Publications by authors named "Yongjun Wu"

91 Publications

Application of logistic regression and convolutional neural network in prediction and diagnosis of high-risk populations of lung cancer.

Eur J Cancer Prev 2021 Apr 13. Epub 2021 Apr 13.

Departments of Toxicology Occupational and Environmental Health Nutrition and Food Hygiene, College of Public Health, Zhengzhou University Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou University, Zhengzhou, Henan Province, China.

Objectives: The early detection, early diagnosis, and early treatment of lung cancer are the best strategies to improve the 5-year survival rate. Logistic regression analysis can be a helpful tool in the early detection of high-risk groups of lung cancer. Convolutional neural network (CNN) could distinguish benign from malignant pulmonary nodules, which is critical for early precise diagnosis and treatment. Here, we developed a risk assessment model of lung cancer and a high-precision classification diagnostic model using these technologies so as to provide a basis for early screening of lung cancer and for intelligent differential diagnosis.

Methods: A total of 355 lung cancer patients, 444 patients with benign lung disease and 472 healthy people from The First Affiliated Hospital of Zhengzhou University were included in this study. Moreover, the dataset of 607 lung computed tomography images was collected from the above patients. The logistic regression method was employed to screen the high-risk groups of lung cancer, and the CNN model was designed to classify pulmonary nodules into benign or malignant nodules.

Results: The area under the curve of the lung cancer risk assessment model in the training set and the testing set were 0.823 and 0.710, respectively. After finely optimizing the settings of the CNN, the area under the curve could reach 0.984.

Conclusions: This performance demonstrated that the lung cancer risk assessment model could be used to screen for high-risk individuals with lung cancer and the CNN framework was suitable for the differential diagnosis of pulmonary nodules.
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http://dx.doi.org/10.1097/CEJ.0000000000000684DOI Listing
April 2021

Plasmonic TiO@Au NPs//CdS QDs photocurrent-direction switching system for ultrasensitive and selective photoelectrochemical biosensing with cathodic background signal.

Anal Chim Acta 2021 Apr 7;1153:338283. Epub 2021 Feb 7.

College of Public Health, Zhengzhou University, Zhengzhou, 450001, China; College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:

An ultrasensitive and selective photoelectrochemical (PEC) biosensor with cathodic background signal was developed for the detection of carcinoembryonic antigen (CEA) based on innovative plasmonic TiO@Au nanoparticles//CdS quantum dots (TiO@Au NPs//CdS QDs) photocurrent-direction switching system, coupling with hybridization chain reaction (HCR) for the signal amplification. Firstly, innovative TiO@Au NPs were successfully fabricated through in situ ascorbic acid-reduction of Au NPs dispersed on TiO surface, and TiO@Au NPs as the photoactive material showed a cathodic background signal. When target CEA existed, a sandwich-type reaction was performed in capture CEA aptamer-modified TiO@Au NPs and trigger CEA aptamer. Interestingly, after HCR triggered by target CEA, a mass of CdS QDs were introduced into the biosensing platform, resulting in the formation of TiO@Au NPs//CdS QDs system, along with the switch of photocurrents from cathodic to anodic. The obtained remarkable anodic photocurrent was depended on the localized surface plasmon resonance (LSPR) effect of Au between TiO and CdS. Under the optimal conditions, plasmonic TiO@Au NPs//CdS QDs photocurrent-direction switching PEC biosensing platform with cathodic background signal exhibited ultrasensitive for the determination of CEA with a low limit of detection of 18.9 fg/mL. Importantly, the proposed PEC biosensor can eliminate the interferences of the initial photocurrent and background signal, and has high-efficiency anti-interference ability, satisfactory stability and excellent reproducibility, which may have great potentials in bioanalysis and disease diagnosis.
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http://dx.doi.org/10.1016/j.aca.2021.338283DOI Listing
April 2021

Multifunctional Artificial Artery from Direct 3D Printing with Built-In Ferroelectricity and Tissue-Matching Modulus for Real-Time Sensing and Occlusion Monitoring.

Adv Funct Mater 2020 Sep 21;30(39). Epub 2020 Jul 21.

Department of Materials Science and Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.

Treating vascular grafts failure requires complex surgery procedures and is associated with high risks. A real-time monitoring vascular system enables quick and reliable identification of complications and initiates safer treatments early. Here, an electric fieldassisted 3D printing technology is developed to fabricate in situ-poled ferroelectric artificial arteries that offer battery-free real-time blood pressure sensing and occlusion monitoring capability. The functional artery architecture is made possible by the development of a ferroelectric biocomposite which can be quickly polarized during printing and reshaped into devised objects. The synergistic effect from the potassium sodium niobite particles and the polyvinylidene fluoride polymer matrix yields a superb piezoelectric performance (bulk-scale > 12 pC N). The sinusoidal architecture brings the mechanical modulus close to the level of blood vessels. The desired piezoelectric and mechanical properties of the artificial artery provide an excellent sensitivity to pressure change (0.306 mV mmHg, > 0.99) within the range of human blood pressure (11.25-225.00 mmHg). The high pressure sensitivity and the ability to detect subtle vessel motion pattern change enable early detection of partial occlusion (e.g., thrombosis), allowing for preventing grafts failure. This work demonstrates a promising strategy of incorporating multifunctionality to artificial biological systems for smart healthcare systems.
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http://dx.doi.org/10.1002/adfm.202002868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928534PMC
September 2020

Cerebral venous sinus thrombosis secondary to tonsillectomy.

Auris Nasus Larynx 2021 Feb 23. Epub 2021 Feb 23.

Department of ENT, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. Electronic address:

Cerebral venous sinus thrombosis(CVST) is considered to be a rare, high-risk, easily misdiagnosed disease with a mortality rate of 9.4%. Early diagnosis and timely anticoagulant thrombolytic therapy can reduce the mortality and disability rate and improve the prognosis of patients. This report describes the situation of a young male patient with bilateral tonsillectomy who, after going under low temperature plasma and general anesthesia surgery, presented with headache on the 4th day after the operation, and was diagnosed to be CVST by computed tomography(CT) and Magnetic Resonance Imaging(MRI). Due to severe pharynx swallowing pain after the surgery, his total daily intake was less than 2000 ml. After treatment, his prognosis was optimistic. The rarity and high risk of CVST after tonsillectomy suggest that we should pay attention to the related problems in the perioperative management of tonsillectomy include Bacterial infections, high condensation state of dehydration, using hemostatic drugs sparingly, etc.
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http://dx.doi.org/10.1016/j.anl.2020.11.017DOI Listing
February 2021

In situ detection of plasma exosomal microRNA for lung cancer diagnosis using duplex-specific nuclease and MoS nanosheets.

Analyst 2021 Mar 25;146(6):1924-1931. Epub 2021 Jan 25.

College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

MicroRNAs (miRNAs) encapsulated in tumor-derived exosomes are becoming ideal biomarkers for the early diagnosis and prognosis of lung cancer. However, the accuracy and sensitivity are often hampered by the extraction process of exosomal miRNA using traditional methods. Herein, this study developed a fluorogenic quantitative detection method for exosomal miRNA using the fluorescence quenching properties of molybdenum disulfide (MoS) nanosheets and the enzyme-assisted signal amplification properties of duplex-specific nuclease (DSN). First, a fluorescently-labeled nucleic acid probe was used to hybridize the target miRNA to form a DNA/RNA hybrid structure. Under the action of the DSN, the DNA single strand in the DNA/RNA hybrid strand was selectively digested into smaller oligonucleotide fragments. At the same time, the released miRNA target triggers the next reaction cycle, so as to achieve signal amplification. Then, MoS was used to selectively quench the fluorescence of the undigested probe leaving the fluorescent signal of the fluorescently-labeled probe fragments. The fluorometric signals for miRNA-21 had a maximum excitation/emission wavelength of 488/518 nm. Most importantly, the biosensor was then applied for the accurate quantitative detection of miRNA-21 in exosome lysates extracted from human plasma and this method was able to successfully distinguish lung cancer patients from healthy people. This biosensor provides a simple, rapid, and a highly specific quantitative method for exosomal miRNA and has promising potential to be used in the early diagnosis of lung cancer.
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http://dx.doi.org/10.1039/d0an02193hDOI Listing
March 2021

Phosphine-Catalyzed [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates with Isoxazole-Based Alkenes.

J Org Chem 2021 Feb 5;86(3):2090-2099. Epub 2021 Jan 5.

Department of Chemistry, China Agricultural University, Beijing 100193, China.

A phosphine-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with 3-methyl-4-nitro-5-styrylisoxazoles has been developed to afford various multifunctional isoxazoles in moderate to good yields with moderate to excellent diastereoselectivities. With a spirocyclic chiral phosphine as the catalyst, up to 89% ee was obtained.
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http://dx.doi.org/10.1021/acs.joc.0c01948DOI Listing
February 2021

Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract.

Medicina (Kaunas) 2020 Dec 29;57(1). Epub 2020 Dec 29.

Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. BEAS-2B cells treated with 3.0 μg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer.
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http://dx.doi.org/10.3390/medicina57010024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823543PMC
December 2020

Simultaneous Detection of VEGF and CEA by Time-Resolved Chemiluminescence Enzyme-Linked Aptamer Assay.

Int J Nanomedicine 2020 14;15:9975-9985. Epub 2020 Dec 14.

College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, People's Republic of China.

Background: As two important tumor markers, vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) have a great value for clinical application in the early diagnosis of cancer. Due to the complex composition of biological samples, the results from combined detection of CEA and VEGF are often taken as a comprehensive indicator in order to make an accurate judgment on a disease. However, most of the current methods can only be used to detect the content of one biomarker. Therefore, it is necessary to explore a simple, rapid, low-cost, and highly sensitive method for the simultaneous detection of CEA and VEGF.

Methods: Based on specific aptamers and magnetic separation, a time-resolved chemiluminescence enzyme-linked aptamer assay was developed for the simultaneous detections of CEA and VEGF in serum samples.

Results: Under the optimal conditions, the linear range of the calibration curve for VEGF was from 0.5 to 80 ng mL, and the limit of detection was 0.1 ng mL. The linear range of the calibration curve for CEA was 0.5 to 160 ng mL, and the limit of detection was 0.1 ng mL. The established method was applied to detect VEGF and CEA in serum samples. The results were consistent with those of commercial kits.

Conclusion: The method has high sensitivity and can quickly obtain accurate results, which could greatly improve the measurement efficiency, reduce the cost, and also reduce the volume of sample consumed. It can be seen that the method established in this study has important application value and broad application prospect in clinical diagnosis.
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http://dx.doi.org/10.2147/IJN.S286317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754089PMC
January 2021

Predisposing factors and radiological features in patients with internal carotid artery dissection or vertebral artery dissection.

BMC Neurol 2020 Dec 10;20(1):445. Epub 2020 Dec 10.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No.58 Zhongshan Road 2, Guangzhou, 510080, China.

Background: Cervicocerebral artery dissection is an important cause of ischemic stroke in young and middle-aged individuals. However, very few studies have compared the differential features between internal carotid artery dissection (ICAD) and vertebral artery dissection (VAD), including both cervical and intracranial artery dissections. We conducted a study to investigate the predisposing factors and radiological features in patients with ICAD or VAD.

Methods: All cases diagnosed with cervicocerebral artery dissection, ICAD, or VAD were identified through a medical records database, between January 2010 and January 2020. Baseline characteristics, predisposing factors, and radiological features of ICAD versus VAD were compared.

Results: A total of 140 patients with cervicocerebral artery dissection were included in the study, including 84 patients in the ICAD group and 56 in the VAD group. The mean age of patients in the ICAD and VAD groups was 43.37 ± 14.01 and 41.00 ± 12.98 years old, respectively. Patients with ICAD were more likely to be men compared with VAD (85.71% vs. 67.86%, p = 0.012). The frequency of hypertension, diabetes, smoking, drinking, and cervical trauma did not differ between ICAD and VAD. Dissections of ICAD were more frequently at the extracranial portions of the artery compared with those of VAD (70.24% vs. 44.64%, p = 0.003). In contrast, dissections of VAD were more common in the intracranial artery (55.36% vs. 29.76%, p = 0.003). Radiologically, double lumen (36.90% vs. 19.64%, p = 0.029) and intimal flap (11.90% vs. 1.79%, p = 0.029) were more frequently observed in ICAD than in VAD, and dissecting aneurysms were less frequent (13.10% vs. 26.79%, p = 0.041).

Conclusions: The distributions of cervical and intracranial artery dissections were different between ICAD and VAD. The frequencies of radiological features detected in patients with ICAD and VAD also differed.
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http://dx.doi.org/10.1186/s12883-020-02020-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731460PMC
December 2020

The Research Progression and Clinical Significance of Circular RNAs in Head and Neck Cancers.

Biomed Res Int 2020 21;2020:2712310. Epub 2020 Oct 21.

Department of Pathology, Affiliated Xiangtan Hospital, University of South China, Xiangtan, Hunan Province, China.

With rapid development of science technique and molecular research, a large number of circular RNAs (circRNAs) were discovered. CircRNAs that are a heterogeneous endogenous group of non-coding RNA not only are abundantly and diffusely expressed in mammals but also participate in many biological processes, such as in tumor ingenuity and progress. CircRNAs have rarely open reports in the head and neck cancers (HNC), which are an aggressive malignant tumor with unsatisfactory overall survival rates. The diagnostics and treatments continue to improve while the survival rate of HNC patients has no more obvious improvement. Recent studies that are aimed at exploring the molecular mechanisms of occurrence and progression of circRNAs in HNC provide a valuable insight into potential novel diagnostic and therapeutic approaches. In this review, we summarize the increasing number of published researches on the research progression of circRNAs in HNC, as well as their possible clinical implications on HNC.
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http://dx.doi.org/10.1155/2020/2712310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603539PMC
October 2020

Polymorphism in the Androgen Biosynthesis Gene (CYP17), a Risk for Prostate Cancer: A Meta-Analysis.

Am J Mens Health 2020 Sep-Oct;14(5):1557988320959984

College of Public Health, Zhengzhou University, Zhengzhou, China.

Gene polymorphism is one of the few factors that increases the risk of prostate cancer. T to C substitution in the 5' promoter region of the CYP17 gene is hypothesized to increase the rate of gene transcription, increase androgen production, and thereby increase the risk of prostate cancer. Nevertheless, the inconsistencies originating from studies on CYP17 polymorphism and prostate cancer prompted this meta-analysis, to decipher the association between CYP17 polymorphism and prostate cancer. Most case-control studies addressing CYP17 polymorphism and prostate cancer were exhaustively searched from Web of Science, Google Scholar, and PubMed. The various genotype distributions as well as the minor allele distributions were retrieved. Pooled odds ratios (s) with their 95% CI and estimates of the Hardy-Weinberg Equilibrium were calculated. Analyses were performed using the RevMan v.5.3 software and SPSS v.21. There was high-pooled heterogeneity ( = 87.0%, = .42, CI [.39, .45], and < .001) among the A2 versus A1 allele. With the per-allele model (A2 versus A1), ethnicity was a major risk factor to prostate cancer, with Asians recording the highest risk ( = 12.61, 95% CI [8.77, 18.12]). From the genotype models, A1/A1 versus A2/A2 ( = 3.02, 95% CI [2.65, 3.44]) and A1/A2 versus A2/A2 ( = 4.39, 95% CI [3.86, 5.00]) were all significantly associated with prostate cancer. Although some genotype models were associated with the risk of prostate cancer, we should be mindful when interpreting the results of this study because of the limited number of studies and the small sample size used.
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http://dx.doi.org/10.1177/1557988320959984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518003PMC
September 2020

Highly Sensitive Fluorescence-Linked Immunosorbent Assay for the Determination of Human IgG in Serum Using Quantum Dot Nanobeads and Magnetic FeO Nanospheres.

ACS Omega 2020 Sep 31;5(36):23229-23236. Epub 2020 Aug 31.

College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The aim of this study is to establish a new method with high sensitivity, accuracy, and stability for the determination of human IgG and then expand it to analyze severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)-specific IgM and IgG, which is of great significance for the screening and diagnosis of COVID-19. In this study, the magnetic FeO nanospheres coupled with mouse antihuman IgG (Ab1) were used as an immune capture probe (FeO@Ab1) to capture and separate the target, and rabbit antihuman IgG (Ab2) coupled with highly luminescent quantum dot nanobeads (QBs) as a fluorescence detection probe (QBs@Ab2) was used to realize high sensitivity detection. After the formation of a sandwich immunocomplex, the fluorescence intensity of the precipitate after magnetic separation was measured at the excitation wavelength of 370 nm. Under optimal conditions, a wide linear range varying from 0.005 to 40 ng·mL was obtained for the detection of human IgG with a lower limit of detection at 4 pg·mL (S/N = 3). The recoveries of intra- and interassays were 90.0-101.9 and 96.0-106.6%, respectively, and the relative standard deviations were 6.3-10.2 and 2.6-10.5%, respectively. Furthermore, the proposed method was successfully demonstrated to detect human IgG in serum samples, and the detection results were not statistically different ( > 0.05) from commercial enzyme-linked immunosorbent assay kits. This method is sensitive, fast, and accurate, which could be expanded to detect the specific IgM and IgG antibodies against SARS-CoV-2.
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http://dx.doi.org/10.1021/acsomega.0c02987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495760PMC
September 2020

Hollow NiAl(OH) Nanocapsules to Enable Effective Glucose Oxidase Delivery and Synergistic Therapy.

J Biomed Nanotechnol 2020 May;16(5):640-651

Cellular starvation induced by glucose oxidase (GOx) had been extensively explored as a potential approach for tumor therapy. However, the therapeutic efficacy suffers daunting challenges due to the unsatisfactory intracellular transportation of GOx molecules. Herein for the first time, hydroxide nanoparticles with unique hollow microstructure (denoted as H-NiAl(OH)) were designed and synthesized for GOx delivery. In this system, despite its intrinsic degradation properties in acidic tumor microenvironment, Ni ions released during degradation may catalyze a Fenton reaction to induce considerable production of cytotoxic hydroxyl radicals (OH). The cavity of hollow nanocapsules provides large surface area, and favors GOx capsulation and delivery. The findings indicate the intracellular glucose can be effectively consumed by GOx transported, and the reaction products consisting of acid and H₂O₂ facilitate the OH induction of nanocapsules in a synergistic manner. Both and antitumor properties have been consequently achieved by H-NiAl(OH)/GOx systems. This study offering catalytic nanocapsules based on Ni ions may spark a series of follow-on explorations in constructing drug delivery and therapeutic systems for synergistic tumor treatment.
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http://dx.doi.org/10.1166/jbn.2020.2913DOI Listing
May 2020

Palladium-Catalyzed [5 + 2] Annulation of Vinylethylene Carbonates with Barbiturate-Derived Alkenes.

Org Lett 2020 09 3;22(18):7158-7163. Epub 2020 Sep 3.

Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P.R. China.

A palladium/XantPhos-catalyzed [5 + 2] annulation of VECs with electron-deficient alkenes having an isolated carbon-carbon double bond has been developed to afford spirobarbiturate-tetrahydrooxepines. This study provides an expedient assembly of biologically interesting spirobarbiturate-tetrahydrooxepines. The easy scalability and versatile transformability of the reaction products were also exhibited.
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http://dx.doi.org/10.1021/acs.orglett.0c02508DOI Listing
September 2020

Comparative analysis of three data mining techniques in diagnosis of lung cancer.

Eur J Cancer Prev 2021 Jan;30(1):15-20

College of Public Health, Zhengzhou University.

There is a lot of abnormal information in the development of lung cancer, and how to extract useful knowledge is urgent from massive information. Data mining technology has become a popular tool for medical classification and prediction. However, each technology has its advantage and disadvantage, and several data mining methods will be applied to conduct the in-depth analysis step by step. And the prediction results of different models are compared. A total of 180 lung cancer patients and 243 lung benign individuals were collected from the First Affiliated Hospital of Zhengzhou University from October 2014 to March 2016, and the prediction models based on epidemiological data, clinical features and tumor markers were developed by artificial neural network (ANN), decision tree C5.0 and support vector machine (SVM). The results showed that there were significant differences between the lung cancer group and the lung benign group in terms of seven tumor markers and 10 epidemiological and clinical indicators. The accuracy rates of ANN, C5.0 and SVM were 76.47, 89.92 and 85.71%, respectively. The results of receiver operating characteristic curve (ROC) curve revealed the area under the ROC curve (AUC) of ANN was 0.811 (0.770-0.847), the AUC of C5.0 was 0.897 (0.864-0.924) and the AUC of SVM was 0.878 (0.843-0.908). It was shown that the decision tree C5.0 model has the least error rate and highest accuracy, and it could be used to diagnose lung cancer.
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http://dx.doi.org/10.1097/CEJ.0000000000000598DOI Listing
January 2021

Organocatalytic Asymmetric C(sp )-H Allylic Alkylation: Enantioselective Synthesis of Tetrasubstituted Allenoates.

Angew Chem Int Ed Engl 2020 11 24;59(45):19820-19824. Epub 2020 Sep 24.

Department of Chemistry, China Agricultural University, 2 West Yuanmingyuan Road, Beijing, 100193, P. R. China.

Herein we describe the first organocatalytic asymmetric C(sp )-H allylation of racemic trisubstituted allenoates with Morita-Baylis-Hillman (MBH) carbonates to access axially chiral tetrasubstituted allenoates. Various trisubstituted allenoates and MBH carbonates were well tolerated under mild reaction conditions, providing novel chiral tetrasubstituted allenoates with adjacent axial chirality and tertiary carbon stereocenters in high yields with good to excellent diastereoselectivities and enantioselectivities.
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http://dx.doi.org/10.1002/anie.202009460DOI Listing
November 2020

ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable HS-amplified synergistic therapy.

Theranostics 2020 18;10(17):7671-7682. Epub 2020 Jun 18.

State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, P.R. China.

Abnormal tumor microenvironment, such as hypoxia, interstitial hypertension and low pH, leads to unexpected resistance for current tumor treatment. The development of versatile drug delivery systems which present responsive characteristics to tumor microenvironment (TME) has been extensively carried out, but remains challenging. In this study, zeolitic imidazolate framework-8 (ZIF-8) coated ZnS nanoparticles have been designed and prepared for co-delivery of ICG/TPZ molecules, denoted as ZSZIT, for HS-amplified synergistic therapy. The ZSZ nanoparticles were characterized using SEM, TEM and XRD. The viabilities of cancer cells cultured with ZSZIT under normoxia/hypoxia conditions were evaluated by cell counting kit-8 (CCK-8) assay. In addition, anti-tumor effect was also performed using male Balb/c nude mice as animal model. ZSZIT shows cascade PDT and hypoxia-activated chemotherapeutic effect under an 808nm NIR irradiation. Meanwhile, ZSZIT degrades under tumor acidic environment, and HS produced by ZnS cores could inhibit the expression of catalase, which subsequently favors the hypoxia and antitumor effect of TPZ drug. Both and studies demonstrate the HS-sensitized synergistic antitumor effect based on cascade PDT/chemotherapy. This cascade HS-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.
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http://dx.doi.org/10.7150/thno.45079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359076PMC
June 2020

A population-base survey on knowledge, attitude and awareness of the general public on antibiotic use and resistance.

Antimicrob Resist Infect Control 2020 07 11;9(1):105. Epub 2020 Jul 11.

College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.

Objectives: This study was designed to assess the awareness and knowledge of antibiotic usage and antibiotic resistance among the general public in the Cape Coast metropolis of Ghana. It also tries to decipher whether the level of education and the professional status of an individual has a positive association with the level of knowledge on antibiotic resistance.

Methods: A population-base survey involving members of the public was conducted from August to November 2019. A structured questionnaire was developed to collect data from 632 respondents. Data were analyzed through SPSS v.21 using Chi square statistics and multivariate regression. Differences in knowledge were evaluated using ANOVA and the assumption of equal variance was tested with Levene statistics.

Results: The response rate was 74.3%. Lower educational status group had a greater knowledge level (39.7%) on antibiotic resistance. Despite the high score, the lowest educational status group, (M = 1.82, SD = 0.769), middle educational status group (M = 1.98, SD = 0.748), and the high educational status group (M = 1.88, SD = 0.773) were not significantly different from each other with regard to their general knowledge level on antibiotic resistance (P < 0.05). The study revealed that, working in the healthcare sector is a major contributor to the level of knowledge on antibiotic resistance.

Conclusion: Given the scale of the issue on antibiotic resistance and the fact that attempts to resolve it will involve efforts on the part of all, it is important that the public is aware of the importance of the issue of antibiotic resistance, its implications and what they can do to address it. The level of knowledge among respondents with lower educational status should be enough evidence to introduce more educational campaigns on antibiotic resistance.
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http://dx.doi.org/10.1186/s13756-020-00768-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353772PMC
July 2020

Enhancing osteogenic differentiation of BMSCs on high magnetoelectric response films.

Mater Sci Eng C Mater Biol Appl 2020 Aug 17;113:110970. Epub 2020 Apr 17.

School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Zhejiang University, Hangzhou 310027, China. Electronic address:

High performance of biomaterial surfaces provides a sound basis to mediate cellular growth behavior. In this work, we attempted to incorporate both positive and negative magnetostriction particles of CoFeO (CFO) and TbDyFe alloy (TD) into piezoelectric poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) for forming high magnetoelectric effect films, on which osteogenic differentiation could be dynamically mediated by a magnetic-field-induced surface potential (φ).The negatively poled film with TD/CFO volume ratio of 1:4 (1T4C) showed a highest magnetoelectric effect with φ of -171 mV at 2800 Oe. Compared with CFO/P(VDF-TrFE) and TD/P(VDF-TrFE) films, the φ increased about 213% and 173%, respectively. This could result from that P(VDF-TrFE) dipole domains receive a larger off-axial stress caused by the distribution characteristic of CFO and TD in P(VDF-TrFE), consequently to facilitate P(VDF-TrFE) dipole domain rearrangement. When MSCs were cultured on 1T4C film for 7 or 14 days, the magnetic actuation was setup to begin at the 4th or 8th day after the culture. The 7-day osteogenic differentiation was hardly affected for magnetic actuation at 4th day, moreover, the 14-day differentiation was significantly enhanced for magnetic actuation at 8th day. The enhancement appears just at a relatively late period of the cell growth, probably because the cells need a steady change in cell membrane potential to disassociate pairs of β-catenin and E-cadherin and activate osteogenic-related signaling pathway. This work could provide an alternative way to promote performance for magnetoelectric materials, and get insight into understanding of interactions of surface potential with cells.
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http://dx.doi.org/10.1016/j.msec.2020.110970DOI Listing
August 2020

Identification and analysis of key lncRNAs in malignant-transformed BEAS-2B cells induced with coal tar pitch by microarray analysis.

Environ Toxicol Pharmacol 2020 Oct 12;79:103376. Epub 2020 May 12.

Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. Electronic address:

This study aims to explore the key and differentially expressed long non-coding RNAs (lncRNAs) and elucidates their possible mechanisms in malignant-transformed Human bronchial epithelial (BEAS-2B) cells induced by coal tar pitch extracts (CTPE). BEAS-2B cells were stimulated with 2.4 μg/ml CTPE, then passaged for three times which were named CTPE1 and then passaged until passage 30 (CTPE30). The results showed that cells of CTPE30 appeared abnormal morphology. Furthermore, migration, clonality and proliferation of cells in CTPE group were significantly increased compared with those in control groups. However, the apoptosis of cells in CTPE group was inhibited. A total of 569 differentially expressed mRNAs and 707 differentially expressed lncRNAs were screened out, among which four lncRNAs were validated and were consistent with the microarray results. 32 target genes were screened out by Co-expression network. The study suggests that differentially expressed lncRNAs may play a potential role in lung carcinogenesis.
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http://dx.doi.org/10.1016/j.etap.2020.103376DOI Listing
October 2020

Development of a machine learning-based multimode diagnosis system for lung cancer.

Aging (Albany NY) 2020 05 23;12(10):9840-9854. Epub 2020 May 23.

College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

As an emerging technology, artificial intelligence has been applied to identify various physical disorders. Here, we developed a three-layer diagnosis system for lung cancer, in which three machine learning approaches including decision tree C5.0, artificial neural network (ANN) and support vector machine (SVM) were involved. The area under the curve (AUC) was employed to evaluate their decision powers. In the first layer, the AUCs of C5.0, ANN and SVM were 0.676, 0.736 and 0.640, ANN was better than C5.0 and SVM. In the second layer, ANN was similar with SVM but superior to C5.0 supported by the AUCs of 0.804, 0.889 and 0.825. Much higher AUCs of 0.908, 0.910 and 0.849 were identified in the third layer, where the highest sensitivity of 94.12% was found in C5.0. These data proposed a three-layer diagnosis system for lung cancer: ANN was used as a broad-spectrum screening subsystem basing on 14 epidemiological data and clinical symptoms, which was firstly adopted to screen high-risk groups; then, combining with additional 5 tumor biomarkers, ANN was used as an auxiliary diagnosis subsystem to determine the suspected lung cancer patients; C5.0 was finally employed to confirm lung cancer patients basing on 22 CT nodule-based radiomic features.
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http://dx.doi.org/10.18632/aging.103249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288961PMC
May 2020

Systematic Identification and Analysis of Light-Responsive Circular RNA and Co-expression Networks in Lettuce ().

G3 (Bethesda) 2020 07 7;10(7):2397-2410. Epub 2020 Jul 7.

College of Life Sciences, and

Circular RNA (circRNA) is a covalently-closed single-stranded RNA molecule that plays an important role in transcriptional regulation of gene expression in a variety of species. Light intensity is a pivotal environmental factor affecting plant growth and development. However, little is known regarding photoresponsive plant circRNAs. Here, we aimed to investigate the expression and function of circRNAs in lettuce leaves in response to different light intensity treatments. We performed RNA sequencing (RNA-Seq) on leaves of lettuce () to determine circRNA expression profiles and reverse-transcription polymerase chain reaction (PCR) to validate the candidate circRNA molecules. We then combined bioinformatics approach to explore the function of the parental genes of circRNA, including network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We identified 1650 circRNAs in lettuce, of which 1508 (86.40%) were derived from exons. Using real-time PCR, we characterized 10 validated differentially expressed circRNAs and their parental genes, all of which showed expression patterns consistent with RNA-Seq data. Interestingly, the expression of circRNA was, in some cases, inversely correlated with the expression of the parental gene. Furthermore, analysis of the circRNA-microRNA-mRNA network suggests that circRNAs may be involved in plant hormone signaling and chlorophyll metabolism during photoreactivity. These findings provide an essential reference basis for studying circRNAs' biological mechanisms in light-treated plants.
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http://dx.doi.org/10.1534/g3.120.401331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341150PMC
July 2020

Implantable fibrous 'patch' enabling preclinical chemo-photothermal tumor therapy.

Colloids Surf B Biointerfaces 2020 Apr 13;192:111005. Epub 2020 Apr 13.

Department of General Surgery, Key Laboratory of Laparoscopic Technology of Zhejiang Province, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310016, China. Electronic address:

Localized drug delivery systems (LDDSs), in the forms of fibers or hydrogel, have emerged as an alternative approach for effective cancer treatment, but suffer challenges in the limited efficacy originated from sole therapeutic functionality. Herein, a multifunctional LDDS, showing feasibility for minimally-invasive implantation, was designed and synthesized for on-site chemo-photothermal synergistic therapy. In this system, polydopamine (PDA) nanoparticles, loaded with doxorubicin (DOX), were assembled at the surface of electrospun PCL-gelatin (PG) fibers (PG@PDA-DOX). The composite PG@PDA-DOX nanofibers could effectively transform NIR light into heat and present excellent photostability. In addition, low pH and NIR irradiation enabled remarkably accelerated DOX release. The in vitro study of PG@PDA-DOX fibers showed effective anti-cancer effect with irradiation of 808 nm NIR by inducing cell apoptosis and suppressing cell proliferation. The in vivo study, by implanting PG@PDA-DOX nanofibers in the patient derived xenograft (PDX) model via minimally-invasive surgery, presented that the composite fibers can effectively inhabit tumor growth by the combined chemo-photothermal effect without clear systematic side-effects. This study has therefore demonstrated a minimally-invasive platform, in a fibrous mesh form, with both high therapeutic efficacy and considerable potential in clinical translation for liver cancer treatment.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111005DOI Listing
April 2020

Palladium-Catalyzed Asymmetric [4+2] Cycloaddition of 2-Methylidenetrimethylene Carbonate with Alkenes: Access to Chiral Tetrahydropyran-Fused Spirocyclic Scaffolds.

Angew Chem Int Ed Engl 2020 07 11;59(28):11316-11320. Epub 2020 May 11.

College of Science, China Agricultural University, 2 West Yuanmingyuan Road, Beijing, 100193, China.

A palladium-catalyzed asymmetric [4+2] cycloaddition of 2-methylidenetrimethylene carbonate with alkenes derived from pyrazolones, indandione, or barbiturate has been successfully developed, affording pharmacologically interesting chiral tetrahydropyran-fused spirocyclic scaffolds. The target compounds were generated in good to excellent yields and with high enantioselectivity (up to 99 % ee). Furthermore, this cycloaddition reaction could be efficiently scaled up, and several synthetic transformations were accomplished for the construction of other useful chiral spiropyrazolone and spiroindandione derivatives.
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http://dx.doi.org/10.1002/anie.202002765DOI Listing
July 2020

FeS@BSA Nanoclusters to Enable HS-Amplified ROS-Based Therapy with MRI Guidance.

Adv Sci (Weinh) 2020 Apr 19;7(7):1903512. Epub 2020 Feb 19.

Key Laboratory of Endoscopic Technique Research of Zhejiang Province Sir Run Run Shaw Hospital Zhejiang University Hangzhou Zhejiang 310016 P. R. China.

Therapeutic systems to induce reactive oxygen species (ROS) have received tremendous success in the research of tumor theranostics, but suffered daunting challenges in limited efficacy originating from low presence of reactants and reaction kinetics within cancer cells. Here, ferrous sulfide-embedded bovine serum albumin (FeS@BSA) nanoclusters, in an amorphous nature, are designed and synthesized via a self-assembly approach. In acidic conditions, the nanoclusters degrade and simultaneously release HS gas and Fe ions. The in vitro study using Huh7 cancer cells reveals that Fe released from FeS@BSA nanoclusters induces the toxic hydroxyl radical (·OH) effectively via the Fenton reaction. More interestingly, HS gas released intracellularly presents the specific suppression effect to catalase activity of cancer cells, resulting in the promoted presence of HO that facilitates the Fenton reaction of Fe and consequently promotes ROS induction within the cells remarkably. After intravenous administration, the nanoclusters accumulate in the tumors of mice via the enhanced permeability and retention effect and present strong magnetic resonance imaging (MRI) signals. The findings confirm this therapeutic system can enable superior anti-tumor performance with MRI guidance and negligible side effects. This study, therefore, offers an alternative gas-amplified ROS-based therapeutic platform for synergetic tumor treatment.
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http://dx.doi.org/10.1002/advs.201903512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141047PMC
April 2020

Phosphine-Catalyzed Cascade Michael Addition/[4+2] Cycloaddition Reaction of Allenoates and 2-Arylidene-1,3-indanediones.

Org Lett 2020 04 18;22(7):2675-2680. Epub 2020 Mar 18.

College of Public Health, Zhengzhou University, Zhengzhou 450001, P. R. China.

The phosphine-catalyzed cascade Michael addition/[4+2] cycloaddition reaction of tetrahydrobenzofuranone-derived allenoates and 2-arylidene-1,3-indanediones has been reported, affording spirocyclic 1,3-indanedione derivatives in moderate to high yields with moderate to good diastereoselectivities. A scaled-up reaction worked well under mild conditions, and a plausible mechanism is proposed.
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http://dx.doi.org/10.1021/acs.orglett.0c00637DOI Listing
April 2020

Fluorometric immunoassay for the simultaneous determination of the tumor markers carcinoembryonic antigen and cytokeratin 19 fragment using two kinds of CdSe/ZnS quantum dot nanobeads and magnetic beads.

Mikrochim Acta 2020 02 15;187(3):171. Epub 2020 Feb 15.

College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.

A method is described for the simultaneous determination of the carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1). Two kinds of CdSe/ZnS quantum dot nanobeads (QBs), with emission maxima at 530 nm (green) and 585 nm (yellow), were used as labels, and magnetic beads (MBs) for separation. The MBs were used as substrates to couple CEA and CYFRA21-1 antibody for isolating the proteins. Then, the differently colored QBs were linked to the antibodies against CEA and CYFRA21-1, respectively. Following the formation of the immunocomplex, the intensities of the green and yellow emissions were measured at the same excitation wavelength of 340 nm. The detection limits are 0.1 ng⋅mL for CEA, and of 0.2 ng⋅mL for CYFRA21-1. The recoveries from spiked serum are 92.1 - 118.1% for CEA, and from 90.8% to 115.2% for CYFRA21-1, with the relative standard deviations of 6.3 - 12.3% and 7.1 - 11.8%. The method was successfully applied to the simultaneous determination of the two proteins in human serum sample (n = 45). The results correlated well with those of the chemiluminescent enzyme immunoassay kit. Graphical AbstractSchematic presentation of the fluorescence immunoassay for the simultaneous determination of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) based on quantum dot nanobeads (QBs) and magnetic beads (MBs) is reported. The intensities of two kinds of CdSe/ZnS QBs, with the emission maxima at 530 nm (green) and 585 nm (yellow) were measured at the same excitation wavelength of 340 nm.
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http://dx.doi.org/10.1007/s00604-019-3914-7DOI Listing
February 2020

Effect of Ultrasonic Bending Vibration Introduced by the L-shaped Ultrasonic Rod on Solidification Structure and Segregation of Large 2A14 Ingots.

Materials (Basel) 2020 Feb 10;13(3). Epub 2020 Feb 10.

College of Mechanical and Electrical Engineering, Central South University, Changsha 410083, China.

In order to achieve long-term and stable ultrasonic treatment in the direct chill semi-continuous casting process, a new L-shaped ceramic ultrasonic wave guide rod is designed to introduce ultrasonic bending vibration into 2A14 aluminum alloy melt. The effect of ultrasonic bending vibration on the solidification structure and composition segregation of large 2A14 aluminum alloy ingots (φ 830 mm × 6000 mm) in the process of semi-continuous casting were studied by means of a direct reading spectrometer, scanning electron microscope, metallographic microscope, and hardness test. The ultrasonic ingot treated by bending vibration was compared with the ingot without ultrasonic treatment and the ingot treated by the traditional straight-rod titanium alloy wave guide rod. The results show that, during the solidification of 2A14 aluminum alloy, ultrasonic treatment can significantly refine the grain, break up the agglomerated secondary phase, and make its distribution uniform. The macro-segregation degree of solute including the negative segregation at the edge of the ingots and the positive segregation in the center can be reduced. Through comparative analysis, the macrostructure of the ingot, treated by the L-shaped ceramic ultrasonic wave guide rod, was found to be better than that of the ingot treated by the traditional straight-rod titanium alloy wave guide rod. In particular, the grain refinement effect at the edge of the ingot was the best, the secondary phase was smaller, more solute elements can be dissolved into the α-Al matrix, and the ability of the L-shaped ultrasonic wave guide rod to restrain segregation was stronger at the edge of the ingot.
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http://dx.doi.org/10.3390/ma13030807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040891PMC
February 2020

Identification of Three Differentially Expressed miRNAs as Potential Biomarkers for Lung Adenocarcinoma Prognosis.

Comb Chem High Throughput Screen 2020 ;23(2):148-156

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China.

Objective: The aim of this study areto screen MicroRNAs (miRNAs) related to the prognosis of lung adenocarcinoma (LUAD) and to explore the possible molecular mechanisms.

Methods: The data for a total of 535 patients with LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database. The miRNAs for LUAD prognosis were screened by both Cox risk proportional regression model and Last Absolute Shrinkage and Selection Operator (LASSO) regression model. The performances of the models were verified by time-dependent Receiver Operating Characteristic (ROC) curve. The possible biological processes linked to the miRNAs' target genes were analyzed by Gene Ontology (GO), Kyoto gene and genome encyclopedia (KEGG).

Results: Among 127 differentially expressed miRNAs identified from the screening analysis, there are 111 up-regulated and 16 down-regulated miRNAs. Three of them, hsa-miR-1293, hsa-miR-490 and hsa-miR- 5571, were also significantly associated with the survival of the LUAD patients. The targets of the three miRNAs are significantly enriched in systemic lupus erythematosus pathways.

Conclusion: Hsa-miR-1293, hsa-miR-490 and hsa-miR-5571 can be potentially used as novel biomarkers for the prognosis prediction of LUAD.
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http://dx.doi.org/10.2174/1386207323666200124123103DOI Listing
April 2021

Klebsiella pneumoniae: an increasing threat to public health.

Ann Clin Microbiol Antimicrob 2020 Jan 9;19(1). Epub 2020 Jan 9.

College of Public Health, Zhengzhou University, Zhengzhou, 450001, China.

Objectives: This review fills the paucity of information on K. pneumoniae as a nosocomial pathogen by providing pooled data on epidemiological risk factors, resistant trends and profiles and resistant and virulent genes of this organism in Asia.

Methods: Exhaustive search was conducted using PubMed, Web of Science, and Google scholar for most studies addressing the prevalence, risk factors, drug resistant-mediated genes and/or virulent factors of K. pneumoniae in Asia. Data extracted for meta-analysis were analyzed using comprehensive meta-analysis version 3. Trends data for the isolation rate and resistance rates were entered into Excel spread sheet and the results were presented in graphs.

Results: The prevalence rate of drug resistance in K. pneumoniae were; amikacin (40.8%) [95% CI 31.9-50.4], aztreonam (73.3%) [95% CI 59.9-83.4], ceftazidime (75.7%) [95% CI 65.4-83.6], ciprofloxacin (59.8%) [95% CI 48.6-70.1], colistin (2.9%) [95% CI 1.8-4.4], cefotaxime (79.2%) [95% CI 68.0-87.2], cefepime (72.6) [95% CI 57.7-83.8] and imipenem (65.6%) [95% CI 30.8-89.0]. TEM (39.5%) [95% CI 15.4-70.1], SHV-11 (41.8%) [95% CI 16.2-72.6] and KPC-2 (14.6%) [95% CI 6.0-31.4] were some of the resistance mediated genes observed in this study. The most virulent factors utilized by K. pneumoniae are; hypermucoviscous phenotype and mucoviscosity-related genes, genes for biosynthesis of lipopolysaccharide, iron uptake and transport genes and finally, adhesive genes.

Conclusion: It can be concluded that, antimicrobial resistant in K. pneumoniae is a clear and present danger in Asia which needs strong surveillance to curb this menace. It is very important for public healthcare departments to monitor and report changes in antimicrobial-resistant isolates.
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http://dx.doi.org/10.1186/s12941-019-0343-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050612PMC
January 2020