Publications by authors named "Lihong Li"

218 Publications

Strategy of Virtual Screening Based Discovery of HSP90 C-terminal Inhibitors and Network Pharmacological Analysis.

Curr Pharm Biotechnol 2021 Sep 9. Epub 2021 Sep 9.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Dagong Road No. 2, Panjin, 124221. China.

Background: HSP90 has been considered as an important anticancer target for several decades, but traditional HSP90 N-terminal inhibitors often suffered from organ toxicity and/or drug resistance.

Methods: The development of HSP90 C-terminal inhibitors represents a reliable alternative strategy. In the view of rare examples of structure based identification of HSP90 C-terminal inhibitors, we reported a virtual screening based strategy for the discovery of HSP90 C-terminal inhibitors as anticancer agents from natural products.

Results & Discussion: 13 chemical ingredients from licorice were identified as possible HSP90 inhibitors and 3 of them have been reported as anticancer agents. The binding modes of them towards HSP90 C-terminus were predicted by molecular docking and refined by molecular dynamics stimulation.

Conclusion: Further network pharmacological analysis predicted overall possible targets involved in the pathways in cancer and revealed that 8 molecules possibly interact with HSP90.
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http://dx.doi.org/10.2174/1389201022666210910101419DOI Listing
September 2021

Clinical Significance of the Serum lncRNA NORAD Expression in Patients with Neonatal Sepsis and Its Association with miR-410-3p.

J Inflamm Res 2021 26;14:4181-4188. Epub 2021 Aug 26.

Department of Neonatology, Weifang Maternal and Child Health Hospital, Weifang, Shandong, People's Republic of China.

Purpose: Neonatal sepsis (NS) is one of the most crucial causes of death in newborns. This investigation aimed to validate the expression level of NORAD and the probable mechanism underlying the function of NORAD in NS.

Patients And Methods: The expression of NORAD and miR-410-3p was identified by qRT-PCR. The diagnostic sensitivity and specificity of NORAD were examined by the ROC curve. The NS cell models were established by the treatment of lipopolysaccharide (LPS) in the macrophage RAW264.7 cells. The luciferase report assay was performed to detect the target relationship between NORAD and miR-410-3p and the association between them was revealed by Pearson correlation.

Results: The expression of NORAD was at a higher level in the NS group than in the pneumonia controls. The levels of NORAD could sever as a diagnostic marker on discriminating NS patients from pneumonia neonates. The expression of IL-6, IL-8, and TNF-α was enhanced in the macrophage cells under LPS circumstances, while NORAD knockdown reversed the overexpression of these pro-inflammatory cytokines. Besides, miR-410-3p was a possible ceRNA of NORAD by the finding that the luciferase activity fell in the co-transfection of miR-410-3p mimics and WT-NORAD group. In vitro, LPS management could inhibit the expression of miR-410-3p, while silenced NORAD ameliorated the suppressed miR-410-3p levels. Decreased expression of miR-410-3p was discovered in NS patients and the changes of miR-410-3p expression were correlated with the levels of NORAD in the NS patients.

Conclusion: We found a raised level of NORAD in the NS patients and it might be a diagnostic indicator for NS patients. NORAD elimination meliorated the inflammation actions steered by LPS. MiR-410-3p was a target of NORAD and lowly expressed in the NS patients.
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http://dx.doi.org/10.2147/JIR.S315985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405162PMC
August 2021

Virtual screening based identification of miltefosine and octenidine as inhibitors of heat shock protein 90.

Naunyn Schmiedebergs Arch Pharmacol 2021 Aug 18. Epub 2021 Aug 18.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Dagong Road 2, Liaodongwan district, Panjin, 124221, China.

The molecular chaperone HSP90 facilitates the maturation of newly synthesized and unfolded proteins. The client proteins of HSP90 are involved in many processes of cancer occurrence and development, and therefore, HSP90 is considered as a promising target for the development of anticancer drugs. In contrast to N-terminal inhibitor, C-terminal inhibitor does not induce the pro-survival heat shock response. In order to get novel HSP90 C-terminal inhibitors and more evidences that HSP90 inhibitors could be applied in the therapy of cancer, we conducted a virtual screening toward HSP90 C-terminus from FDA-approved drugs. In this study, miltefosine and octenidine were identified as new HSP90 inhibitors. Miltefosine and octenidine exhibited strong and broad-spectrum anticancer activity and inhibited the proliferation of cancer cell by promoting apoptosis. Western blotting analysis revealed that miltefosine and octenidine significantly down-regulated the expression levels of HSP90 client proteins including p-AKT, CDK6, and ERK, and did not induce overexpression of heat shock proteins including HSP70 and HSP90 in MCF-7 cells. These results were in accordance with the characteristics of HSP90 C-terminal inhibitor. In conclusion, miltefosine and octenidine could disrupt the molecular chaperone function of HSP90, and thus, their strong and broad-spectrum anticancer activity is at least in part attributed to the inhibition activity against HSP90.
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http://dx.doi.org/10.1007/s00210-021-02133-yDOI Listing
August 2021

Mutation and methylation profiles of ectopic and eutopic endometrial tissues.

J Pathol 2021 Aug 16. Epub 2021 Aug 16.

Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Adenomyosis and peritoneal endometriosis are common gynecologic lesions; they are characterized by aberrant locations of normal-appearing endometrium in myometrium and peritoneal surface, respectively. Both ectopic lesions are speculated to originate from uterine eutopic endometrium, which is composed of epithelium and stroma, but how these two different tissue types co-evolve in ectopic locations remains unclear. Here, we analyzed exome-wide mutations and global methylation in microdissected epithelium and stroma separately in paired adenomyosis, peritoneal endometriosis, and endometrium to investigate their relationship. Analyses of somatic mutations and their allele frequencies indicate monoclonal development not only in epithelium but also in the stroma of adenomyosis and peritoneal endometriosis. Our preliminary phylogenetic study suggests a plausible clonal derivation in epithelium and stroma of both ectopic and eutopic endometrium from the same founder epithelium-stroma progenitor cells. While a patient-specific methylation landscape is evident, adenomyosis epithelium and stroma can be distinguished from normal-appearing eutopic endometrium epigenetically. In summary, endometrial stroma, like its epithelial counterpart, could be clonal and both ectopic and eutopic endometrium following divergent evolutionary trajectories. Our data also warrant future investigations into the role of endometrial stroma in the pathobiology of endometrium-related disorders. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/path.5778DOI Listing
August 2021

A Novel ZIP4-HDAC4-VEGFA Axis in High-Grade Serous Ovarian Cancer.

Cancers (Basel) 2021 Jul 29;13(15). Epub 2021 Jul 29.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, 950 W. Walnut St. R2-E380, Indianapolis, IN 46202, USA.

We have recently identified ZIP4 as a novel cancer stem cell (CSC) marker in high-grade serous ovarian cancer (HGSOC). While it converts drug-resistance to cisplatin (CDDP), we unexpectedly found that ZIP4 induced sensitization of HGSOC cells to histone deacetylase inhibitors (HDACis). Mechanistically, ZIP4 selectively upregulated HDAC IIa HDACs, with little or no effect on HDACs in other classes. HDAC4 knockdown (KD) and LMK-235 inhibited spheroid formation in vitro and tumorigenesis in vivo, with hypoxia inducible factor-1 alpha (HIF1α) and endothelial growth factor A (VEGFA) as functional downstream mediators of HDAC4. Moreover, we found that ZIP4, HDAC4, and HIF1α were involved in regulating secreted VEGFA in HGSOC cells. Furthermore, we tested our hypothesis that co-targeting CSC via the ZIP4-HDAC4 axis and non-CSC using CDDP is necessary and highly effective by comparing the effects of ZIP4-knockout/KD, HDAC4-KD, and HDACis, in the presence or absence of CDDP on tumorigenesis in mouse models. Our results showed that the co-targeting strategy was highly effective. Finally, data from human HGSOC tissues showed that ZIP4 and HDAC4 were upregulated in a subset of recurrent tumors, justifying the clinical relevance of the study. In summary, our study provides a new mechanistic-based targeting strategy for HGSOC.
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http://dx.doi.org/10.3390/cancers13153821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345154PMC
July 2021

ZEB2, interacting with MDM2, contributes to the dysfuntion of brain microvascular endothelial cells and brain injury after intracerebral hemorrhage.

Cell Cycle 2021 Aug 2:1-16. Epub 2021 Aug 2.

Department of Neurosurgery, Xing Yuan Hospital of Yulin, Yulin, Shaanxi, China.

ZEB2 has been shown to be upregulated in the brain tissues of rats with intracerebral hemorrhage (ICH), but its role in ICH-caused brain injury remains unclear. Here, an ICH rat model was established via intracerebral injection of autologous blood, and the lentivirus-mediated ZEB2 short hairpin RNA (sh-ZEB2) or negative control (scramble) were administered 0.5 hours after ICH. Silencing ZEB2 alleviated ICH-induced neurologic deficits and the increase of BBB permeability, brain water content and ZEB2 expression. Next, OGD (oxygen glucose deprivation) plus hemin was used to treat primary brain microvascular endothelial cells (BMECs) to simulate the ICH condition . OGD plus hemin upregulated ZEB2 expression and apoptosis, but reduced cell viability, migration, TEER (transendothelial electric resistance) and the expression of vascular-endothelial (VE-) cadherin, occludin and claudin-5, which was reversed by inhibiting ZEB2. Mechanism researches showed that ZEB2 interacted with MDM2 to up-regulate MDM2 protein expression, and then increased E2F1 protein level by suppressing its ubiquitination, which in turn promoted the transcription of ZEB2 to induce its protein expression, so as to enhance the interaction between ZEB2 and MDM2, thereby contributing to OGD plus hemin-induced endothelial dysfunction. Additionally, the joint interference of ZEB2 and MDM2 had better mitigative effects on ICH-induced brain injury compared with silencing ZEB2 alone. In summary, ZEB2 interacted with MDM2 to promote BMEC dysfunction and brain damage after ICH.
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http://dx.doi.org/10.1080/15384101.2021.1959702DOI Listing
August 2021

Activating Caspase-8/Bid/ROS Signaling to Promote Apoptosis of Breast Cancer Cells by Folate-modified Albumin Baicalin-loaded Nanoparticles.

Nanotechnology 2021 Jul 30. Epub 2021 Jul 30.

Jinan University, College of Pharmacy, Jinan University, Guangzhou 510632, China, Guangzhou, 510632, CHINA.

Abnormal apoptosis can lead to uncontrolled cell growth, aberrant homeostasis or the accumulation of mutations. Therapeutic agents that re-establish the normal functions of apoptotic signaling pathways offer an attractive strategy for the treatment of breast cancer. Baicalin (BA) is one of the natural compounds with anti-proliferation and pro-apoptosis activities against numerous tumor cells. However, low bioavailability restricts the clinical application of BA. In order to improve its therapeutic efficacy and study the mechanism of actions, active targeting delivery systems were developed for targeting tumor environment and selective cell killing effects. It emphasized on the construction of folate-conjugated albumin nanoparticles loaded with baicalin (FA-BSANPs/BA) and mechanisms of which on the promotion of breast cancer apoptosis. The physicochemical properties and structural characteristics of FA-BSANPs/BA were investigated. Cell experiments were carried out to study the targeted anti-breast cancer effects of FA-BSANPs/BA and its mechanism. The results showed that FA-BSANPs/BA was successfully constructed with stable structural characteristics and sustained release effects. Cellular uptake and MTT showed that it increased targeted uptake efficiency and cytotoxicity. Flow cytometry and western blot confirmed that it promoted apoptosis by increasing the expression of caspase-8 and ROS, and decreasing the level of Bid. It is suggested that the pro-apoptotic mechanism of FA-BSANPs/BA is related to regulation of key proteins in extrinsic apoptotic pathway. In conclusion, FA-BSANPs/BA is a good delivery carrier and significantly inhibits the breast cancer growth compared with free BA. The mechanism of FA-BSANPs/BA promoting apoptosis of breast cancer may be due to its action on the caspase-8/Bid/ROS pathway.
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http://dx.doi.org/10.1088/1361-6528/ac197bDOI Listing
July 2021

A pilot behavioural and neuroimaging investigation on photothrombotic stroke models in rhesus monkeys.

J Neurosci Methods 2021 Oct 20;362:109291. Epub 2021 Jul 20.

National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. Electronic address:

Background: Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans.

Results: The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke.

Comparison With Existing Methods: The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect.

Conclusions: The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109291DOI Listing
October 2021

Efficient biosynthesis of D-allulose in Bacillus subtilis through D-psicose 3-epimerase translation modification.

Int J Biol Macromol 2021 Sep 20;187:1-8. Epub 2021 Jul 20.

College of Light Industry and Food Engineering, Guangxi University, 100 Daxue Road, Nanning 530004, Guangxi, China; Sugar Industry Collaborative Innovation Center, Guangxi University, 100 Daxue Road, Nanning 530004, Guangxi, China. Electronic address:

The combined catalysis of glucose isomerase (GI) and D-psicose 3-epimerase (DPEase) provided a convenient route for the direct synthesis of D-allulose from d-glucose, whose cost is lower than d-fructose. In the present research, the weak activity of DPEase was the key rate-limiting step and resulted in the accumulation of d-fructose in engineered Bacillus subtilis. Then, the 5'-untranslated region (5'-UTR) structure of the mRNA translational initiation region was optimized for the precise control of DPEase expression. The manipulation of the 5'-UTR region promoted the accessibility to ribosome binding and the stability of mRNA, resulting in a maximum of 1.73- and 1.98-fold increase in DPEase activity and intracellular mRNA amount, respectively. Under the optimal catalytic conditions of 75 °C, pH 6.5, 110 g/L d-glucose, and 1 mmol/L Co, the reaction equilibrium time was reduced from 7.6 h to 6.1 h. We hope that our results could provide a facilitated strategy for large-scale production of D-allulose at low-cost.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.093DOI Listing
September 2021

A Combined Effect of Self and Reward: Relationship of Self- and Reward-Bias on Associative Learning.

Front Psychol 2021 17;12:647443. Epub 2021 Jun 17.

Department of Psychology, Seton Hall University, South Orange, NJ, United States.

Previous studies have demonstrated that individuals process information related to themselves or a high reward quickly and have referred to this as self-bias or reward-bias. However, no previous study has presented self- and reward-bias simultaneously. The present study investigated perceptual processing using the associated learning paradigm when both self and reward were prioritized (condition of double salience) as well as when only self or reward was prioritized (condition of single salience). The present study established these two conditions by manipulating self-relevance (self vs. stranger in Experiment 1; self vs. friend in Experiment 2). The results showed that (1) when the self was pitted against a stranger and received a high or low reward, perceptual processing of the participants mainly involved self-bias (Experiment 1); (2) when the self was pitted against a friend, perceptual processing involved both self-bias and reward-bias (Experiment 2). The study revealed a complex relationship between self- and reward-bias, which depends on the degree of affinity between oneself and others.
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http://dx.doi.org/10.3389/fpsyg.2021.647443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245683PMC
June 2021

miR-133a-3p regulates the proliferation and apoptosis of intestinal epithelial cells by modulating the expression of TAGLN2.

Exp Ther Med 2021 Aug 2;22(2):824. Epub 2021 Jun 2.

Medical College of Air Force Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

Sepsis is one of the most common diseases in patients in intensive care units. Intestinal barrier dysfunction serves a critical role in the pathogenesis and progression of sepsis. Therefore, preservation of the intestinal epithelial barrier function is an area of ongoing research in the treatment of sepsis. The present study investigated the effects of miR-133a-3p on the proliferation and apoptosis of intestinal epithelial cells and the possible mechanism underlying its actions. miR-133a-3p was used to upregulate the intestinal epithelial FHs 74 Int cell line and cell proliferation and apoptosis were investigated. A luciferase reporter assay was used to determine whether the 3'-UTR of TAGLN2 mRNA was a binding target of miR-133a-3p. FHs 74 Int cells were transfected with TAGLN2 shRNA and the effects of TAGLN2 on the proliferation and apoptosis of intestinal epithelial cells were investigated. It was found that miR-133a-3p inhibited the proliferation and promoted the apoptosis of intestinal epithelial cells. A luciferase reporter assay confirmed that miR-133a-3p targeted TAGLN2 directly. In addition, low expression of TAGLN2 inhibited the proliferation and promoted the apoptosis of intestinal epithelial cells. The results of the present study suggested that the miR-133a-3p inhibition of proliferation and promotion of apoptosis occurred via the inhibition of TAGLN2. These results suggested that miR-133a-3p may be a promising therapeutic target for the diagnosis and treatment of gut-origin sepsis.
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http://dx.doi.org/10.3892/etm.2021.10256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200801PMC
August 2021

High retinoic acid receptor-related orphan receptor A gene expression in peripheral blood leukocytes may be related to acute myocardial infarction.

J Int Med Res 2021 Jun;49(6):3000605211019663

Department of Cardiology, Third Hospital of Jilin University, Jilin Provincial Cardiovascular Research Institute, Jilin, China.

Objective: This study aimed to investigate whether differential expression of the retinoic acid receptor-related orphan receptor A () gene is related to occurrence of acute myocardial infarction (AMI).

Methods: This was a retrospective study. White blood cells of 93 patients with acute myocardial infarction and 74 patients with stable coronary artery disease were collected. Reverse transcription quantitative polymerase chain reaction and western blotting were used to measure RORA mRNA and protein expression, respectively.

Results: mRNA expression levels in peripheral blood leukocytes in patients with AMI were 1.57 times higher than those in patients with stable coronary artery disease. Protein RORA levels in peripheral blood of patients with AMI were increased. Binary logistic regression analysis showed that high expression of was an independent risk factor for AMI, and it increased the risk of AMI by 2.990 times.

Conclusion: expression levels in patients with AMI is significantly higher than that in patients with stable coronary artery disease. High expression of is related to AMI and it may be an independent risk factor for AMI.
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http://dx.doi.org/10.1177/03000605211019663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191083PMC
June 2021

A review of nanoparticle drug delivery systems responsive to endogenous breast cancer microenvironment.

Eur J Pharm Biopharm 2021 Sep 8;166:30-43. Epub 2021 Jun 8.

College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Key Lab of Traditional Chinese Medicine Information Technology, Jinan University, Guangzhou 510632, PR China; Cancer Research Institute, Jinan University, Guangzhou 510632, PR China. Electronic address:

Breast cancer, as a malignant disease that seriously threatens women's health, urgently needs to be researched to develop effective and safe therapeutic drugs. Nanoparticle drug delivery systems (NDDS), provide a powerful means for drug targeting to the breast cancer, enhancing the bioavailability and reducing the adverse effects of anticancer drug. However, the breast cancer microenvironment together with heterogeneity of cancer, impedes the tumor targeting effect of NDDS. Breast cancer microenvironment, exerts endogenous stimuli, such as hypoxia, acidosis, and aberrant protease expression, shape a natural shelter for tumor growth, invasion and migration. On the basis of the ubiquitous of endogenous stimuli in the breast cancer microenvironment, researchers exploited them to design the stimuli-responsive NDDS, which response to endogenous stimulus, targeted release drug in breast cancer microenvironment. In this review, we highlighted the effect of the breast cancer microenvironment, summarized innovative NDDS responsive to the internal stimuli in the tumor microenvironment, including the material, the targeting groups, the loading drugs, targeting position and the function of stimuli-responsive nanoparticle drug delivery system. The limitations and potential applications of the stimuli-responsive nanoparticle drug delivery systems for breast cancer treatment were discussed to further the application.
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http://dx.doi.org/10.1016/j.ejpb.2021.05.029DOI Listing
September 2021

Screening of metabolites in the treatment of liver cancer xenografts HepG2/ADR by psoralen-loaded lipid nanoparticles.

Eur J Pharm Biopharm 2021 Aug 29;165:337-344. Epub 2021 May 29.

College of Pharmacy, Jinan University, Guangzhou, Guangdong 510632, PR China; Cancer Institute of Jinan University, Guangzhou, Guangdong 510632, PR China; Guangdong Key Lab of Traditional Chinese Medicine Information Technology, Jinan University, Guangzhou 510632, PR China. Electronic address:

Objective: Our study aimed to find potential biomarkers for drug resistance in liver cancer cells using metabolomics and further to evaluate the potential of psoralen-loaded polymer lipid nanoparticles (PSO-PLNs) to reverse the resistance of cells to doxorubicin.

Methods: We used LC-MS-based non-targeted metabolomics, also known as global metabolite profiling, to screen in serum and urine of mice engrafted with a liver cancer cell line sensitive (HepG2/S) or resistant to doxorubicin (HepG2/ADR) for differentially regulated metabolites. We subsequently quantified the abundance of these metabolites in serum and the urine of mice. The mice were engrafted with HepG2 cells resistant against doxorubicin and were treated with I) doxorubicin, II) a combination of doxorubicin and psoralen and III) a combination of doxorubicin and psoralen packed in polymer lipid nanoparticles.

Results: Metabolites found to be differentially present in urine of mice engrafted with resistant HepG2 cells were: hippuric acid, hyaluronic acid, pantothenic acid, and betaine; retinoic acid and α-linolenic acid were found to be reduced in serum samples of mice with HepG2 cells resistant to doxorubicin. The targeted analysis showed that the degree of regression of metabolic markers in groups differed: treatment group 2 had stronger degree of regression than treatment group 1 and the negative control group had the smallest, which indicates that the PSO-PLNs have superior properties compared with other treatments.

Conclusion: Psoralen reverses drug resistance of liver cancer cells and its efficacy can be increased by encapsulation in polymer lipid nanoparticles.
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http://dx.doi.org/10.1016/j.ejpb.2021.05.025DOI Listing
August 2021

Expression and purification of functional recombinant CUL2•RBX1 from E. coli.

Sci Rep 2021 May 27;11(1):11224. Epub 2021 May 27.

Department of Biochemistry, Purdue University, West Lafayette, IN, USA.

Cullin-2 (CUL2) based cullin-RING ligases (CRL2s) comprise a family of ubiquitin E3 ligases that exist only in multi-cellular organisms and are crucial for cellular processes such as embryogenesis and viral pathogenesis. CUL2 is the scaffold protein that binds one of the interchangeable substrate receptor modules, which consists of adaptor proteins and the substrate receptor protein. The VHL protein is a substrate receptor known to target hypoxia-inducible factor α (HIF1α) for ubiquitination and degradation. Because of its critical role in the ubiquitination of important cellular factors such as HIF1α, CRL2s have been investigated for their biological functions and the development of novel therapeutics against diseases. Given the importance of CRL2s in biological and biomedical research, methods that efficiently produce functional CUL2 proteins will greatly facilitate studies on the mechanism and regulation of CRL2s. Here, we report two cost-effective systems for the expression and purification of recombinant human CUL2 from E. coli cells. The purified CUL2 proteins were ~ 95% pure, could bind their substrate receptor modules, and were enzymatically active in transferring ubiquitin or ubiquitin-like protein to the corresponding substrate in in vitro assays. The presented methodological advancements will help advance research in CRL2 function and regulation.
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http://dx.doi.org/10.1038/s41598-021-90770-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160325PMC
May 2021

Multiplexed detection of bacterial pathogens based on a cocktail of dual-modified phages.

Anal Chim Acta 2021 Jun 1;1166:338596. Epub 2021 May 1.

Department of Chemical Biology, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Key Laboratory for Chemical Biology of Fujian Province, Collaborative Innovation Center of Chemistry for Energy Materials, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, People's Republic of China. Electronic address:

Rapid, quantitative, and sensitive assays for the multiplexed detection of bacterial pathogens are urgently needed for public health. Here, we report the generation of dual-modified phage sensors for the simultaneous detection of multiple pathogenic bacteria. The M13KE phage was dual modified to display the targeting peptide on the minor coat protein pIII (∼5 copies) and the streptavidin-binding (StrB) peptide on the major coat protein pVIII (∼2700 copies). The targeting peptide specifically recognizes the target bacteria, and the StrB peptide acts as the efficient signal amplification and transduction unit upon binding with fluorescently tagged streptavidin. The bright fluorescence emitted from individual target bacteria can be clearly distinguished from the background via both the flow cytometry and fluorescence microscopy. Three different dual-modified phages targeting E. coli O157:H7, Salmonella Typhimurium, and Pseudomonas aeruginosa were constructed, and high specificity was verified via a large excess of other non-target bacteria. Using a 40 mL sample volume, the target bacteria detection limit was approximately 10 cells/mL via flow cytometry measurement in the presence of other non-target bacteria. By combining these three dual-modified phages into a cocktail, simultaneous detection and quantification of three target bacterial pathogens was demonstrated with good linearity. The strategy of constructing dual-modified phage represents a promising tool in the detection of bacterial pathogens.
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http://dx.doi.org/10.1016/j.aca.2021.338596DOI Listing
June 2021

Personalized Prechemotherapy Education Reduces Peri-Chemotherapy Anxiety in Colorectal Cancer Patients.

Dis Markers 2021 18;2021:6662938. Epub 2021 Mar 18.

Department of Oncology, 2nd Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Rd, Harbin 150086, China.

Objective: To evaluate the effect of personalized prechemotherapy education in the reduction of peri-chemotherapy anxiety in patients with colorectal cancer.

Methods: Patients admitted to the Department of Oncology with a diagnosis of stage III or IV colorectal cancer and scheduled for initial chemotherapy from January 1, 2017, to June 30, 2019, were retrieved. Patients in the educated group completed the GAD-7 form to evaluate their anxiety level at admission and 14 days after personalized prechemotherapy education, the educator team of which included both physician and nurse staff. Patients in the control group only completed GAD-7 forms at admission and 14 days thereafter without personalized education.

Results: Three hundred and sixty-four patients were enrolled for analysis, including 127 patients who received personalized prechemotherapy education and 237 patients who did not receive education. There were no significant differences in age, gender, education level, or pretreatment GAD-7 scores between the two groups, but significantly lower posttreatment GAD-7 score, and fewer medium to severe posttreatment anxiety patients in the educated group.

Conclusion: Personalized prechemotherapy education involving physician for medical treatment and nursing staff for peri-treatment care, in contrast to traditional brief discussion with physicians during clinic visits and unified informed consent before treatments, may reduce peri-chemotherapy anxiety more efficiently.
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http://dx.doi.org/10.1155/2021/6662938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110412PMC
March 2021

Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia.

Hematology 2021 Dec;26(1):371-379

Department of Hematology, Chinese PLA General Hospital, Beijing, People's Republic of China.

Objectives: The outcome of elderly acute myeloid leukemia (AML) patients is poor, which was traditionally attributed to patient- and leukemia-related factors. However, studies about the genetic features of these elderly patients have not been integrated and the genetic mechanism of their poor outcome is less known.

Methods: Here, we used next generation sequencing (NGS) to identify the genetic features of elderly AML patients and confirmed the efficacy of chemotherapy based on molecular aberrations. Mutations in 111 genes relevant to hematological malignancy was analysed by virtue of NGS and the genetic differences were compared between elderly (n=52) and young (n=161) AML patients. Furthermore, the outcome of decitabine-based chemotherapy was identified in elderly patients.

Results: Frequencies of adverse genetic alterations, such as and secondary-type mutations (, 2 and ), were much higher in elderly patients, while the frequency of mutations was much lower. Moreover, epigenetic mutations such as , , and , were also more common in elderly patients. Furthermore, there were 39 elderly patients receiving the decitabine-based chemotherapy, and the results showed that the overall response rate (ORR) and complete remission rate (CR) were 76.9% and 71.8%, respectively. The median overall survival (OS) for those older patients was 12 months, and the 2-year OS probability was 20.5%.

Discussion: Our study provides deep understanding into the molecular mechanisms of the poor outcome of elderly AML patients.

Conclusion: Epigenetic mutations play an important role, and decitabine-based regimen can be used as alternative first-line chemotherapy for elderly patients.
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http://dx.doi.org/10.1080/16078454.2021.1921434DOI Listing
December 2021

Polymeric Lipid Hybrid Nanoparticles as a Delivery System Enhance the Antitumor Effect of Emodin in Vitro and in Vivo.

J Pharm Sci 2021 08 15;110(8):2986-2996. Epub 2021 Apr 15.

College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou 510632, China; Guangdong Key Lab of Traditional Chinese Medicine Information Technology, College of Pharmacy, Jinan University, Guangzhou 510632, China; Cancer Research Institute of Jinan University, Guangzhou 510632, China. Electronic address:

This study aimed to evaluate the therapeutic efficacy of Emodin-loaded polymer lipid hybrid nanoparticles (E-PLNs) for breast cancer. The size, Zeta potential, surface morphology, encapsulation efficiency, stability, in vitro drug release of E-PLNs prepared by the nanoprecipitation method were characterized. The uptake, in-vitro cytotoxicities and apoptosis of free drug, E-PLNs were investigated against MCF-7 cells. The efficacy of E-PLNs in tumor bearing nude mice has also been studied.The average particle size of the experimentally prepared E-PLNs was (122.7±1.79) nm, and the encapsulation rate was 72.8%. Compared with free Emodin (EMO), E-PLNs showed greater toxicity to MCF-7 cells by promoting the uptake of EMO, and can promote the early apoptosis of MCF-7 cells. In addition to the morphological changes of apoptotic cells, the ratio of Bax/Bcl-2 was significantly increased, which indicated that E-PLNs can induce apoptosis in MCF-7 cells to achieve anticancer effect. Finally, E-PLNs significantly inhibited tumor growth by more than 60%, which may be related to its passive targeting effect on tumor site. Our results suggest that E-PLNs have shown good anti-breast cancer effect than free EMO. Moreover, the effect of E-PLNs on MCF-7 cells is mainly related to the induction of apoptosis.
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http://dx.doi.org/10.1016/j.xphs.2021.04.006DOI Listing
August 2021

Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial.

EClinicalMedicine 2021 Feb 28;32:100732. Epub 2021 Jan 28.

Head Trauma Center, Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University/School of Medicine, Shanghai Institute of Head Trauma, Shanghai, China.

Background: Therapeutic hypothermia may need prolonged duration for the patients with severe traumatic brain injury (sTBI).

Methods: The Long-Term Hypothermia trial was a prospective, multicenter, randomized, controlled clinical trial to examine the safety and efficacy in adults with sTBI. Eligible patients were 18-65, Glasgow Coma Scale score at 4 to 8, and initial intracranial pressure (ICP) ≥ 25 mm Hg, randomly assigned to the long-term mild hypothermia group (34-35 °C for 5 days) or normothermia group at 37 °C. The primary outcome was the Glasgow outcome scale (GOS) at 6 months. Secondary outcomes included ICP control, complications and laboratory findings, the length of ICU and hospital stay, and GOS at 6 months in patients with initial ICP ≥ 30 mm Hg. This trial is registered with ClinicalTrials.gov, NCT01886222.

Findings: 302 patients were enrolled from June 25, 2013, to December 31, 2018, with 6 months follow-up in 14 hospitals, 156 in hypothermia group and 146 in normothermia group. There was no difference in favorable outcome (OR 1·55, 95%CI 0·91-2·64;  = 0·105) and in mortality ( = 0·111) between groups. In patients with an initial ICP ≥ 30 mm Hg, hypothermic treatment significantly increased favorable outcome over normothermia group (60·82%, 42·71%, respectively; OR 1·861, 95%CI 1·031-3·361;  = 0·039). Long-term mild hypothermia did not increase the incidences of complications.

Interpretation: Long-term mild hypothermia did not improve the neurological outcomes. However, it may be a potential option in sTBI patients with initial ICP ≥ 30 mm Hg.

Funding: : Shanghai municipal government and Shanghai Jiao Tong University/School of Medicine.
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http://dx.doi.org/10.1016/j.eclinm.2021.100732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910713PMC
February 2021

Author Correction: CTCF interacts with the lytic HSV-1 genome to promote viral transcription.

Sci Rep 2021 Feb 25;11(1):5039. Epub 2021 Feb 25.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Kunming, 650223, China.

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http://dx.doi.org/10.1038/s41598-021-84469-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907186PMC
February 2021

Multimodal Image Analysis of Sexual Dimorphism in Developing Childhood Brain.

Brain Topogr 2021 05 25;34(3):257-268. Epub 2021 Feb 25.

Department of Instrument Science and Engineering, School of EIEE, Shanghai Jiao Tong University, Shanghai, 200240, China.

It is well known that there exist great differences in human brain anatomy and functions between males and females. With the development of noninvasive neuroimaging techniques, the sex differences in adult human brain have been well studied in some researches. However, the sexual dimorphism of human brain anatomy and functions has not been sufficiently described during the developmental period of early childhood brain when the sex differences emerge in behavior. This study was to identify specific patterns of the sexual dimorphism in developing brain structure of early childhood using multimodal brain image analysis. We have performed a multivariate and data-driven analysis by combining multiple neuroimaging technologies including the 3D T1-weighted structural MR images (sMRI) and diffusion tensor imaging (DTI) in a prospective cohort of 188 children (128 males and 60 females) between the ages of 0 and 15. First, the brain images were segmented into 90 regions of interest (ROIs) based on the AAL template to extract the ROI volume and connectivity features. Then, the individual multimodal imaging biomarkers were identified associated with the sex differences. Finally, the selected features from multi-modality neuroimages were combined using multi-kernel support vector machine for classifications of male or female. The method achieved sex classification accuracy 72% for the children between the ages of 0 and 15. And the volumes of right precuneus and right postcentral were more related to sexual dimorphism of developing brain structure than those of other regions in sMRI (p < 0.002). In DTI, the connections between right middle occipital gyrus and right inferior occipital gyrus, between left superior marginal gyrus and left middle temporal gyrus, and between right triangle inferior frontal gyrus and right putamen are also more relevant to the sexual dimorphism than others (p < 0.005). The brain regions and connections related to the sexual differences were identified with sMRI and DTI in early developing brain structure by using the multimodal image analysis. And these sexually dimorphic patterns of brain may be related to the observed sex differences in developing childhood brain structure and connectivity.
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http://dx.doi.org/10.1007/s10548-021-00823-7DOI Listing
May 2021

Intraductal papillary neoplasm of intrahepatic bile ducts complicated by chronic disseminated intravascular coagulation and thrombosis: A case report.

Medicine (Baltimore) 2021 Feb;100(5):e24454

Center of Hepatopancreatobiliary Diseases.

Rationale: Intraductal papillary neoplasm of the bile ducts (IPNB) is a relatively rare tumor that is clinically characterized by digestive symptoms. The concurrent occurrence of chronic disseminated intravascular coagulation (DIC) with thrombosis is an extremely rare combination, reported in patients with IPNB. The clinical features of chronic DIC include microangiopathic hemolytic anemia, thrombocytopenia, and hypofibrinogenemia. Here, we report the case of a mucin-producing IPNB patient with hematological abnormalities.

Patient Concerns: A 58-year-old male patient suffered from abdominal distension for more than 2 months with obstructive jaundice appearance. Abdominal contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography showed a neoplasm in the right hepatic lobe. Multiple intravascular fillings were found in the inferior vena cava, pulmonary artery, and right atrium. Anemia and hypofibrinogenemia were discovered through routine laboratory tests. The count of platelets began to decline 25 days after admission, while 1 month after hospitalization, the patient developed abdominal pain, fever, and shock.

Diagnosis: Pathological examination demonstrated IPNB with a part of high-grade intraepithelial neoplasia. Cardiac and inferior vena cava emboli were diagnosed as thrombi without neoplastic cells. Immunohistochemically, tumor cells were positive for Vimentin (mesenchyme), CK7, CK19, MUC-1, MUC-5AC, MUC-6, S-100p (focal), Ki-67 (12%), and negative for Inhibin-α, ER, CK20, CEA, and MUC-2. Additionally, immunohistochemistry indicated that IPNB was a mucus-secretion gastric type. The laboratory tests confirmed the presence of chronic DIC.

Interventions: The patient was given anticoagulant therapy before hepatectomy and right atrium thrombectomy was performed under cardiopulmonary bypass.

Outcomes: After anticoagulant therapy, the levels of hemoglobin, platelet, and fibrinogen of the patient returned to normal. Hepatectomy and thrombus removal was successfully performed. Then, the patient was discharged 12 days after the operation. After 12 months of follow-up, the patient recovered well without any hematologic abnormalities and no signs of tumor recurrence were observed.

Lessons: IPNB may cause hematological complications, which can be easily misdiagnosed. It is essential to pay particular attention to the hematological abnormalities of patients with IPNB. Early detection and differential diagnosis of chronic DIC and thrombosis are necessary. We note that anticoagulant therapy coupled with surgery is an effective strategy to treat these complications.
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http://dx.doi.org/10.1097/MD.0000000000024454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870212PMC
February 2021

Ultrafast fluorescent probe with near-infrared analytical wavelength for fluoride ion detection in real samples.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 2;252:119518. Epub 2021 Feb 2.

Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, PR China; College of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001, PR China; Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, PR China. Electronic address:

The first ultrafast fluorescence probe with response time in seconds (10 s) for fluoride ions (F) has been proposed by conjugating dimethylthiophosphoryl group as a recognition unit with the near-infrared fluorophore of hemicyanine. The response mechanism is the F-induced cleavage of the dimethylthiophosphoryl group, along with the liberation of the fluorophore, which results in a distinctly enhanced fluorescence intensity at 730 nm (λ = 680 nm). The fluorescence enhancement of the probe is directly proportional to the F concentration in the range of 10-300 µM with the detection limit of 4.28 µM. The probe has been successfully used to determine F concentration in real water and toothpaste samples as well as image F in living cells. The simplicity and quick response of this probe endow it with the ability of detecting F rapidly in real samples.
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http://dx.doi.org/10.1016/j.saa.2021.119518DOI Listing
May 2021

The impact of palliative care education and training program on the resident physicians.

Ann Palliat Med 2021 Mar 7;10(3):2758-2765. Epub 2021 Feb 7.

Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China.

Background: Due to the advancements in medicine coupled with the aging population, palliative care has become widely needed. In many countries, medical students are trained in palliative care in their postgraduate courses. However, palliative care education is not available as an independent course or standardized training for residents in China.

Methods: This parallel randomized controlled trial was conducted in the Department of Internal Medicine, Beijing Chao-yang Hospital, Capital Medical University, between June 2016 and August 2017. The aim of the study was to explore the impact of the palliative care education and training program on 72 residents who were trained in standardization and were randomly divided into experimental and control groups at the ratio 1:1. The experimental group received resident physician standardized training and palliative care training program, while the control group received only standardized training. Standardized training included training in humanistic medical skills. The two groups were tested after training. A questionnaire survey was carried out to analyze the effect of palliative care education in humanistic medical skills.

Results: The total score of humanistic medical skills assessment of residents in the experimental group was higher compared to the control group (82.92±8.39 vs. 77.36±7.41, t =2.978, P=0.004). The experimental group performed better in terms of medical skills and the ability to care for dying patients.

Conclusions: Palliative care education and training program should be required for residents as it is very useful. The purpose of palliative care education is to translate the knowledge in practice, truly implement the idea of palliative care, and relieve patients of terminal discomfort. The educational promotion of palliative care is of great value in China.
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http://dx.doi.org/10.21037/apm-20-1625DOI Listing
March 2021

Role of microRNA-335 carried by bone marrow mesenchymal stem cells-derived extracellular vesicles in bone fracture recovery.

Cell Death Dis 2021 02 4;12(2):156. Epub 2021 Feb 4.

Department of Orthopaedics, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

Mesenchymal stem cells (MSCs) have the potential to reduce healing time and treat nonunion in fracture patients. In this study, bone marrow MSCs-derived extracellular vesicles (B-EVs) were firstly extracted and identified. CD9 and normal mice were enrolled for the establishment of fracture models and then injected with B-EVs. Osteoblast differentiation and fracture recovery were estimated. The levels of osteoblast-related genes were detected, and differentially expressed microRNAs (miRs) in B-EVs-treated normal fracture mice were screened and verified. The downstream mechanisms of miR were predicted and assessed. The loss-of functions of miR-335 in B-EV and gain-of-functions of VapB were performed in animal and cell experiments to evaluate their roles in bone fracture. Collectively, B-EVs promoted bone fracture recovery and osteoblast differentiation by releasing miR-335. miR-335 downregulation in B-EVs impaired B-EV functions in fracture recovery and osteoblast differentiation. miR-335 could target VapB, and VapB overexpression reversed the effects of B-EVs on osteoblast differentiation. B-EV treatment activated the Wnt/β-catenin pathway in fracture mice and osteoblasts-like cells. Taken together, the study suggested that B-EVs carry miR-335 to promote bone fracture recovery via VapB and the Wnt/β-catenin pathway. This study may offer insights into bone fracture treatment.
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http://dx.doi.org/10.1038/s41419-021-03430-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862274PMC
February 2021

Cohesin promotes HSV-1 lytic transcription by facilitating the binding of RNA Pol II on viral genes.

Virol J 2021 01 23;18(1):26. Epub 2021 Jan 23.

Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Healthy Aging Research of Yunnan Province, Kunming Institute of Zoology, Kunming, 650223, Yunnan, China.

Background: Herpes Simplex Virus type I (HSV-1) is a large double-stranded DNA virus that enters productive infection in epithelial cells and reorganizes the host nucleus. Cohesin, a major constituent of interphase and mitotic chromosomes comprised of SMC1, SMC3, and SCC1 (Mcd1/Rad21), SCC3 (SA1/SA2), have diverse functions, including sister chromatid cohesion, DNA double-stranded breaks repair, and transcriptional control. Little is known about the role of cohesin in HSV-1 lytic infection.

Methods: We measured the effect on HSV-1 transcription, genome copy number, and viral titer by depleting cohesin components SMC1 or Rad21 using RNAi, followed by immunofluorescence, qPCR, and ChIP experiments to gain insight into cohesin's function in HSV-1 transcription and replication.

Results: Here, we report that cohesion subunits SMC1 and Rad21 are recruited to the lytic HSV-1 replication compartment. The knockdown results in decreased viral transcription, protein expression, and maturation of viral replication compartments. SMC1 and Rad21 knockdown leads to the reduced overall RNA pol II occupancy level but increased RNA pol II ser5 phosphorylation binding on viral genes. Consistent with this, the knockdown increased H3K27me3 modification on these genes.

Conclusions: These results suggest that cohesin facilitates HSV-1 lytic transcription by promoting RNA Pol II transcription activity and preventing chromatin's silencing on the viral genome.
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http://dx.doi.org/10.1186/s12985-021-01495-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825184PMC
January 2021

Personalized Preoperative Education Reduces Perioperative Anxiety in Old Men with Benign Prostatic Hyperplasia: A Retrospective Cohort Study.

Gerontology 2021 15;67(2):177-183. Epub 2021 Jan 15.

Department of Urology, 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.

Introduction: Psychological health is important to old patients with benign prostatic hyperplasia (BPH) after prostatic surgery. In this retrospective cohort study, we evaluated the effect of personalized preoperative education in the reduction of perioperative anxiety in old BPH patients after prostatic surgery.

Methods: Senior patients (≥65 years) admitted with a diagnosis of BPH and scheduled for initial transurethral resection of the prostate from January 1, 2017 to November 30, 2019 were retrieved. Patients in the preoperatively educated group completed the Chinese version of generalized anxiety disorder 7-item scale (GAD-7) form to evaluate their anxiety level at admission and 14 days clinical visits after individual preoperative education. Patients in the control group completed GAD-7 forms but did not receive personalized preoperative education. Patients in both groups discussed their disease with physicians during clinic visits and after admission, and were given an informed consent about their treatment plans.

Results: Seven hundred and twenty-four patients were retrieved, including 312 patients who received preoperative education and 412 patients who did not. There were significantly lower postoperative GAD-7 score and fewer moderate to severe postoperative anxiety patients in the preoperatively educated group (p < 0.01). Patients with education above secondary education level had less perioperative anxiety.

Conclusion: Personalized education incorporated with shared valuable physiological and psychological experience and expectations dealing with BPH, in comparison to traditional uniformed patient education and informed consent before surgery, may reduce perioperative anxiety more efficiently in BPH patients. A higher educational level helps patients reduce perioperative anxiety before and after their personalized preoperative education.
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http://dx.doi.org/10.1159/000511913DOI Listing
January 2021

Role of inflammatory microenvironment: potential implications for improved breast cancer nano-targeted therapy.

Cell Mol Life Sci 2021 Mar 2;78(5):2105-2129. Epub 2021 Jan 2.

College of Pharmacy, Jinan University, Guangzhou, 510632, China.

Tumor cells, inflammatory cells and chemical factors work together to mediate complex signaling networks, which forms inflammatory tumor microenvironment (TME). The development of breast cancer is closely related to the functional activities of TME. This review introduces the origins of cancer-related chronic inflammation and the main constituents of inflammatory microenvironment. Inflammatory microenvironment plays an important role in breast cancer growth, metastasis, drug resistance and angiogenesis through multifactorial mechanisms. It is suggested that inflammatory microenvironment contributes to providing possible mechanisms of drug action and modes of drug transport for anti-cancer treatment. Nano-drug delivery system (NDDS) becomes a popular topic for optimizing the design of tumor targeting drugs. It is seen that with the development of therapeutic approaches, NDDS can be used to achieve drug-targeted delivery well across the biological barriers and into cells, resulting in superior bioavailability, drug dose reduction as well as off-target side effect elimination. This paper focuses on the review of modulation mechanisms of inflammatory microenvironment and combination with nano-targeted therapeutic strategies, providing a comprehensive basis for further research on breast cancer prevention and control.
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http://dx.doi.org/10.1007/s00018-020-03696-4DOI Listing
March 2021

LGAN: Lung segmentation in CT scans using generative adversarial network.

Comput Med Imaging Graph 2021 01 16;87:101817. Epub 2020 Nov 16.

The City University of New York, New York 10016, USA. Electronic address:

Lung segmentation in Computerized Tomography (CT) images plays an important role in various lung disease diagnosis. Most of the current lung segmentation approaches are performed through a series of procedures with manually empirical parameter adjustments in each step. Pursuing an automatic segmentation method with fewer steps, we propose a novel deep learning Generative Adversarial Network (GAN)-based lung segmentation schema, which we denote as LGAN. The proposed schema can be generalized to different kinds of neural networks for lung segmentation in CT images. We evaluated the proposed LGAN schema on datasets including Lung Image Database Consortium image collection (LIDC-IDRI) and Quantitative Imaging Network (QIN) collection with two metrics: segmentation quality and shape similarity. Also, we compared our work with current state-of-the-art methods. The experimental results demonstrated that the proposed LGAN schema can be used as a promising tool for automatic lung segmentation due to its simplified procedure as well as its improved performance and efficiency.
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http://dx.doi.org/10.1016/j.compmedimag.2020.101817DOI Listing
January 2021
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