Publications by authors named "Zhu Zhan"

9 Publications

  • Page 1 of 1

Early Improvement of Acute Respiratory Distress Syndrome in Patients With COVID-19 in the Intensive Care Unit: Retrospective Analysis.

JMIR Public Health Surveill 2021 03 9;7(3):e24843. Epub 2021 Mar 9.

Department of Intensive Care Unit, Chongqing Sixth People's Hospital, Chongqing, China.

Background: Since the start of the COVID-19 pandemic, there have been over 2 million deaths globally. Acute respiratory distress syndrome (ARDS) may be the main cause of death.

Objective: This study aimed to describe the clinical features, outcomes, and ARDS characteristics of patients with COVID-19 admitted to the intensive care unit (ICU) in Chongqing, China.

Methods: The epidemiology of COVID-19 from January 21, 2020, to March 15, 2020, in Chongqing, China, was analyzed retrospectively, and 75 ICU patients from two hospitals were included in this study. On day 1, 56 patients with ARDS were selected for subgroup analysis, and a modified Poisson regression was performed to identify predictors for the early improvement of ARDS (eiARDS).

Results: Chongqing reported a 5.3% case fatality rate for the 75 ICU patients. The median age of these patients was 57 (IQR 25-75) years, and no bias was present in the sex ratio. A total of 93% (n=70) of patients developed ARDS during ICU stay, and more than half had moderate ARDS. However, most patients (n=41, 55%) underwent high-flow nasal cannula oxygen therapy, but not mechanical ventilation. Nearly one-third of patients with ARDS improved (arterial blood oxygen partial pressure/oxygen concentration >300 mm Hg) in 1 week, which was defined as eiARDS. Patients with eiARDS had a higher survival rate and a shorter length of ICU stay than those without eiARDS. Age (<55 years) was the only variable independently associated with eiARDS, with a risk ratio of 2.67 (95% CI 1.17-6.08).

Conclusions: A new subphenotype of ARDS-eiARDS-in patients with COVID-19 was identified. As clinical outcomes differ, the stratified management of patients based on eiARDS or age is highly recommended.
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http://dx.doi.org/10.2196/24843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945975PMC
March 2021

Urine α-fetoprotein and orosomucoid 1 as biomarkers of hepatitis B virus-associated hepatocellular carcinoma.

Am J Physiol Gastrointest Liver Physiol 2020 02 18;318(2):G305-G312. Epub 2019 Nov 18.

Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Hepatocellular carcinoma (HCC) is the sixth common malignant tumor worldwide, but current efficient and convenient screening methods remain lacking. This study aimed to discover a diagnostic or a screening biomarker from the urine of hepatitis B virus (HBV)-related HCC patients. We used iTRAQ coupled with mass spectrometry to identify candidate urinary proteins in a discovery cohort ( = 40). The selected proteins were confirmed using ELISA in a validation cohort ( = 140). Diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC) and qualitative diagnostic analysis. A total of 96 differentially expressed proteins were identified. Urinary α-fetoprotein (u-AFP) and orosomucoid 1 (u-ORM1) were selected as target proteins by bioinformatics analysis and were significantly higher in HCC than in non-HCC patients, as validated by Western blot analysis and ELISA. u-AFP had a strong correlation with serum AFP-L3 (Pearson's  = 0.944, < 0.0001), indicating that u-AFP may be derived from circulating blood. The area under the curve (AUC) of u-AFP was 0.795 with a sensitivity of 62.5% and a specificity of 95.4%, which showed no significantly difference with serum AFP (se-AFP). The AUC was 0.864 as u-AFP and u-ORM1 were combined, and they performed much better than u-AFP or u-ORM1 alone. Qualitative diagnostic analysis showed that the positive predictive value of u-AFP was 90.1% and the diagnostic sensitivity of parallel combination of u-AFP and u-ORM1 was 85.1%. Taken together, AFP and ORM1 in the urine may be used as a diagnostic or screening biomarker of HCC, and studies on large samples are needed to validate the result. This study provides a novel way to find biomarkers of hepatocellular carcinoma (HCC) and a new perspective of α-fetoprotein clinical application. The urine reagent strips may be helpful in high epidemic areas of HCC and in low-resource settings.
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http://dx.doi.org/10.1152/ajpgi.00267.2019DOI Listing
February 2020

Identification of key genes, pathways and potential therapeutic agents for liver fibrosis using an integrated bioinformatics analysis.

PeerJ 2019 22;7:e6645. Epub 2019 Mar 22.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Chongqing Medical University, Chongqing, China.

Background: Liver fibrosis is often a consequence of chronic liver injury, and has the potential to progress to cirrhosis and liver cancer. Despite being an important human disease, there are currently no approved anti-fibrotic drugs. In this study, we aim to identify the key genes and pathways governing the pathophysiological processes of liver fibrosis, and to screen therapeutic anti-fibrotic agents.

Methods: Expression profiles were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were identified by R packages (Affy and limma). Gene functional enrichments of each dataset were performed on the DAVID database. Protein-protein interaction (PPI) network was constructed by STRING database and visualized in Cytoscape software. The hub genes were explored by the CytoHubba plugin app and validated in another GEO dataset and in a liver fibrosis cell model by quantitative real-time PCR assay. The Connectivity Map L1000 platform was used to identify potential anti-fibrotic agents.

Results: We integrated three fibrosis datasets of different disease etiologies, incorporating a total of 70 severe (F3-F4) and 116 mild (F0-F1) fibrotic tissue samples. Gene functional enrichment analyses revealed that cell cycle was a pathway uniquely enriched in a dataset from those patients infected by hepatitis B virus (HBV), while the immune-inflammatory response was enriched in both the HBV and hepatitis C virus (HCV) datasets, but not in the nonalcoholic fatty liver disease (NAFLD) dataset. There was overlap between these three datasets; 185 total shared DEGs that were enriched for pathways associated with extracellular matrix constitution, platelet-derived growth-factor binding, protein digestion and absorption, focal adhesion, and PI3K-Akt signaling. In the PPI network, 25 hub genes were extracted and deemed to be essential genes for fibrogenesis, and the expression trends were consistent with GSE14323 (an additional dataset) and liver fibrosis cell model, confirming the relevance of our findings. Among the 10 best matching anti-fibrotic agents, Zosuquidar and its corresponding gene target ABCB1 might be a novel anti-fibrotic agent or therapeutic target, but further work will be needed to verify its utility.

Conclusions: Through this bioinformatics analysis, we identified that cell cycle is a pathway uniquely enriched in HBV related dataset and immune-inflammatory response is clearly enriched in the virus-related datasets. Zosuquidar and ABCB1 might be a novel anti-fibrotic agent or target.
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http://dx.doi.org/10.7717/peerj.6645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6432904PMC
March 2019

Comparative Genomics, Whole-Genome Re-sequencing and Expression Profile Analysis of Nucleobase:Cation Symporter 2 () Genes in Maize.

Front Plant Sci 2018 28;9:856. Epub 2018 Jun 28.

National Engineering Laboratory of Crop Stress Resistance Breeding, School of Life Sciences, Anhui Agricultural University, Hefei, China.

Nucleobase:cation symporter 2 (NCS2) proteins are important for the transport of free nucleobases, participating in diverse plant growth and developmental processes, as well as response to abiotic stress. To date, a comprehensive analysis of the gene family has not been performed in maize. In this study, we conducted a comparative genomics analysis of genes in 28 plant species, ranging from aquatic algae to land plants, concentrating mainly on maize. Gene duplication events contributed to the expansion of genes from lower aquatic plants to higher angiosperms, and whole-genome/segmental and single-gene duplication events were responsible for the expansion of the maize gene family. Phylogenetic construction showed three subfamilies, I, II, and III. According to homology-based relationships, members of subfamily I are genes, whereas those in subfamilies II and III are s. Moreover, subfamily I exhibited ancient origins. A motif compositional analysis showed that one symbolic motif (motif 4) of the genes was absent in subfamily I. In maize, three and 21 genes were identified, and purifying selection influenced the duplication of maize genes. Additionally, a population genetic analysis of genes revealed that showed the greatest diversity between the 78 inbred and 22 wild surveyed maize populations. An expression profile analysis using transcriptome data and quantitative real-time PCR revealed that genes in maize are involved in diverse developmental processes and responses to abiotic stresses, including abscisic acid, salt (NaCl), polyethylene glycol, and low (4°C) and high (42°C) temperatures. genes with relatively close relationships had similar expression patterns, strongly indicating functional redundancy. Finally, and localize in the plasma membrane, which confirmed their predicted membrane structures. These results provide a foundation for future studies regarding the functions of ZmNCS2 proteins, particularly those with potentially important roles in plant responses to abiotic stresses.
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http://dx.doi.org/10.3389/fpls.2018.00856DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031955PMC
June 2018

[Nitrogen application technology in dwarfed apple trees.]

Ying Yong Sheng Tai Xue Bao 2018 May;29(5):1429-1436

College of Horticulture Science and Enginee-ring, Shandong Agricultural University/State Key Laboratory of Crop Biology, Tai'an 271018, Shandong, China.

N trace technique was used to explore the characteristics of N-urea absorption, utilization, loss and fruit quality of eight-year-old 'Yanfu3'/M26/Malus hupehensis Rehd. seedlings. There were three different nitrogen fertilization treatments: one-time nitrogen application in spring (1), two times nitrogen application (2), the intensive technique of nitrogen application with several times application and reduction in amount (3). The results showed that leaf area, chlorophyll content (SPAD value), photosynthetic rate (P), total N content of leaves and the total biomass per plant (except fruit), as well as the root-shoot ratio of treatment 3 were obviously higher than those in the treatments of 1 and 2. Treatment 3 significantly increased the protective enzymes (SOD, POD and CAT) activities and decreased the malondialdehyde (MDA) content in leaves. Significant differences were found on the N derived from fertilizer (Ndff value) of different organs, with the fruit Ndff showing the highest, followed by the one-year-old branches, leaves and roots of the three treatments. The Ndff values of each organ were the highest in the treatment 3. At fruit maturity stage, total N content of plant in treatment 3 was 93.0 mg·kg, which was obviously higher than that in the treatments 1 (70.2 mg·kg) and 2 (81.9 mg·kg). N nitrogen utilization ratio of treatment 3 was 33.6%, which was obviously higher than that in the treatments 1 (20.4%) and 2 (26.0%). The N loss rate was 46.9% in treatment 3, being obviously lower than that in the treatments 1 (56.5%) and 2 (52.9%). There were significant differences of fruit mass, soluble solid, fruit firmness, soluble sugar content, titratable acids and sugar-acid ratio among different treatments, with the highest values in the treatment 3 and the lowest values in treatment 1.
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http://dx.doi.org/10.13287/j.1001-9332.201805.027DOI Listing
May 2018

[Effects of nitrogen-supply levels on leaf senescence and characteristics of distribution and utilization of C and N in Fuji 3 apple grafted on different stocks].

Ying Yong Sheng Tai Xue Bao 2017 Jul;28(7):2239-2246

College of Horticulture Science and Engineering, Shandong Agricultural University/State Key Laboratory of Crop Biology, Tai'an 271018, Shandong, China.

Two-year-old potted Fuji 3 apple trees on different rootstocks [Fuji 3/M. micromalus Makin (joe), Fuji 3/M7 (semi-dwarf) and Fuji 3/M26/M. micromalus Makin (dwarf)] were used to study leaf morphology and photosynthesis and the characteristics of distribution and utilization of C and N at different nitrogen supply levels (0N, 25%N and 100%N, the N content in 100% N treatment was the same as that in Hoagland complete nutrient solution) under sand culture condition. The main results were as follows: At shoot growth cessation stage in autumn, the leaf chlorophyll content (SPAD), leaf nitrogen content and photosynthetic rate were found the highest in Fuji 3/M. micromalus Makin, followed by Fuji 3/M7, and the lowest was found in Fuji 3/M26/M. micromalus Makin under the same nitrogen stress treatments (0N and 25%N), however, under normal nitrogen treatment (100%N) Fuji 3/M26/M. micromalus Makin had the highest leaf SPAD value, photosynthetic rate and the nitrogen content, followed by Fuji 3/M7, and the lowest was found in Fuji 3/M. micromalus Makin. The leaf SOD and CAT activities showed Fuji 3/M. micromalus Makin > Fuji 3/M7 > Fuji 3/M26/M. micromalus Makin under the same nitrogen stress treatments, but showed Fuji 3/M26/M. micromalus Makin > Fuji 3/M7 > Fuji 3/M. micromalus Makin under the normal nitrogen treatment. There were significant differences in the distributions of N and C in root and leaf in the 3 scion-stock combinations, and the distribution rates of N and C in roots were the highest under nitrogen stress treatments and in the order of Fuji 3/M. micromalus Makin > Fuji 3/M7 > Fuji 3/M26/M. micromalus Makin. The distribution rates of N and C in leaves were the highest under the normal nitrogen treatment and in the order of Fuji 3/M26/M. micromalus Makin > Fuji 3/M7 > Fuji 3/M. micromalus Makin. The N utilization ratio differed significantly among the 3 scion-stock combinations under different nitrogen application levels and was in the order of Fuji 3/M. micromalus Makin (44.3%, 37.5% and 31.4%)> Fuji 3/M7 (38.8%,30.7% and 26.6%) > Fuji 3/M26/M. micromalus Makin (32.0%,27.2% and 22.5%).
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http://dx.doi.org/10.13287/j.1001-9332.201707.005DOI Listing
July 2017

Curc-mPEG454, a PEGylated Curcumin Derivative, Improves Anti-inflammatory and Antioxidant Activities: a Comparative Study.

Inflammation 2018 Mar;41(2):579-594

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.

We previously demonstrated that a PEGylated curcumin (Curc-mPEG454) significantly inhibited cyclooxygenase 2 (COX-2) expression and improved the progression of liver fibrosis. The current study systematically evaluates its anti-inflammatory and antioxidant activities in vitro in a comparative study with curcumin, aspirin, NS-398, and vitamin C. RAW264.7 murine macrophages were pretreated with Curc-mPEG454, curcumin, aspirin, NS-398, or vitamin C at the indicated concentration for 2 h; then, the cells were stimulated with 1 μg/mL lipopolysaccharide (LPS) for 24 h. The levels of pro-inflammatory cytokines and mediators, including IL-6, TNF-α, PGE2, NO, and GSH, and the activities of COX-2, SOD, and CAT, and the transcription factors involved in inflammation, such as NF-κB, c-Jun, and Nrf2, were measured. Curc-mPEG454 showed lower cytotoxicity (IC50 57.8 μM) when compared with that of curcumin (IC50 32.6 μM) and inhibited the release of the inflammatory cytokines IL-6, TNF-α, IL-1β, and MCP-1 in a concentration-dependent manner. At 16 μM, Curc-mPEG454 was most potent in the suppression of COX-2 expression at a transcriptional level rather than in the suppression of the catalytic activity of COX-2. Like curcumin, Curc-mPEG454 significantly reduced intracellular ROS production and enhanced the activities of SOD and CAT and the level of GSH to protect cells from LPS-induced oxidative injury. Further, its anti-inflammatory and antioxidation mechanisms are related to inhibition of NF-κB p65 nuclear translocation and c-Jun phosphorylation and to activation of Nrf2. Taken together, these findings indicate that PEGylation of curcumin not only improves its biological properties but also interferes with multiple targets involved in the inflammatory response. Curc-mPEG454 is a powerful and beneficial anti-inflammatory and antioxidant agent that merits further investigation. Graphical Abstract ᅟ.
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http://dx.doi.org/10.1007/s10753-017-0714-2DOI Listing
March 2018

PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR-/CD36 Pathway.

Biomed Res Int 2017 9;2017:8234507. Epub 2017 Jul 9.

Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor- (PPAR-), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR- expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.
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http://dx.doi.org/10.1155/2017/8234507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523402PMC
April 2018

[Serum procalcitonin in cirrhotic patients with sepsis].

Zhonghua Gan Zang Bing Za Zhi 2015 Jun;23(6):428-32

Department of Infectious Diseases, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Objective: To assess the clinical value ofprocalcitonin in cirrhotic patients with severe infection by comparing the serum procalcitonin levels in those patients with and without liver cirrhosis when suffering from sepsis.

Methods: A total of 225 septic patients were included in the study,including 91 patients without hepatopathy, 80 patients with cirrhosis, and 54 patients with chronic liver disease. The serum procalcitonin level was measured in all patients and statistically assessed for correlation with relevant clinical biochemistry indicators. The t-test, ANOVA test, Mann-Whitney U test, chi-square test and Spearman's correlation analysis were used for statistical analyses.

Results: The patients with cirrhosis showed significantly lower serum procalcitonin levels (0.84 (0.32-3.44) ng/ml) than the patients with no hepatopathy (2.17 (0.70-9.18) ng/ml) or the patients with chronic liver disease (2.12 (0.33-13.61) ng/ml) (both P less than 0.05); the patients in the no hepatopathy group and the chronic liver disease group showed statistically similar levels of serum procalcitonin (P=0.616). The patients with cirrhosis of Child-Pugh grade C showed significantly higher level of serum procalcitonin (1.25 (0.54-4.61) ng/ml) than those patients with Child-Pugh grade B (0.33 (0.14-1.31) ng/ml; P=0.026), suggesting that patients with Child-Pugh C stage cirrhosis may be more susceptible to gram-negative bacterial infection. In the cirrhosis group,serum procalcitonin level was positively correlated with white blood cell (WBC) count (r=0.312) and percentage of neutrophils (N%) (r=0.228) (both P less than 0.05). Correlation analysis of the no hepatopathy group and the chronic liver disease group showed no correlation between serum procalcitonin level and either WBC or N%.

Conclusion: Under the sepsis condition, cirrhotic patients have lower serum procalcitonin level than patients without cirrhosis, and the serum procalcitonin level is positively correlated with WBC count and N%.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2015.06.007DOI Listing
June 2015