conclusion: Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.
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http://dx.doi.org/10.1186/s12935-020-01695-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788978PMC
January 2021

A critical analysis and review of Lancet COVID-19 hydroxychloroquine study.

J Mark Access Health Policy 2020 Sep 10;8(1):1809236. Epub 2020 Sep 10.

Department of Public Health, Aix-Marseille University, Marseille, France.

A international registry analysis led by Mehra et al. to investigate the use of hydroxychloroquine (HCQ) and chloroquine (CQ) with or without a macrolide in 96,032 hospitalised COVID-19 patients were published on Lancet, which has raised considerable discussions in the public health community. This study aimed to critically review the quality and limitations of the Mehra et al. publication and discuss the potential influences on the use of HCQ/CQ worldwide. A critical review of this publication was conducted to examine the potential study bias in the study objectives, methodology, confounding factors and outcomes and summarise the external reviews. The very high homogeneity of the patients' characteristics at baseline was inconsistent with region specific epidemiology and several critical confounding factors. The results indicated that angiotensin converting enzyme inhibitors were associated with a hazard ratio of 0.5, which suggested a technical problem in the estimation of the propensity scores. Several major risk factors for mortality identified in the analysis were treated as a minor risk or neutral or even protective factors. Antiviral treatments were recognised as an effective method to reduce mortality and were neither further studied nor integrated in the multivariate Cox model. This research appeared to carry multiple biases. An extensive audit of the study, conditions of review and acceptance for publication in the Lancet of that study are requested to avoid damage to the publics' trust on the scientific community at this critical time of COVID-19 pandemic.
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http://dx.doi.org/10.1080/20016689.2020.1809236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733902PMC
September 2020

Optimized preparation of eugenol microcapsules and its effect on hepatic steatosis in HepG cells.

Drug Dev Ind Pharm 2021 Feb 28;47(2):225-234. Epub 2020 Dec 28.

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China.

This study was aimed at evaluating the potential of peach gum (PG) and gelatin in the microencapsulation of eugenol and the intervention of eugenol microcapsules on hepatic steatosis . Response surface method (RSM) was used to optimize the encapsulation conditions of eugenol microcapsules. The microcapsules were characterized by scanning electron microscopy (SEM), dynamic Light Scattering (DLS), Fourier transform infrared spectroscopy (FT-IR) and release behavior was determined. The effect of eugenol microcapsules on free fatty acids (FFA) treated hepatocellular cells (HepG) cells was evaluated by oil red O staining and intracellular total cholesterol (TC) and triglyceride (TG) determination. The results showed that the optimal encapsulation conditions were as follows: the PG-gelatin ratio was 1.6:1.4, the core-wall ratio was 1.6:1.4, the pH was 4 and the emulsification speed was 9000 r/min. The optimized microcapsules were smooth spherical with a size of about 3.09 ± 0.58 μm and the encapsulation was confirmed by FT-IR. release behavior showed that eugenol microcapsules could be released stably in a neutral environment for 72 h. Oil red O staining showed that 50 and 100 μM eugenol microcapsules could significantly inhibit the lipid accumulation and reduce the TC and TG in steatotic HepG cells induced by FFA. Therefore, PG and gelatin can be used as excellent carriers for the microencapsulation of volatile compounds in the field of biomedical industry, and eugenol microcapsules is a promising preparation for the treatment of nonalcoholic fatty liver disease (NAFLD).
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http://dx.doi.org/10.1080/03639045.2020.1863421DOI Listing
February 2021

Relations of COVID-19-Related Stressors and Social Support With Chinese College Students' Psychological Response During the COVID-19 Pandemic.

Front Psychiatry 2020 30;11:551315. Epub 2020 Oct 30.

CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

This study examines the main and interactive relations of stressors and social support with Chinese college students' psychological symptoms (e.g., anxiety, depression) during the COVID-19 pandemic. All the constructs are assessed by self-report in an anonymous survey during the pandemic outbreak. The results show that the number of stressors has a positive relation with psychological symptoms, and social support has a negative relation with psychological symptoms. In addition, social support serves as a buffer against the negative impact of stressors. These findings hold implications for university counseling services during times of acute, large-scale stressors. Specifically, effective screening procedures should be developed to identify students who experience large number of stressors and provide suitable psychological intervention for them.
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http://dx.doi.org/10.3389/fpsyt.2020.551315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667466PMC
October 2020

Prognostic value of liver biochemical parameters for COVID-19 mortality.

Ann Hepatol 2021 Mar-Apr;21:100279. Epub 2020 Nov 4.

Department of Dermatology, Hunan Engineering Research Center of Skin Health and Disease, Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address:

Introduction: Coronavirus disease 2019 (COVID-19) has brought great challenges to global public health. However, a comprehensive analysis of the relationship between liver biochemical parameters and COVID-19 mortality is quite limited.

Methods: We searched the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, Scopus, Wanfang and China National Knowledge Infrastructure database until May 5, 2020. STATA software was used for the statistical analyses.

Results: A total of 25 studies involving 5971 COVID-19 patients were included in our analysis. Compared with non-survivors, survivors had lower levels of aspartate aminotransferase (AST) (weighted mean difference [WMD]=-16.71U/L, 95%CI=[-21.03,-12.40], P<0.001), alanine transaminase (ALT) (WMD=-5.20U/L, 95%CI=[-8.00,-2.41], P<0.001), total bilirubin (TBIL) (WMD=4.40μmol/L, 95%CI=[-5.11,-3.70], P<0.001) and lactic dehydrogenase (LDH) (WMD=-252.44U/L, 95%CI=[-289.57,-215.30], P<0.001), and higher albumin (ALB) level (WMD=4.47g/L, 95%CI=[3.47,5.47], P<0.001). Besides, survivors had lower proportions of these abnormally increased parameters (AST: OR=0.25, 95%CI=[0.15,0.41], P<0.001; ALT: OR=0.49, 95%CI=[0.37,0.64], P<0.001; TBIL: (OR=0.20, 95%CI=[0.12,0.34], P<0.001; LDH, OR=0.09, 95%CI=[0.06,0.14], P<0.001), and lower proportion of abnormally decreased ALB (OR=0.16, 95%CI=[0.07,0.38], P<0.001). Meta-analysis based on standard mean difference and sensitivity analysis did not change the conclusions. Egger test did not detect the presence of publication bias.

Conclusions: Liver biochemical parameters were strongly correlated with COVID-19 mortality. Measurement of these liver biochemical parameters might assist clinicians to evaluate the prognosis of COVID-19.
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http://dx.doi.org/10.1016/j.aohep.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609230PMC
March 2021

Discovery of novel artemisinin-sulfonamidehybrids as potential carbonicanhydraseIX inhibitors with improved antiproliferative activities.

Bioorg Chem 2020 11 8;104:104347. Epub 2020 Oct 8.

Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016 China. Electronic address:

A series of artemisinin-sulfonamide hybrids (1-16) have been designed and synthesized by using molecular hybridization approach and investigated for the inhibitory activity of four human (h) carbonic anhydrases (CAs, EC 4.2.1.1), hCA I, II, IX and XII. The results indicated most of the target compounds showed better CA IX and CA XII inhibitory activity than the starting segment sulfanilamide. Among all the compounds, compound 3 (IC: 5 nM) showed the best CA IX inhibitory efficacy. The p-aminobenzenesulfonamide derivatives showed significant antiproliferative activities against MDA-MB-231 breast cancer cell line and HT-29 colon cancer cell line under hypoxic conditions where CA IX and CA XII are overexpressed and most of them showed no apparent cytotoxic effects toward MCF-10A normal mammary epithelial cell. Among these derivatives, compound 3 displayed the most potent antiproliferative activities (IC: 0.65 μM) against HT-29 cell line under hypoxia and low cytotoxicity (IC: 78.0 μM) toward normal cell line. Meanwhile, compound 3 was found to efficiently decrease the hypoxia-induced extracellular acidification in both cancer cells. Molecular docking studies of compounds 3, 4, 5 and 9 revealed the proper interactions between the hybrid molecules and the active site of CA IX. All the results proved the effectiveness of the hybridization approach to develop novel artemisinin-sulfonamide compounds targeting CA IX for cancer treatment.
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http://dx.doi.org/10.1016/j.bioorg.2020.104347DOI Listing
November 2020

Chinese guidelines related to novel coronavirus pneumonia.

J Mark Access Health Policy 2020 Oct 8;8(1):1818446. Epub 2020 Oct 8.

Public Health Department, Aix Marseille University, Marseille Cedex 05, France.

China has managed to control the coronavirus disease (COVID-19) with confinement measurements and treatment strategies, while other countries are struggling to contain the spread. This study discusses the guidelines related to COVID-19 in China in order to provide important references for other countries in the fight against COVID-19. Chinese guidelines relevant to COVID-19 were systematically searched via the China National Knowledge Infrastructure database, YiMaiTong database, and World Health Organization (WHO) COVID-19 database on March 20, 2020. Guideline information was extracted, including date of publication, source, objectives and the target population. Guidelines specific to the pharmacological treatment of COVID-19 were further investigated to identify the types of antivirus drugs recommended and to report on how treatment recommendations for COVID-19 have evolved overtime. A total of 100 guidelines were identified, of which 74 were national guidelines and 26 were regional guidelines. The scope of included guidelines consisted of: the diagnosis and treatment of COVID-19, the management of hospital departments and specific diseases during the outbreak of COVID-19. Fifty-one of the included guidelines targeted overall COVID-19 patients, while the remaining guidelines concentrated on special patient populations (i.e. geriatric population, pediatric population, and pregnant population) or patients with coexisting diseases. Fifteen guidelines focused on the pharmacological treatments for all COVID-19 patients. Interferon, Lopinavir/Ritonavir, Ribavirin, Chloroquine, and Umifenovir represented the most recommended antivirus drugs. Among them, 7 Chinese guidelines have recommended Chloroquine Phosphate or Hydroxychloroquine for the treatment of COVID-19. : China has generated a plethora of guidelines covering almost all aspects of COVID-19. Chloroquine, as one widely affordable treatment, was recommended by Chinese national guidelines and provincial guidelines. Considering the continuous debates around Chloroquine, confirmatory studies with robust methodology are awaited to address the unanswered questions on its potential benefits and risks on COVID-19.
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http://dx.doi.org/10.1080/20016689.2020.1818446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580738PMC
October 2020

MicroRNA-185 reduces the expression of hepatitis B virus surface antigen by targeting PRKCH in HepG2 2.2.15 cells.

Acta Virol 2020 ;64(3):297-306

MicroRNAs (miRNAs) are single-stranded noncoding RNAs with 18 to 25 nucleotides and play critical roles in a wide spectrum of biological processes. We repored that miR-185 inhibited hepatitis B surface antigen (HBsAg) expression and hepatitis B virus (HBV) replication without affecting the proliferation of HepG2 2.2.15 cells, compared with the controls. We identified that protein kinase C eta (PRKCH) is a direct target gene of miR-185 that affects HBV replication and protein expression and that the miR-185 may suppress HBV replication. Our results provide more information for gene therapy in HBV infection. Keywords: miR-185; HBV; HBV surface antigen; viral replication; PRKCH.
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http://dx.doi.org/10.4149/av_2020_304DOI Listing
January 2021

Design, synthesis and biological evaluation of novel carbohydrate-based sulfonamide derivatives as antitumor agents.

Bioorg Chem 2020 11 27;104:104237. Epub 2020 Aug 27.

Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

A series of novel carbohydrate-based sulfonamides were designed and synthesized by the sugar-tail approach. The classical aromatic sulfonamide pharmacophore (ArSONH) was directly linked to a hydrophilic sugar-tail moiety through a rigid 1, 2, 3-triazole linker by the click chemistry reaction. The inhibitory activity against three carbonic anhydrase (CA, EC 4.2.1.1) isozymes (hCA I, hCA II and hCA IX) of all new compounds so designed were investigated in vitro and efficient inhibition against all three CA isoforms, especially the tumor-associated hCA IX, were observed. These glycoconjugate sulfonamide derivatives displayed better inhibitory efficacy in comparison with the starting segments (SA and p-hydroxybenzene sulfonamide). In particular, compound 12g was found to be the most effective and rather selective inhibitor of hCA IX with inhibitory constant (IC) value of 7 nM, being four times more potent than the clinical used agent acetazolamide (AAZ) (IC = 30 nM). Meanwhile, almost all compounds showed moderate antiproliferative activities against two cancer cell lines (HT-29 and MDA-MB-231) in both hypoxic and normoxic conditions while compound 12g also exhibited the most prominent antitumor activity. Furthermore, evident recovery (20-35% reduction of IC values) of cytotoxic efficiency of doxorubicin with the combination of compounds 12d, 12g and 22d as CAIs were detected on MDA-MB-231 cell line under hypoxic environment. In addition, docking studies revealed that the sugar-tail fragment of the target compounds participated in interactions with hydrophilic subpocket at the surface of hCA IX active site and supported the CA IX inhibitory activities of carbohydrate-based sulfonamide derivatives.
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http://dx.doi.org/10.1016/j.bioorg.2020.104237DOI Listing
November 2020

Utility of Circulating Tumor Cells for Detection of Early-Stage Luminal A Breast Cancer.

Am J Med Sci 2020 11 7;360(5):543-551. Epub 2020 Feb 7.

School of Clinical Medicine, Jinzhou Medical University, Jinzhou, Liaoning Province, China.

Background: Patients with early-stage luminal A breast cancer (LABC) have better prognoses. However, follow-up examinations are frequent and remain complex. The present study examined whether circulating tumor cell (CTC) detection could be used as an earlier and more reproducible indicator of disease status among patients with early-stage LABC, and given China's healthcare resource challenges, whether it could periodically replace follow-up routine imaging.

Methods: A total of 135 postoperative Chinese patients with early-stage LABC were randomly assigned to a CTC group (68 patients underwent alternating assessments using CTC detection and routine re-examination) or control group (67 patients underwent only routine re-examination). The prognosis and patient-covered costs of the various assessments were calculated for the 2 groups.

Results: No patients had normal CTCs and simultaneous abnormal imaging findings. There were no differences in overall survival, disease-free survival and total patient-covered cost of follow-up between the 2 groups (all P > 0.05). However, there was a significant difference in the average patient-covered cost (P < 0.001). Furthermore, significant intergroup differences were observed in the total and average hospitalization times (P < 0.05).

Conclusions: Among Chinese patients with low-risk LABC, CTC detection was highly reliable and relatively low cost. Therefore, CTC detection may be used to reduce the number of routine imaging follow-ups.
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http://dx.doi.org/10.1016/j.amjms.2020.01.020DOI Listing
November 2020

Acupuncture combined with medication for opioid use disorder in adults: a protocol for systematic review and meta-analysis.

BMJ Open 2020 06 21;10(6):e034554. Epub 2020 Jun 21.

School of Chinese Classics, Chengdu University of Traditional Chinese Medicine, Chengdu, China

Introduction: Opioid use disorder (OUD) is a worldwide health problem. Clinical trials indicated that acupuncture combined with medication is effective in OUD, however, there are different conclusions presented by previous trials. This study is designed to evaluate the efficacy and safety of acupuncture combined with medication in OUD.

Methods And Analysis: PubMed, CENTRAL, Embase, Web of Science, CINAHL, PsycINFO, ProQuest Dissertation and Theses, AMED, OpenGrey, Clinicaltrials.gov and who.int/trialsearch will be searched in September 2019 without a language restriction. Randomised controlled trials (RCTs) and quasi-RCTs which included participants with OUD receiving acupuncture therapy combined with medication versus control group will be included in this study. Two reviewers will independently screen studies, extract data, assess risk of bias by the Cochrane risk of bias assessment tool and assess quality of evidence by Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Any disagreements will be arbitrated by the third reviewer. Data synthesis and analysis will be conducted by using RevMan V.5.3. Subgroup analyses, sensitivity analysis, meta-regression and reporting bias assessment will be conducted if necessary and appropriate.

Ethics And Dissemination: On account of the nature of this systematic review and meta-analysis, ethical approval is not required. The results will be published in a peer-reviewed journal.

Prospero Registration Number: CRD42019123436.
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http://dx.doi.org/10.1136/bmjopen-2019-034554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310998PMC
June 2020

Nanoparticles modified by polydopamine: Working as "drug" carriers.

Bioact Mater 2020 Sep 18;5(3):522-541. Epub 2020 Apr 18.

Department of Oral & Cranio-Maxillofacial Surgery, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, 200011, PR China.

Inspired by the mechanism of mussel adhesion, polydopamine (PDA), a versatile polymer for surface modification has been discovered. Owing to its unique properties like extraordinary adhesiveness, excellent biocompatibility, mild synthesis requirements, as well as distinctive drug loading approach, strong photothermal conversion capacity and reactive oxygen species (ROS) scavenging facility, various PDA-modified nanoparticles have been desired as drug carriers. These nanoparticles with diverse nanostructures are exploited in multifunctions, consisting of targeting, imaging, chemical treatment (CT), photodynamic therapy (PDT), photothermal therapy (PTT), tissue regeneration ability, therefore have attracted great attentions in plenty biomedical applications. Herein, recent progress of PDA-modified nanoparticle drug carriers in cancer therapy, antibiosis, prevention of inflammation, theranostics, vaccine delivery and adjuvant, tissue repair and implant materials are reviewed, including preparation of PDA-modified nanoparticle drug carriers with various nanostructures and their drug loading strategies, basic roles of PDA surface modification, etc. The advantages of PDA modification in overcoming the existing limitations of cancer therapy, antibiosis, tissue repair and the developing trends in the future of PDA-modified nanoparticle drug carriers are also discussed.
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http://dx.doi.org/10.1016/j.bioactmat.2020.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170807PMC
September 2020

Efficacy and safety of Yiqi Huoxue Jiedu decoction for the treatment of advanced epithelial ovarian cancer patients: a double-blind randomized controlled clinical trial.

J Tradit Chin Med 2020 02;40(1):103-111

Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.

Objective: To further evaluate the complementary effect of Yiqi Huoxue Jiedu decoction (YHJD) on patients with advanced epithelial ovarian cancer (EOC).

Methods: All 330 enrolled participants diagnosed with stage Ⅲc EOC were randomly divided into two groups that received YHJD or a placebo. The primary end point was health-related quality of life (HRQL) measured by the functional assessment of cancer therapy-ovary cancer (FACT-O) questionnaire. The secondary end point was progression-free survival (PFS).

Results: A total of 299 participants completed the trial with 153 and 146 in YHJD and control groups, respectively. After 6 months of treatment, YHJD increased physical wellbeing (PWB), functional wellbeing (FWB), additional concerns (AC), and the trial outcome index (TOI) (P < 0.05) by various degrees compared with the baseline. YHJD also had notable advantages over the placebo at 3 and 6 months in terms of PWB, FWB, AC (P < 0.05), and TOI (P < 0.01). In addition, YHJD had a significant advantage in terms of PFS compared with the placebo (21 vs 18 months, P < 0.05). No adverse events were reported.

Conclusion: YHJD is an effective and safe choice as a complementary therapy to improve HRQL and prolong PFS of stage Ⅲc EOC patients.
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February 2020

Colloidal clusters of icosahedrons and face-centred cubes.

J Colloid Interface Sci 2020 Mar 23;563:308-317. Epub 2019 Dec 23.

Key Laboratory of Colloid and Interface Chemistry (Shandong University), Ministry of Education, Jinan 250100, People's Republic of China. Electronic address:

Synthetically colloidal clusters with new functions and well-controlled size distribution can in principle be constructed using colloidal particles. The building units could be integrated into dense-packed and desired structured with novel functions by means of an efficient strategy or binding patterns. Here we synthesized colloidal clusters of icosahedrons and long-range ordered face-centered cubes (FCCs) via emulsion self-assembly using fluorescence upconversion nanoparticles NaGdF: Yb, Er as building blocks. The icosahedrons and FCCs structure may generate spontaneously due to an entropy-driven process. The morphology and structure of colloidal clusters have noticeable transformation from icosahedron-like symmetry to FCC symmetry with the increasing size of clusters. Furthermore, the colloidal clusters could be decorated with cationic polyethyleneimine (PEI) via electrostatic interaction. When copper ions are added, the amino groups of PEI could coordinate with Cu forming low toxic PEI-Cu layers, which can further serve as energy receptors to quench upconversion fluorescence with 980 nm laser excitation. Our results reflect that the colloidal clusters not only can serve as a fluorescence platform of detection and analysis but also may represent advancement in the field of colloidal and interface sciences.
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http://dx.doi.org/10.1016/j.jcis.2019.12.084DOI Listing
March 2020

Design, synthesis and biological evaluation of carbohydrate-based sulphonamide derivatives as topical antiglaucoma agents through selective inhibition of carbonic anhydrase II.

J Enzyme Inhib Med Chem 2020 Dec;35(1):383-390

Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, China.

A series of new carbohydrate-based sulphonamide derivatives were designed, synthesised by employing the so-call 'sugar-tail' approach. The compounds were evaluated against a panel of CAs. Compared to their parent compound -sulfamoylbenzoic acid, these compounds showed nearly 100-fold improvement in their binding affinities against hCA II . All of compounds showed great water solubility and the pH value of their water solutions of compounds is 7.0. Such properties are advantageous to make them much less irritating to the eye when applied topical glaucomatous drugs, compared to the relatively highly acidic dorzolamide preparations (pH 5.5). Notably, compounds , , demonstrated to topically lower intraocular pressure (IOP) in glaucomatous animals better than brinzolamide when applied as a 1% solution directly into the eye. Low cytotoxicity on human cornea epithelial cell was observed in the tested concentrations by the MTT assay.
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http://dx.doi.org/10.1080/14756366.2019.1705293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6968511PMC
December 2020

Stimuli-Responsive Fluorescent Nanoswitches: Solvent-Induced Emission Enhancement of Copper Nanoclusters.

Chemistry 2020 Mar 28;26(16):3545-3554. Epub 2020 Jan 28.

Key Laboratory of Colloid and Interface Chemistry, (Ministry of Education)&, State Key Laboratory of Crystal Materials, Shandong University, Jinan, 250100, P.R. China.

Copper nanoclusters (CuNCs) as a new class of fluorescent materials have attracted a great deal of interest due to their outstanding fluorescence properties. In this work, a variety of organic solvents were used to induce self-assembly of glutathione-capped CuNCs (GSH-CuNCs) to form ordered assemblies with enhanced fluorescence properties. Assemblies with multicolor fluorescence emission were constructed on the basis of the aggregation-induced emission (AIE) of GSH-CuNCs and the solvent effect. The fluorescence emission from these GSH-CuNCs assemblies can also be tuned from yellow to purple by changing the organic solvent. A possible mechanism based on the size of the assemblies and electron transfer was explored to explain the solvent effects on GSH-CuNCs. Stimuli-responsive nanoswitches with excellent reversibility can be controlled by changing the type of organic solvent and the ratio of the organic solvent to the aqueous solution of GSH-CuNCs. As the CuNCs assemblies exhibit strong, stable, and color-tunable fluorescence, they were employed as color-conversion materials for recognizing different organic solvents.
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http://dx.doi.org/10.1002/chem.201905094DOI Listing
March 2020

Dual pH-Responsive Polymer Nanogels with a Core-Shell Structure for Improved Cell Association.

Langmuir 2019 12 9;35(51):16869-16875. Epub 2019 Dec 9.

Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education, School of Chemistry and Chemical Engineering , Shandong University , Jinan , Shandong 250100 , China.

We report the fabrication of polymer nanogels with a pH-responsive core and a pH-sheddable shell and investigate the pH-dependent cell association of the pH-responsive polymer nanogels. The pH-responsive core composed of poly(2-diisopropylaminoethyl methacrylate) (PDPA) with a p ≈ 6.2 was synthesized by using polymerization in emulsion droplets. The pH-sheddable poly(ethylene glycol) (PEG) shell was coated on the amine-modified PDPA nanogels by an acid-degradable amide bond. The PEG shell is cleavable in response to the acidic tumor microenvironment, and subsequently, the surface charge of the nanogels can be reversed, which effectively enhances cellular association of these nanogels. The reported pH-responsive polymer nanogels provide a promising way for the better understanding of bio-nano interactions and potentially enrich the application of therapeutic delivery for cancer therapy.
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http://dx.doi.org/10.1021/acs.langmuir.9b03107DOI Listing
December 2019

A randomized controlled dose-escalation study of SSS07, a humanized rabbit anti-human TNF alpha antibody, in healthy Chinese adults.

Int Immunopharmacol 2019 Oct 12;75:105807. Epub 2019 Aug 12.

Department of Pharmacy, Peking University People's Hospital, Beijing, China. Electronic address:

Aims: SSS07 is a rabbit derived humanized anti-human TNF-α antibody. This study aimed to explore the pharmacokinetics, safety, and immunogenicity of SSS07 when administrated subcutaneously in healthy adults.

Methods: This was a double-blind, dose-escalation study of SSS07 in 71 adults. Dose cohorts were set to 5 mg, 15 mg, 30 mg, 50 mg, 75 mg, and 100 mg. In each dosage group, other than 100 mg, twelve healthy participants were randomly assigned to receive a single dose of SSS07 (n = 10) or placebo (n = 2). Blood samples were taken for pharmacokinetics and immunogenicity analysis.

Results: No deaths, serious adverse events or drug-related withdrawals occurred in this trial. No drug limited toxicity appeared. After subcutaneous injection, SSS07 was absorbed slowly with T ranging from 60 to 264 h but eliminated quickly with a short half-life ranging from 21.69 to 78.4 h (1-3 days). From 5 mg to 100 mg, dose-exposure proportionality analysis found a 90% confidence interval (CI) of β of C (1.015-1.193), AUC (1.096-1.263) and AUC (0.999-1.174) partially within the range 0.926-1.074. The plasma concentration of TNF-α decreased significantly post-dose, but a few days later, levels of TNF-α elevated rapidly and exceeded its baseline value. All participants receiving SSS07 were found to be anti-drug antibody positive during the study.

Conclusions: A single-dose injection of SSS07 was safe and well-tolerated in healthy adults. Doses of SSS07 from 5 mg to 100 mg could not be regarded as nonlinear, based on dose-exposure proportionality analysis. A high incidence of anti-drug antibodies indicated strong immunogenicity, which may influence the pharmacokinetics profile and interfere with the TNF-α inhibition capability of SSS07.
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http://dx.doi.org/10.1016/j.intimp.2019.105807DOI Listing
October 2019

Mindfulness changes construal level: An experimental investigation.

J Exp Psychol Gen 2019 Sep 29;148(9):1656-1664. Epub 2019 Jul 29.

UTS Business School, University of Technology Sydney.

Mindfulness involves paying attention to the present moment and accepting any thoughts or feelings that might arise without judgment. Mindfulness can influence a number of outcomes. Currently, we are interested if it influences people's level of mental construal. Two central dimensions of mindfulness (focusing on the present, and Openness to Experience) can lead to diverging predictions. While focusing on the present may produce a concrete construal level, openness to experience may facilitate an abstract construal level instead. We conducted 2 experiments to test the effect of a brief mindfulness induction on construal level. Mindfulness prompted participants to think more abstractly (Experiment 1), which was mediated by Openness to Experience (Experiment 2). Thus, mindfulness may prompt how people process information more broadly. We situate our research in the broader literature on mindfulness and reconcile our findings with previous work. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/xge0000654DOI Listing
September 2019

Ionic-surfactants-based thermotropic liquid crystals.

Phys Chem Chem Phys 2019 Jul;21(28):15256-15281

Key Laboratory of Colloid and Interface Chemistry, Shandong University, Ministry of Education, Jinan, Shandong Province 250100, China.

Thermotropic liquid crystals (TLCs) are a series of soft materials with ordered arrangements of repeating structural units in a certain range of temperature. Specifically, the TLCs constructed by the electrostatic combination between ionic surfactants and other oppositely charged groups have received great attention in the field of optoelectronic devices, material transportation and separation, smart materials as well as biosensing. As typical amphiphilic molecules, ionic surfactants with charged head-groups and long alkyl tails exhibit unique self-assembly behaviors, being preferable as flexible building blocks of TLCs. In this review, we have discussed the TLCs formed by salt-free catanionic surfactants and ionic surfactants with other functional groups, including metal ions, nanoclusters, biomolecules, and polyelectrolytes. The design of such TLC molecules, the influencing factors of the mesophases, and the related applications of the TLCs are discussed in detail. Because of their easy preparation and variable structure, these TLCs are expected to greatly widen the application scope of the relevant functional molecules. At the end of this review, we put forward some ideas with regard to the aspects that are required to be improved and propose the possible development trend in this direction. It is expected that through this review, the important roles of ionic surfactants in building TLCs will be highlighted and thus, more studies will be inspired to exploit more TLCs based on ionic surfactants with excellent properties.
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http://dx.doi.org/10.1039/c9cp02697eDOI Listing
July 2019

Comparative analysis of radiofrequency ablation and resection for colorectal liver metastases in caudate lobe: a retrospective study.

Acta Chir Belg 2020 Oct 21;120(5):321-328. Epub 2019 Jun 21.

Department of Gastrointestinal Surgery, The Second People's Hospital of Liaocheng, Liaocheng, PR China.

To assess the therapeutic efficiency of radiofrequency ablation (RFA) for colorectal liver metastases (CRLM) in the caudate lobe compared with that of surgical resection. After approved by institutional review board, we retrospectively reviewed 20 patients with caudate CRLM treated by RFA or resection between 2006 and 2017. Comparative analysis was performed based on the different therapies, including patient characteristics, therapeutic outcomes, recurrences, and survivals. During the median follow-up of 7 years (range, 2 -11 years), no differences in complications and recurrences were found between RFA and surgery groups ( > .05). The median overall survival (OS) of patients after RFA and resection were 41 months (95% confidence interval (CI) 23.5-70.5) and 54 months (95% CI 31.1-77.7), respectively ( = .627, hazard radio (HR) 0.7, 95% CI 0.2-2.6). However, OS of resection group was better than that of RFA group for large caudate CRLMs (>3 cm) ( = .042, HR 4.4, 95% CI 0.6-32.6). RFA is a feasible, safe, and effective treatment for CRLM in the caudate. Surgical resection revealed superior outcomes in the treatment of caudate CRLMs, particularly in cases with a hepatic tumor size  >3 cm.
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http://dx.doi.org/10.1080/00015458.2019.1631614DOI Listing
October 2020

Simultaneously Enhanced Strength and Ductility of Al⁻Mg⁻Si Alloys during Aging Process Induced by Electro-Pulsing Treatment.

Materials (Basel) 2019 Apr 28;12(9). Epub 2019 Apr 28.

Key Laboratory of Automobile Materials, Ministry of Education and School of Materials Science and Engineering, Jilin University, No. 5988 Renmin Street, Changchun 130022, China.

Most methods used for strengthening metallic materials, such as thermal-mechanical treatment, will sacrifice the ductility. A novel technology, electric pulsing treatment (EPT), is applied to break this trade-off, which produces an Al-Mg-Si alloy with superior ductility and higher strength within only 560 ms. Systematic electron microscopy characterization and finite element simulation reveal that EPT promotes the formation of clusters Mg(Si,Cu) and sub-grain boundaries. The results of quantitative calculation indicate that the dislocation entanglement is delayed due to the existence of clusters and longer dislocation glide distance, so that ultimate strength is fully improved. Moreover, the superior ductility is mainly governed by sub-grains which lead to higher mobile dislocation density, appearance of new crystal orientations, and prevention of crack propagation. Thereupon, this interesting finding paves the way in developing the Al-Mg-Si alloy with higher mechanical properties efficiently.
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http://dx.doi.org/10.3390/ma12091383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538987PMC
April 2019

Microgels in biomaterials and nanomedicines.

Adv Colloid Interface Sci 2019 Apr 8;266:1-20. Epub 2019 Feb 8.

Key Laboratory of Colloid and Interface Chemistry & Key Laboratory of Special Aggregated Materials (Shandong University), Ministry of Education, Jinan 250100, PR China. Electronic address:

Microgels are colloidal particles with crosslinked polymer networks and dimensions ranging from tens of nanometers to micrometers. Specifically, smart microgels are fascinating capable of responding to biological signals in vivo or remote triggers and making the possible for applications in biomaterials and biomedicines. Therefore, how to fundamentally design microgels is an urgent problem to be solved. In this review, we put forward our important fundamental opinions on how to devise the intelligent microgels for cancer therapy, biosensing and biological lubrication. We focus on the design ideas instead of specific implementation process by employing reverse synthesis analysis to programme the microgels at the original stage. Moreover, special insights will be, for the first time, as far as we know, dedicated to the particles completely composed of DNA or proteins into microgel systems. These are discussed in detail in this review. We expect to give readers a broad overview of the design criteria and practical methodologies of microgels according to the application fields, as well as to propel the further developments of highly interesting concepts and materials.
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http://dx.doi.org/10.1016/j.cis.2019.01.005DOI Listing
April 2019

Eu-Controlled Fluorescent Bilayer Vesicles.

Langmuir 2019 03 1;35(11):4125-4132. Epub 2019 Mar 1.

Key Laboratory of Colloid and Interface Chemistry & Key Laboratory of Special Aggregated Materials , Shandong University, Ministry of Education , Jinan 250100 , China.

By appropriate substitution, polyoxometalates (POMs) can be modified to be organic-inorganic supramolecules (OISMs) that are nonaqueous or water soluble and form aggregates in solution. Here, we report a new OISM, (TBA)POM-PPCT, that can self-assemble to form bilayer vesicles controlled by Eu in nonaqueous solution. Dynamic light scattering, transmission and scanning electron microscopy techniques, and atomic force microscopy clearly demonstrated the controllable formation of stable bilayer vesicles with an average hydrodynamic radius of about 510 nm. Because of the coordination between (TBA)POM-PPCT and Eu, the stable vesicles possess fluorescence, determined by studying fluorescence spectra, and show highly selective response to Cu, allowing them to function as an ion-detecting platform to Cu.
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http://dx.doi.org/10.1021/acs.langmuir.9b00302DOI Listing
March 2019