Publications by authors named "Di Song"

122 Publications

Diagnostic performance of elastography for breast non-mass lesions: A systematic review and meta-analysis.

Eur J Radiol 2021 Oct 2;144:109991. Epub 2021 Oct 2.

Department of Ultrasound, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China. Electronic address:

Purpose: This systematic review and meta-analysis aimed to evaluate the diagnostic performance of ultrasound elastography in the differentiation of benign and malignant breast non-mass lesions (NMLs).

Methods: PubMed, Cochrane Library, and Embase databases were searched for eligible studies up to end of June 2021. The diagnostic performance of elastography for NMLs was investigated using pooled sensitivity and specificity, likelihood ratio, diagnostic odds ratio (DOR), post-test probability, and the area under hierarchical summary receiver operating characteristic curve (HSROC).

Results: Eleven studies involving 812 NMLs (malignant 414) were included. The pooled sensitivity, specificity, DOR, positive likelihood ratio, and negative likelihood of elastography for the differentiation of benign and malignant breast NMLs were 79% (95 %CI: 71-85), 86% (95 %CI: 79-91), 23.32 (95 %CI: 13.38-40.66), 5.67 (95 %CI: 3.79-8.47), and 0.24 (95 %CI: 0.17-0.34), respectively. No significant publication bias existed. The area under the HSROC curve was 90% (95 %CI: 87-92). Fagan plots demonstrated good clinical utility. However, substantial heterogeneity existed. Country, measurement index, and number of lesions served as potential sources of heterogeneity.

Conclusions: The results of this study suggest that elastography has high diagnostic accuracy in differentiating between malignant and benign NMLs. Elastography can be a feasible and non-invasive tool for breast NMLs.
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http://dx.doi.org/10.1016/j.ejrad.2021.109991DOI Listing
October 2021

Screening for Susceptibility-Related Biomarkers of Diclofenac-Induced Liver Injury in Rats Using Metabolomics.

Front Pharmacol 2021 23;12:693928. Epub 2021 Sep 23.

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Early identification of individuals susceptible to idiosyncratic drug-induced liver injury (IDILI) is a challenging unmet demand. Diclofenac, one of the most widely available over-the-counter drugs for pain management worldwide, may induce liver dysfunction, acute liver failure, and death. Herein, we report that diclofenac-related hepatobiliary adverse reactions occurred more frequently in cases with immune activation. Furthermore, experiments with rats demonstrated divergent hepatotoxicity responses in individuals exposed to diclofenac, and modest inflammation potentiated diclofenac-induced liver injury. Susceptible rats had unique plasma metabolomic characteristics, and as such, the metabolomic approach could be used to distinguish susceptible individuals. The 23 identified susceptibility-related metabolites were enriched by several metabolic pathways related to acute-phase reactions of immunocytes and inflammatory responses, including sphingolipid, tyrosine, phenylalanine, tryptophan, and lipid metabolism pathways. This finding implies a mechanistic role of metabolic and immune disturbances affects susceptibility to diclofenac-IDILI. Further nine metabolite biomarkers with potent diagnostic capabilities were identified using receiver operating characteristic curves. These findings elucidated the potential utility of metabolomic biomarkers to identify individuals susceptible to drug hepatotoxicity and the underlying mechanism of metabolic and immune disturbances occurring in IDILI.
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http://dx.doi.org/10.3389/fphar.2021.693928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494976PMC
September 2021

Solvent Effect on Excited-State Intramolecular Proton-Coupled Charge Transfer Reaction in Two Seven-Membered Ring Pyrrole-Indole Hydrogen Bond Systems.

J Phys Chem B 2021 10 29;125(40):11275-11284. Epub 2021 Sep 29.

Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

In the past decades, tremendous efforts have been invested into organic molecules involved in the excited-state intramolecular proton transfer (ESIPT) reaction due to their enormously Stokes-shifted fluorescence and distinctive photophysical properties. The alterations of the environmental medium can effectively adjust the luminous performance of ESIPT molecules, which inspires us to unravel the solvent effect on the ESIPT mechanism. Here, we report the solvent-dependent excited-state properties of two new seven-membered ring pyrrole-indole ESIPT molecules, and , by steady-state spectra, picosecond transient fluorescence spectra, femtosecond transient absorption spectra, and theoretical calculations. The bathochromic-shifted normal fluorescence and the negligibly shifted tautomer fluorescence suggest the occurrence of an excited-state intramolecular proton-coupled charge transfer reaction. Thus, the solvent effect plays a vital role in stabilizing the intramolecular charge transferred state, resulting in a higher ESIPT reaction barrier in more polar solvents. Additionally, the observation of the slight dynamic difference between with different π-conjugation positions provides a new strategy to adjust the performance of ESIPT molecules.
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http://dx.doi.org/10.1021/acs.jpcb.1c07438DOI Listing
October 2021

The FSHR G-29A variant is not associated with the ovarian response to exogenous FSH stimulation.

Am J Reprod Immunol 2021 Sep 23:e13500. Epub 2021 Sep 23.

NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China.

A common genetic variant in the follicle stimulating hormone receptor gene (FSHR) 5'-untranslated region has been previously reported to influence FSHR gene expression. However, studies on the ovarian response to exogenous gonadotropin stimulation are limited. The aim of this study was to evaluate the association of variants at positions -29 of the FSHR gene with the ovarian response to exogenous FSH stimulation in Chinese women. The genotypes of the FSHR gene were assayed using the Sequenom MassARRAY system. Total RNA and protein was extracted from granulosa cells, and FSHR expression at the mRNA and protein levels was assessed using quantitative PCR and western blotting. Our data revealed that there was no association between the FSHR genotype at the -29 position and the outcome of controlled ovarian stimulation. The expression of FSHR, at both the mRNA and protein levels, was similar amongst the different FSHR genotypes assessed, but was significantly reduced in the low responders. These results indicate that the variants caused by mutations at position -29 are not associated with ovarian response, and the low ovarian response to gonadotropin stimulation may be caused by decreased FSHR expression.
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http://dx.doi.org/10.1111/aji.13500DOI Listing
September 2021

Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS.

Front Immunol 2021 27;12:730483. Epub 2021 Aug 27.

Henan Key Laboratory of Immunology and Targeted Drug, Xinxiang Medical University, Xinxiang, China.

The antiviral innate immunity is the first line of host defense against viral infection. Mitochondrial antiviral signaling protein (MAVS, also named Cardif/IPS-1/VISA) is a critical protein in RNA virus-induced antiviral signaling pathways. Our previous research suggested that E3 ubiquitin-protein ligases RING-finger protein (RNF90) negatively regulate cellular antiviral responses by targeting STING for degradation, though its role in RNA virus infection remains unknown. This study demonstrated that RNF90 negatively regulated RNA virus-triggered antiviral innate immune responses in RNF90-silenced PMA-THP1 cells, RNF90-deficient cells (including HaCaTs, MEFs, and BMDMs), and RNF90-deficient mice. However, RNF90 regulated RNA virus-triggered antiviral innate immune responses independent of STING. RNF90 promoted K48-linked ubiquitination of MAVS and its proteasome-dependent degradation, leading to the inhibition of innate immune responses. Altogether, our findings suggested a novel function and mechanism of RNF90 in antiviral innate immunity.
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http://dx.doi.org/10.3389/fimmu.2021.730483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429505PMC
August 2021

Modification of 5-methylphenanthridium from benzothiazoles to indoles as potent FtsZ inhibitors: Broadening the antibacterial spectrum toward vancomycin-resistant enterococci.

Eur J Med Chem 2021 Nov 26;224:113723. Epub 2021 Jul 26.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan, 250012, China. Electronic address:

The death caused by pathogenic bacteria has always been a severe threat to mankind. The prevalence of drug resistance among bacteria underscores an urgent goal for new antibacterial agents with novel mode of action. Here we first designed and synthesized a class of benzothiazolyl-5-methylphenanthridium derivatives and evaluated their antibacterial activity. On this basis, we further designed and synthesized another class of novel indolyl-5-methylphenanthridium derivatives by optimizing the benzothiazolyl-5-methylphenanthridium core and evaluated their antibacterial activity targeting the bacterial cell division protein FtsZ. The results showed that the indolyl-5-methylphenanthridium derivatives had greatly improved activity against various drug-resistant bacterial strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus (VRE). Among them, compound C5 displayed excellent antibacterial activity against susceptible (MIC = 1 μg/mL), methicillin-resistant and clinical isolated S. aureus (MIC = 2 μg/mL). With low hemolytic activity towards mice red blood cells, C5 exhibited good antibacterial effect in vivo in preliminary pharmacodynamic assay. More importantly, C5 was difficult to induce bacterial resistance. Further mechanism studies proved that C5 could inhibit bacterial cell division by promoting FtsZ polymerization, leading to disorderly polymerization and disordered knots. Therefore, our findings suggest that this class of novel indolyl-5-methylphenanthridium derivatives are promising for future antibacterial agents.
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http://dx.doi.org/10.1016/j.ejmech.2021.113723DOI Listing
November 2021

Lupus Nephritis with Obvious IgA deposits in the Kidneys.

Am J Med Sci 2021 Jul 29. Epub 2021 Jul 29.

Department of Nephrology, Peking University International Hospital, Beijing 102206, PR. China. Electronic address:

Objective: The purpose of the current study was to describe the clinico-pathological characteristics and outcomes in patients with lupus nephritis with IgA deposits in the kidneys.

Materials And Methods: A total of 258 patients with lupus nephritis with complete clinical data and follow-up was enrolled. They were divided into two groups: the IgA deposits group and the non-IgA deposits group. Their clinico-pathological features and outcomes between the two groups were further compared.

Results: Patients with IgA deposits had significantly lower prevalence of acute kidney failure, higher eGFR, lower plasma levels of C3a, and lower renal pathological chronicity indices scores than those with non-IgA deposits (19.4% vs. 31.8%, 80.9±35.6 vs. 69.1±39.6 ml/min/1.73m, 1045.48 [559.41, 1796.34] vs. 1920.77 [1155.08, 2986.96]ng/ml, and 2 [1, 3] vs. 2.5 [2, 4], respectively, all P<0.05). Patients with IgA deposits also had a higher frequency of the CFH rs6677604-AA/GA genotype in comparison with those with non-IgA deposits (12.0% vs. 8.2%, P=0.469). Using the multivariable Cox hazard analysis, the IgA deposits were identified as a protective factor of survival from the composite events (HR 0.423; 95% CI, 0.219 to 0.816; P=0.01).

Conclusions: Patients with IgA deposits presented with milder renal damage and a good prognosis, which suggested its protective role in lupus nephritis.
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http://dx.doi.org/10.1016/j.amjms.2020.11.032DOI Listing
July 2021

Development and validation of a nomogram based on multiparametric magnetic resonance imaging and elastography-derived data for the stratification of patients with prostate cancer.

Quant Imaging Med Surg 2021 Jul;11(7):3252-3262

Department of Ultrasound, Shenzhen Medical Ultrasound Engineering Center, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.

Background: This study sought to develop and validate a nomogram combining the elastographic Q-analysis score (EQS), the Prostate Imaging Reporting and Data System (PI-RADS) score, and clinical parameters for the stratification of patients with prostate cancer (PCa).

Methods: A retrospective study was conducted of 375 patients with 375 lesions who underwent volume-navigation transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (MP-MRI)-fusion targeted biopsies between April 2017 and January 2020. Based on a multivariate logistic regression model, a nomogram was created to assess any PCa and high-risk PCa [Gleason score (GS) ≥4+3] using data from patients diagnosed between April 2017 and June 2019 (n=271), and was validated in patients diagnosed after July 2019 (n=104). The nomogram's performance was evaluated based on its discrimination, calibration, and clinical usefulness.

Results: The areas under the curve (AUCs) of the nomogram for predicting any PCa and high-risk PCa were 0.949 [95% confidence interval (CI), 0.921 to 0.978] and 0.936 (95% CI, 0.906 to 0.965), respectively, in the training cohort, and 0.946 (95% CI, 0.894 to 0.997) and 0.971 (95% CI, 0.9331 to 1), respectively, in the validation cohort. The nomogram was well calibrated, and no significant difference was found between the predicted and observed probabilities. A decision curve analysis (DCA) for the nomogram with and without the EQS showed that the threshold probability of for any PCa was <67%.

Conclusions: The nomogram that combined elastography-derived and MP-MRI data was more clinically useful than the model based on PI-RADS and clinical parameters alone. Our nomogram could aid urologists to make decisions and avoid unnecessary biopsies.
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http://dx.doi.org/10.21037/qims-20-978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250010PMC
July 2021

Design, synthesis and structure-activity relationships of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives against various resistant bacteria.

Bioorg Chem 2021 08 18;113:104992. Epub 2021 May 18.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, PR China. Electronic address:

Bacterial infections are still the main significant problem of public health in the world, and their elimination will greatly rely on the discovery of antibacterial drugs. In the processes of our searching for novel macrolide derivatives with excellent activity against sensitive and resistant bacteria, three series of novel N11-, C12- and C13-substituted 15-membered homo-aza-clarithromycin derivatives were designed and synthesized as Series A, B and C by creatively opening the lactone ring of clarithromycin (CAM), introducing various 4-substituted phenyl-1H-1,2,3-triazole side chains at the N11, C12 or C13 position of CAM and macrolactonization. The results from their in vitro antibacterial activity demonstrated that compounds 20c, 20d and 20f displayed not only the most potent activity against S. aureus ATCC25923 with the MIC values of 0.5, 0.5 and 0.5 µg/mL, but also greatly improved activity against B. subtilis ATCC9372 with the MIC values of less than or equal to 0.25, 0.25 and 0.25 µg/mL, respectively. In particular, compound 11g exhibited the strongest antibacterial effectiveness against all the tested resistant bacterial strains and had well balanced activity with the MIC values of 4-8 µg/mL. Further study on minimum bactericidal concentration and kinetics confirmed that compound 11g possessed a bacteriostatic effect on bacterial proliferation. Moreover, the results of molecular docking revealed an potential additional binding force between compound 11g and U790 in addition to the normal binding force of macrolide skeleton, which may explain why this compound performed the most potent activity against resistant bacteria. The results of cytotoxic assay indicated that compounds 20c, 20d and 20f were non-toxic to human breast cancer MCF-7 cells at its effective antibacterial concentration.
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http://dx.doi.org/10.1016/j.bioorg.2021.104992DOI Listing
August 2021

Detection of chlorophyll fluorescence parameters of potato leaves based on continuous wavelet transform and spectral analysis.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Oct 2;259:119768. Epub 2021 Apr 2.

Key Laboratory of Modern Precision Agriculture System Integration Research, Ministry of Education, China Agricultural University, Beijing 100083, China. Electronic address:

The tuber development and nutrient transportation of potato crops are closely related to canopy photosynthesis dynamics. Chlorophyll fluorescence parameters of photosystem II, especially the maximum quantum yield of primary photochemistry (Fv/Fm), are intrinsic indicators for plant photosynthesis. Rapid detection of Fv/Fm of leaves by spectroscopy method instead of time-consuming pulse amplitude modulation technique could help to indicate potato development dynamics and guide field management. Accordingly, this study aims to extract fluorescence signals from hyperspectral reflectance to detect Fv/Fm. Hyperspectral imaging system and closed chlorophyll fluorescence imaging system were applied to collect the spectral data and values of Fv/Fm of 176 samples. The spectral data were decomposed by continuous wavelet transform (CWT) to obtain wavelet coefficients (WFs). Three mother wavelet functions including second derivative of Gaussian (gaus2), biorthogonal 3.3 (bior3.3) and reverse biorthogonal 3.3 (rbio3.3) were compared and the bior3.3 showed the best correlation with Fv/Fm. Two variable selection algorithms were used to select sensitive WFs of Fv/Fm including Monte Carlo uninformative variables elimination (MC-UVE) algorithm and random frog (RF) algorithm. Then the partial least squares (PLS) regression was used to establish detection models, which were labeled as bior3.3-MC-UVE-PLS and bior3.3-RF-PLS, respectively. The determination coefficients of prediction set of bior3.3-MC-UVE-PLS and bior3.3-RF-PLS were 0.8071 and 0.8218, respectively, and the root mean square errors of prediction set were 0.0181 and 0.0174, respectively. The bior3.3-RF-PLS had the best detection performance and the corresponding WFs were mainly distributed in the bands affected by fluorescence emission (650-800 nm), chlorophyll absorption and reflection. Overall, this study demonstrated the potential of CWT in fluorescence signals extraction and can serve as a guide in the quick detection of chlorophyll fluorescence parameters.
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http://dx.doi.org/10.1016/j.saa.2021.119768DOI Listing
October 2021

Design, synthesis and evaluation of novel 9-arylalkyl-10-methylacridinium derivatives as highly potent FtsZ-targeting antibacterial agents.

Eur J Med Chem 2021 Oct 28;221:113480. Epub 2021 Apr 28.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan, 250012, China. Electronic address:

With the increasing incidence of antibiotic resistance, new antibacterial agents having novel mechanisms of action hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Four novel series of substituted 9-arylalkyl-10-methylacridinium derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. The results demonstrated that they exhibited broad-spectrum activities with substantial efficacy against MRSA and VRE, which were superior or comparable to the berberine, sanguinarine, linezolid, ciprofloxacin and vancomycin. In particular, the most promising compound 15f showed rapid bactericidal properties, which avoid the emergence of drug resistance. However, 15f showed no inhibitory effect on Gram-negative bacteria but biofilm formation study gave possible answers. Further target identification and mechanistic studies revealed that 15f functioned as an effective FtsZ inhibitor to alter the dynamics of FtsZ self-polymerization, which resulted in termination of the cell division and caused cell death. Further cytotoxicity and animal studies demonstrated that 15f not only displayed efficacy in a murine model of bacteremia in vivo, but also no significant hemolysis to mammalian cells. Overall, this compound with novel skeleton could serve as an antibacterial lead of FtsZ inhibitor for further evaluation of drug-likeness.
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http://dx.doi.org/10.1016/j.ejmech.2021.113480DOI Listing
October 2021

Screening of hepatotoxic compounds in Psoralea corylifolia L., a traditional Chinese herbal and dietary supplement, using high-resolution mass spectrometry and high-content imaging.

Biomed Chromatogr 2021 Sep 27;35(9):e5140. Epub 2021 Apr 27.

School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.

Owing to the complexity of the composition of herbal and dietary supplements, it is a challenging problem to efficiently screen and identify active or toxic compounds. Psoralea corylifolia L. (PCL) was selected as the subbject to establish a methodology for rapid screening and identification of hepatotoxic compounds. High-content imaging, ultra-performance liquid chromatography and high-resolution mass spectrometry were used in this study to detect the hepatotoxicity and identify unknown compounds in PCL samples. Then, putative toxic compounds which are highly related to hepatotoxicity were screened by spectrum-toxicity correlation analysis, and the toxicity intensity verified by high-content imaging. The maximum nontoxic dose of processed samples with good detoxification effect reduced more than 9 times compared with unprocessed raw medicinal materials. Spectrum-toxicity correlation analysis showed that bavachinin A, bavachin, isobavachalcone and neobavaisoflavone had high correlation with the hepatotoxicity of PCL, and psoralen and isopsoralen had low correlation with hepatotoxicity. This study verified the hepatotoxicity of these six putative compound monomers, proving the results of spectrum-toxicity correlation analysis. Based on the correlation analysis of high-resolution mass spectrometry of detection compounds and high-content imaging of hepatocyte toxicity data, the potential toxic compound of herbal and dietary supplement products can be quickly and accurately screened.
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http://dx.doi.org/10.1002/bmc.5140DOI Listing
September 2021

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin.

Neuropsychiatr Dis Treat 2021 1;17:695-702. Epub 2021 Mar 1.

Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Objective: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats.

Methods: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke.

Results: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (<0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (>0.05).

Conclusion: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.
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http://dx.doi.org/10.2147/NDT.S290148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935344PMC
March 2021

The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients.

Dis Markers 2021 8;2021:8868370. Epub 2021 Feb 8.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Background: At present, the diagnostic accuracy of alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) surveillance is insufficient. It remains controversial whether prothrombin induced by vitamin K absence II (PIVKA-II) has a better diagnostic value than AFP for HCC patients.

Objective: To investigate the diagnostic role of PIVKA-II alone or in combination with AFP in Chinese HCC patients.

Methods: Serum AFP and PIVKA-II levels were detected and analyzed in 308 HCC afflicted patients and 120 unafflicted controls. The receiver operator curve (ROC) and area under the curve (AUC) were conducted to evaluate the clinical value of AFP and PIVKA-II for diagnosing HCC and early HCC.

Results: In the whole HCC cohort, the diagnostic values of PIVKA-II were better than that of AFP. The AUC of PIVKA-II and AFP was 0.90 (95% CI 0.87-0.94) and 0.79 (95% CI 0.74-0.84), respectively. "AFP + PIVKA-II" yielded a high sensitivity of 95.1% and a specificity of 83.3%, with the AUC 0.89 (95% CI 0.85-0.93). In the early stage HCC group, the diagnostic accuracy of PIVKA-II was also better than that of AFP. The AUC of PIVKA-II and AFP was 0.83 (95% CI 0.77-0.89) and 0.75 (95% CI 0.68-0.81), respectively. "AFP + PIVKA-II" achieved the sensitivity of 83.3% and specificity of 89.1%, with an AUC of 0.86 (95% CI 0.81-0.91). Moreover, for AFP-negative HCC patients, serum PIVKA-II showed good diagnostic performance, with an AUC of 0.804 (95% CI 0.720-0.887). Besides, elevated PIVKA-II level was a strong independent risk factor for HCC patients with portal vein tumor thrombus (PVTT) (OR = 4.890, = 0.020).

Conclusion: PIVKA-II is superior to AFP in HCC screening, and AFP in combination with PIVKA-II significantly improves the diagnostic value for Chinese HCC patients. PIVKA-II could effectively indicate HCC accompanied by PVTT and help to optimize the therapeutic strategy.
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http://dx.doi.org/10.1155/2021/8868370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884179PMC
February 2021

Development and validation of a prognostic nomogram for the pre-treatment prediction of early metachronous metastasis in endemic nasopharyngeal carcinoma: a big-data intelligence platform-based analysis.

Ther Adv Med Oncol 2020 21;12:1758835920978132. Epub 2020 Dec 21.

Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China.

Background: Early failure of cancer treatment generally indicates a poor prognosis. Here, we aim to develop and validate a pre-treatment nomogram to predict early metachronous metastasis (EMM) in nasopharyngeal carcinoma (NPC).

Methods: From 2009 to 2015, a total of 9461 patients with NPC (training cohort:  = 7096; validation cohort:  = 2365) were identified from an institutional big-data research platform. EMM was defined as time to metastasis within 2 years after treatment. Early metachronous distant metastasis-free survival (EM-DMFS) was the primary endpoint. A nomogram was established with the significant prognostic factors for EM-DMFS determined by multivariate Cox regression analyses in the training cohort. The Harrell Concordance Index (C-index), area under the receiver operator characteristic curve (AUC), and calibration curves were applied to evaluate this model.

Results: EMM account for 73.5% of the total metachronous metastasis rate and is associated with poor long-term survival in NPC. The final nomogram, which included six clinical variables, achieved satisfactory discriminative performance and significantly outperformed the traditional tumor-node-metastasis (TNM) classification for predicting EM-DMFS: C-index: 0.721 0.638,  < 0.001; AUC: 0.730 0.644,  < 0.001. The calibration curves showed excellent agreement between the predicted and actual EM-DMFS. The nomogram can stratify patients into three risk groups with distinct EM-DMFS (2-year DMFS: 96.8% 90.1% 80.3%,  < 0.001). A validation cohort supported the results. The three identified risk groups are correlated with the efficacy of different treatment regimens.

Conclusion: Our established nomogram can reliably predict EMM in patients with NPC and might aid in formulating risk-adapted treatment decisions and personalized patient follow-up strategies.
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http://dx.doi.org/10.1177/1758835920978132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758560PMC
December 2020

[Clinical cases and experimental evaluation of liver injury related to anti-psoriasis Keyin Pills].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(20):5017-5023

China Military Institute of Chinese Medicine, the Fifth Medical Center of Chinese PLA General Hospital Beijing 100039, China.

Keyin Pills is a kind of traditional Chinese medicine for the treatment of psoriasis, but it has been reported that it can cause serious liver injury. In this paper, we used the integrated evidence chain method to retrieve and reevaluate the adverse drug reaction database, CNKI literature and cases of liver injury relating to Keyin Pills in specialist hepatology hospitals. We screened out 23 cases with the causal relationship of the possible grade and above. Among them, 11 cases showed the positive causal relationship only with Keyin Pills, accounting for 47.83%, suggesting that there was objective liver injury caused by Keyin Pills. The incubation period of liver injury caused by Keyin Pills is 1-90 days, and the cumulative dosage span is 20-1 800 g. There were obvious individual diffe-rences. There was no relationship between liver injury as well as dose and course of treatment, suggesting that Keyin Pills could induce immune idiosyncratic liver injury. Furthermore, based on the liver injury model induced by immunological stress, it was confirmed that Keyin Pills could induce acute liver injury in a dose-dependent manner in rats with immunological stress. The toxic dose(14 g·kg~(-1)) of a single dose was 6.7 times of the clinical equivalent dose, and had no significant effect on the biochemical index of liver function and histopathology in normal rats. Decomposition experiments showed that Dictamnus dasycarpus in Keyin Pills is the main medicinal flavor that causes special liver injury, and the other three medicines had neither liver injury nor compatibility attenuation effect. The results suggest that clinical medication shall pay attention to the risk of liver injury caused by Keyin Pills in patients with immunological stress.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200302.507DOI Listing
October 2020

Genetic Variant CFH rs6677604 Might Play a Protective Role in lupus Nephritis.

Am J Med Sci 2021 03 9;361(3):336-343. Epub 2020 Oct 9.

Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, PR China; Department of Nephrology, Peking University International Hospital, Beijing, PR China.

Background: This study aimed to explore the associations between the complement factor H (CFH) rs6677604 and clinico-pathological characteristics of lupus nephritis.

Materials And Methods: A total of 188 patients with lupus nephritis with complete clinico-pathological data were enrolled and genotyping of CFH rs6677604 was conducted by TaqMan SNP genotyping assays. Patients were divided into two groups by rs6677604-AA/AG or -GG, and the clinico-pathological features between the two groups were further compared.

Results: We found that patients with rs6677604-AA/AG presented with lower prevalence of anti-dsDNA antibody (12/24 [50.0%] vs 121/164 [73.8%], P = 0.028), higher level of plasma C3a (2642.96 ± 1575.05 vs 1640.01 ± 1209.40, ng/ml, P = 0.024), and a tendency for higher level of plasma CFH (505.76 ± 169.28 vs 397.67 ± 179.11, μg/ml, P = 0.087). Patients with rs6677604-AA/AG had milder renal histopathological features, including total activity indices score (4.5[0, 13] vs 8[0, 19], P = 0.013), endocapillary hypercellularity (1.5[0, 3] vs 3[0, 3], P = 0.013), sub-endothelial hyaline deposits (0.5[0, 3] vs 1[0,3], P = 0.021), glomerular leukocyte infiltration (0.5[0, 1] vs 1[0, 12], P = 0.023) and tubular atrophy (1[0, 1] vs 1[0, 3], P = 0.027) than those with rs6677604-GG, which was further confirmed by the stratified analysis. The rs6677604-A was not a risk factor for patients' renal outcomes (hazard ratio=0.898; 95% CI: 0.264-3.059, P = 0.863).

Conclusions: The rs6677604-A genotype in CFH was associated with milder renal pathological features in lupus nephritis, and its protective effect on the pathogenesis of the disease remained to be elucidated.
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http://dx.doi.org/10.1016/j.amjms.2020.10.008DOI Listing
March 2021

Development of a Nomogram Model for Treatment of Nonmetastatic Nasopharyngeal Carcinoma.

JAMA Netw Open 2020 12 1;3(12):e2029882. Epub 2020 Dec 1.

Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Department of Molecular Diagnostics, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Importance: Because of tumor heterogeneity, overall survival (OS) differs significantly among individuals with nasopharyngeal carcinoma (NPC), even among those with the same clinical stage. Relying solely on TNM staging to guide treatment remains imperfect.

Objectives: To establish a comprehensive nomogram to estimate individualized OS and to explore stratified treatment regimens for risk subgroups in nonmetastatic NPC.

Design, Setting, And Participants: This cohort study included 8093 patients diagnosed with NPC at a single center in China from April 2009 to December 2015. The sample was split into a training cohort (5398 participants [66.7%]) and validation cohort (2695 [33.3%]). Data were analyzed in May 2020.

Exposures: Age, T stage, N stage, Epstein-Barr virus (EBV) DNA level, serum lactate dehydrogenase (LDH) levels, and albumin (ALB) levels.

Main Outcomes And Measures: The primary end point was OS. The nomogram for estimating OS was generated based on multivariate Cox proportional hazards regression. The performance of the nomogram was quantified using Harrell concordance index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, and a calibration curve. OS rates were established using the Kaplan-Meier method, and intersubgroup differences were examined by the log-rank test.

Results: Among the 8093 participants, 5688 (70.3%) were men, and the median age at diagnosis was 45 years (range, 7-85 years). Six variables (age, T stage, N stage, EBV DNA levels, LDH levels, and ALB levels) were identified through multivariate Cox regression and incorporated into a nomogram to estimate OS. The resulting nomogram showed excellent discriminative ability and significantly outperformed the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for estimating OS (C index, 0.716 [95% CI, 0.698-0.734] vs 0.643 [95% CI, 0.624-0.661]; P < .001; AUC, 0.717 [95% CI, 0.698-0.737] vs 0.643 [95% CI, 0.623-0.662]; P < .001), and the calibration curves showed satisfactory agreement between the actual and nomogram-estimated OS rates. The validation cohort confirmed the results. Patients were stratified into 4 risk groups based on the 25th, 50th, and 75th percentile score values estimated from the nomogram. The 4 nomogram-defined risk groups demonstrated significantly different intergroup OS (3-year OS rates: risk group 1, 1328 of 1345 [98.7%]; risk group 2, 1289 of 1341 [96.1%]; risk group 3, 1222 of 1321 [92.5%]; risk group 4, 1173 of 1391 [84.3%]; P < .001). These risk groups were associated with the efficacy of different treatment regimens. For example, for risk group 4, induction chemotherapy with concurrent chemoradiotherapy was associated with a significantly better OS than concurrent chemoradiotherapy (log-rank P = .008) and intensity-modulated radiotherapy alone (log-rank P < .001).

Conclusions And Relevance: In this study, the proposed nomogram model enabled individualized prognostication of OS and could help to guide risk-adapted treatment for patients with nonmetastatic NPC.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.29882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733160PMC
December 2020

Antimicrobial Action and Reversal of Resistance in MRSA by Difluorobenzamide Derivatives Targeted at FtsZ.

Antibiotics (Basel) 2020 Dec 5;9(12). Epub 2020 Dec 5.

Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide 5000, South Australia, Australia.

The bacterial cell division protein, FtsZ, has been identified as a target for antimicrobial development. Derivatives of 3-methoxybenzamide have shown promising activities as FtsZ inhibitors in Gram-positive bacteria. We sought to characterise the activity of five difluorobenzamide derivatives with non-heterocyclic substituents attached through the 3-oxygen. These compounds exhibited antimicrobial activity against methicillin resistant (MRSA), with an isopentyloxy-substituted compound showing modest activity against vancomycin resistant (VRE). The compounds were able to reverse resistance to oxacillin in highly resistant clinical MRSA strains at concentrations far below their MICs. Three of the compounds inhibited an strain lacking the AcrAB components of a drug efflux pump, which suggests the lack of Gram-negative activity can partly be attributed to efflux. The compounds inhibited cell division by targeting FtsZ, producing a dose-dependent increase in GTPase rate which increased the rate of FtsZ polymerization and stabilized the FtsZ polymers. These compounds did not affect the polymerization of mammalian tubulin and did not display haemolytic activity or cytotoxicity. These derivatives are therefore promising compounds for further development as antimicrobial agents or as resistance breakers to re-sensitive MRSA to beta-lactam antibiotics.
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http://dx.doi.org/10.3390/antibiotics9120873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762090PMC
December 2020

Discovery of γ-Lactam Alkaloid Derivatives as Potential Fungicidal Agents Targeting Steroid Biosynthesis.

J Agric Food Chem 2020 Dec 22;68(49):14438-14451. Epub 2020 Nov 22.

National Biopesticide Engineering Research Centre, Hubei Biopesticide Engineering Research Centre, Hubei Academy of Agricultural Science, Wuhan 430064, China.

Biological control of plant pathogens is considered as one of the green and effective technologies using beneficial microorganisms or microbial secondary metabolites against plant diseases, and so microbial natural products have played important roles in the research and development of new and green agrochemicals. To explore the potential applications for natural γ-lactam alkaloids and their derivatives, 26 γ-lactams that have flexible substituent patterns were synthesized and characterized, and their antifungal activities against eight kinds of plant pathogens belonging to oomycetes, basidiomycetes, and deuteromycetes were fully evaluated. In addition, the high potential compounds were further tested using an assay against blight of pepper to verify a practical application for controlling oomycete diseases. The potential modes of action for compound against were also investigated using microscopic technology (optical microscopy, scanning electron microscopy, and transmission electron microscopy) and label-free quantitative proteomics analysis. The results demonstrated that compound may be a potential novel fungicidal agent against oomycete diseases (EC = 4.9748 μg·mL for and EC = 5.1602 μg·mL for ) that can act on steroid biosynthesis, which can provide a certain theoretical basis for the development of natural lactam derivatives as potential antifungal agents.
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http://dx.doi.org/10.1021/acs.jafc.0c05823DOI Listing
December 2020

Development and validation of a nomogram for predicting prostate cancer in men with prostate-specific antigen grey zone based on retrospective analysis of clinical and multi-parameter magnetic resonance imaging/transrectal ultrasound fusion-derived data.

Transl Androl Urol 2020 Oct;9(5):2179-2191

Department of Ultrasound, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology (Shenzhen People's Hospital), Shenzhen Medical Ultrasound Engineering Center, Shenzhen, China.

Background: Urologists face a dilemma when deciding whether prostate biopsy is required for patients with prostate-specific antigen (PSA) levels in the grey zone (4 to 10 ng/mL).

Methods: We retrospectively analyzed data from consecutive patients with PSA levels in grey zone, who underwent targeted multiparametric magnetic resonance imaging (MP-MRI)/transrectal ultrasound (TRUS) fusion biopsy with elastography between November 2017 and December 2019 in our hospital. The patientse data including age, PSA, fPSA (free PSA), fPSA/PSA, PSA density (PSAD), prostate volume, elastography Q-analysis score (EQS), and prostate imaging-reporting and data system (PI-RADS) score were collected. The nomogram was built using logistic regression and the final cohort of patients was randomly divided into a training cohort (70%) and a validation cohort (30%) by R software. The models were evaluated by receiver operating characteristic curve (ROC) analysis and calibration curve analysis. The nomogram was constructed from the best model.

Results: The final study cohort consisted of 155 patients (training cohort, 109 patients; validation cohort, 46 patients) with PSA in the grey zone, of which 36 patients were pathologically diagnosed with PCa. The EQS model, -EQS model, +EQS model were built. The +EQS model that consisted of fPSA/PSA, EQS, and PI-RADS score had the best PCa diagnostic accuracy (development and validation, 0.783 and 0.781) and probability score (development and validation, 0.939 . 0.622). The new nomogram based on this model was constructed, in which fPSA/PSA ratio had the largest impact, followed by PI-RADS and EQS.

Conclusions: Elastography and pre-biopsy MP-MRI has clinical significance for patients with PSA in the grey zone. The new nomogram, which is based on pre biopsy data including serological analysis, PI-RADS score, and EQS, can be helpful for clinical decision-making to avoid unnecessary biopsy.
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http://dx.doi.org/10.21037/tau-20-1154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658138PMC
October 2020

Design and synthesis of novel 4-substituted quinazoline-2-carboxamide derivatives targeting AcrB to reverse the bacterial multidrug resistance.

Bioorg Chem 2020 12 21;105:104394. Epub 2020 Oct 21.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. Electronic address:

Novel 4-substituted quinazoline-2-carboxamide derivatives targeting AcrB were designed, synthesized and evaluated for their biological activity as AcrB inhibitors. In particular, the ability of the compounds to potentiate the activity of antibiotics, to inhibit Nile Red efflux and to target AcrB was investigated. In this study, 19 compounds were identified to reduce the MIC values of at least one tested antibacterial by 2- to 16-fold at a lower concentration. Identified modulating compounds also possessed considerable inhibition on Nile red efflux at concentrations as low as 50 µM and did not display off-target effects on the outer membrane. Among the above compounds with characteristics of ideal AcrB inhibitors, the most outstanding ones are A15 and B5-B7. In particular, A15 and B7 exhibited not only the most prominent performance in the synergistic effect, but also completely abolished Nile Red efflux at concentrations of 50 and 100 μM, respectively. In docking simulations, A15 was observed to have the most favorable docking score and was predicted to bind in the hydrophobic trap as has been noted with other inhibitors such as MBX2319. It is worth noting that the 4-morpholinoquinazoline-2-carboxamide core appears to be a promising chemical skeleton to be further optimized for the discovery of more potent AcrB inhibitors.
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http://dx.doi.org/10.1016/j.bioorg.2020.104394DOI Listing
December 2020

Design, synthesis of novel 4,5-dihydroisoxazole-containing benzamide derivatives as highly potent FtsZ inhibitors capable of killing a variety of MDR Staphylococcus aureus.

Bioorg Med Chem 2020 11 27;28(21):115729. Epub 2020 Aug 27.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. Electronic address:

Antibiotic resistance among clinically significant bacterial pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) is becoming a prevalent threat to public health, and new antibacterial agents with novel mechanisms of action hence are in an urgent need. As a part of continuing effort to develop antibacterial agents, we rationally designed and synthesized two series of 4,5-dihydroisoxazol-5-yl and 4,5-dihydroisoxazol-3-yl-containing benzamide derivatives that targeted the bacterial cell division protein FtsZ. Evaluation of their activity against a panel of Gram-positive and -negative pathogens revealed that compound A16 possessing the 4,5-dihydroisoxazol-5-yl group showed outstanding antibacterial activity (MIC, ≤0.125-0.5 μg/mL) against various testing strains, including methicillin-resistant, penicillin-resistant and clinical isolated S. aureus strains. Besides, further mouse infection model revealed that A16 could be effective in vivo and non-toxic to Hela cells. Finally, a detailed discussion of structure-activity relationships was conducted, referring to the docking results. It is worth noting that substituting a 4,5-dihydroisoxazole ring for the isoxazole ring not only broadened the antibacterial spectrum but also resulted in a significant increase in antibacterial activity against S. aureus strains. Taken together, these results suggest a promising chemotype for the development of new FtsZ-targeting bactericidal agents.
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http://dx.doi.org/10.1016/j.bmc.2020.115729DOI Listing
November 2020

Total Synthesis of Semaglutide Based on a Soluble Hydrophobic-Support-Assisted Liquid-Phase Synthetic Method.

ACS Comb Sci 2020 12 15;22(12):821-825. Epub 2020 Oct 15.

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China.

Considering the high cost of the production of semaglutide, which is currently the most promising antidiabetic drug especially for the treatment of type 2 diabetes mellitus, a new synthetic route of semaglutide production that possesses excellent yield and high purity is of vital importance. Herein, we reported a newly developed synthetic route of semaglutide that is simple and efficient, based on a soluble hydrophobic-support-assisted liquid-phase synthetic method by applying Alloc-chemistry to the synthesis of the main chain peptide and side chain peptide of semaglutide. With careful optimization of the reaction conditions and innovative strategy of post-synthetic treatments, the total yield and purity of the crude semaglutide was improved satisfactorily.
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http://dx.doi.org/10.1021/acscombsci.0c00134DOI Listing
December 2020

Hypermethylation of SCAND3 and Myo1g Gene Are Potential Diagnostic Biomarkers for Hepatocellular Carcinoma.

Cancers (Basel) 2020 Aug 18;12(8). Epub 2020 Aug 18.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

Presently, there is a lack of effective blood-based biomarkers facilitating the diagnosis of hepatocellular carcinoma (HCC). Thus, we aimed to investigate novel methylation markers for HCC diagnosis, and explore relationships between biomarker methylation and clinicopathology of HCC. The methylation status of the SCAN domain containing three (SCAND3) and myosin 1g (Myo1g) genes in HCC cell lines and tissues were detected by digital droplet PCR. The serum SCAND3 and Myo1g methylation levels were analyzed in HCC-afflicted patients and unafflicted controls. The results indicated SCAND3 and Myo1g methylation were abnormally high in the HCC cell lines and tissues. The values of serum SCAND3, Myo1g, and SCAND3 + Myo1g methylation with respect to facilitating the detection, and early detection of HCC were better than for alpha-fetoprotein (AFP) alone. Furthermore, when we combined SCAND3 + Myo1g with AFP, a high sensitivity and specificity resulted. Notably, in the AFP-negative HCC group, the methylation of SCAND3 and Myo1g also showed an excellent diagnostic performance. Besides this, a high serum SCAND3 methylation level was an independent risk factor for predicting portal vein tumor thrombus (PVTT) in HCC patients (OR = 4.746, = 0.013). Finally, SCAND3 and Myo1g enhanced the HCC diagnostics as noninvasive serum methylation biomarkers, and the SCAND3 methylation status effectively indicated HCC accompanied by PVTT.
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http://dx.doi.org/10.3390/cancers12082332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465898PMC
August 2020

Structure Characterization and Solubility Analysis of the Existent Gum of the Fischer-Tropsch Synthetic Crude.

ACS Omega 2020 Aug 24;5(30):18778-18786. Epub 2020 Jul 24.

School of Chemical Engineering, Northwest University, Xi'an 710069, People's Republic of China.

The existent gum content of the Fisher-Tropsch synthetic crude exceeded the standard seriously, affecting its transportation and use. To determine the structure of the existent gum extracted from the Fisher-Tropsch synthetic crude, elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, nuclear magnetic resonance (NMR), and X-ray photoelectron spectroscopy (XPS) were employed to determine the chemical structure of the gum. The Brown-Ladner method is used to calculate the average structural parameters and the average molecular formula of the existent gum. The results show that the existent gum of the Fisher-Tropsch synthetic crude is composed of heterocyclic aromatic hydrocarbons and short-carbon paraffins. Compared with petroleum gums and coal tar gums, the existent gum content of the Fisher-Tropsch synthetic crude has the characteristics of high aromaticity, short side chains, and nitrogen-containing heterocycles. After being oxidized, its aromaticity further increases, more closed loops are formed, and the side chain is further shortened. This is caused by a complex oxidation reaction during the oxidation process. Molecular dynamics simulation calculations were performed to reveal the T-stacked morphology of the existent gum of the Fisher-Tropsch synthetic crude in a mixed solvent of acetone and toluene.
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http://dx.doi.org/10.1021/acsomega.0c01871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408234PMC
August 2020

Antiscalants in RO membrane scaling control.

Water Res 2020 Sep 18;183:115985. Epub 2020 Jun 18.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, PR China. Electronic address:

Reverse osmosis (RO) plays an important role in freshwater production. Mineral scaling is an inevitable problem in the RO desalination process. Various methods, including the pretreatment of feed water, the optimization of operational processes, the development of novel membrane materials, and the addition of antiscalants, have been developed to mitigate scale formation in RO systems. Among these methods, the addition of antiscalants is a relatively cost-effective and convenient technique for membrane scaling control. In the current work, various kinds of antiscalants, scale inhibition mechanisms, and their applications to RO membrane scaling control are reviewed. Weakness of existing antiscalants and challenge arising from their practical applications, such as membrane fouling caused by antiscalants, increased bacterial growth, dosing control, and the disposal of resultant concentrates, are also presented. To effectively alleviate scaling on RO membrane by using antiscalants, the development of novel, high-performance, and environment-friendly antiscalants on the basis of an in-depth study of the inhibition mechanisms and well-established structure-activity relationships is urgently necessary. The optimization of antiscalants and their combinations with other pretreatments in practical RO operations are essential in efficient scaling control.
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http://dx.doi.org/10.1016/j.watres.2020.115985DOI Listing
September 2020

Risk stratification for nasopharyngeal carcinoma: a real-world study based on locoregional extension patterns and Epstein-Barr virus DNA load.

Ther Adv Med Oncol 2020 12;12:1758835920932052. Epub 2020 Jun 12.

Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.

Aim: The present study aimed to evaluate the combined value of locoregional extension patterns (LEPs) and circulating cell-free Epstein-Barr virus (cf EBV) DNA for risk stratification of locoregionally advanced nasopharyngeal carcinoma (LA-NPC) to better guide therapeutic strategies.

Methods: A total of 7227 cases of LA-NPC were reviewed retrospectively and classified into six groups according to their LEP (ascending, descending, or mixed type) and pre-treatment cf EBV-DNA load (⩾ <4000 copy/ml). Using a supervised statistical clustering approach, patients in the six groups were clustered into low, intermediate, and high-risk clusters. Progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were calculated using the Kaplan-Meier method and differences were compared using the log-rank test.

Results: Survival curves for the low, intermediate, and high-risk clusters were significantly different for all endpoints. The 5-year survival rate for the low, intermediate, and high-risk clusters, respectively, were: PFS (83.5%, 73.2%, 62.6%,  < 0.001), OS (91.0%, 82.7%, 73.2%,  < 0.001), DMFS (92.3%, 83.0%, 73.4%,  < 0.001), and LRRFS (91.0%, 88.0%, 83.3%,  < 0.001). The risk clusters acted as independent prognostic factors for all endpoints. Among the patients in the high-risk cluster, neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (CCRT) significantly improved the patients 5-year PFS (66.4% 57.9%,  = 0.014), OS (77.6% 68.6%;  < 0.002), and DMFS (76.6% 70.6%;  = 0.028) compared with those treated with CCRT.

Conclusion: Our results could facilitate the development of risk-stratification and risk-adapted therapeutic strategies for patients with LA-NPC.
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http://dx.doi.org/10.1177/1758835920932052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294474PMC
June 2020

Deprotonation of Guanine Radical Cation G Mediated by the Protonated Water Cluster.

J Phys Chem A 2020 Jul 9;124(29):6076-6083. Epub 2020 Jul 9.

College of Chemistry, Beijing Normal University, Beijing 100875, P. R. China.

Proton transfer is regarded as a fundamental process in chemical reactions of DNA molecules and continues to be an active research theme due to the connection with charge transport and oxidation damage of DNA. For the guanine radical cation (G) derived from one-electron oxidation, experiments suggest a facile proton transfer within the G:C base pair, and a rapid deprotonation from N1 in free base or single-strand DNA. To address the deprotonation mechanism, we perform a thorough investigation on deprotonation of G in free G base by combining density functional theory (DFT) and laser flash photolysis spectroscopy. Experimentally, kinetics of deprotonation is monitored at temperatures varying from 280 to 298 K, from which the activation energy of 15.1 ± 1.5 kJ/mol is determined for the first time. Theoretically, four solvation models incorporating explicit waters and the polarized continuum model (PCM), i.e., 3HO-PCM, 4HO-PCM, 5HO-PCM, and 7HO-PCM models are used to calculate deprotonation potential energy profile, and the barriers of 5.5, 13.4, 14.4, and 13.7 kJ/mol are obtained, respectively. It is shown that at least four explicit waters are required for properly simulating the deprotonation reaction, where the participation of protonated water cluster plays key roles in facilitating the proton release from G.
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http://dx.doi.org/10.1021/acs.jpca.0c03748DOI Listing
July 2020

Circulating anti-C3b IgG in lupus nephritis: A large cohort study.

Clin Immunol 2020 08 18;217:108514. Epub 2020 Jun 18.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, PR China; Peking-Tsinghua Center for Life Sciences; Beijing, 100084, PR. China; Institute of Nephrology, Peking University, Beijing 100034, PR China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, PR China; Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, PR China.

The current study aimed to analyze the clinical significance and bio-functional properties of anti-C3b IgG based on a lupus nephritis cohort. We found that the prevalence of anti-C3b IgG in our cohort was 47.8%. Patients with positive anti-C3b IgG had significantly higher SLEDAI, lower circulating C3 and C4 levels. Anti-C3b IgG levels were positively correlated with C3 or C1q deposition in kidneys and several active pathological lesions. The positivity of anti-C3b IgG was an independent risk factor for the composite endpoints in the subgroup of proliferative lupus nephritis patients. In vitro, the purified IgG fractions from positive patients resulted in increased C3a generation through the alternative pathway, and interfered factor H and CR1 binding to C3b. Our findings indicated that anti-C3b IgG associated with local renal injury and long-term outcomes in lupus nephritis patients, possibly through leading to the complement alternative pathway over-activation.
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http://dx.doi.org/10.1016/j.clim.2020.108514DOI Listing
August 2020
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