Publications by authors named "Yiwen Zhou"

70 Publications

Epidemiological and clinical characteristics of respiratory viruses in 4403 pediatric patients from multiple hospitals in Guangdong, China.

BMC Pediatr 2021 Jun 17;21(1):284. Epub 2021 Jun 17.

Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Acute respiratory infections (ARI) cause considerable morbidity and mortality worldwide, especially in children. Unfortunately, there are limited multi-center data on common viral respiratory infections in south China.

Methods: A total of 4403 nasal swabs were collected from children in 10 cities in Guangdong, China in 2019. Seven respiratory viruses, influenza A virus (IFA), influenza B virus (IFB), respiratory syncytial virus (RSV), adenoviruses (ADV) and parainfluenza virus types 1-3 (PIV1, PIV2 and PIV3), were detected by direct immunofluorescence antibody assay. The personal information and clinical characteristics were recorded and analyzed.

Results: The results showed that at least one virus was detected in 1099 (24.96 %) samples. The detection rates of RSV, IFA, ADV, PIV3, PIV1 and PIV2 were 7.13 % (314/4403), 5.31 % (234/4403), 4.02 % (177/4403), 3.04 % (134/4403), 1.70 % (75/4403) and 1.16 % (51/4403), respectively. The detection rate of RSV was highest in 0-6-month-old children at 18.18 % (106/583), while the detection rate of IFA was highest in 12-18-year-old children at 20.48 % (17/83). The total detection rates in winter and spring were 35.67 % (219/614) and 34.56 % (403/1166), higher than those in summer, 17.41 % (284/1631), and autumn, 19.46 % (193/992).

Conclusions: RSV and IFA were the main respiratory viruses in children. With increasing age the detection rate of RSV decreased in children, but the trends for the detection rates of IFA and IFB were the opposite. This study provided the viral etiology and epidemiology of pediatric patients with ARI in Guangdong, China.
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http://dx.doi.org/10.1186/s12887-021-02759-0DOI Listing
June 2021

Acute lymphoblastic leukemia-derived exosome inhibits cytotoxicity of natural killer cells by TGF-β signaling pathway.

3 Biotech 2021 Jul 4;11(7):313. Epub 2021 Jun 4.

Shenzhen Maternal and Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, 2004 Hongli road, Futian District, Shenzhen, Guangdong China.

This study was conducted to explore whether acute lymphoblastic leukemia (ALL)-derived exosomes affect natural killer (NK) cells. Exosomes were isolated and identified from Jurkat cells and co-cultured with NK cells. Then, the cytotoxicity, viability, and release of perforin and granzyme B in NK92-MI cells were measured. PCR arrays were used to detect gene expression alterations in the transforming growth factor (TGF)-β pathway of NK92-MI cells treated or not treated with exosomes. The morphology and size of the exosomes isolated from Jurkat cells showed typical characteristics of exosomes, and the expression of cluster of differentiation 63 was detected. Jurkat-derived exosomes were internalized by NK92-MI cells, further inhibiting the proliferation and cytotoxicity of NK92-MI cells. An enzyme-linked immunosorbent assay revealed that the release of perforin and granzyme B from NK92-MI cells decreased after co-culture with exosomes. Similarly, western blot and immunofluorescence staining verified that Jurkat-derived exosomes inhibited the expression of granzyme B and perforin. Furthermore, Jurkat-derived exosomes enhanced the signaling of the TGF-β pathway in NK92-MI cells via the MDS1 and EVI1 complex loci and homeodomain interacting protein kinase 2. In conclusion, we found that ALL-derived exosomes inhibit the biological function of NK cells and provide support for the immunotherapy of ALL.
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http://dx.doi.org/10.1007/s13205-021-02817-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178429PMC
July 2021

A Deep Learning Model for Screening Multiple Abnormal Findings in Ophthalmic Ultrasonography (With Video).

Transl Vis Sci Technol 2021 Apr;10(4):22

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

Purpose: The purpose of this study was to construct a deep learning system for rapidly and accurately screening retinal detachment (RD), vitreous detachment (VD), and vitreous hemorrhage (VH) in ophthalmic ultrasound in real time.

Methods: We used a deep convolutional neural network to develop a deep learning system to screen multiple abnormal findings in ophthalmic ultrasonography with 3580 images for classification and 941 images for segmentation. Sixty-two videos were used as the test dataset in real time. External data containing 598 images were also used for validation. Another 155 images were collected to compare the performance of the model to experts. In addition, a study was conducted to assess the effect of the model in improving lesions recognition of the trainees.

Results: The model achieved 0.94, 0.90, 0.92, 0.94, and 0.91 accuracy in recognizing normal, VD, VH, RD, and other lesions. Compared with the ophthalmologists, the modal achieved a 0.73 accuracy in classifying RD, VD, and VH, which has a better performance than most experts (P < 0.05). In the videos, the model had a 0.81 accuracy. With the model assistant, the accuracy of the trainees improved from 0.84 to 0.94.

Conclusions: The model could serve as a screening tool to rapidly identify patients with RD, VD, and VH. In addition, it also has potential to be a good tool to assist training.

Translational Relevance: We developed a deep learning model to make the ultrasound work more accurately and efficiently.
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http://dx.doi.org/10.1167/tvst.10.4.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083108PMC
April 2021

Spatio-temporal landscape of mouse epididymal cells and specific mitochondria-rich segments defined by large-scale single-cell RNA-seq.

Cell Discov 2021 May 18;7(1):34. Epub 2021 May 18.

Institute of Reproductive Medicine, Medical School of Nantong University, Nantong, Jiangsu 226019, China.

Spermatozoa acquire their fertilizing ability and forward motility during epididymal transit, suggesting the importance of the epididymis. Although the cell atlas of the epididymis was reported recently, the heterogeneity of the cells and the gene expression profile in the epididymal tube are still largely unknown. Considering single-cell RNA sequencing results, we thoroughly studied the cell composition, spatio-temporal differences in differentially expressed genes (DEGs) in epididymal segments and mitochondria throughout the epididymis with sufficient cell numbers. In total, 40,623 cells were detected and further clustered into 8 identified cell populations. Focused analyses revealed the subpopulations of principal cells, basal cells, clear/narrow cells, and halo/T cells. Notably, two subtypes of principal cells, the Prc7 and Prc8 subpopulations were enriched as stereocilia-like cells according to GO analysis. Further analysis demonstrated the spatially specific pattern of the DEGs in each cell cluster. Unexpectedly, the abundance of mitochondria and mitochondrial transcription (MT) was found to be higher in the corpus and cauda epididymis than in the caput epididymis by scRNA-seq, immunostaining, and qPCR validation. In addition, the spatio-temporal profile of the DEGs from the P42 and P56 epididymis, including transiting spermatozoa, was depicted. Overall, our study presented the single-cell transcriptome atlas of the mouse epididymis and revealed the novel distribution pattern of mitochondria and key genes that may be linked to sperm functionalities in the first wave and subsequent wave of sperm, providing a roadmap to be emulated in efforts to achieve sperm maturation regulation in the epididymis.
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http://dx.doi.org/10.1038/s41421-021-00260-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129088PMC
May 2021

The potential protective effects of miR-497 on corneal neovascularization are mediated via macrophage through the IL-6/STAT3/VEGF signaling pathway.

Int Immunopharmacol 2021 Jul 10;96:107745. Epub 2021 May 10.

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan 430061, Hubei Province, PR China. Electronic address:

Corneal neovascularization (CoNV) can cause abnormal blood vessels to grow in the transparent cornea, leading to various sight-threatening eye diseases. MicroRNAs are known to play essential roles in the regulation of numerous biological functions. We try to clarify the role of a specific microRNA, miR‑497, which has been shown to regulate the growth of tumor cells and angiogenesis on the basis of available data. However, the association between miR-497 and vascularized cornea remains unclear. Therefore, it is urgently needed to understand the molecular mechanism of miR497 in the progress of corneal neovascularization. Animal model of CoNV was established in wildtype (WT) C57BL/6 mice, CRISPR/Cas9 mediated miR-497 knockout (KO) and overexpressed (TG) C57BL/6 mice. MiR-497, expressed in corneas, was actively involved in alkali burn-induced corneal neovascularization via targeting STAT3 and negatively regulating its expression, attenuating macrophage infiltration and M2 polarization. Knockdown of miR-497 enhanced the formation of corneal angiogenesis through targeting STAT3 and facilitating its expression, promoting recruitment of macrophages, while overexpression of miR-497 restrained blood vessel sprouting via regulating downstream STAT3 and VEGFA expression, reducing macrophage activation and inhibiting M2 polarization. Moreover, miR-497 knockout-mediated damage effect can be rescued through the inhibition of STAT3 signaling. Mechanically, miR-497 might serve as a potential strategy for pathological corneal neovascularization via macrophage through the IL-6/STAT3/VEGFA signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2021.107745DOI Listing
July 2021

Bmal1 Regulates Macrophage Polarize Through Glycolytic Pathway in Alcoholic Liver Disease.

Front Pharmacol 2021 10;12:640521. Epub 2021 Mar 10.

School of Pharmacy, Anhui Medical University, Hefei, China.

Hepatic macrophages play a critical role in inflammation caused by alcohol feeding. During this process, variation of macrophage phenotypes triggers inflammatory responses in a variety of ways. Moreover, there is increasing evidence that Brain and Muscle Arnt-Like Protein-1 (Bmal1) is regarded as a key regulator of macrophage transformation. In our study, Bmal1 was detected to be low expressed in EtOH-fed mice tissue samples and ethanol-induced RAW264.7 cells. After hepatic specific overexpression of Bmal1, M1 macrophage markers were evidently down-regulated, while M2 markers were on the contrary, showing an upward trend. Furthermore, alcoholic liver lesions were also improved in alcohol feeding mice with overexpressed Bmal1. On this basis, we also found that the glycolytic pathway can regulate macrophage polarization. , blocking of glycolytic pathway can significantly inhibit M1-type polarization. Importantly, glycolysis levels were also restrained after Bmal1 overexpression. What's more, Bmal1 exerts a negative regulatory effect on glycolysis by interacting with S100A9 protein. Further studies showed that the alleviation of alcoholic liver disease (ALD) by Bmal1 was associated with glycolytic pathway suppression and M1 macrophage polarization. In summary, we demonstrated that Bmal1 is a gene capable of relieving ALD, and this effect may provide new insights for altering macrophage phenotypes to regulate inflammatory responses in ALD.
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http://dx.doi.org/10.3389/fphar.2021.640521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006279PMC
March 2021

Dynamic Elimination of Enrofloxacin Under Varying Temperature and pH in Aquaculture Water: An Orthogonal Study.

Bull Environ Contam Toxicol 2021 May 25;106(5):866-872. Epub 2021 Mar 25.

Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, 214081, PR China.

Orthogonal experiments were used to simulate the enrofloxacin (ENR) elimination dynamic in deeper water of aquaculture. Two factors at values common in fishery water (temperature of 20°C, 25°C, and 30°C; pH of 5, 7, and 9) were studied. The degradation of ENR in the nine treatment groups ranged from 44.7 to 80.1%. Variance analysis indicated that pH had a strong impact on the elimination of ENR, while temperature changes showed little effect. The ENR removal rate was highest at a combination of 25°C and pH 5. The optimal conditions of eliminating ENR were performed for exploring the generation of ciprofloxacin (CIP), which indicated that higher ENR concentrations led to the production of greater amounts of CIP. The half-time of ENR was increased 2.02-times in the ENR concentrations increasing from 20 to 2000 ng/mL. This study could increase our understanding of the behaviors of ENR and CIP during the aquaculture process.
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http://dx.doi.org/10.1007/s00128-021-03199-3DOI Listing
May 2021

The Novel Key Genes of Non-obstructive Azoospermia Affect Spermatogenesis: Transcriptomic Analysis Based on RNA-Seq and scRNA-Seq Data.

Front Genet 2021 26;12:608629. Epub 2021 Feb 26.

Department of Emergency Laboratory, Clinical Laboratory Medical Center, Shenzhen Hospital, Southern Medical University, Shenzhen, China.

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. It is mainly characterized by the absence of sperm in semen repeatedly or the number of sperm is small and not fully developed. At present, its pathogenesis remains largely unknown. The goal of this study is to identify hub genes that might affect biomarkers related to spermatogenesis. Using the clinically significant transcriptome and single-cell sequencing data sets on the Gene Expression Omnibus (GEO) database, we identified candidate hub genes related to spermatogenesis. Based on them, we performed Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses, protein-protein interaction (PPI) network analysis, principal component analysis (PCA), cell cluster analysis, and pseudo-chronological analysis. We identified a total of 430 differentially expressed genes, of which three have not been reported related to spermatogenesis (C22orf23, TSACC, and TTC25), and the expression of these three hub genes was different in each type of sperm cells. The results of the pseudo-chronological analysis of the three hub genes indicated that TTC25 was in a low expression state during the whole process of sperm development, while the expression of C22orf23 had two fluctuations in the differentiating spermatogonia and late primary spermatocyte stages, and TSACC showed an upward trend from the spermatogonial stem cell stage to the spermatogenesis stage. Our research found that the three hub genes were different in the trajectory of sperm development, indicating that they might play important roles in different sperm cells. This result is of great significance for revealing the pathogenic mechanism of NOA and further research.
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http://dx.doi.org/10.3389/fgene.2021.608629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959792PMC
February 2021

Association of Survival and Immune-Related Adverse Events With Anti-PD-1/PD-L1 and Anti-CTLA-4 Inhibitors, Alone or Their Combination for the Treatment of Cancer: A Systematic Review and Meta-Analysis of 13 Clinical Trials.

Front Oncol 2021 25;11:575457. Epub 2021 Feb 25.

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

Background: Cancer, with sustained high mortality, is a worldwide threat to public health. Despite the survival benefit over conventional therapies shown in immune checkpoint inhibitor (ICI), only a minority of patients benefit from single ICI. But combination therapy holds the promise of achieving better efficacy over monotherapy. We performed a systematic review and meta-analysis to assess the efficacy and safety of ICI-based combination therapy for cancer.

Methods: A search was conducted to retrieve relevant studies in electronic databases and major conferences. Two investigators independently performed data extraction, making a systematic data extraction, assembly, analysis and interpretation to compare the overall survival (OS), progression-free survival (PFS), overall response rate (ORR), all and high grade immune related adverse events (IRAEs) between combination therapy and monotherapy. Therefore, only the studies satisfying the criteria were included. Finally, we performed subgroup, sensitivity, and publication bias analysis to examine the heterogeneity and bias of resources.

Results: A total of 2,532 patients from thirteen studies were enrolled. Compared to ICI alone, combination therapy, with a high risk and high grade IRAEs for the majority of all, offers a better survival benefit (OS: HR: 0.86, 95% CI: 0.76 to 0.98; PFS: HR: 0.79, 95% CI: 0.69 to 0.90) and objective response (ORR: RR: 1.91, 95% CI: 1.40 to 2.60).

Conclusions: ICI-based combination therapy was confirmed as the optimum treatment for cancer, especially when using specific dosage and regimen to treat certain tumor types with no absolute demand for the detection of PD-L1 expression. Meanwhile, attention should also be paid on potential toxicity, especially the IRAEs.
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http://dx.doi.org/10.3389/fonc.2021.575457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947606PMC
February 2021

Dot1l Aggravates Keratitis Induced by Herpes Simplex Virus Type 1 in Mice via p38 MAPK-Mediated Oxidative Stress.

Oxid Med Cell Longev 2021 15;2021:6612689. Epub 2021 Feb 15.

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China.

Background: Disruptor of telomeric silencing 1-like (Dot1l) plays a vital role in biological processes as a well-known methyltransferase. However, its role in herpes simplex virus type 1- (HSV-1-) infected keratitis remains unclear.

Methods: and models were assessed to investigate the role of Dot1l in HSV-1 induced keratitis. C57BL/6 mice corneas were infected with HSV-1 for different days, with or without Dot1l inhibitor, to demonstrate the regulation of Dot1l in herpes simplex keratitis (HSK). Human corneal epithelial (HCE) cells were cultured and infected with HSV-1 to identify the molecular mechanisms involved.

Results: In this study, we found that Dot1l was positively related to HSK. Inhibition of Dot1l with EPZ004777 (EPZ) alleviated corneal injury, including oxidative stress and inflammation . Similarly, the inhibition of Dot1l with either EPZ or small interfering RNA (siRNA) showed an inhibitory effect on HSV-1-induced oxidative stress and inflammation in HCE cells. Moreover, our study revealed that the expression of p38 MAPK was elevated after HSV-1 infection in HCE cells, and the inhibition of Dot1l could reduce the increased expression of p38 MAPK induced by HSV-1 infection and .

Conclusion: Our results demonstrated that the inhibition of Dot1l alleviated corneal oxidative stress and inflammation by inhibiting ROS production through the p38 MAPK pathway in HSK. These findings indicated that Dot1l might be a valuable therapeutic target for HSK.
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http://dx.doi.org/10.1155/2021/6612689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899779PMC
February 2021

Polymeric non-spherical coarse microparticles fabricated by double emulsion-solvent evaporation for simvastatin delivery.

Colloids Surf B Biointerfaces 2021 Mar 6;199:111560. Epub 2021 Jan 6.

Biomedical Barriers Research Center, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin, 300192, China. Electronic address:

Polymeric particles with non-spherical shape or coarse surface have distinct advantages for drug delivery, tissue regeneration and immunomodulation respectively, but it is not easy to control polymeric microparticles in required geometry and surface texture simultaneously. In this study, polymeric non-spherical microparticles with coarse surface were successfully prepared by double emulsion-solvent evaporation technique in the presence of ammonium bicarbonate and the formation mechanism was proposed. In addition, simvastatin was encapsulated in poly[lactic-co-(glycolic acid)] (PLGA) non-spherical microparticles with coarse surface by the same technique and the release kinetics in vitro was fitted as well, which not only enrich the encapsulation techniques of liposoluble drugs in polymeric non-spherical carriers but also envision the potential application for alveolar ridge preservation with local delivery of simvastatin.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111560DOI Listing
March 2021

CDH1 is Identified as A Therapeutic Target for Skin Regeneration after Mechanical Loading.

Int J Biol Sci 2021 1;17(1):353-367. Epub 2021 Jan 1.

a Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, P.R. China.

Mechanical stimuli in the microenvironment are considered key regulators of cell function. Clinically, mechanical force (tissue expander) is widely used to regenerate skin for post-burn or trauma repair, implying that mechanical stretching can promote skin cell regeneration and proliferation. However, the underlying mechanism remains unknown. Microarray analysis was utilized to detect the hub gene. The expression of Cdh1 as examined in cells and tissues by western blot, q-PCR and immunohistochemistry staining respectively. Biological roles of Cdh1 was revealed by a series of functional in vitro and in vivo studies. Microarray analysis identified as a hub gene related to skin regeneration during rat cutaneous mechanical loading. In vitro studies suggested that both mechanical loading and interference induced keratinocyte dedifferentiation and enhanced stemness, promoting cell proliferation and prevent apoptosis. Furthermore, the forkhead box O1/Krüppel-like factor 4 (FOXO1/KLF4) pathway was activated and contributed to the keratinocyte dedifferentiation. In vivo studies showed that mechanical loading and interference facilitated epidermal dedifferentiation and promoted dermal collagen deposition, and that overexpression could block such influence. In this study, we show that E-cadherin (CDH1), a well-known cell-cell adhesion molecule, plays a crucial role in mechanical stretch-induced skin cell regeneration and proliferation. We have shown for the first time the process by which mechanical stress is transmitted to the epidermis and induces a downstream signaling pathway to induce epidermal cells to differentiate. These findings demonstrate that -induced keratinocyte dedifferentiation is a crucial event in mechanical stretch-mediated skin regeneration and that may serve as a potential therapeutic target for promoting skin regeneration.
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http://dx.doi.org/10.7150/ijbs.51309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757047PMC
January 2021

Evaluation of Procalcitonin and C-reactive Protein in Early Differential Diagnosis of Neonatal Jaundice.

Clin Lab 2020 Dec;66(12)

Background: The purpose of this study was to investigate the clinical value of procalcitonin (PCT) and C-reactive protein (CRP) in the differential diagnosis of neonatal jaundice.

Methods: Eighty-five cases of neonatal jaundice in our hospital from January 2016 to March 2019 were selected as research subjects, including 30 cases of physiological jaundice, 23 cases of infectious jaundice, and 32 cases of he-molytic jaundice. Five milliliters of non-anticoagulated venous peripheral blood and 3 mL EDTA-K+ anticoagulated venous peripheral blood were sampled from each newborn when the symptoms of jaundice occurred. The non-anticoagulated blood samples were then centrifuged at 3,500 rpm for 7 minutes and the serum was used for PCT and bilirubin examinations, and the anticoagulated blood samples were prepared for CRP examination. Receiver operating characteristic (ROC) curve analysis was performed for the evaluation of differential diagnosis of neonatal jaundice by PCT, CRP, and bilirubin levels.

Results: Analyses of variance showed the postnatal age of jaundice occurring in the physiological jaundice group was older than those in the infectious jaundice and hemolytic jaundice groups (p < 0.001), and the PCT and CRP levels in the infectious jaundice group were higher than those in the hemolytic jaundice and physiological jaundice groups (p < 0.001). Pearson's correlation analysis indicated that the levels of PCT and CRP were negatively correlated with postnatal age in the physiological jaundice group (p < 0.05). ROC curve analysis demonstrated that PCT and CRP had the highest differential diagnosis efficacy of neonatal pathological and neonatal physiological jaundice with PCT and CRP at 0.70 µg/L and 8.50 mg/L, respectively, as well as the highest differential diagnosis efficacy of neonatal infectious jaundice and neonatal hemolytic jaundice with PCT and CRP at 1.84 µg/L and 13.50 mg/L, respectively.

Conclusions: This study suggested that PCT and CRP possessed important clinical values in the differential diagnosis of neonatal jaundice, and PCT was superior to the differential diagnosis of neonatal infectious jaundice.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200330DOI Listing
December 2020

Temperature and oxygen level determine N O respiration activities of heterotrophic N O-reducing bacteria: Biokinetic study.

Biotechnol Bioeng 2021 Mar 31;118(3):1330-1341. Epub 2020 Dec 31.

Department of Chemical Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Nitrous oxide (N O), a potent greenhouse gas, is reduced to N gas by N O-reducing bacteria (N ORB), a process which represents an N O sink in natural and engineered ecosystems. The N O sink activity by N ORB depends on temperature and O exposure, yet the specifics are not yet understood. This study explores the effects of temperature and oxygen exposure on biokinetics of pure culture N ORB. Four N ORB, representing either clade I type nosZ (Pseudomonas stutzeri JCM5965 and Paracoccus denitrificans NBRC102528) or clade II type nosZ (Azospira sp. strains I09 and I13), were individually tested. The higher activation energy for N O by Azospira sp. strain I13 (114.0 ± 22.6 kJ mol ) compared with the other tested N ORB (38.3-60.1 kJ mol ) indicates that N ORB can adapt to different temperatures. The O inhibition constants (K ) of Azospira sp. strain I09 and Ps. stutzeri JCM5965 increased from 0.06 ± 0.05 and 0.05 ± 0.02 μmol L to 0.92 ± 0.24 and 0.84 ± 0.31 μmol L , respectively, as the temperature increased from 15°C to 35°C, while that of Azospira sp. strain I13 was temperature-independent (p = 0.106). Within the range of temperatures examined, Azospira sp. strain I13 had a faster recovery after O exposure compared with Azospira sp. strain I09 and Ps. stutzeri JCM5965 (p < 0.05). These results suggest that temperature and O exposure result in the growth of ecophysiologically distinct N ORB as N O sinks. This knowledge can help develop a suitable N O mitigation strategy according to the physiologies of the predominant N ORB.
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http://dx.doi.org/10.1002/bit.27654DOI Listing
March 2021

Neutrophil Surface CD64 Stimulation Index Detection Assay in Diagnosing Mycobacterium tuberculosis Infection.

Clin Lab 2020 Nov;66(11)

Background: This study aimed to develop a method for assessing the sensitivity and diagnostic performance of the neutrophil surface CD64 stimulation index (SI) in tuberculosis infection.

Methods: A total of 149 samples were divided into three groups (tuberculosis group, n = 51; nontuberculosis infection group, n = 50; and healthy control group, n = 48). Flow cytometry was used to detect the sensitivity of CD64 SI on the surface of neutrophils. The sensitivities of CD64 SI before and after stimulation with ESAT-6 and CFP-10 antigens were compared using interferon-gamma release assay-enzyme-linked immunosorbent assay (IGRA-ELISA).

Results: The diagnostic threshold for CD64 SI based on the receiver operating characteristic curve was found to be 2.025, which is the standard for judging tuberculosis infection. The IGRA-ELISA and the CD64 SI assays were highly consistent with a kappa value of 0.635 (p < 0.003, 95% CI: 0.002 - 0.003).

Conclusions: The neutrophil surface CD64 SI value detection method may serve as one of the new diagnostic methods for active Mycobacterium tuberculosis infection.
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http://dx.doi.org/10.7754/Clin.Lab.2020.200214DOI Listing
November 2020

The Platelet microRNA Profile of Kawasaki Disease: Identification of Novel Diagnostic Biomarkers.

Biomed Res Int 2020 17;2020:9061568. Epub 2020 Jul 17.

Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200062, China.

Challenging diagnosis and unknown etiology of Kawasaki disease (KD) increase the coronary artery lesions incidence. microRNAs (miRNAs) are the most promising biomarkers because of their stability in peripheral blood and noninvasive measurement procedure, whose potential utility have been proved in cancers. To explore the utility of differentially expressed (DE) miRNAs as early diagnostic markers, 44 patients (25 incomplete KD and 19 complete KD) and 31 febrile controls were recruited for small RNA sequencing. From all the 1922 expressed miRNA, 210 DE miRNAs were found between KD and febrile control groups. Though platelet miRNA profiles of complete KD incomplete KD were much similar through cluster analysis, the DE miRNAs were not identical. Eight DE miRNAs were validated by real-time quantitative PCR (qRT-PCR) in complete or incomplete KD groups using a normalizer, miR-126-3p, which was identified by geNorm and NormFinder tools. The expression level of miRNAs continuous changed over time was observed and the function analysis showed the potential role of miRNAs as therapeutic biomarkers. Additionally, the prediction model for KD showed a sensitivity of 78.8% and a specificity of 71.4%, respectively. This study used small RNA sequencing to identify miRNA biomarkers KD diagnosis based on a large sample size. Our findings shine a light on the understanding of molecular pathogenesis of KD and may improve the accuracy of KD diagnosis and prognosis in clinical.
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http://dx.doi.org/10.1155/2020/9061568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383328PMC
April 2021

Prevalence, serotypes, and antimicrobial resistance of Salmonella isolates from patients with diarrhea in Shenzhen, China.

BMC Microbiol 2020 07 6;20(1):197. Epub 2020 Jul 6.

Shenzhen Hospital, Southern Medical University, Xinhu Road 1333, Baoan District, Shenzhen, 518110, Guangdong, China.

Background: Salmonella is one of the main causative agents of diarrhea which results in substantial disease burden. To determine the prevalence, serotype distribution, and antimicrobial resistance profiles of clinical Salmonella isolates in Shenzhen, a 6-year surveillance study was conducted.

Results: A total of 297 (5.7%) Salmonella strains were isolated from stool samples from 5239 patients. Among the 42 serotypes identified, serotype Typhimurium was the most common one which represented 39.7% of the isolates (118), followed by serotype Enteritidis (71, 23.9%), London (12, 4.0%), 4, 5, 12: i: - (11, 3.7%), and Senftenberg (8, 2.7%). A high frequency of resistance was found in ampicillin (70.6%), piperacillin (64.5%), tetracycline (63.5%), and streptomycin (54.3%). Resistance to ampicillin and tetracycline was observed in 95.3% of S. Typhimurium isolates; and nalidixic acid in 93.1% of S. Enteritidis isolates. Resistance to 5 or more antimicrobial agents was found in 78.8% of S. Typhimurium and 69.0% of S. Enteritidis isolates. A decreased susceptibility to ciprofloxacin and levofloxacin was associated with amino acid alteration in gyrA gene. Point mutations without amino acid changes were seen in gyrB, parC, and parE genes.

Conclusions: A broad range of serotypes are responsible for Salmonellosis in Shenzhen, with Enteritidis and Typhimurium being the most common serotypes. The high level of antibiotic resistance is of public health significance and ongoing monitoring combined with rational use of antibiotics are recommended. Point mutations in gyrA gene might play an important role in the resistance to fluoroquinolones.
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http://dx.doi.org/10.1186/s12866-020-01886-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339465PMC
July 2020

Nonlinear response of methane release to increased trophic state levels coupled with microbial processes in shallow lakes.

Environ Pollut 2020 Oct 4;265(Pt B):114919. Epub 2020 Jun 4.

Department of Chemical Engineering, Tokyo University of Agriculture and Technology, Tokyo, 184-8588, Japan.

Shallow lakes are a crucial source of methane (CH), a potent greenhouse gas, to the atmosphere. However, large uncertainties still exist regarding the response of CH emissions to the increasing trophic levels of lakes as well as the underlying mechanisms. Here, we investigate the CH emission flux from lakes with different trophic states in the middle and lower reaches of the Yangtze River basin, China to evaluate the effect of the trophic lake index (TLI) on CH emissions. The mean CH emission fluxes from mesotrophic, eutrophic, middle-eutrophic, and hyper-eutrophic lakes were 0.1, 4.4, 12.0, and 130.4 mg m h, respectively. Thus, the CH emission flux ranged widely and was positively correlated with the degree of eutrophication. The relative abundance of methanogens with respect to the total population for the mesotrophic, eutrophic, mid-eutrophic, and hyper-eutrophic states was 0.03%, 0.35%, 0.94%, and 1.17%, respectively. The biogeographic-scale pattern of lakes classified as each of these four trophic states indicated that CH emissions could be well-predicted by the NH-N concentration in the water column, as both NH-N and CH were produced during mineralisation of labile organic matter in lake sediment. In addition, the shift from clear to turbid water, which is an unhealthy evolution for lakes, was associated with a nonlinear increase in the CH emissions from the studied lakes. In particular, the hypereutrophic lakes functioned as CH emission hotspots. Our findings highlight that nutrient levels, as a potential facilitator of CH emissions, should be considered in future research to accurately evaluate the greenhouse gas emissions from shallow lakes.
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http://dx.doi.org/10.1016/j.envpol.2020.114919DOI Listing
October 2020

Isorhamnetin Induces Melanoma Cell Apoptosis via the PI3K/Akt and NF-B Pathways.

Biomed Res Int 2020 5;2020:1057943. Epub 2020 May 5.

Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.

Malignant melanoma is characterized by its bad prognosis for aggressiveness, drug resistance, and early metastasis. Isorhamnetin (3'-methoxy-3,4',5,7-tetrahydroxyflavone; IH) is a natural flavonoid that has been investigated for its antitumor effects in breast cancer, colon cancer, and gastric cancer through inducing cell apoptosis. Given its role in tumor inhibition, no research has been conducted concerning its effect against melanoma. In the present study, we found that IH could significantly inhibit B16F10 cell proliferation and migration and induce B16F10 cell apoptosis. The examination on molecular mechanism revealed that IH could suppress the phosphorylation of Akt and the translocation of NF-B, which are key factors in apoptosis-related pathways. We also detected that this process was related to the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 4 (PFKFB4) by PFKFB4 knockdown experiment. In line with in vitro study, we further provided that IH effectively inhibited tumor growth in vivo. Taken together, IH was proven to induce melanoma cell apoptosis in vitro and in vivo, which may serve as a potential agent in malignant melanoma treatment in the future.
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http://dx.doi.org/10.1155/2020/1057943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225865PMC
February 2021

Becoming a Faithful Defender: Traditional Chinese Medicine against Coronavirus Disease 2019 (COVID-19).

Am J Chin Med 2020 29;48(4):763-777. Epub 2020 Apr 29.

The First Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, P. R. China.

The outbreak caused by COVID-19 is causing a major challenge to clinical management and a worldwide threat to public health. So far, there is no specific anti-coronavirus therapy approved for the treatment of COVID-19. Recently, as the efficacy and safety of traditional Chinese medicine (TCM) is widely acknowledged, it has been brought to a crucial status by the public, governments, and World Health Organization (WHO). For a better popularization of TCM, governments have made several advances in regulations and policies for treatment and measures of novel coronavirus pneumonia (NCP). Therefore, on the basis of epidemiology and virology information, we reviewed relevant meta-analysis and clinical studies of anti-coronavirus therapeutics by TCM, in the aspect of mortality, symptom improvement, duration and dosage of corticosteroid, incidence of complications and the like. In addition, we also summarized preclinical rationale for anti-coronavirus activity by TCM in terms of virion assembly and release, as well as viral entry and replication, which could be a useful contribution for figuring out effective Chinese herbal medicine (CHM) for coronavirus, including ingredients from single monomeric compounds, Chinese herbs, Chinese herb extracts and Chinese herb formulas, or potential targets for medicine. We would like to see these relevant studies, ranging from basic researches to clinical application, could provide some idea on effects of CHM to combat COVID-19 or other coronaviruses, and also offer new thinking for the exploration of therapeutic strategies under the guidance of TCM.
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http://dx.doi.org/10.1142/S0192415X2050038XDOI Listing
June 2020

Cordycepin protects against acute pancreatitis by modulating NF-κB and NLRP3 inflammasome activation via AMPK.

Life Sci 2020 Jun 5;251:117645. Epub 2020 Apr 5.

School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu, China. Electronic address:

Acute pancreatitis (AP) is a noninfectious inflammatory disease with high morbidity and mortality, which is characterized by severe inflammation and tissue necrosis. Cordycepin (CRD), derived from Cordyceps militaris, possesses anti-inflammatory effects and immunomodulation properties. Here, we investigated the protective effects of CRD on pancreatic injury and clarified potential mechanisms in AP model. There were established caerulein-induced AP and CRD pretreatment models in vivo and in vitro, as showed by serum enzymes, histopathological alterations and pro-inflammatory cytokines. Pretreatment with CRD notably downregulated the serum amylase and lipase levels and apparently reduced pancreatic histopathological alterations in AP mice. Meanwhile, the MPO staining confirmed that CRD pretreatment modulated the infiltration of neutrophils in AP mice. Furthermore, CRD markedly decreased the levels of pro-inflammatory factors (IL-6, IL-1β, and TNF-α) though inhibiting the activation of nuclear factor-κB (NF-κB) and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in AP mice. In pancreatic acinar cancer cell 266-6, CRD pretreatment decreased cholecystokinin(CCK)-induced inflammatory response was consistent with those in vivo. Mechanistically, CRD was also revealed to activate activated protein kinase (AMPK) and attenuated inflammation both in vivo and in vitro. On the whole, this study indicated that CRD protects mice from pancreatic inflammatory process and damage by suppressed NF-κB and NLRP3 inflammasome activation via AMPK, which probably contributed to the potential therapy for AP.
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http://dx.doi.org/10.1016/j.lfs.2020.117645DOI Listing
June 2020

A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family.

Clin Genet 2020 07 16;98(1):69-73. Epub 2020 Apr 16.

Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Early embryonic arrest is one of the major causes of recurrent assisted reproduction failure. It is characterized by delayed embryonic development and failure to form viable eight-cell stage embryos on day 3 of an assisted reproduction cycle. A recent study reported that biallelic mutations in NLRP5 can cause early embryonic arrest. NLRP5 is a member of subcortical maternal complex, which plays a significant role in embryogenesis. In this study, we described a female in a consanguineous Chinese family who displayed clinical features of early embryonic arrest and identified a novel homozygous variant c.1061C>T (p.Pro354Leu) in NLRP5. This is the second report of the biallelic NLRP5 variant that associates with early embryonic arrest in humans, further confirming the role of NLRP5 variants in early embryonic arrest and expanding the spectrum of known pathogenic variants in NLRP5.
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http://dx.doi.org/10.1111/cge.13744DOI Listing
July 2020

To be or not to be: whether anti-angiogenic agent combined with immune checkpoint inhibitoris necessary in the treatment of advanced or metastatic renal cell carcinoma.

Med Oncol 2020 Feb 1;37(2):15. Epub 2020 Feb 1.

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, Zhejiang, China.

Although it's widely known that targeted therapy against angiogenesis and immunotherapy agents showed survival benefit over chemoradiotherapy in advanced or metastatic renal cell carcinoma, some patients still cannot receive a satisfied prognosis. We performed a systematic review and meta-analysis to explore the efficacy and safety of anti-angiogenic agents combined with immune checkpoint inhibitors. We conducted a search for randomized controlled trials in Pubmed, Embase, Cochrane, and major conference. Enrolled eligible studies and extracted data were completed by two investigators to compare OS, PFS, and ORR both in PD-L1 and ITT subset. Then, we calculated the pooled RR and 95% CI of all-grade and high-grade adverse effects to study its safety. Besides, we assessed the heterogeneity through subgroup and sensitivity analysis. A total of three RCTs covering 2662 patients were enrolled. In PFS analysis, the estimated HR for ITT subset was 0.74 with 95% CI of 0.65 to 0.84 and for PD-L1 subset was 0.65 with 95% CI of 0.56 to 0.76. And in OS analysis, the result was 0.74 with 95% CI of 0.53 to 1.03 in ITT subset and 0.74 with 95% CI of 0.56 to 0.96 in PD-L1 subset. As for ORR analysis, combination therapy showed advantage rather than monotherapy in ITT subset (RR 1.54; 95% CI 1.11 to 2.14), but conversely in PD-L1 positive subset (RR 1.64; 95% CI 0.94 to 2.84). Additionally, combination therapy failed to show obvious safety in most immune-related adverse events, whatever in all-grade or high grade.
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http://dx.doi.org/10.1007/s12032-020-1340-7DOI Listing
February 2020

Downregulation of CFTR Is Involved in the Formation of Hypertrophic Scars.

Biomed Res Int 2020 2;2020:9526289. Epub 2020 Jan 2.

Department of Plastic & Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, China.

Hypertrophic Scars (HTSs) are a complex fibroproliferative disorder, and their exact mechanism is still not fully understood. In this study, we first found that cystic fibrosis transmembrane conductance regulator (CFTR) expression was downregulated in human hypertrophic scars at the RNA and protein levels by microarray data analysis, RT-PCR, and immunofluorescence (IF) staining. To validate that this downregulation of CFTR is involved in the formation of HTSs, we then applied a mechanical overloading intervention in both wild type and CFTR-mutant mice (ΔF508). Our results showed thatΔF508 mice exhibited delayed wound healing and a significantly larger HTS on day 28. Masson staining revealed that there was more collagen deposition in the HTS, and Sirius red staining and IF staining showed a higher ratio of collagen 1/collagen 3 (Col1/Col3) in ΔF508 mice. Real-time RT-PCR showed that the proinflammatory markers were higher in ΔF508 mice in all phases of scar formation, whereas the proliferation marker was similar. Moreover, we harvested the fibroblasts from both mice. Western blotting showed that the expression of Col1 was the same in both mice, and the expression of Col3 was significantly lower in ΔF508 mice. However, in a mechanical overloading condition, the expression of Col1 was significantly higher in ΔF508 mice, and the expression of Col3 was the same in both mice. Taken together, our results indicate that the downregulation of CFTR might affect the function of fibroblasts, resulting in a lower level of collagen type 3 and a higher ratio of Col1/Col3, and thus aggravate the formation of HTSs in mechanical overloading conditions.
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http://dx.doi.org/10.1155/2020/9526289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970488PMC
September 2020

MicroRNA-708 represses hepatic stellate cells activation and proliferation by targeting ZEB1 through Wnt/β-catenin pathway.

Eur J Pharmacol 2020 Mar 18;871:172927. Epub 2020 Jan 18.

Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China. Electronic address:

Liver fibrosis is caused by a sustained wound healing response to chronic liver injury, and the activation of insubstantial hepatic stellate cells (HSCs) is the key process involved. The progression of liver fibrosis may be attenuated by suppressing activation and proliferation of the HSCs. MicroRNA (miRNA) have emerged as major players in governing fundamental biological processes through multiple mechanisms MiR-708 is known to inhibit the development of hepatocellular carcinoma. However, whether miR-708 can function as a transcriptional regulator in liver fibrosis remains unclear. Our study demonstrated that miR-708 expression was inhibited in fibrotic liver tissues and in activated HSCs, accompanied by an increase of the Zinc finger E-box binding homeobox 1 (ZEB1) level. Besides, overexpression of miR-708 and silencing of ZEB1 inhibited the activation and proliferation of LX-2 cells. While knockdown of miR-708 or overexpression of ZEB1 showed reversed results. Further, dual luciferase reporter assays showed that miR-708 directly targeted ZEB1 in vitro. Interestingly, ZEB1 was found to be involved in HSCs by regulating Wnt/β-catenin signaling pathway. Together, our data showed that miR-708 may be a potential therapeutic target in liver fibrosis therapy.
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http://dx.doi.org/10.1016/j.ejphar.2020.172927DOI Listing
March 2020