Publications by authors named "Xing Wang"

1,578 Publications

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Androgen receptor transactivates KSHV noncoding RNA PAN to promote lytic replication-mediated oncogenesis: A mechanism of sex disparity in KS.

PLoS Pathog 2021 Sep 20;17(9):e1009947. Epub 2021 Sep 20.

Key Laboratory of Gastrointestinal Cancer (Ministry of Education), School of Basic Medical Sciences, Fujian Medical University, Fuzhou, P.R. China.

Kaposi's sarcoma-associated herpesvirus (KSHV) preferentially infects and causes Kaposi's sarcoma (KS) in male patients. However, the biological mechanisms are largely unknown. This study was novel in confirming the extensive nuclear distribution of the androgen receptor (AR) and its co-localization with viral oncoprotein of latency-associated nuclear antigen in KS lesions, indicating a transcription way of AR in KS pathogenesis. The endogenous AR was also remarkably higher in KSHV-positive B cells than in KSHV-negative cells and responded to the ligand treatment of 5α-dihydrotestosterone (DHT), the agonist of AR. Then, the anti-AR antibody-based chromatin immunoprecipitation (ChIP)-associated sequencing was used to identify the target viral genes of AR, revealing that the AR bound to multiple regions of lytic genes in the KSHV genome. The highest peak was enriched in the core promoter sequence of polyadenylated nuclear RNA (PAN), and the physical interaction was verified by ChIP-polymerase chain reaction (PCR) and the electrophoretic mobility shift assay (EMSA). Consistently, male steroid treatment significantly transactivated the promoter activity of PAN in luciferase reporter assay, consequently leading to extensive lytic gene expression and KSHV production as determined by real-time quantitative PCR, and the deletion of nuclear localization signals of AR resulted in the loss of nuclear transport and transcriptional activity in the presence of androgen and thus impaired the expression of PAN RNA. Oncogenically, this study identified that the AR was a functional prerequisite for cell invasion, especially under the context of KSHV reactivation, through hijacking the PAN as a critical effector. Taken together, a novel mechanism from male sex steroids to viral noncoding RNA was identified, which might provide a clue to understanding the male propensity in KS.
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http://dx.doi.org/10.1371/journal.ppat.1009947DOI Listing
September 2021

Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure.

Bioact Mater 2022 Feb 23;8:165-176. Epub 2021 Jun 23.

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.

A spatiotemporally dynamic therapy (SDT) is proposed as a powerful therapeutic modality that provides spatially dynamic responses of drug-carriers for adapting to the wound microenvironment. Herein, dynamic chitosan-poly (ethylene glycol) (CP) Schiff-base linkages are employed to perform SDT by directly converting a liquid drug (KFX) into a gel formation. The obtained KFX-CP drug-gel with shape-adaptive property is used to treat a representative oral mucositis (OM) model in a spatiotemporally dynamic manner. The KFX-CP drug-gel creates an instructive microenvironment to regulate signaling biomolecules and endogenous cells behavior, thereby promoting OM healing by the rule of dynamically adjusting shape to fit the irregular OM regions first, and then provides space for tissue regeneration, over KFX potion control and the general hydrogel group of CP hydrogel and KFX-F127. Most interestingly, the regenerated tissue has ordered structure like healthy tissue. Therefore, the SDT provides a new approach for the design of next generation of wound dressing and tissue engineering materials.
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http://dx.doi.org/10.1016/j.bioactmat.2021.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424390PMC
February 2022

High efficacy of tetra-PEG hydrogel sealants for sutureless dural closure.

Bioact Mater 2022 Feb 27;8:12-19. Epub 2021 Jun 27.

Department of Orthopaedics, Peking University Third Hospital, Beijing, 100191, China.

Advances in meticulous dural closure technique remain a great challenge for watertight dural closure in the aged society, because the cerebrospinal fluid (CSF) leakage after spinal surgery is often accompanied with the disgusting wound infection, meningitis and pseudomeningocele. Here, a tetra-poly (ethylene glycol) (PEG)-based hydrogel sealant is developed with collective advantages of facile operation, high safety, quick set time, easy injectability, favorable mechanical strength and powerful tissue adhesion for effective sutureless dural closure during the surgery procedure. Impressively, this tetra-PEG sealant can instantaneously adhere to the irregular tissue surfaces even in a liquid environment, and effectively prevent or block off the intraoperative CSF leakage for sutureless dural closure and dura regeneration. Together, this sutureless tetra-PEG adhesive can be utilized as a very promising alternative for high-efficient watertight dural closure of the clinical patients who incidentally or deliberately undergo the durotomy during the spinal surgery.
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http://dx.doi.org/10.1016/j.bioactmat.2021.06.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424082PMC
February 2022

Effects of physical exercise on working memory in older adults: a systematic and meta-analytic review.

Eur Rev Aging Phys Act 2021 Sep 17;18(1):18. Epub 2021 Sep 17.

School of Physical Education and Health, Shanghai Lixin University of Accounting and Finance, 2800 Wenxiang Road, Shanghai, 201620, China.

Background: This systematic and meta-analytic review aimed to investigate the effects of physical exercise on the working memory of older adults, and to identify the moderators of these effects.

Methods: We searched six electronic databases for randomized controlled trials on the effects of physical exercise on working memory that were published before or on May 15, 2020. The PEDro scale was used to evaluate the methodological quality of the included studies. Stata 14.0 software was used to perform the meta-analysis, subgroup analysis, and publication bias testing.

Results: A total of 28 studies and 2156 participants were included. The methodological quality of the included studies was fair to excellent, and there was no publication bias. Overall, we found that physical exercise had a significant effect on working memory in older adults (standardized mean difference = 0.30, p < 0.0001). The effects of physical exercise on working memory were moderated by exercise frequency, intensity, type, duration, cognitive status, and control subgroup (active/passive), but not by intervention period or age of participant.

Conclusion: Physical exercise can effectively improve the working memory of older adults. The recommended physical exercise is multi-component exercise or mind-body exercise of moderate intensity for 45-60 min 3 times a week, for more than 6 months.
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http://dx.doi.org/10.1186/s11556-021-00272-yDOI Listing
September 2021

A fluorescent probe for rapid detection of low concentration mercury ions and its application in biological cells.

Anal Methods 2021 Sep 16;13(35):3987-3993. Epub 2021 Sep 16.

Department of Pharmacy, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, 138 Xianlin Dadao, Nanjing 210023, China.

As a toxic substance, mercury can easily cause harm to organisms and humans. The development of methods that allow rapid detection of low concentrations of mercury ions has a positive effect on the natural environment and human health. The fluorescent probe RBSH reported in this paper has a detection limit as low as 5.9 nM, and a fast response time and allows naked eye detection. We characterized its structure by nuclear magnetic resonance and mass spectrometry, and explored the response mechanism of the probe using Job's plot, and H NMR and mass spectrometry. UV-vis spectrophotometry and fluorescence spectroscopy show the excellent optical properties of the probe RBSH. The low toxicity and high cell penetration capacity demonstrated by the cellular assay open up the possibility of biological experiments. By selecting hosts (natural water samples, soybean plants and zebrafish) where mercury ions are likely to be present in the biological chain for low concentration Hg detection, the results all demonstrated the excellent performance of the probe RBSH.
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http://dx.doi.org/10.1039/d1ay01109jDOI Listing
September 2021

Ultra-processed food consumption and the risk of non-alcoholic fatty liver disease in the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study.

Int J Epidemiol 2021 Sep 16. Epub 2021 Sep 16.

Nutritional Epidemiology Institute and School of Public Health, Tianjin Medical University, Tianjin, China.

Background: Growing evidence supports a link between ultra-processed food consumption and human health outcomes. However, the association between ultra-processed food consumption and non-alcoholic fatty liver disease (NAFLD) is not known. We aimed to explore the association between ultra-processed food consumption and risk of NAFLD.

Methods: The prospective study included 16 168 participants aged 18-90 years from the Tianjin Chronic Low-grade Systemic Inflammation and Health (TCLSIH) Cohort Study. Information on ultra-processed food consumption was collected at baseline using a validated food frequency questionnaire. NAFLD was defined as the presence of sonographic fatty liver in the absence of significant alcohol intake (≥210 g/week for men and ≥140 g/week for women, respectively) and other liver diseases. Multivariable Cox proportional hazards models were used to examine the association between ultra-processed food consumption and risk of NAFLD.

Results: During 56 935 person-years of follow-up, we documented 3752 incident NAFLD cases. After adjusting for age, sex, body mass index, smoking, alcohol drinking, education, occupation, income, physical activity, total energy intake, personal and family history of disease and overall diet quality, the multivariable hazard ratios (95% confidence interval) of NAFLD across increasing quartiles of ultra-processed food consumption were 1.00 (reference), 0.99 (0.90, 1.08), 1.13 (1.03, 1.25) and 1.18 (1.07, 1.30), respectively (P for trend <0.0001). The hazard ratio (95% confidence interval) per one standard deviation increase in ultra-processed food consumption, equivalent to a 62.7 g/1000 kcal per day, was 1.06 (1.03, 1.09), P = 0.0001.

Conclusions: Our study indicates that higher ultra-processed food consumption is associated with a higher risk of NAFLD. This finding suggests that ultra-processed food, which is widely consumed worldwide, might be a modifiable dietary target to reduce the risk of NAFLD.
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http://dx.doi.org/10.1093/ije/dyab174DOI Listing
September 2021

Activation of β3-adrenoceptor increases the number of readily releasable glutamatergic vesicle via activating Ca/calmodulin/MLCK/myosin II pathway in the prefrontal cortex of juvenile rats.

Sci Rep 2021 Sep 15;11(1):18300. Epub 2021 Sep 15.

School of Life Science, Nanchang University, Nanchang, 330031, China.

It is well known that β3-adrenoceptor (β3-AR) in many brain structures including prefrontal cortex (PFC) is involved in stress-related behavioral changes. SR58611A, a brain-penetrant β3-AR subtypes agonist, is revealed to exhibit anxiolytic- and antidepressant-like effects. Whereas activation of β3-AR exerts beneficial effects on cognitive function, the underlying cellular and molecular mechanisms have not been fully determined. In this study, whole cell patch-clamp recordings were employed to investigate the glutamatergic transmission of layer V/VI pyramidal cells in slices of the rat PFC. Our result demonstrated that SR58611A increased AMPA receptor-mediated excitatory postsynaptic currents (AMPAR-EPSCs) through activating pre-synaptic β3-AR. SR58611A enhanced the miniature EPSCs (mEPSCs) and reduced paired-pulse ratio (PPR) of AMPAR-EPSCs suggesting that SR58611A augments pre-synaptic glutamate release. SR58611A increased the number of readily releasable vesicle (N) and release probability (Pr) with no effects on the rate of recovery from vesicle depletion. Influx of Ca through L-type Ca channel contributed to SR58611A-mediated enhancement of glutamatergic transmission. We also found that calmodulin, myosin light chain kinase (MLCK) and myosin II were involved in SR58611A-mediated augmentation of glutamate release. Our current data suggest that SR58611A enhances glutamate release by the Ca/calmodulin/MLCK/myosin II pathway.
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http://dx.doi.org/10.1038/s41598-021-97769-4DOI Listing
September 2021

Identification of metabolism-associated molecular subtype in ovarian cancer.

J Cell Mol Med 2021 Sep 15. Epub 2021 Sep 15.

Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Ovarian cancer (OC) is the most lethal gynaecological cancer with genomic complexity and extensive heterogeneity. This study aimed to characterize the molecular features of OC based on the gene expression profile of 2752 previously characterized metabolism-relevant genes and provide new strategies to improve the clinical status of patients with OC. Finally, three molecular subtypes (C1, C2 and C3) were identified. The C2 subtype displayed the worst prognosis, upregulated immune-cell infiltration status and expression level of immune checkpoint genes, lower burden of copy number gains and losses and suboptimal response to targeted drug bevacizumab. The C1 subtype showed downregulated immune-cell infiltration status and expression level of immune checkpoint genes, the lowest incidence of BRCA mutation and optimal response to targeted drug bevacizumab. The C3 subtype had an intermediate immune status, the highest incidence of BRCA mutation and a secondary optimal response to bevacizumab. Gene signatures of C1 and C2 subtypes with an opposite expression level were mainly enriched in proteolysis and immune-related biological process. The C3 subtype was mainly enriched in the T cell-related biological process. The prognostic and immune status of subtypes were validated in the Gene Expression Omnibus (GEO) dataset, which was predicted with a 45-gene classifier. These findings might improve the understanding of the diversity and therapeutic strategies for OC.
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http://dx.doi.org/10.1111/jcmm.16907DOI Listing
September 2021

Maritimibacter alexandrii sp. nov., a New Member of Rhodobacteraceae Isolated from Marine Phycosphere.

Curr Microbiol 2021 Sep 14. Epub 2021 Sep 14.

Department of Marine Chemistry, College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan, China.

Marine phycosphere hosts cross-kingdom algae-bacteria interactions playing a variety of crucial roles in aquatic ecosystems especially for the prevention and control of harmful algal blooms (HABs). During the investigation of structural composition of phycosphere microbiota (PM) of diverse marine HAB dinoflagellates, a Gram-negative, strictly aerobic, non-motile and rod-shaped bacterium designated LZ-17 was isolated from the phycosphere of highly toxic Alexandrium catenella LZT09. The 16S rRNA gene sequence analysis and the multilocus sequence analysis (MLSA) based on five protein-coding housekeeping genes (atpD, gyrB, mutL, topA and rpoD) indicated that strain LZ-17 was affiliated to the genus Maritimibacter within the family Rhodobacteraceae, and closely related to Maritimibacter alkaliphilus HTCC2654 (99.1%), 'Maritimibacter harenae' DP07 (97.9%) and M. lacisalsi X12M-4 (95.7%). The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain LZ-17 and the type strain of M. alkaliphilus were 96.9% and 74.7%. However, strain LZ-17 could be clearly distinguished from its closest by the phenotypical and phenotypical characteristics. Strain LZ-17 contained Q-10 as its major isoprenoid quinone, and summed feature 8 (C ω7c and/or C ω6c), C and C 2-OH as the predominant fatty acids (>10%). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylcholine. The DNA G + C content was 64.3 mol%. Based on the polyphasic taxonomic characterization, strain LZ-17 represents a novel species of the genus Maritimibacter, for which the name Maritimibacter alexandrii sp. nov. is proposed, with the type strain LZ-17 (=CCTCC 2019005 = KCTC 72193).
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http://dx.doi.org/10.1007/s00284-021-02645-zDOI Listing
September 2021

Effects of Smoking on Short-Term and Long-Term Mortality after Aneurysmal Subarachnoid Hemorrhage.

Cerebrovasc Dis 2021 Sep 9:1-11. Epub 2021 Sep 9.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Objective: The relationship between smoking and clinical outcomes after aneurysmal subarachnoid hemorrhage (aSAH) is poorly clarified, and current pieces of evidence are inconsistent. The purpose of this multicenter cohort study is therefore to explore the relationship between smoking and mortality as well as several complications after aSAH.

Methods: Databases of patient records were from 4 tertiary hospitals. We assessed the impact of tobacco use and tobacco dose (categorized based on smoking index [SI]) on several complication and overall outcome variables. The primary outcome was mortality within the longest follow-up. Logistic models were used to investigate univariate and multivariate relationships between predictors and outcomes. We also developed a propensity score matching for smoking status by using all known confounders.

Results: A total of 6,578 patients with aSAH were analyzed. Current smoking and former smoking did not show association with mortality within the longest follow-up (odds ratio [OR], 0.95, 95% confidence interval [CI]: 0.69-1.30, p = 0.726; OR, 0.66, 95% CI: 0.38-1.15, p = 0.139, respectively). In addition, patients who were current smokers showed an independent association with the decreased occurrence of hydrocephalus (OR, 0.60; 95% CI: 0.41-0.88; p = 0.009) after matching all known confounders. We also found moderate smoking (SI between 384 and 625) was associated with reduced mortality in hospital.

Conclusions: Our results indicated that in patients with aSAH, current smoking or former smoking was not associated with all-cause mortality up to 7-year follow-up.
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http://dx.doi.org/10.1159/000518730DOI Listing
September 2021

Comparison of efficacy and safety of four surgical approaches for acute appendicitis in children: A systematic review and network meta-analysis of randomized clinical trials.

Asian J Surg 2021 Sep 9. Epub 2021 Sep 9.

Department of Pediatric Surgery, The First Clinical Medical College of Lanzhou University, The First Hospital of Lanzhou University, Lanzhou, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2021.08.009DOI Listing
September 2021

The Synergistic Anti-Tumor Activity of EZH2 Inhibitor SHR2554 and HDAC Inhibitor Chidamide through ORC1 Reduction of DNA Replication Process in Diffuse Large B Cell Lymphoma.

Cancers (Basel) 2021 Aug 24;13(17). Epub 2021 Aug 24.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing 100142, China.

Background: Upregulation of H3K27me3 induced by EZH2 overexpression or somatic heterozygous mutations were implicated in lymphomagenesis. It has been demonstrated that several EZH2-target agents have notable therapeutic effects in EZH2-mutant B-cell lymphoma patients. Here we present a novel highly selective EZH2 inhibitor SHR2554 and possible combination strategy in diffuse large B-cell lymphoma (DLBCL).

Methods: Cell proliferation, cell cycle and apoptosis were analyzed by CellTiter-Glo Luminescent Cell Viability Assay and flow cytometry. Western Blot was used to detect the expression of related proteins. The gene expression profiling post combination treatment was analyzed by RNA-Seq. Finally, CDX and PDX models were used to evaluate the synergistic anti-tumor effects of the combination treatment in vivo.

Results: The novel EZH2 inhibitor SHR2554 inhibited proliferation and induced G1 phase arrest in EZH2-mutant DLBCL cell lines. The combination of EZH2 inhibitor SHR2554 with histone deacetylase (HDAC) inhibitor chidamide (hereafter referred to as HBI8000) exerted synergistic anti-proliferative activity in vitro and in vivo. Gene expression profile analysis revealed dramatic inhibition of the DNA replication process in combined treatment.

Conclusions: SHR2554, a potent, highly selective small molecule inhibitor of EZH2, inhibited EZH2-mutant DLBCL more significantly in vitro and in vivo. The combination of HDAC inhibitor HBI8000 with EZH2 inhibitor SHR2554 exhibited dramatic anti-tumor activity in both mutant and wild-type DLBCL, which may become a potential therapeutic modality for the treatment of DLBCL patients.
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http://dx.doi.org/10.3390/cancers13174249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428225PMC
August 2021

BHBA regulates the expressions of lipid synthesis and oxidation genes in sheep hepatocytes through the AMPK pathway.

Res Vet Sci 2021 Aug 30;140:153-163. Epub 2021 Aug 30.

College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071001, China. Electronic address:

Pregnancy toxemia (PT) is the most frequent metabolic disease of sheep during late pregnancy, which can lead to enormous economic losses in sheep farm industry. However, the underlying mechanism of PT in sheep has not been fully elucidated. High levels of β-hydroxy butyric acid (BHBA) exist in PT sheep. The AMP-activated protein kinase (AMPK) pathway plays a major role in regulating liver function. The aim of this study was to explore the effects of gradient concentrations of BHBA on lipid metabolism of sheep hepatocytes and the underlying molecular mechanism in vitro. The results showed that 0.6, 1.2 mmol/L BHBA could activate AMPKα, promoted the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and its target genes, and inhibited the expressions of sterol regulatory element binding protein-1c (SREBP-1c) as well as its downstream genes. When the concentration of BHBA was beyond 1.2 mmol/L, the expressions of the above-mentioned proteins and genes were just the opposite. However, the expressions of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) did not change significantly. The levels of very low density lipoprotein (VLDL), triglyceride (TG) and cholesterol (T-CHOL) showed a gradually increasing trend with the increase of BHBA concentration. According to the results above, it demonstrates that high levels of BHBA can inhibit the expression of the AMPK pathway and cause lipid metabolism disorders in sheep hepatocytes, which may lead to the occurrence of PT.
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http://dx.doi.org/10.1016/j.rvsc.2021.08.016DOI Listing
August 2021

Optimal extent of lymphadenectomy for radical surgery of pancreatic head adenocarcinoma: 2-year survival rate results of single-center, prospective, randomized controlled study.

Medicine (Baltimore) 2021 Sep;100(35):e26918

Department of Pancreatic Surgery, West China Hospital, Sichuan University, Chengdu, China.

Background: Radical pancreaticoduodenectomy is the only possible cure for pancreatic head adenocarcinoma, and although several RCT studies have suggested the extent of lymph node dissection, this issue remains controversial. This article wanted to evaluate the survival benefit of different lymph node dissection extent for radical surgical treatment of pancreatic head adenocarcinoma.

Methods: A total of 240 patients were assessed for eligibility in the study, 212 of whom were randomly divided into standard lymphadenectomy group (SG) or extended lymphadenectomy group (EG), there were 97 patients in SG and 95 patients in EG receiving the radical pancreaticoduodenectomy.

Result: The demography, histopathology and clinical characteristics were similar between the 2 groups. The 2-year overall survival rate in the SG was higher than the EG (39.5% vs 25.3%; P = .034). The 2-year overall survival rate in the SG who received postoperative adjuvant chemotherapy was higher than the EG (60.7% vs 37.1%; P = .021). There was no significant difference in the overall incidence of complications between the 2 groups (P = .502). The overall recurrence rate in the SG and EG (70.7% vs 77.5%; P = .349), and the patterns of recurrence between 2 groups were no significant differences.

Conclusion: In multimodality therapy system, the efficacy of chemotherapy should be based on the appropriate lymphadenectomy extent, and the standard extent of lymphadenectomy is optimal for resectable pancreatic head adenocarcinoma. The postoperative slowing of peripheral blood lymphocyte recovery might be 1 of the reasons why extended lymphadenectomy did not result in survival benefits.

Clinical Trial Registration: This trial was registered at ClinicalTrials.gov (NCT02928081) in October 7, 2016. https://clinicaltrials.gov/.
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http://dx.doi.org/10.1097/MD.0000000000026918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415937PMC
September 2021

Multiparametric dual-energy CT to differentiate stage T1 nasopharyngeal carcinoma from benign hyperplasia.

Quant Imaging Med Surg 2021 Sep;11(9):4004-4015

Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China.

Background: Stage T1 nasopharyngeal carcinoma (NPC) and benign hyperplasia (BH) are 2 common causes of nasopharyngeal mucosa/submucosa thickening without specific clinical symptoms. The treatment management of these 2 entities is significantly different. Reliable differentiation between the 2 entities is critical for the treatment decision and prognosis of patients. Therefore, our study aims to explore the optimal energy level of noise-optimized virtual monoenergetic images [VMI (+)] derived from dual-energy computed tomography (DECT) to display NPC and BH and to explore the clinical value of DECT for differentiating these 2 diseases.

Methods: A total of 91 patients (44 NPC, 47 BH) were enrolled. The demarcation of the lesion margins and overall image quality, noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were evaluated for 40-80 kiloelectron volts (keV) VMIs (+) and polyenergetic images in the contrast-enhanced phase. Image features were assessed in the contrast-enhanced images with optimal visualization of NPC and BH. The demarcation of NPC and BH in iodine-water maps was also assessed. The contrast-enhanced images were used to calculate the slope of the spectral Hounsfield unit curve (λ) and normalized iodine concentration (NIC). The nonenhanced phase images were used to calculate the normalized effective atomic number (NZ). The attenuation values on 40-80 keV VMIs (+) in the contrast-enhanced phase were recorded. The diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis.

Results: The 40 keV VMI (+) in the enhanced phase yielded higher demarcation of the lesion margins scores, overall image quality scores, noise, SNR, and CNR values than 50-80 keV VMIs (+) and polyenergetic images. NPC yielded higher attenuation values on VMI (+) at 40 keV (A), NIC, λ, and NZ values than BH. The multivariate logistic regression model combining image features (tumor symmetry) with quantitative parameters (A, NIC, λ, and NZ) yielded the best performance for differentiating the 2 diseases (AUC: 0.963, sensitivity: 89.4%, specificity: 93.2%).

Conclusions: The combination of DECT-derived image features and quantitative parameters contributed to the differentiation between NPC and BH.
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http://dx.doi.org/10.21037/qims-20-1269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339654PMC
September 2021

Amide alkaloids characterization and neuroprotective properties of Piper nigrum L.: A comparative study with fruits, pericarp, stalks and leaves.

Food Chem 2021 Aug 10;368:130832. Epub 2021 Aug 10.

Beijing Key Lab of TCM Collateral Disease Theory Research, School of Traditional Chinese Medicine, Capital Medical University, 10 Youanmenwai, Xitoutiao, Beijing 100069, China. Electronic address:

Piper nigrum L. is commonly used worldwide and its pericarp, stalks, leaves will be major wastes materials. 42 amide alkaloids were identified in black, white pepper and pericarp by UHPLC-LTQ-Orbitrap HRMS method, followed by 40 constituents in stalks and 36 constituents in leaves. 8 amide alkaloids were reported for the first time in P. nigrum. An ultra-high-performance supercritical fluid chromatography (UHPSFC)-MS method was firstly applied to simultaneously determine 9 characteristic constituents (piperine, piperlonguminine, piperanine, pipercallosine, dehydropipernonaline, pipernonatine, retrofractamide B, pellitorine and guineensine). The most abundant compound in each extract was piperine with a concentration from 0.10 to 12.37 mg/g of dry weight. The fruits, pericarp and leaves extracts could improve cell viability in 6-OHDA-induced SK-N-SH and SH-SY5Y cells. The results showed the characteristics of amide alkaloids of different parts of P. nigrum and evaluated their neuroprotective activities.
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http://dx.doi.org/10.1016/j.foodchem.2021.130832DOI Listing
August 2021

C3-Arylation of indoles with aryl ketones C-C/C-H activations.

Chem Commun (Camb) 2021 Sep 2. Epub 2021 Sep 2.

Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Shanghai 201203, China.

C3-Arylation of indoles with aryl ketones is accomplished palladium-catalyzed ligand-promoted Ar-C(O) cleavage and subsequent C-H arylation of indole. Various (hetero)aryl ketones are compatible in this reaction, affording the corresponding 3-arylindoles in moderate to good yields. Further introduction of an indole moiety into the natural products desoxyestrone and evodiamine demonstrate the synthetic utility of this protocol.
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http://dx.doi.org/10.1039/d1cc03954gDOI Listing
September 2021

Barriers and facilitators to implementing measurement-based care for depression in Shanghai, China: a situational analysis.

BMC Psychiatry 2021 09 1;21(1):430. Epub 2021 Sep 1.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients.

Objective: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China.

Methods: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis.

Results: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai.

Conclusions: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.
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http://dx.doi.org/10.1186/s12888-021-03442-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411506PMC
September 2021

Multifunctional microcapsules: A theranostic agent for US/MR/PAT multi-modality imaging and synergistic chemo-photothermal osteosarcoma therapy.

Bioact Mater 2022 Jan 29;7:453-465. Epub 2021 May 29.

Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

Development of versatile theranostic agents that simultaneously integrate therapeutic and diagnostic features remains a clinical urgent. Herein, we aimed to prepare uniform PEGylated (lactic-co-glycolic acid) (PLGA) microcapsules ([email protected]([email protected]) MCs) with superparamagnetic FeO nanoparticles embedded in the shell and Prussian blue (PB) NPs inbuilt in the cavity via a premix membrane emulsification (PME) method. On account of the eligible geometry and multiple load capacity, these MCs could be used as efficient multi-modality contrast agents to simultaneously enhance the contrasts of US, MR and PAT imaging. In-built PB NPs furnished the MCs with excellent photothermal conversion property and embedded FeO NPs endowed the magnetic location for fabrication of targeted drug delivery system. Notably, after further in-situ encapsulation of antitumor drug of DOX, (PB+DOX)@([email protected]) MCs possessed more unique advantages on achieving near infrared (NIR)-responsive drug delivery and magnetic-guided chemo-photothermal synergistic osteosarcoma therapy. and studies revealed these biocompatible (PB+DOX)@([email protected]) MCs could effectively target to the tumor tissue with superior therapeutic effect against the invasion of osteosarcoma and alleviation of osteolytic lesions, which will be developed as a smart platform integrating multi-modality imaging capabilities and synergistic effect with high therapy efficacy.
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http://dx.doi.org/10.1016/j.bioactmat.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379422PMC
January 2022

Restrictive versus liberal transfusion thresholds in very low birth weight infants: A systematic review with meta-analysis.

PLoS One 2021 30;16(8):e0256810. Epub 2021 Aug 30.

Affiliated Hospital & Clinical Medical College of Chengdu University, Chengdu, Sichuan, China.

Background: To assess the efficacy and safety of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants.

Methods: We searched MEDLINE, EMBASE, and Cochrane database without any language restrictions. The last search was conducted in August 15, 2020. All randomized controlled trials comparing the use of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight (VLBW) infants were selected. Pooled risk ratio (RR) for dichotomous variable with 95% confidence intervals were assessed by a random-effects model. The primary outcome was all-cause mortality.

Results: Overall, this meta-analysis included 6 randomized controlled trials comprising 3,483 participants. Restrictive transfusion does not increase the risk of all-cause mortality (RR, 0.99; 95% CI, 0.84 to 1.17; I2 = 0%; high-quality evidence), and does not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01, 95% CI, 0.93-1.09; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume.

Conclusions: In very low birth weight infants, a restrictive threshold for red blood cell transfusion was not associated with increased risk of all-cause mortality, in either short term or long term.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256810PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405031PMC
August 2021

Microenvironment Influences on Human Umbilical Cord Mesenchymal Stem Cell-Based Bone Regeneration.

Stem Cells Int 2021 17;2021:4465022. Epub 2021 Aug 17.

Institute of Stomatology & Oral Maxilla Facial Key Laboratory, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.

The microenvironment, or niche, regulates stem cell fate and improves differentiation efficiency. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are ideal cell source for bone tissue engineering. However, the role of the microenvironments in hUC-MSC-based bone regeneration is not yet fully understood. This study is aimed at investigating the effects of the culture microenvironment (hUC-MSCs, nano-hydroxyapatite/collagen/poly (L-lactide) (nHAC/PLA), osteogenic media (OMD), and recombinant human bone morphogenetic protein-7 (rhBMP-7)) and the transplanted microenvironment (ectopic and orthotopic) on bone regeneration ability of hUC-MSCs. The isolated hUC-MSCs showed self-renewal potential and MSCs' characteristics. In the two-dimensional culture microenvironment, OMD or OMD with rhBMP-7 significantly enhanced hUC-MSCs' osteocalcin immunofluorescence staining, alkaline phosphatase, and Alizarin red staining; OMD with rhBMP-7 exhibited the highest ALP secretion and mineralized matrix formation. In the three-dimensional culture microenvironment, nHAC/PLA supported hUC-MSCs' adhesion, proliferation, and differentiation; the microenvironment containing OMD or OMD and rhBMP-7 shortened cell proliferation progression and made osteogenic differentiation progression advance; rhBMP-7 significantly attenuated the inhibiting effect of OMD on hUC-MSCs' proliferation and significantly enhanced the promoting effect of OMD on gene expression and protein secretion of osteogenic differentiation markers, calcium and phosphorous concentration, and mineralized matrix formation. The three-dimensional culture microenvironment containing OMD and rhBMP-7 induced hUC-MSCs to form the most new bones in ectopic or orthotopic microenvironment as proved by microcomputed tomography and hematoxylin and eosin staining, but bone formation in orthotopic microenvironment was significantly higher than that in ectopic microenvironment. The results indicated that the combination of hUC-MSCs+nHAC/PLA+OMD+rhBMP-7 microenvironment and orthotopic microenvironment provided a more optimized niche for bone regeneration of hUC-MSCs. This study elucidates that hUC-MSCs and their local microenvironment, or niche, play an important role in hUC-MSC-based bone regeneration. The endogenously produced BMP may serve an important regulatory role in the process.
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http://dx.doi.org/10.1155/2021/4465022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384552PMC
August 2021

Role of White Matter Hyperintensities and Related Risk Factors in Vascular Cognitive Impairment: A Review.

Biomolecules 2021 07 27;11(8). Epub 2021 Jul 27.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

White matter hyperintensities (WMHs) of presumed vascular origin are one of the imaging markers of cerebral small-vessel disease, which is prevalent in older individuals and closely associated with the occurrence and development of cognitive impairment. The heterogeneous nature of the imaging manifestations of WMHs creates difficulties for early detection and diagnosis of vascular cognitive impairment (VCI) associated with WMHs. Because the underlying pathological processes and biomarkers of WMHs and their development in cognitive impairment remain uncertain, progress in prevention and treatment is lagging. For this reason, this paper reviews the status of research on the features of WMHs related to VCI, as well as mediators associated with both WMHs and VCI, and summarizes potential treatment strategies for the prevention and intervention in WMHs associated with VCI.
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http://dx.doi.org/10.3390/biom11081102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391787PMC
July 2021

Conjugates Derived from Lapatinib Derivatives with Cancer Cell Stemness Inhibitors Effectively Reversed Drug Resistance in Triple-Negative Breast Cancer.

J Med Chem 2021 Sep 26;64(17):12877-12892. Epub 2021 Aug 26.

Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, People's Republic of China.

Increasing evidence indicates that the cancer stem cell (CSC) subpopulation contributes to the therapeutic resistance and metastasis of tumors, leading to patient recurrence and death. Herein, we designed and synthesized several compounds by conjugating lapatinib derivatives with different CSC inhibitors to treat with lapatinib-induced MDA-MB-231 drug-resistant cells. biological studies indicated that showed strong cytotoxicity and EGFR enzyme inhibitory activity and effectively reversed lapatinib-mediated resistance of MDA-MB-231 cells via inhibiting triple-negative breast cancer (TNBC) cell stemness and the AKT/ERK signaling pathway. In addition, was capable of strongly suppressing the invasion and migration of TNBC cells by inhibiting the Wnt/β-catenin signaling pathway and MMP-2 and MMP-9 protein expression. tumorigenicity tests showed that could inhibit the occurrence of TNBC by inhibiting BCSCs, proving is a potential EGFR and CSC dual inhibitor for TNBC treatment.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01013DOI Listing
September 2021

Nanocages for virus inhibition.

Nat Mater 2021 09;20(9):1176-1177

Nick Holonyak Jr. Micro and Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL, USA.

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http://dx.doi.org/10.1038/s41563-021-01088-yDOI Listing
September 2021

Discovery of natural 15-LOX small molecule inhibitors from Chinese herbal medicine using virtual Screening, biological evaluation and molecular dynamics studies.

Bioorg Chem 2021 Jul 21;115:105197. Epub 2021 Jul 21.

School of Traditional Chinese Medicine, Capital Medical University, Fengtai District, Beijing 100069, China; Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Fengtai District, Beijing 100069, China. Electronic address:

Chinese herbal medicines (CHM) are frequently used to treat different types of inflammatory diseases and 15-Lipoxygenase (15-LOX) is a critical target enzyme for treating various inflammatory diseases. In this study, natural 15-LOX inhibitors were identified in CHM using an approach of virtual screening combined with the biological assays. First, an in-house Chinese medicine database containing 360 compounds was screened using a virtual screening approach based on pharmacophore and molecular docking to uncover several novel potential 15-LOX inhibitors. Secondly, the inhibitory effect of virtual screening hits against the 15-LOX enzyme was validated in an in vitro enzyme inhibition assay. Then, a tumor necrosis factor-α (TNF-α) release assay was carried out to explore the anti-inflammatory response of the active compounds. Furthermore, molecular dynamics (MD) simulation and binding free energy calculation were applied to analyze the process of inhibitors binding and also compared the mode of binding of the inhibitors by using the Molecular Mechanics-Generalized Born Surface Area (MM/GBSA) method. Finally, licochalcone B and eriodictyol were confirmed as inhibitors of the 15-LOX enzyme with IC values of 9.67 and 18.99 μM, respectively. In vitro cell-based assay showed that licochalcone B and eriodictyol inhibited the release of TNF-α factor in RAW264.7 cells stimulated by lipopolysaccharides (LPS) in a dose-dependent manner. Molecular dynamics and binding free energy analysis showed that the two 15-LOX-ligand systems immediately attained equilibrium with almost 1 Å fluctuation, the calculated binding free energies were found around -18.89 and -12.96 kcal/mol for licochalcone B and eriodictyol, respectively. Thr412, Arg415, Val420, Thr429, Ile602 and Trp606 were the main amino acid residues for the inhibition of 15-LOX enzyme activity. The current study confirms that licochalcone B and eriodictyol are 15-LOX inhibitors and can suppress the release of the TNF-α factor in RAW264.7 cells stimulated by LPS, thus providing a basis for the follow-up research and development for 15-LOX inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2021.105197DOI Listing
July 2021

Prostaglandin Reductase 1 as a Potential Therapeutic Target for Cancer Therapy.

Front Pharmacol 2021 6;12:717730. Epub 2021 Aug 6.

Center for Novel Target and Therapeutic Intervention, Institute of Life Sciences, Chongqing Medical University, Chongqing, China.

Altered tumor metabolism is a hallmark of cancer and targeting tumor metabolism has been considered as an attractive strategy for cancer therapy. Prostaglandin Reductase 1 (PTGR1) is a rate-limiting enzyme involved in the arachidonic acid metabolism pathway and mainly responsible for the deactivation of some eicosanoids, including prostaglandins and leukotriene B4. A growing evidence suggested that PTGR1 plays a significant role in cancer and has emerged as a novel target for cancer therapeutics. In this review, we summarize the progress made in recent years toward the understanding of PTGR1 function and structure, highlight the roles of PTGR1 in cancer, and describe potential inhibitors of PTGR1. Finally, we provide some thoughts on future directions that might facilitate the PTGR1 research and therapeutics development.
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http://dx.doi.org/10.3389/fphar.2021.717730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377670PMC
August 2021

Letter to the Editor: Cemented versus uncemented hemiarthroplasty for femoral neck fractures in patients with neuromuscular diseases: a minimum of 2 years' follow-up study.

J Orthop Surg Res 2021 Aug 20;16(1):515. Epub 2021 Aug 20.

Department of Orthopaedic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Road, Wuhou district, Chengdu, 610041, Sichuan, People's Republic of China.

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http://dx.doi.org/10.1186/s13018-021-02670-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377880PMC
August 2021

Precise genome editing without exogenous donor DNA via retron editing system in human cells.

Protein Cell 2021 Aug 17. Epub 2021 Aug 17.

Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China.

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http://dx.doi.org/10.1007/s13238-021-00862-7DOI Listing
August 2021

Thymectomy with angioplasty through a thoracoscopic subxiphoid approach with double elevation of the sternum in Masaoka stage III thymoma.

JTCVS Tech 2021 Aug 10;8:208-210. Epub 2021 Apr 10.

Thoracic Surgery Department, Tongji University Affiliated Shanghai Pulmonary Hospital, Shanghai, China.

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http://dx.doi.org/10.1016/j.xjtc.2021.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350786PMC
August 2021

MicroRNA-4458 Regulates PD-L1 Expression to Enhance Anti-tumor Immunity in NSCLC via Targeting STAT3.

Mol Biotechnol 2021 Aug 12. Epub 2021 Aug 12.

Department of Oncology, The People's Hospital of Dongying, No. 317, Nanyi Road, Dongcheng District, Dongying, 257091, Shandong, China.

MicroRNA-4458 (miR-4458) has been reported to be associated with several cancers including non-small-cell lung cancer (NSCLC), while its role in tumor immunity remains unclear. The purpose of the current research was to explore the anti-tumor immunity of miR-4458 in NSCLC. The results showed that the expression level of miR-4458 decreased and STAT3 increased in NSCLC tissues and cells. For in vitro experiments, miR-4458 mimics suppressed cell proliferation and decreased the expression level of PD-L1. Moreover, STAT3 was confirmed as a target gene of miR-4458. Upregulation of STAT3 level ameliorated the inhibitive effects of miR-4458 on cells proliferation and PD-L1 expression in cells. For in vivo studies, overexpression of miR-4458 hindered tumor growth, decreased the proportion of PD-1 T cells, the expression of PD-L1 and IL-10, upregulated the proportion of CD4 T, CD8 T cells as well as the expression of IFN-γ and IL-2, which were all reversed by overexpression of STAT3, and the effects of STAT3 were counteracted after knockdown of PD-L1. MiR-4458 overexpression enhanced anti-tumor immunity via targeting STAT3 to block the PD-L1/PD-1 pathway.
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http://dx.doi.org/10.1007/s12033-021-00379-8DOI Listing
August 2021
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