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1.
Org Lett ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026228

RESUMO

The first Pd/Cu catalyzed selective C2-alkenylation of pyridines with internal alkynes has been developed via the pyridinium salt activation strategy. Importantly, the configuration of the product alkenylpyridines could be tuned by the choice of the proper N-alkyl group of the pyridinium salts, thus allowing for both the Z- and E-alkenylpyridines synthesized with good regio- and stereoselectivity. A plausible mechanism was proposed based on the Hammett study and KIE experiment.

2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 216-222, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981275

RESUMO

Objective: To observe whether the mechanism of small dose capsaicin (Cap) against pulmonary fibrosis in mouse is mediated by agitating transient receptor potential vanilloid 1 (TRPV1). Methods: A total of 60 BALB/c mice were randomly divided into control (CON) group, bleomycin (BLM)group, Cap (0.5, 1,2 mg/kg) groups and Cap (2 mg/kg) plus SB-452533 (2.5 mg/kg) group. C57BL/6 mice were intratracheally injected with 3.5 mg/kg BLM to induce pulmonary fibrosis model. Animals for drugs treatment received daily drug via subcutaneous injection for 21 days. The morphological changes and collagen deposition in lung tissues were analysed by HE staining, Masson staining and immunohistochemistry. The concentration of calcitonin gene-related peptide (CGRP) in plasma was determined by ELISA. The mRNA and (or) proteins levels of α-CGRP, ß-CGRP, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), vimentin, alpha smooth muscle actin (α-SMA), TRPV1, p-ERK1/2 and eukaryotic initiation factor 3a (eIF3a) were detected by qPCR and (or) Western blot. Results: Compared with the BLM group, small dose Cap significantly reduced bleomycin-induced pulmonary fibrosis in mice and obviously reversed alveolar epithelial cells epithelial-mesenchymal transition (EMT) (the expression of E-cadherin and ZO-1 were increased(P<0.05 or P<0.01)and the expression of α-SMA and Vimentin were decreased (P<0.05 or P<0.01) after drugs treatment for 21 day, concomitantly with the increase the expressions of TRPV1 and CGRP (P<0.05 or P<0.01), and inhibiting ERK1/2 phosphorylation and eIF3a expression (P<0.05 or P<0.01). These effects of small dose Cap were abolished in the presence of TRPV1 receptor antagonist SB-452533. Conclusion: The results suggest that small dose Cap can reverse alveolar epithelial cells EMT and alleviate bleomycin-induced pulmonary fibrosis in mice by inhibiting ERK1/2/eIF3asignaling pathway, which is related to agitating TRPV1 receptor and releasing of CGRP.

3.
Chembiochem ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32961013

RESUMO

Photoactivatable fluorophores are emerging optical probes for biological applications. Most photoactivatable fluorophores are relatively large in size and need to be activated using ultraviolet light, dramatically limiting their applications. To introduce photoactivatable fluorophores into proteins, recent investigations have explored several protein labeling technologies, including fluorescein arsenical hairpin (FlAsH) Tag, HaloTag labeling, SNAPTag labeling, and bioorthogonal conjugation. However, these techniques require a multi-step labeling process. Here, by using Genetic Code Expansion and a single sulfur-for-oxygen atom replacement within an existing fluorescent amino acid, we have site-specifically incorporated the photoactivatable fluorescent amino acid thioacridonylalanine (SAcd) into proteins in a single step. Moreover, upon exposure to visible light, SAcd can be efficiently desulfurized to its oxo derivatives, thus restoring the strong fluorescence of labeled proteins.

4.
Bioorg Chem ; 104: 104265, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32919128

RESUMO

A series of benzophenone derivatives bearing naphthalene moiety were designed, synthesized, characterized by 1H NMR, 13C NMR, and HRMS and evaluated for their antiproliferative activity against human breast cancer cell line (MCF-7). Most of the tested derivatives showed good to moderate cytotoxicity against MCF-7 cell line. Among them, compound 4u (IC50 = 1.47 ± 0.14 µM) was found to be the most active compound, which is more active than the standard drug cisplatin (IC50 = 15.24 ± 1.27 µM). In vitro tubulin polymerization inhibition assay, EBI competition assay, cell cycle analysis, and cell apoptosis assay identified that compound 4u was a new tubulin polymerization inhibitor by targeting the colchicine binding site. Besides, molecular docking study showed that compound 4u has high binding affinities with the colchicine binding site of tubulin through hydrogen bond, cation-π, and hydrophobic interaction.

5.
Mikrochim Acta ; 187(8): 450, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32676787

RESUMO

A photoelectrochemical (PEC) aptasensing platform is devised for sensitive detection of an organophosphorus pesticide based on dissolution of core-shell MnO2 nanoflower@CdS (MnO2 NF@CdS) by thiocholine (TCh). TCH is produced from the butyrylcholinesterase-acetylthiocholine system, accompanied by target-triggered rolling circle amplification (RCA). The core-shell MnO2 NF@CdS with excellent PEC performance was synthesized and employed as a photo-sensing platform. The target was detected on a functionalized magnetic probe with the corresponding aptamer. Upon malathion introduction, the aptamer was detached from the magnetic beads, while capture DNA (cDNA, with primer fragment) remained on the beads. The primer fragment in cDNA can trigger the RCA reaction to form a long single-stranded DNA (ssDNA). Furthermore, a large number of butyrylcholinesterase (BChE) were assembled on the long ssDNA strands through the hybridization with the S2-Au-BChE probe. Thereafter, TCh generated from hydrolysis of ATCh by BChE can reduce MnO2 NF (core) to Mn2+ and release the CdS nanoparticles (shell) from the platform electrode, significantly enhancing the PEC signal. Under optimal conditions, the proposed aptasensor exhibited high sensitivity for malathion with a low detection limit of 0.68 pg mL-1. Meanwhile, it also presents outstanding specificity, reproducibility, and stability. Importantly, the sensing platform provides a new concept for detection of pesticide. Graphical abstract Herein, this work devised a photoelectrochemical (PEC) aptasensing platform for sensitive detection of organophosphorus pesticide based on dissolution of core-shell MnO2 nanoflower@CdS (MnO2 NF@CdS) by the as-produced thiocholine (TCh) from the butyrylcholinesterase-acetylthiocholine system, accompanying with the target-triggered rolling circle amplification (RCA).

6.
Anal Bioanal Chem ; 412(25): 6939-6945, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32691085

RESUMO

Organophosphorus pesticides (OPs) are extensively used worldwide as agrochemicals; however, excess use may threaten the health of humans. Thus, it is an urgent need to develop a sensitive method for determination of OPs. Herein, a simple and sensitive split-type electrochemical method was developed by using MnO2 nanoflower-electron mediator as a signal transduction element. The MnO2 nanoflower-electron mediator was synthesized and shows an excellent electrochemical signal attributed to the high specific surface area of MnO2 nanoflower. Meanwhile, the inhibition of OPs on butyrylcholinesterase (BChE) was carried out in the homogeneous system. In the absence of target molecule, a large number of thiocholines (TCh) were yielded from hydrolysis of acetylthiocholine (ATCh) by BChE. The MnO2 nanoflower was cracked, and subsequently, multiple electron mediator molecules were released from the platform after treated with TCh, thus decreasing the electrochemical response. Furthermore, the inhibition of OPs on BChE resulted in the reduced generation of TCh, thus inducing the recovery of electrochemical signal. Under the optimal experimental, dichlorvos can be detected in a wide range of 10-6-10-10 M, with a detection limit of 3 × 10-10 M. Moreover, the assay was successfully used to analyze dichlorvos in cucumber juice and pear juice, showing a great promising potential for detecting organophosphorus pesticides in complex samples. Graphical abstract In this assay, a split-type electrochemical biosensor was proposed for the ultrasensitive determination of organophosphorus pesticides based on the MnO2 nanoflower-electron mediator as an electrochemical signal component.

7.
Zhongguo Zhong Yao Za Zhi ; 45(13): 3220-3227, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32726032

RESUMO

This project is to study the metabolites of Laportea bulbifera extract in rat feces. After the SD rats were gavaged with the extract(136 g·kg~(-1), according to the crude drug dose), the metabolites in their feces were detected by UHPLC-Q-TOF-MS~E technique, and the obtained mass spectrometry data was combined with UNIFI software for prediction. The prototype components and metabolites in rat feces were identified with reference materials and related literature. A total of 43 metabolites were identified(including 8 prototype components and 35 metabolites). The metabolic pathways mainly include monocaffeoylquinic acid(hydrogenation reduction, ring-opening cracking, sulfation, hydroxylation, glucuronidation), quercetin(O-C2 bond ring-opening cleavage, C2-C3 double bond reduction, rutin carbonylation) and so on. The metabolites and metabolic process of L. bulbifera extract in rat feces were clarified, which provided a basis for the study of the active substances and its mechanism of action.


Assuntos
Urticaceae , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Fezes , Extratos Vegetais , Ratos , Ratos Sprague-Dawley
9.
Biochem Biophys Res Commun ; 528(1): 62-70, 2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32456796

RESUMO

The acquisition of chemoresistance is a major clinical challenge for pancreatic cancer (PC) treatment. Chemoresistance is largely attributed to aberrant DNA damage repair. However, the underlying mechanisms of chemoresistance in pancreatic cancer remain unclear. Here, we showed that CD147 was strongly correlated to DNA damage response (DDR) indices and poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients. CD147 knockdown or monoclonal antibodies improved the killing effects of gemcitabine in gemcitabine resistant cells, exhibiting reduced activation of ATM/p53. Moreover, we found the interaction of CD147 with ATM, ATR and p53, which was augmented in gemcitabine resistant cells. High CD147/p-ATM/p-ATR/p-p53 cytoplasmic expression associated with poor survival of PC patients. Our studies thus identify CD147 as a critical player in DDR programing that affects gemcitabine therapeutic outcomes of pancreatic cancer patients.

11.
Zhongguo Zhong Yao Za Zhi ; 45(2): 405-411, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-32237325

RESUMO

This work aimed to investigate the intestinal absorption characteristics of Laportea bulbifera extract in normal and rheumatoid arthritis model rats. The contents of neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, kaempferol-3-O-rutinoside, galuteolin, quercetin and isoquercetin in intestinal absorption solution samples were detected by UPLC-MS/MS with 5.0 g·L~(-1) as the absorption concentration. The cumulative absorption(Q) and absorption rate constant(K_a) were calculated, and the absorption characteristics of different components of L. bulbifera in intestinal absorption solution of normal rats and rheumatoid arthritis rats were compared. The results showed that all the eight index components in the extract of L. bulbifera could be absorbed into the intestinal capsule, the cumulative absorption-time curve of each component showed an upward trend without saturation, and the correlation regression coefficient(R~2) was greater than 0.92, which is consistent with the zero-order absorption rate process. It was speculated that the possible absorption mode of each component was passive diffusion. In normal condition, the absorption of ileum was the best(except chlorogenic acid), and in pathological condition, duodenum was the best. The total absorption of 8 components in each intestinal segment of RA rats was better than that of normal rats, which speculated that rheumatoid arthritis may change the specific site of drug absorption. The experimental results showed that rheumatoid arthritis could change the intestinal absorption of the extract of L. bulbifera, and its mechanism needs further study.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Absorção Intestinal , Extratos Vegetais/uso terapêutico , Urticaceae/química , Animais , Cromatografia Líquida de Alta Pressão , Intestinos/efeitos dos fármacos , Ratos , Espectrometria de Massas em Tandem
13.
Endocrine ; 69(1): 113-125, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32189188

RESUMO

OBJECTIVE: Distant metastases are rarely observed in patients with initial pathologically proven benign follicular nodules of the thyroid. This study aimed to evaluate the clinicopathological features and independent variables associated with survival in such patients with distant metastases. METHODS: In total, 10,992 consecutive differentiated thyroid cancer (DTC) patients treated with 131I after total or near-total thyroidectomy from 2000 to 2018 were retrospectively reviewed. RESULTS: Thirty-nine patients with initial pathologically proven benign follicular nodules of the thyroid were enrolled. Among them, 26 were pathologically diagnosed as thyroid adenoma, 8 as benign nodular goiter, 4 as thyroid adenoma combined with benign nodular goiter, and 1 as normal thyroid tissue. Of 26 patients with the initial pathological slides obtained, eight cases were rediagnosed as minimally invasive thyroid carcinoma (MI-FTC), 10 as follicular tumor of uncertain malignant potential (FT-UMP), and five as well-differentiated tumor of UMP (WDT-UMP). Monitoring of thyroglobulin (Tg) changes after initial thyroidectomy and preablation-stimulated Tg (psTg) level were significantly associated with 5-year OS rate (P = 0.007 and P = 0.005, respectively). The presence of radioactive-refractory DTC (RR-DTC), monitoring of Tg changes after initial thyroidectomy, and psTg level had significant effects on 10-year OS rate (P = 0.002, P < 0.001, and P = 0.005, respectively). Lack of monitoring of Tg changes after initial thyroidectomy and RR-DTC were independent factors associated with poor prognosis (P = 0.003 and P = 0.008, respectively). CONCLUSIONS: MI-FTC, FT-UMP, and WDT-UMP tended to be ignored and/or misdiagnosed as benign follicular lesions. Lack of monitoring of Tg changes after initial thyroidectomy and the presence of RR-DTC were identified as independent factors associated with poor survival.

14.
Environ Pollut ; 261: 114129, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32045792

RESUMO

Glyphosate is the most popular herbicide used worldwide. This study aimed to investigate the adverse effects of glyphosate on the small intestine and gut microbiota in rats. The rats were gavaged with 0, 5, 50, and 500 mg/kg of body weight glyphosate for 35 continuous days. The different segments of the small intestine were sampled to measure indicators of oxidative stress, ion concentrations and inflammatory responses, and fresh feces were collected for microbiota analysis. The results showed that glyphosate exposure decreased the ratio of villus height to crypt depth in the duodenum and jejunum. Decreased activity of antioxidant enzymes (T-SOD, GSH, GSH-Px) and elevated MDA content were observed in different segments of the small intestine. Furthermore, the concentrations of Fe, Cu, Zn and Mg were significantly decreased or increased. In addition, the mRNA expression levels of IL-1ß, IL-6, TNF-α, MAPK3, NF-κB, and Caspase-3 were increased after glyphosate exposure. The 16 S rRNA gene sequencing results indicated that glyphosate exposure significantly increased α-diversity and altered bacterial composition. Glyphosate exposure significantly decreased the relative abundance of the phylum Firmicutes and the genus Lactobacillus, but several potentially pathogenic bacteria were enriched. In conclusion, this study provides important insight to reveal the negative influence of glyphosate exposure on the small intestine, and the altered microbial composition may play a vital role in the process.


Assuntos
Microbioma Gastrointestinal , Herbicidas , Animais , Glicina/análogos & derivados , Intestino Delgado , Ratos
15.
Water Res ; 172: 115477, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31945650

RESUMO

The polymer coagulant aid can effectively enhance the coagulation-ultrafiltration (C-UF) process for the purification of drinking water. However, when coagulant aid entered the filtration, it may also cause serious membrane fouling as polymer. In-situ Raman spectroscopy and electrochemical impedance spectroscopy(EIS) were applied to monitor the effects of coagulant aids on the membrane. The causes of fouling were assisted discussed through stage cleaning of the membrane. The equivalent circuit fitting was performed on the EIS data and the Raman spectral data were statistically analyzed after peak fitting. EIS and the cluster analysis of Raman spectroscopy provided an earlier feedback on membrane fouling layers compared to flux. The cause of membrane fouling was explained via variation of characteristic functional groups obtained by Raman spectroscopy. When the molecular weight of the coagulant aid was 160 times,80 times and 16 times larger than the MWCO of the UF membrane, the equivalent circuit obtained by fitting the EIS of the UF system satisfied Rs + c(QpRp), Rs(QcRc)(QpRp) and Rs(Qt(Rc(QpRp))) respectively. Partial correlation analysis showed that the corresponding factors causing irreversible fouling of membrane were humic acid(HA), HA and coagulant aids, coagulant aids. Combined with the mean roughness (Ra) of membrane, the coagulant aid performed differently in the cleaning of contaminated membrane and also affected the cleaning of HA.


Assuntos
Ultrafiltração , Purificação da Água , Espectroscopia Dielétrica , Substâncias Húmicas , Membranas Artificiais , Análise Espectral Raman
16.
Theranostics ; 10(3): 1230-1244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938062

RESUMO

Rationale: Glycogen synthase kinase-3ß (GSK-3ß) plays key roles in metabolism and many cellular processes. It was recently demonstrated that overexpression of GSK-3ß can confer tumor growth. However, the expression and function of GSK-3ß in hepatocellular carcinoma (HCC) remain largely unexplored. This study is aimed at investigating the role and therapeutic target value of GSK-3ß in HCC. Methods: We firstly clarified the expression of GSK-3ß in human HCC samples. Given that deviated retinoid signalling is critical for HCC development, we studied whether GSK-3ß could be involved in the regulation. Since sorafenib is currently used to treat HCC, the involvement of GSK-3ß in sorafenib treatment response was determined. Co-immunoprecipitation, GST pull down, in vitro kinase assay, luciferase reporter and chromatin immunoprecipitation were used to explore the molecular mechanism. The biological readouts were examined with MTT, flow cytometry and animal experiments. Results: We demonstrated that GSK-3ß is highly expressed in HCC and associated with shorter overall survival (OS). Overexpression of GSK-3ß confers HCC cell colony formation and xenograft tumor growth. Tumor-associated GSK-3ß is correlated with reduced expression of retinoic acid receptor-ß (RARß), which is caused by GSK-3ß-mediated phosphorylation and heterodimerization abrogation of retinoid X receptor (RXRα) with RARα on RARß promoter. Overexpression of functional GSK-3ß impairs retinoid response and represses sorafenib anti-HCC effect. Inactivation of GSK-3ß by tideglusib can potentiate 9-cis-RA enhancement of sorafenib sensitivity (tumor inhibition from 48.3% to 93.4%). Efficient induction of RARß by tideglusib/9-cis-RA is required for enhanced therapeutic outcome of sorafenib, which effect is greatly inhibited by knocking down RARß. Conclusions: Our findings demonstrate that GSK-3ß is a disruptor of retinoid signalling and a new resistant factor of sorafenib in HCC. Targeting GSK-3ß may be a promising strategy for HCC treatment in clinic.

17.
J Exp Med ; 217(4)2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-31999304

RESUMO

Aberrant NLRP3 inflammasome activation contributes to the development of endotoxemia. The importance of negative regulation of NLRP3 inflammasomes remains poorly understood. Here, we show that the E3 ubiquitin ligase Cbl-b is essential for preventing endotoxemia induced by a sub-lethal dose of LPS via a caspase-11/NLRP3-dependent manner. Further studies show that NLRP3 undergoes both K63- and K48-linked polyubiquitination. Cbl-b binds to the K63-ubiquitin chains attached to the NLRP3 leucine-rich repeat domain (LRR) via its ubiquitin-associated region (UBA) and then targets NLRP3 at K496 for K48-linked ubiquitination and proteasome-mediated degradation. We also identify RNF125 as an additional E3 ubiquitin ligase that initiates K63-linked ubiquitination of the NLRP3 LRR domain. Therefore, NLRP3 is sequentially ubiquitinated by K63- and K48-linked ubiquitination, thus keeping the NLRP3 inflammasomes in check and restraining endotoxemia.

18.
J Sci Food Agric ; 100(3): 1294-1300, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31742701

RESUMO

BACKGROUND: Maize (Zea mays L.) is a staple cereal crop and feed crop throughout the world. In this article, a mineral element fingerprinting technique was applied to single out suitable element indicators to determine the geographical origin of maize. A total of 90 fresh maize samples were collected in 2107 from Jilin, Gansu, and Shandong provinces in China. The contents of 25 mineral elements in all maize samples were measured by inductively coupled plasma mass spectrometry (ICP-MS). The composition of mineral elements was analyzed by multivariate statistical analysis, including one-way analysis of variance (one-way ANOVA), principal component analysis (PCA), k-nearest neighbor (KNN) analysis, and stepwise linear discriminant analysis (SLDA). RESULTS: As compared by one-way ANOVA, the contents of 19 mineral elements in maize samples were significantly different among three provinces. Principal component analysis based on these 19 elements could obtain preliminary visual classification groups of maize samples. K-nearest neighbor analysis produced a total correct classification rate of 83.9% on the training set, and 82.2% on the prediction set. The SLDA model, based on eight indicative elements (Na, Cr, Rb, Sr, Mo, Cs, Ba, and Pb) obtained a total correct classification rate of 92.2% with cross-validation. CONCLUSION: The mineral element fingerprinting technique combined with multivariate statistical analysis could be a helpful method to identify the geographical origin of maize. © 2019 Society of Chemical Industry.


Assuntos
Minerais/análise , Oligoelementos/análise , Zea mays/química , China , Análise Discriminante , Geografia , Análise de Componente Principal , Análise Espectral
19.
J Biol Chem ; 295(3): 690-700, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31771978

RESUMO

Genetic lineage tracing is widely used to study organ development and tissue regeneration. Multicolor reporters are a powerful platform for simultaneously tracking discrete cell populations. Here, combining Dre-rox and Cre-loxP systems, we generated a new dual-recombinase reporter system, called Rosa26 traffic light reporter (R26-TLR), to monitor red, green, and yellow fluorescence. Using this new reporter system with the three distinct fluorescent reporters combined on one allele, we found that the readouts of the two recombinases Cre and Dre simultaneously reflect Cre+Dre-, Cre-Dre+, and Cre+Dre+ cell lineages. As proof of principle, we show specific labeling in three distinct progenitor/stem cell populations, including club cells, AT2 cells, and bronchoalveolar stem cells, in Sftpc-DreER;Scgb1a1-CreER;R26-TLR mice. By using this new dual-recombinase reporter system, we simultaneously traced the cell fate of these three distinct cell populations during lung repair and regeneration, providing a more comprehensive picture of stem cell function in distal airway repair and regeneration. We propose that this new reporter system will advance developmental and regenerative research by facilitating a more sophisticated genetic approach to studying in vivo cell fate plasticity.

20.
Mol Genet Genomic Med ; 8(2): e1071, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31777190

RESUMO

BACKGROUND: There have been many reports on midkine as a promising marker in the diagnosis of hepatocellular carcinoma (HCC). However, the results are inconsistent and even conflicting. METHODS: This meta-analysis was performed to investigate the accuracy of midkine in the diagnosis of HCC. Meta-DiSc 1.4 software was used to extract data and to calculate the overall sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Data are presented as forest plots and summary receiver operating characteristic (SROC) curve analysis was used to summarize the overall test performance. RESULTS: Ten studies with a total of 753 HCC patients and 977 non-HCC patients were included. The overall pooled diagnostic data were as follows: the pooled sensitivity of 0.86 (95% confidence interval [CI]: 083-0.88), the pooled specificity of 0.75 (95% CI: 0.73-0.78), the pooled PLR of 4.71 (95% CI: 2.80-7.90), the pooled NLR of 0.18 (95% CI: 0.11-0.30), and the pooled DOR of 36.83 (95% CI: 13.56-100.05). The area under curve value was 0.9266 in the overall SROC curve. CONCLUSION: Midkine has moderate diagnostic accuracy for HCC. Due to the design limitations, results inpublished studies should be carefully interpreted. In addition, more well-designed studies with large sample sizes should be performed to rigorously evaluate the diagnostic accuracy of the MDK.

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