Publications by authors named "Yue Hu"

861 Publications

Rare novel LPL mutations are associated with neonatal onset lipoprotein lipase (LPL) deficiency in two cases.

BMC Pediatr 2021 Sep 20;21(1):414. Epub 2021 Sep 20.

Department of Neonatology, Hunan Children's Hospital, No.86 Ziyuan Road, Changsha, 410007, China.

Background: Lipoprotein lipase (LPL) deficiency is a monogenic lipid metabolism disorder biochemically characterized by hypertriglyceridemia (HTG) inherited in an autosomal recessive manner. Neonatal onset LPL deficiency is rare. The purpose of this study was to clarify the clinical features of neonatal LPL deficiency and to analyze the genetic characteristics of LPL gene.

Methods: In order to reach a definite molecular diagnose, metabolic diseases-related genes were sequenced through gene capture and next generation sequencing. Meanwhile, the clinical characteristics and follow-up results of the two newborns were collected and analyzed.

Results: Three different mutations in the LPL gene were identified in the two newborns including a novel compound heterozygous mutation (c.347G > C and c.472 T > G) and a reported homozygous mutation (c.836 T > G) was identified. Interestingly, both the two neonatal onset LPL deficiency patients presented with suffered recurrent infection in the hyperlipidemia stage, which was not usually found in childhood or adulthood onset LPL deficiency patients.

Conclusion: The two novel mutaitons, c.347G > C and c.472 T > G, identified in this study were novel, which expanded the LPL gene mutation spectrum. In addition, suffered recurrent infection in the hyperlipidemia stage implied a certain correlation between immune deficiency and lipid metabolism abnormality. This observation further supplemented and expanded the clinical manifestations of LPL deficiency.
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http://dx.doi.org/10.1186/s12887-021-02875-xDOI Listing
September 2021

Restoring fertility in yeast hybrids: Breeding and quantitative genetics of beneficial traits.

Proc Natl Acad Sci U S A 2021 Sep;118(38)

Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, United Kingdom;

Hybrids between species can harbor a combination of beneficial traits from each parent and may exhibit hybrid vigor, more readily adapting to new harsher environments. Interspecies hybrids are also sterile and therefore an evolutionary dead end unless fertility is restored, usually via auto-polyploidisation events. In the genus, hybrids are readily found in nature and in industrial settings, where they have adapted to severe fermentative conditions. Due to their hybrid sterility, the development of new commercial yeast strains has so far been primarily conducted via selection methods rather than via further breeding. In this study, we overcame infertility by creating tetraploid intermediates of interspecies hybrids to allow continuous multigenerational breeding. We incorporated nuclear and mitochondrial genetic diversity within each parental species, allowing for quantitative genetic analysis of traits exhibited by the hybrids and for nuclear-mitochondrial interactions to be assessed. Using pooled F12 generation segregants of different hybrids with extreme phenotype distributions, we identified quantitative trait loci (QTLs) for tolerance to high and low temperatures, high sugar concentration, high ethanol concentration, and acetic acid levels. We identified QTLs that are species specific, that are shared between species, as well as hybrid specific, in which the variants do not exhibit phenotypic differences in the original parental species. Moreover, we could distinguish between mitochondria-type-dependent and -independent traits. This study tackles the complexity of the genetic interactions and traits in hybrid species, bringing hybrids into the realm of full genetic analysis of diploid species, and paves the road for the biotechnological exploitation of yeast biodiversity.
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http://dx.doi.org/10.1073/pnas.2101242118DOI Listing
September 2021

Effect of gap junction blockers on hippocampal ripple energy expression in rats with status epilepticus.

Zhongguo Dang Dai Er Ke Za Zhi 2021 Aug;23(8):848-853

Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing 400136.

Objectives: To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE).

Methods: A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX (=6 each). A rat model of SE induced by lithium-pilocarpine (PILO) was prepared. The QUIN, VPA, and CBX groups were given intraperitoneal injection of QUIN (50 mg/kg), VPA by gavage (200 mg/kg), and intraperitoneal injection of CBX (50 mg/kg) respectively, at 3 days before PILO injection. Electroencephalography was used to analyze the change in hippocampal ripple energy before and after modeling, as well as before and after chloral hydrate injection to control seizures.

Results: Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups (<0.05). The QUIN group had the highest expression level of mean ripple energy 60 minutes after PILO injection. The mean ripple energy returned to normal levels in the three intervention groups immediately after chloral hydrate injection, while in the model group, the mean ripple energy returned to normal levels 1 hour after chloral hydrate injection. The mean ripple energy remained normal till to day 3 after SE in the four groups. The changing trend of maximum ripple energy was similar to that of mean ripple energy.

Conclusions: The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.
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http://dx.doi.org/10.7499/j.issn.1008-8830.2103162DOI Listing
August 2021

Chronic cough caused by choledochoduodenal fistula: a case report.

BMC Pulm Med 2021 Sep 10;21(1):290. Epub 2021 Sep 10.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: Chronic cough is characterized by cough as the only or main symptom, with a duration of more than 8 weeks and no obvious abnormality in chest X-ray examination. Its etiology is complex, including respiratory disease, digestive system disease, circulation system disease, and psychological disease. Although a set of etiological diagnosis procedures for chronic cough have been established, it is still difficult to diagnose chronic cough and there are still some patients with misdiagnosis.

Case Presentation: We present a case of a 54-year-old female patient who had chronic cough for 28 years. Physical examination had no positive signs and she denied any illness causing cough like tuberculosis, rhinitis. Recurrent clinic visits and symptomatic treatment didn't improve the condition. Finally, gastroscopy identified the possible etiology of choledochoduodenal fistula that was proved by surgery. And after surgery, the patient's cough symptoms were significantly improved.

Conclusion: We report a rare case of chronic cough caused by choledochoduodenal fistula which demonstrates our as yet inadequate recognition of the etiology and pathogenesis. Written informed consent was obtained from the patient.
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http://dx.doi.org/10.1186/s12890-021-01658-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434707PMC
September 2021

Hierarchical N-doped CNTs grafted onto MOF-derived porous carbon nanomaterials for efficient oxygen reduction.

J Colloid Interface Sci 2021 Aug 28;606(Pt 2):1833-1841. Epub 2021 Aug 28.

School of Materials and Energy, Guangdong University of Technology, Guangzhou, PR China.

The rational design and preparation of nonprecious metal-based oxygen reduction reaction (ORR) catalysts to facilitate electron and mass transport are of great significance in oxygen-involved energy applications. Herein, a stepwise approach to synthesize a type of hierarchically porous N-doped carbon nanotubes (CNTs) grafted onto zinc-based coordination polymer derived carbon nanomaterials (M-NCNT, M = Fe/Co/Ni) is proposed. At first, an isostructural zinc-based metal-organic framework (MOF) to HKUST-1(Cu) (ZnHKUST-1) is solvothermally prepared, and then under pyrolysis to obtain MOF-derived porous carbon. After the secondary calcination, the in-situ formed N-doped CNTs are efficiently catalyzed by iron group metal-based nanoparticles (Fe/Co/Ni), which are thermally reduced by porous carbon together with additional urea. The synergistic effect between ultrahigh porosity, large surface area, suitable N-doping, high graphitization degree, and ultrafine metal particles prompts M-NCNT series to exhibit satisfactory electrocatalysis in oxygen reduction. Among them, Fe-NCNT owns the optimal ORR activity with high positive onset potential (0.987 V), half-wave potential (0.860 V) and large diffusion-limited current density (4.893 mA cm). Meanwhile, it shows a high current retention of 90.7% after the 24-hour stability, and the obtained Zn-air battery by Fe-NCNT with open-circuit voltage of 1.44 V owns moderate capacity and satisfying stability. The demonstrated method to prepare hierarchically porous N-doped carbon nanomaterials stemmed from MOF precursors unfolds a new route for the facile construction of efficient nanocatalysts for advanced energy applications.
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http://dx.doi.org/10.1016/j.jcis.2021.08.180DOI Listing
August 2021

Spatial distribution and human health risk assessment of soil heavy metals based on sequential Gaussian simulation and positive matrix factorization model: A case study in irrigation area of the Yellow River.

Ecotoxicol Environ Saf 2021 Sep 8;225:112752. Epub 2021 Sep 8.

College of Natural Resources and Environment, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:

The content of Cd, Cu, Pb, Zn, Cr, Ni and As from 250 soil samples was measured in agricultural soil of Ningxia section of the Yellow River. Positive matrix factorization (PMF) was to identify the main sources of these heavy metals; Sequential Gaussian Simulation (SGS) was to identify their spatial distribution and high-risk areas; and Human Health risk (HHR) model was to measure the health risk. Results showed that the average content of Cd and As exceeds the risk screening value of "Soil Environmental Quality-Agricultural Land Soil Pollution Risk Control Standard" (GB 15618-2018), which belongs to slight-level pollution. Although the content of other types of HMs (Cu, Pb, Zn, Cr, Ni) is below the risk screening value, they are still included heavily in the soil (except Cr). PMF indicated that mixed sources of agriculture and industry accounted for 27.06%, natural sources accounted for 14.12%, industrial sources accounted for 23.04%, traffic sources accounted for 21.50%, and Yellow River sedimentary sources accounted for 14.28%. PMF-HHR showed that the mixed sources of agriculture and industry are the most important factor causing non-carcinogenic risk (HI) to children (accounting for 55.75%). Industrial sources and traffic sources were the two main factors that cause HI to adults (industrial sources accounted for 25.16%, and traffic sources accounted for 28.78%). Mixed sources of agriculture and industry and natural sources were the two main factors that cause carcinogenic risk (CR) (mixed sources of agriculture and industry account for 35.34%, and natural sources account for 33.23%). SGS indicated that 0.64% and 9.32% of the total areas were posing as higher HI areas to children and adults respectively; in particular, 0.68% and 1.12% of the areas were identified as higher HI of As and Cr areas at a critical probability of 0.9.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112752DOI Listing
September 2021

Research on Integrated Innovation Design Education for Cultivating the Innovative and Entrepreneurial Ability of Industrial Design Professionals.

Front Psychol 2021 17;12:693216. Epub 2021 Aug 17.

School of Design, Jiangnan University, Wuxi, China.

In the industrial design industry, innovation and entrepreneurship made by professional and technical talents will become an important trend in the future development of the economy and society. The great changes in the design industry, such as the diversification and complication of design objects, the relatively restricted knowledge structure of design talents, the lack of entrepreneurial experience, and other reasons, have led to the low success rate of industrial design talent entrepreneurship. The purpose of this research is to analyze and explore the effects of integrated innovation design teaching modes and methods of cultivating the innovative and entrepreneurial abilities of industrial design professionals to help industrial design professionals to improve their success rate of establishing new companies. This research also aims to improve the innovative and entrepreneurial ability of industrial design professionals in terms of integrated innovation and design teaching reform by integrating the theories and methods of industrial design professional training links such as the objectives, teaching contents, teaching modes and methods, performance evaluation of innovation, and design education, combining these with the requirements of the innovative and entrepreneurial ability training of industrial design professionals. In this study, the educational reform of integrated innovation design in a specific Chinese university is taken as an example to carry out theoretical research and practical application. The results of this research show that the theory and method of integrated innovation of design education have made significant contributions to the enhancement of the innovative and entrepreneurial ability of industrial design professionals. This research also reveals a feasible direction for constructing an industrial design innovative and entrepreneurial talent training system that adapts to the transformation and upgrading of the design industry. Meanwhile, methods and teaching modes applied in this research can be promoted in relevant or similar majors to make innovation and entrepreneurship education in colleges and universities more professional, stimulate students' entrepreneurial consciousness, and improve students' abilities of innovation and entrepreneurship.
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http://dx.doi.org/10.3389/fpsyg.2021.693216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416029PMC
August 2021

Alterations of gut microbiota in patients with active pulmonary tuberculosis in China: A pilot study.

Int J Infect Dis 2021 Sep 2. Epub 2021 Sep 2.

Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety (Ministry of Education), Fudan University, Shanghai, China; Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Background: This study aimed to identify the differences in diversity, composition and function of gut microbiota between tuberculosis (TB) patients and healthy controls (HCs).

Methods: A cross-sectional study was conducted in three cities of China. Stools samples from 94 treatment-naive TB patients and 62 HCs were analyzed by 16S rRNA gene sequencing. TB patients were further divided into antibiotic-free and antibiotic-exposure according to their uses of non-specific antibiotics before TB diagnosis.

Results: Compared with HCs, antibiotic-free TB patients presented a different gut microbial community (P<0.005) and decreased shannon diversity (P<0.005). Among TB patients, the relative abundances of short-chain-fatty-acids(SCFA)-producing genera such as Lachnospiraceae ND3007 group (log2(FC)=-2.74) were lower, while several conditional pathogens related genera such as Enterococcus (log2(FC)=12.05) and Rothia (log2(FC)=6.322) were at higher levels. In addition, 41% patients received antibiotics before TB diagnosis. The antibiotics exposure was correlated with additional reduction of α-diversity and depletion of SCFA-producing-bacteria. Microbial functional analysis revealed that the biosynthesis capacity of amino acids and fatty acids was lower among TB patients compared to HCs.

Conclusions: Significant alterations in gut microbiota composition and metabolic pathways of TB patients were observed. Antibiotics exposure could alter gut microbiota of TB patients which should be considered in anti-TB treatment.
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http://dx.doi.org/10.1016/j.ijid.2021.08.064DOI Listing
September 2021

Integrative analysis of the gut microbiome and metabolome in a rat model with stress induced irritable bowel syndrome.

Sci Rep 2021 Sep 2;11(1):17596. Epub 2021 Sep 2.

Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou, 310006, Zhejiang, China.

Stress is one of the major causes of irritable bowel syndrome (IBS), which is well-known for perturbing the microbiome and exacerbating IBS-associated symptoms. However, changes in the gut microbiome and metabolome in response to colorectal distention (CRD), combined with restraint stress (RS) administration, remains unclear. In this study, CRD and RS stress were used to construct an IBS rat model. The 16S rRNA gene sequencing was used to characterize the microbiota in ileocecal contents. UHPLC-QTOF-MS/MS assay was used to characterize the metabolome of gut microbiota. As a result, significant gut microbial dysbiosis was observed in stress-induced IBS rats, with the obvious enrichment of three and depletion of 11 bacterial taxa in IBS rats, when compared with those in the control group (q < 0.05). Meanwhile, distinct changes in the fecal metabolic phenotype of stress-induced IBS rats were also found, including five increased and 19 decreased metabolites. Furthermore, phenylalanine, tyrosine and tryptophan biosynthesis were the main metabolic pathways induced by IBS stress. Moreover, the altered gut microbiota had a strong correlation with the changes in metabolism of stress-induced IBS rats. Prevotella bacteria are correlated with the metabolism of 1-Naphthol and Arg.Thr. In conclusion, the gut microbiome, metabolome and their interaction were altered. This may be critical for the development of stress-induced IBS.
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http://dx.doi.org/10.1038/s41598-021-97083-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413334PMC
September 2021

The association between manganese exposure with cardiovascular disease in older adults: NHANES 2011-2018.

J Environ Sci Health A Tox Hazard Subst Environ Eng 2021 Sep 2:1-7. Epub 2021 Sep 2.

Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.

The aim of the current study was to explore possible connections between manganese exposure and the prevalence of cardiovascular disease (CVD) in older US adults. The relationship between serum manganese levels and CVD was explored in 2427 people aged 60 years and over using data from the National Health and Nutrition Examination Survey (NHANES) (2011-2018). Multivariate linear regression analysis was performed to investigate associations between CVD risk factors and serum manganese concentration. The relationship between manganese levels and the prevalence of CVD was probed using generalized linear models and restricted cubic spline curves. Stratified subgroup analysis was subsequently constructed to rule out spurious interactions between variables and manganese. Compared with the lowest quartile, the modified odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the manganese quartiles were 0.71 (OR: 0.51; CI: 1.00), 0.70 (0.50, 0.99), and 0.49 (0.34, 0.72). In the full adjusted model, a prominent negative relationship was observed between serum manganese concentration and CVD. A restricted cubic spline curve was used to show a nonlinear negative relationship between manganese concentration and CVD. In summary, manganese levels are negatively correlated with the risk of CVD in a nation-wide study of older US adults.
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http://dx.doi.org/10.1080/10934529.2021.1973823DOI Listing
September 2021

Dual-Mode Sensing Platform for Electrochemiluminescence and Colorimetry Detection Based on a Closed Bipolar Electrode.

Anal Chem 2021 09 1;93(36):12367-12373. Epub 2021 Sep 1.

Flexible Printed Electronics Technology Center and College of Science, Harbin Institute of Technology, Shenzhen 518055, Guangdong, P. R. China.

Development of sensors uniting different sensing principles is in line with the concept of reliable, comprehensive, and diversified equipment construction. However, the current exploration in this field is obstructed by compromise of reaction conditions and inevitable mutual interference arising from different sensing modes. This work reported a closed bipolar electrode (c-BPE) strategy for dual-modality detection or dual-target detection. To this end, a c-BPE sensing platform installed in physically separated anode and cathode compartments was well designed and carefully optimized. If luminol was present in the anode section and Prussian blue (PB) was at the cathode part, single stimulation could realize electrochemiluminescence (ECL) from luminol at the anode and conversion of PB to Prussian white (PW) at the cathode. The latter reaction helped elevate the ECL signal and also prepared for colorimetric detection as color change from PW to PB under the trigger of oxidant (like HO) was used to track the content of the oxidant. Thus, dual signals were obtained for dual-modality detection of single target or the detection of different targets was realized at different poles. Detection of glucose was carried out to validate the application for dual-modality detection, while VLDL/AChE and NADH/HO assays illustrated the potential of dual-target detection. The proposed platform possesses outstanding sensing performance including selectivity, repeatability, long-term stability, accuracy, and so forth. This work implements a breakthrough in designing dual-mode sensors and is expected to present a rational basis for development of a diversified sensing platform.
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http://dx.doi.org/10.1021/acs.analchem.1c02184DOI Listing
September 2021

Scale-up reactivation of spent S-Zorb adsorbents for gasoline desulfurization.

J Hazard Mater 2021 Aug 13;423(Pt A):126903. Epub 2021 Aug 13.

State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Qingdao 266555, China; College of Chemical Engineering, China University of Petroleum, Qingdao 266555, China.

Reactivating and recycling spent S-Zorb adsorbents reduce fresh adsorbents consumption and hazardous wastes emissions. Though the spent adsorbents have been successfully reactivated in the laboratory, a pilot-scale practice is indispensable before the industrial production. Herein, the reactivation of spent adsorbents was performed at laboratory (1.0 L), middle (10 L) and pilot (3000 L) scale, respectively. The inert ZnSiO and ZnS over the spent adsorbents are recovered to active ZnO, and the NiS is transformed into NiO. There is almost no amplification effect in pore structure and acidity of the reactivated adsorbents, while NiO particle size reduces slightly with the reactivation scales. The computational fluid dynamic simulation indicates that enhanced contact between spent adsorbents and acid/alkaline reagents at larger scale account for the smaller NiO particle. It provides more hydrogenolysis centers for CS bonds breakage after reduction, increasing initial desulfurization activity. More importantly, the adsorbent reactivated at pilot scale exhibits comparable activity to the fresh one in gasoline desulfurization. The sulfur content in the outlet decreases to less than 10 μg g from 1 h of reaction. Thus, the reactivation of spent S-Zorb adsorbents is successfully scaled up to the pilot scale, accelerating industrial practice in recycling the spent adsorbents.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126903DOI Listing
August 2021

Development and Validation of a Risk Nomogram Model for Predicting Revascularization After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome.

Clin Interv Aging 2021 20;16:1541-1553. Epub 2021 Aug 20.

Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.

Objective: Percutaneous coronary intervention (PCI) is one of the most effective treatments for acute coronary syndrome (ACS). However, the need for postoperative revascularization remains a major problem in PCI. This study was to develop and validate a nomogram for prediction of revascularization after PCI in patients with ACS.

Methods: A retrospective observational study was conducted using data from 1083 patients who underwent PCI (≥6 months) at a single center from June 2013 to December 2019. They were divided into training (70%; n = 758) and validation (30%; n = 325) sets. Multivariate logistic regression analysis was used to establish a predictive model represented by a nomogram. The nomogram was developed and evaluated based on discrimination, calibration, and clinical efficacy using the concordance statistic (C-statistic), calibration plot and decision curve analysis (DCA), respectively.

Results: The nomogram was comprised of ten variables: follow-up time (odds ratio (OR): 1.01; 95% confidence interval (CI): 1.00-1.03), history of diabetes mellitus (OR: 1.83; 95% CI: 1.25-2.69), serum creatinine level on admission (OR: 0.99; 95% CI: 0.98-1.00), serum uric acid level on admission (OR: 1.005; 95% CI: 1.002-1.007), lipoprotein-a level on admission (OR: 1.0021; 95% CI: 1.0013-1.0029), low density lipoprotein cholesterol level on re-admission (OR: 1.33; 95% CI: 0.10-0.47), the presence of chronic total occlusion (OR: 3.30; 95% CI: 1.93-5.80), the presence of multivessel disease (OR: 4.48; 95% CI: 2.85-7.28), the presence of calcified lesions (OR: 1.63; 95% CI: 1.11-2.39), and the presence of bifurcation lesions (OR: 1.82; 95% CI: 1.20-2.77). The area under the receiver operating characteristic curve values for the training and validation sets were 0.765 (95% CI: 0.732-0.799) and 0.791 (95% CI: 0.742-0.830), respectively. The calibration plots showed good agreement between prediction and observation in both the training and validation sets. DCA also demonstrated that the nomogram was clinically useful.

Conclusion: We developed an easy-to-use nomogram model to predict the risk of revascularization after PCI in patients with ACS. The nomogram may provide useful assessment of risk for subsequent treatment of ACS patients undergoing PCI.
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http://dx.doi.org/10.2147/CIA.S325385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384150PMC
August 2021

Overexpression of miR-99a in hippocampus leads to impairment of reversal learning in mice.

Behav Brain Res 2021 Aug 20;416:113542. Epub 2021 Aug 20.

Department of Neurobiology, Institute of Brain Research, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. Electronic address:

As one of the most common human genetic disorders, Down syndrome (DS) is characterized by a mild-to-moderate cognitive disability, which mainly results from genes overexpression on chromosome 21. The expression of miR-99a, a gene harboring on chromosome 21, is increased by 50 folds in DS brain samples. This study aims to investigate the effect of miR-99a overexpression in the hippocampus on mouse behaviors and explore the underlying mechanisms. Lentivirus vectors were delivered into the hippocampus for focal miR-99a overexpression in mice. Then behaviors were observed by an open field, elevated plus maze, rotarod motor test, and Morris water maze. The genes affected by miR-99a were identified by RNA sequencing (RNA-seq) and confirmed by quantitative RT-PCR (qRT-PCR) in samples isolated from the hippocampus injected with lentivirus-GFP-miR-99a or lentivirus-GFP vectors. It was found that the expression of miR-99a with intrahippocampal delivery of lentivirus-GFP-miR-99a resulted in reversal learning impairment in mice although it had no influence on motor function and anxiety. Meanwhile, RNA-seq results showed that 92 genes including mRNAs and microRNAs were significantly regulated by miR-99a, consistent with qRT-PCR consequence. Moreover, dual-luciferase reporter assay showed that miR-99a could directly bind to the 3'-untranslated regions (3'UTR) of target genes (Clic6 and Kcnj13) with an inhibitory effect on their activity. Furthermore, we also found that miR-99a overexpression affected different biological processes by bioinformatic analyses. Our study showed that miR-99a overexpression in the hippocampus leads to cognitive impairment through regulating the expressions of various genes, which reveals a novel function of miR-99a and provides new insights into understanding the pathophysiologic process of DS.
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http://dx.doi.org/10.1016/j.bbr.2021.113542DOI Listing
August 2021

Clinical Value of Fecal Calprotectin in Predicting Mucosal Healing in Patients With Ulcerative Colitis.

Front Med (Lausanne) 2021 3;8:679264. Epub 2021 Aug 3.

Department of Gastroenterology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

This study aimed to evaluate the clinical significance of fecal calprotectin (FC) in assessment of ulcerative colitis (UC) patients' endoscopic patterns and clinical manifestation. A total of 143 UC patients who received colonoscopy and 108 controls were included. After providing stool samples, patients underwent total colonoscopy. FC was measured by an enzyme-linked immunosorbent assay (ELISA). Clinical activity was based on the Mayo score. Endoscopic findings was scored by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). Correlation analysis and receiver-operator characteristic (ROC) analysis were carried out to determine the significance of measurements. The median (interquartile range, IQR) of FC levels was 211 (43-990) μg/g in UC and 87.5 (40.50~181) μg/g in the control group. Fecal calprotectin correlated significantly with both Mayo and UCEIS scores (Spearman's r 0.670 and 0.592, < 0.01). With a cut-off value of 164 μg/g for fecal calprotectin concentration, the area under the curve (AUC) in receiver operator characteristic analysis was 0.830, sensitivity was 85.42%, specificity was 73.68%, positive predictive value (PPV) was 62.12%, and negative predictive value (NPV) was 9.10% in predicting clinical active disease. Similarly, the power of FC to predict mucosal healing (MH) was modest. With a cut-off value of 154.5 μg/g, the AUC was 0.839, sensitivity was 72.34%, and specificity was 85.71%. For evaluating the disease activity of UC, FC is a clinically relevant biomarker for both clinically active disease and MH in patients with UC. But the cut-off value still needs large and multicenter studies for confirmation.
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http://dx.doi.org/10.3389/fmed.2021.679264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369158PMC
August 2021

Magnolol attenuates depressive-like behaviors by polarizing microglia towards the M2 phenotype through the regulation of Nrf2/HO-1/NLRP3 signaling pathway.

Phytomedicine 2021 Oct 30;91:153692. Epub 2021 Jul 30.

School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Purpose: Magnolol (MA) exhibits anti-depressant effect by inhibiting inflammation. However, its effect on microglia polarization remains not fully understood. Herein, our study was performed to evaluate the effect of MA on microglia polarization in chronic unpredictable mild stress (CUMS)-induced depression and explore its potential mechanism.

Study Design: The CUMS procedure was conducted, and the mice were intragastrically treated with MA. BV2 cells were pretreated with MA prior to LPS/ATP challenge.

Methods: The levels of TNF-α, IL-1β, IL-6 and IL-4, IL-10 in brain and BV2 cells were examined by ELISA. The mRNA expressions of Arg1, Ym1, Fizz1 and Klf4 in brains were measured. ROS content was determined using flow cytometry. Immunofluorescence was employed to evaluate Iba-1 level, Nrf2 nuclear translocation, Iba-1CD16/32 and Iba-1CD206 cell population. The protein expressions of Nrf2, HO-1, NLRP3, caspase-1 p20 and IL-1β in brains and BV2 cells were investigated by western blot. Nrf2 siRNA was induced in experiments to explore the role of Nrf2 in MA-mediated microglia polarization. The ubiquitination of Nrf2 was visualized by Co-IP.

Results: The treatment with MA notably relieved depressive like behaviors, suppressed pro-inflammatory cytokines, promoted anti-inflammatory cytokines and the transcription of M2 phenotype microglia-specific indicators. MA upregulated the expression of Nrf2, HO-1, downregulated the expression of NLRP3, caspase-1 p20, IL-1β both in vivo and in vitro. MA also reduced ROS concentration, promoted Nrf2 nucleus translocation and prevented Nrf2 ubiquitination. Nrf2 Knockdown by siRNA abolished the MA-mediated microglia polarization.

Conclusion: The present research demonstrated that MA attenuated CUMS-stimulated depression by inhibiting M1 polarization and inducing M2 polarization via Nrf2/HO-1/NLRP3 signaling.
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http://dx.doi.org/10.1016/j.phymed.2021.153692DOI Listing
October 2021

Acupuncture and moxibustion combined with cupping for the treatment of post-herpetic neuralgia: A meta-analysis.

Medicine (Baltimore) 2021 Aug;100(31):e26785

The First Clinical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

Background: There are still controversies between the curative effect of acupuncture combined with cupping therapy and western medicine for post-herpetic neuralgia (PHN). Our meta-analysis fully incorporates the research of acupuncture combined with cupping therapy versus Western medicine for PHN, aiming to explore the difference in the efficacy of the 2 therapies, so as to provide guidance for clinical treatment.

Methods: We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, CBM, from establishment of the database to September, 2020. Include studies that are clearly defined as PHN or herpes zoster, and exclude duplicate publications; studies with no full text, incomplete information, or inability to extract data; the definition of exposure is quite different from most literature; animal experiments.

Results: The total effective rate (relative ratio [RR] = 1.21, 95% confidence interval [CI]: 1.12-1.31) and the rate of remarkable effect (RR = 1.46, 95% CI: 1.30-1.63) of acupuncture and moxibustion combined with cupping in the treatment of PHN were significantly higher than that of conventional western medicine. The visual analogue scale score of acupuncture and moxibustion combined with cupping for PHN was significantly lower than that of conventional western medicine treatment (WMD = -1.77, 95% CI [-2.79, -0.75]). In addition, acupuncture and moxibustion combined with cupping therapy significantly reduced the occurrence of PHN compared with conventional western medicine treatment after treatment of acute herpes zoster (RR = 0.30, 95% CI: 0.20-0.45). In order to explore the differences in the efficacy and preventive effects of different types of acupuncture and cupping therapy, we have further conducted a subgroup analysis.

Conclusion: The effect of acupuncture and moxibustion combined with cupping in the treatment of PHN is significantly higher than that of conventional western medicine, and it can significantly prevent the occurrence of PHN. Chinese medicine should be used more widely in the treatment of PHN.
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http://dx.doi.org/10.1097/MD.0000000000026785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341313PMC
August 2021

Prognostic Factors of Survival of Advanced Liver Cancer Patients Treated With Palliative Radiotherapy: A Retrospective Study.

Front Oncol 2021 28;11:658152. Epub 2021 Jul 28.

Cancer Center, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, Wuhan, China.

Aims: Survival benefit of liver cancer patients who undergo palliative radiotherapy varies from person to person. The present study aims to identify indicators of survival of advanced liver cancer patients receiving palliative radiotherapy.

Patients And Methods: One hundred and fifty-nine patients treated with palliative radiotherapy for advanced liver cancer were retrospectively assessed. Of the 159 patients, 103 patients were included for prediction model construction in training phase, while other 56 patients were analyzed for external validation in validation phase. In model training phase, clinical characteristics of included patients were evaluated by Kaplan-Meier curves and log-rank test. Thereafter, multivariable Cox analysis was taken to further identify characteristics with potential for prediction. In validation phase, a separate dataset including 56 patients was used for external validation. Harrell's C-index and calibration curve were used for model evaluation. Nomograms were plotted based on the model of multivariable Cox analysis.

Results: Thirty-one characteristics of patients were investigated in model training phase. Based on the results of Kaplan-Meier plots and log-rank tests, 6 factors were considered statistically significant. On multivariable Cox regression analysis, bone metastasis (HR = 1.781, = 0.026), portal vein tumor thrombus (HR = 2.078, = 0.015), alpha-fetoprotein (HR = 2.098, = 0.007), and radiation dose (HR = 0.535, = 0.023) show significant potential to predict the survival of advanced liver cancer patients treated with palliative radiotherapy. Moreover, nomograms predicting median overall survival, 1- and 2-year survival probability were plotted. The Harrell's C-index of the predictive model is 0.709(95%CI, 0.649-0.769) and 0.735 (95%CI, 0.666-0.804) for training model and validation model respectively. Calibration curves of the 1- and 2-year overall survival of the predictive model indicate that the predicted probabilities of OS are very close to the actual observed outcomes both in training and validation phase.

Conclusion: Bone metastasis, portal vein tumor thrombus, alpha-fetoprotein and radiation dose are independent prognostic factors for the survival of advanced liver cancer patients treated with palliative radiotherapy.
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http://dx.doi.org/10.3389/fonc.2021.658152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355619PMC
July 2021

A ratiometric fluorescent sensing of proanthocyanidins by MnO nanosheets simultaneously tuning the photoluminescence of Au/AgNCs and thiamine.

Talanta 2021 Nov 18;234:122607. Epub 2021 Jun 18.

Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, China West Normal University, Nanchong, 637002, China; Institute of Applied Chemistry, China West Normal University, Nanchong, 637002, China. Electronic address:

By simultaneously regulating the photoluminescence of alloy Au/Ag nanoclusters (NCs) and thiamine (VB1) through MnO nanosheets (MnO NS), a novel ratiometric fluorescent probe (RF-probe) was established for sensitively and selectively monitoring proanthocyanidins (PAs). The introduction of Ag (I) ions could enhance significantly the quantum yields (QYs, 11.1%) of AuNCs based on the synthetic method of UVI (UV irradiation) combined with MWH (microwave heating). MnO NS could quench the fluorescence (FL) of Au/AgNCs mainly coming from Förster resonance energy transfer (FRET), while it could act as a nanozyme catalyst for directly catalyzing the oxidation of VB1 to produce highly fluorescent oxVB1. In the presence of PAs, MnO was reduced to Mn, which caused that its quenching capacity and oxidase-like activity were vanished, thus the FL of oxVB1 and Au/AgNCs was reduced and recovered. The concentration of PAs could be monitored by the RF-probe with a linear range of 0.27-22.4 μmol L and corresponding limit of detection (LOD) and limit of quantification (LOQ) were calculated to be 75.9 and 250.5 nmol L. Furthermore, the RF-probe was successfully used for the determination of PAs in mineral water, PAs additive and PAs capsule with satisfactory results compared to the standard HPLC method.
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http://dx.doi.org/10.1016/j.talanta.2021.122607DOI Listing
November 2021

SARS-CoV-2-derived fusion inhibitor lipopeptides exhibit highly potent and broad-spectrum activity against divergent human coronaviruses.

Signal Transduct Target Ther 2021 08 3;6(1):294. Epub 2021 Aug 3.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1038/s41392-021-00698-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330190PMC
August 2021

Genome-Scale Metabolic Models and Machine Learning Reveal Genetic Determinants of Antibiotic Resistance in Escherichia coli and Unravel the Underlying Metabolic Adaptation Mechanisms.

mSystems 2021 Aug 3;6(4):e0091320. Epub 2021 Aug 3.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire, United Kingdom.

Antimicrobial resistance (AMR) is becoming one of the largest threats to public health worldwide, with the opportunistic pathogen Escherichia coli playing a major role in the AMR global health crisis. Unravelling the complex interplay between drug resistance and metabolic rewiring is key to understand the ability of bacteria to adapt to new treatments and to the development of new effective solutions to combat resistant infections. We developed a computational pipeline that combines machine learning with genome-scale metabolic models (GSMs) to elucidate the systemic relationships between genetic determinants of resistance and metabolism beyond annotated drug resistance genes. Our approach was used to identify genetic determinants of 12 AMR profiles for the opportunistic pathogenic bacterium E. coli. Then, to interpret the large number of identified genetic determinants, we applied a constraint-based approach using the GSM to predict the effects of genetic changes on growth, metabolite yields, and reaction fluxes. Our computational platform leads to multiple results. First, our approach corroborates 225 known AMR-conferring genes, 35 of which are known for the specific antibiotic. Second, integration with the GSM predicted 20 top-ranked genetic determinants (including , , , , , , , , and ) essential for growth, while a further 17 top-ranked genetic determinants linked AMR to auxotrophic behavior. Third, clusters of AMR-conferring genes affecting similar metabolic processes are revealed, which strongly suggested that metabolic adaptations in cell wall, energy, iron and nucleotide metabolism are associated with AMR. The computational solution can be used to study other human and animal pathogens. Escherichia coli is a major public health concern given its increasing level of antibiotic resistance worldwide and extraordinary capacity to acquire and spread resistance via horizontal gene transfer with surrounding species and via mutations in its existing genome. E. coli also exhibits a large amount of metabolic pathway redundancy, which promotes resistance via metabolic adaptability. In this study, we developed a computational approach that integrates machine learning with metabolic modeling to understand the correlation between AMR and metabolic adaptation mechanisms in this model bacterium. Using our approach, we identified AMR genetic determinants associated with cell wall modifications for increased permeability, virulence factor manipulation of host immunity, reduction of oxidative stress toxicity, and changes to energy metabolism. Unravelling the complex interplay between antibiotic resistance and metabolic rewiring may open new opportunities to understand the ability of E. coli, and potentially of other human and animal pathogens, to adapt to new treatments.
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http://dx.doi.org/10.1128/mSystems.00913-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409726PMC
August 2021

Enhanced Electrochemical Reduction of CO to CO on Ag/SnO by a Synergistic Effect of Morphology and Structural Defects.

Chem Asian J 2021 Sep 12;16(18):2694-2701. Epub 2021 Aug 12.

Beijing Advanced Innovation Center for Materials Genome Engineering, Beijing Key Laboratory for Magneto-Photoelectrical Composite and Interface Science, School of Mathematics and Physics, University of Science and Technology Beijing, 100083, Beijing, P. R. China.

Silver (Ag)-based materials are considered to be promising materials for electrochemical reduction of CO to produce CO, but the selectivity and efficiency of traditional polycrystalline Ag materials are insufficient; there still exists a great challenge to explore novel modified Ag based materials. Herein, a nanocomposite of Ag and SnO (Ag/SnO ) for efficient reduction of CO to CO is reported. HRTEM and XRD patterns clearly demonstrated the lattice destruction of Ag and the amorphous SnO in the Ag/SnO nanocomposite. Electrochemical tests indicated the nanocomposite containing 15% SnO possesses highest catalytic selectivity featured by a CO faradaic efficiency (FE) of 99.2% at -0.9 V versus reversible hydrogen electrode (vs RHE) and FE>90% for the CO product at a wide potential range from -0.8 V to -1.4 V vs RHE. Experimental characterization and analysis showed that the high catalytic performance is attributed to not only the branched morphology of Ag/SnO nanocomposites (NCs), which endows the maximum exposure of active sites, but also the special adsorption capacity of abundant defect sites in the crystal for *COOH (the key intermediate of CO formation), which improves the intrinsic activity of the catalyst. But equally important, the existed SnO also plays an important role in inhibiting hydrogen evolution reaction (HER) and anchoring defect sites. This work demonstrates the use of crystal defect engineering and synergy in composite to improve the efficiency of electrocatalytic CO reduction reaction (CO RR).
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http://dx.doi.org/10.1002/asia.202100718DOI Listing
September 2021

Can Chronic Disease Diagnosis Urge the Patients to Quit Smoking? - Evidence from the China Health and Nutrition Survey.

Risk Manag Healthc Policy 2021 22;14:3059-3077. Epub 2021 Jul 22.

Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Tobacco consumption is one of the world's largest public health threats. Yet little is known about how chronic disease diagnoses affect individuals' smoking behavior in China, where the world's largest smoking population resides.

Methods: This study analyzes an unbalanced panel dataset on 2986 Chinese males aged 50 or above from the China Health and Nutrition Survey, a household survey covering nine Chinese provinces. We adopt a zero-inflated negative binomial (ZINB) regression framework to account for the count-data nature of the outcome variable of interest, the number of cigarettes one smokes per day. Logit regressions are also adopted to predict one's likelihood of smoking cessation.

Results: First, the estimated ZINB model suggests that the number of chronic disease diagnoses only affects whether one smokes, but conditional on one being a smoker, it does not affect the number of cigarettes one smokes per day. Logit estimates suggest that an additional diagnosed chronic disease is associated with a 4.8 percentage-point increase in the likelihood of smoking cessation. Second, while the diagnoses of all four chronic conditions examined are found to increase the likelihood of smoking cessation, the diagnosis of myocardial infarction has the largest impact, followed by diabetes diagnosis.

Conclusion: While chronic disease diagnoses reduce smoking in China, their effects are small. Healthcare policies and relevant measures (such as helping smoking patients switch to a diet with more foods enriched with antioxidants) are thus needed to reduce the adverse effects that continued smoking might impose on their health.
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http://dx.doi.org/10.2147/RMHP.S315358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313401PMC
July 2021

Alliance between doping Ag and dual ligands-enhanced fluorescent gold nanoclusters for the assays of vitamin B12 and chlortetracycline hydrochloride.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Dec 18;263:120194. Epub 2021 Jul 18.

Chemical Synthesis and Pollution Control Key Laboratory of Sichuan Province, China West Normal University, Nanchong 637002, China; Institute of Applied Chemistry, China West Normal University, Nanchong 637002, China. Electronic address:

A stable, water-soluble, heightened quantum yields (QYs) Au nanoclusters by the alliance between doping Ag and dual ligands (thiosalicylic acid and bovine serum albumin) (TSA/BSA-Au/AgNCs) was prepared using one-step wet chemical synthesis. The effect of different types of aromatic thiols and the molar ratio of Au-Ag on the photo-luminescence performance of AuNCs was discussed in detail. The alloy NCs is shown to be viable fluorescent method for vitamin B12 (VB12) and chlortetracycline hydrochloride (CCH) assays, and become an excellent temperature sensor in the range of 10-50 °C. The fluorescence (FL) of TSA/BSA-Au/AgNCs was quenched with the addition of VB12 or CCH coming from Förster resonance energy transfer (FRET) combined with inner filter effect (IFE). The method can detect VB12/CCH by fluorometry with a linear response in the range of 0.33-60.0/0.33-60.0 μmol·L and a 71.0/64.0 nmol·L detection limit (at 3σ/slope). Furthermore, the proposed method was extended to the assays of VB12 in mineral water or tablets and CCH in veterinary drug or ointment with satisfactory results.
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http://dx.doi.org/10.1016/j.saa.2021.120194DOI Listing
December 2021

Multiparametric MRI-based Radiomics approaches on predicting response to neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer.

Abdom Radiol (NY) 2021 Jul 24. Epub 2021 Jul 24.

Department of Biomedical Engineering, School of Fundamental Sciences, China Medical University, Shenyang, 110122, People's Republic of China.

Purpose: To investigate the value of multiparametric MRI-based radiomics on predicting response to nCRT in patients with rectal cancer.

Methods: This study enrolled 193 patients with pathologically confirmed LARC who received nCRT treatment between Apr. 2014 and Jun. 2018. All patients underwent baseline T1-weighted (T1W), T2-weighted (T2W) and T2-weighted fat-suppression (T2FS) MRI scans before neoadjuvant chemoradiotherapy. Radiomics features were extracted and selected from the MRI data to establish the radiomics signature. Important clinical predictors were identified by Mann-Whitney U test and Chi-square test. The nomogram integrating the radiomics signature and important clinical predictors was constructed using multivariate logistic regression. Prediction capabilities of each model were assessed with receiver operating characteristic (ROC) curve analysis. Performance of the nomogram was evaluated by its calibration and potential clinical usefulness.

Results: For the prediction of good response (GR) and pathologic complete response (pCR), the developed radiomics signature comprising 10 and 7 features, respectively, were significantly associated with the therapeutic response to nCRT. The nomogram incorporating the radiomics signature and important clinical predictors (CEA and CA19-9 for predicting GR; CEA, posttreatment length and posttreatment thickness for predicting pCR) achieved favorable prediction efficacy, with AUCs of 0.918 (95% confidence interval [CI]: 0.867-0.971, Sen = 0.972, Spe = 0.828) and 0.944 (95% CI: 0.891-0.997, Sen = 0.943, Spe = 0.828) in the training and validation cohort for predicting GR, respectively; with AUCs of 0.959 (95% CI: 0.927-0.991, Sen = 1.000, Spe = 0.833) and 0.912 (95% CI: 0.843-0.982, Sen = 1.000, Spe = 0.815) in the training and validation cohort for predicting pCR, respectively. Decision curve analysis confirmed potential clinical usefulness of our nomogram.

Conclusions: This study demonstrated that the MRI-based radiomics nomogram is predictive of response to nCRT and can be considered as a promising tool for facilitating treatment decision-making for patients with LARC.
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http://dx.doi.org/10.1007/s00261-021-03219-0DOI Listing
July 2021

Serum Heparanase: A New Clinical Biomarker Involved in Senile Metabolic Inflammatory Syndrome.

Diabetes Metab Syndr Obes 2021 13;14:3221-3228. Epub 2021 Jul 13.

Department of Geriatrics, Huashan Hospital, National Clinical Research Center for Aging and Medicine, Fudan University, Shanghai, 200040, People's Republic of China.

Aim: Metabolic inflammation syndrome (MIS) can lead to a series of complications, but its exact inflammatory mechanism is still unclear. The aim of this study was to explore the correlation between heparanase (HPA) and MIS, and the close relationship between HPA and other chronic low-grade inflammation index, such as C-reactive protein (CRP) and interleukin-6 (IL-6).

Methods: A total of 105 patients with MIS in the physical examination population of Huashan Hospital affiliated to Fudan University from May to June 2018 were selected as the MIS group, and 52 patients who were relatively healthy during the same period were used as the control group. The basic clinical data of the selected candidates were collected, the levels of serum HPA, CRP and IL-6 were measured by ELISA, and the levels of blood glucose and blood lipids were also detected.

Results: Compared with the control group, the levels of HPA, CRP, IL-6, FBG, HbA, and TG of MIS group were all significantly elevated (all P<0.05), and HDL-C levels were considerably reduced (P<0.05). Correlation analysis showed that there was a noticeably positive correlation between serum HPA level and CRP, IL-6 levels (P<0.05).

Conclusion: Higher HPA levels might play a certain role in the occurrence and development of MIS. There was a certain close correlation between serum HPA level and CRP and IL-6 levels, and which indicated that HPA was involved in the chronic low-grade inflammatory reaction process of MIS.
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http://dx.doi.org/10.2147/DMSO.S291612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286426PMC
July 2021

Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis.

Cancers (Basel) 2021 Jul 5;13(13). Epub 2021 Jul 5.

Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes.

Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of was most common (72%), followed by (69%); losses were most prevalent for (74%) and (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of , and and mutual exclusivity of CNAs of and mutations and CNAs of and mutations were revealed.

Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.
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http://dx.doi.org/10.3390/cancers13133366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267950PMC
July 2021

Long non‑coding RNA DANCR represses the viability, migration and invasion of multiple myeloma cells by sponging miR‑135b‑5p to target KLF9.

Mol Med Rep 2021 Sep 19;24(3). Epub 2021 Jul 19.

Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.

Multiple myeloma (MM) is a malignancy of plasma cells that leads to marrow failure and bone lesions. Numerous studies have verified the link between long non‑coding RNAs (lncRNAs) and MM. The present study aimed to examine the role and underlying mechanism of differentiation antagonizing non‑protein coding RNA (DANCR) in MM cells. The relative expression levels of DANCR, microRNA (miR)‑135b‑5p and Krüppel‑like factor 9 (KLF9) were examined using reverse transcription‑quantitative PCR. Cell viability was assessed using the MTT assay, while relative cell migration and invasion were evaluated using Transwell assays. Moreover, the dual‑luciferase reporter assay was used to examine the interplay between DANCR, miR‑135b‑5p and KLF9. Western blotting was performed to determine the expression level of KLF9. It was found that lncRNA DANCR and KLF9 were downregulated, while miR‑135b‑5p was upregulated in the serum of patients with MM and in MM cells compared with the controls. Overexpressing DANCR or knocking down miR‑135b‑5p reduced the viability of the MM cells, as well as restrained MM cells from migrating and invading. Furthermore, DANCR directly targeted miR‑135b‑5p and was negatively correlated with miR‑135b‑5p. It was also found that KLF9 was targeted by miR‑135b‑5p and was inversely correlated with miR‑135b‑5p expression. The impact of lncRNA DANCR‑mediated suppression on cell viability, invasion and migration was partially abolished by short hairpin RNA KLF9 or miR‑135b‑5p mimics transfection in MM cells. Thus, it was suggested that lncRNA DANCR repressed the viability, migration and invasion of MM cells by sponging miR‑135b‑5p to target KLF9.
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http://dx.doi.org/10.3892/mmr.2021.12288DOI Listing
September 2021

Melatonin protects cochlear hair cells from nicotine-induced injury through inhibiting apoptosis, inflammation, oxidative stress and endoplasmic reticulum stress.

Basic Clin Pharmacol Toxicol 2021 Oct 28;129(4):308-318. Epub 2021 Jul 28.

Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Hearing loss positively links with cigarette smoking. However, the involved mechanism and treatment strategies are largely unrevealed. This study aimed to investigate the damaging effect of nicotine on cochlear hair cells, reveal the underlying mechanism and evaluate the therapeutic effect of melatonin on nicotine-induced injury. The results showed that nicotine induced cytotoxicity of House Ear Institute-Organ of Corti 1 (HEI-OC1) cochlear hair cells in a dose-dependent manner (0, 2.5, 5, 10, 20, 40 and 80 μM). Functional investigations showed that nicotine (10 μM) stimulation dramatically promoted apoptosis, inflammatory response, oxidative stress and endoplasmic reticulum stress in HEI-OC1 cells. Moreover, melatonin treatment dose-dependently alleviated the nicotine-induced cytotoxicity in HEI-OC1 cells (0, 10 25, 50 and 100 μM). Further investigation showed that melatonin (100 μM) effectively attenuated the nicotine-induced apoptosis, inflammation, oxidative stress and endoplasmic reticulum stress in HEI-OC1 cells. Collectively, we demonstrated that nicotine induced apoptosis, inflammation, oxidative stress and endoplasmic reticulum stress of cochlear hair cells in an in vitro cell model. Melatonin showed protective effect on these aspects, suggesting that melatonin may be a potential agent for treating smoking-induced hearing loss.
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http://dx.doi.org/10.1111/bcpt.13638DOI Listing
October 2021

Polymorphism of Antifolate Drug Resistance in From Local Residents and Migrant Workers Returned From the China-Myanmar Border.

Front Cell Infect Microbiol 2021 24;11:683423. Epub 2021 Jun 24.

Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming, China.

Drug-resistant  malaria impedes efforts to control, eliminate, and ultimately eradicate malaria in Southeast Asia. resistance to antifolate drugs derives from point mutations in specific parasite genes, including the dihydropteroate synthase (), dihydrofolate reductase (), and GTP cyclohydrolase I () genes. This study aims to investigate the prevalence and spread of drug resistance markers in populating the China-Myanmar border. Blood samples were collected from symptomatic patients with acute infection. Samples with single-clone infections were sequenced for and genesand genotyped for 6 flanking microsatellite markers. Copy number variation in the gene was also examined. Polymorphisms were observed in six different codons of the  gene (382, 383, 512, 549, 553, and 571) and six different codons of the  gene (13, 57, 58, 61, 99, 117) in two study sites. The quadruple mutant haplotypes 57I/L/58R/61M/117T of gene were the most common (comprising 76% of cases in Myitsone and 43.7% of case in Laiza). The double mutant haplotype 383G/553G of  gene was also prevalent at each site (40.8% and 31%). Microsatellites flanking the gene differentiated clinical samples from wild type and quadruple mutant genotypes ( = 0.259-0.3036), as would be expected for a locus undergoing positive selection. The lack of copy number variation of suggests that SP-resistant may harbor alternative mechanisms to secure sufficient folate.
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http://dx.doi.org/10.3389/fcimb.2021.683423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265503PMC
July 2021
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