1.Application value of NRS-2002 combined with L3-SMI in the prognosis of patients with hepatitis B-related acute-on-chronic liver failure
Yuwen ZHAO ; Qingling CHEN ; Qiao ZHAN ; Jun LI ; Zuhu HUANG ; Chuanlong ZHU
Chinese Journal of Hepatology 2024;32(12):1134-1140
Objective:To explore the predictive value of nutrition risk screening score 2002 (NRS-2002) and L3 skeletal muscle index (L3-SMI) for mortality within 90 days in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:A retrospective analysis was conducted on 162 cases with HBV-ACLF who were diagnosed and treated at the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2023. Patients were divided into a survival and death group according to the 90-day survival status following diagnosis, and the clinical data between the two groups were compared. Binary logistic regression analysis was used to screen out the influencing factors related to the occurrence of mortality events. The receiver operating characteristic (ROC) curve was plotted to compare the predictive value of NRS-2002 and L3-SMI for mortality within 90 days in patients with HBV-ACLF.Results:There were statistically significant differences in lymphocyte count (LY), platelet (PLT), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), total bilirubin (TBil), urea, model for end-stage liver disease (MELD) score, NRS-2002 score, and L3-SMI between the death and the survival group ( P<0.05). Multivariate analysis showed that higher levels of INR [odds ratio ( OR)=4.412, 95% confidence interval ( CI): 1.974-9.959, P<0.001], TBil ( OR=1.004, 95% CI: 1.001-1.007, P<0.05), MELD score ( OR=1.148, 95% CI: 1.071-1.232, P<0.001), NRS-2002 score ( OR=1.526, 95% CI: 1.194-1.950, P<0.05), and lower levels of LY ( OR=0.351, 95% CI: 0.103-0.755, P<0.01), and L3-SMI ( OR=0.902, 95% CI: 0.854-0.953, P<0.001) were independent risk factors for 90-day mortality in patients with HBV-ACLF. The ROC curve showed that AUCL3-SMI was 0.706 and AUCNRS-2002 was 0.712. Multivariate logistic analysis showed that the optimal cutoff point for the prediction of 90-day mortality was 0.5. The area under the ROC curve was 0.841 (95% CI: 0.763-0.926), which was significantly higher than the single application of the MELD, NRS-2002, and L3-SMI indicators. Conclusion:The 90-day mortality risk has a correlation with low L3-SMI and high NRS-2002 scores in patients with HBV-ACLF. The SNM model has a certain predictive value for mortality within 90 days in patients with HBV-ACLF.
2.Application value of NRS-2002 combined with L3-SMI in the prognosis of patients with hepatitis B-related acute-on-chronic liver failure
Yuwen ZHAO ; Qingling CHEN ; Qiao ZHAN ; Jun LI ; Zuhu HUANG ; Chuanlong ZHU
Chinese Journal of Hepatology 2024;32(12):1134-1140
Objective:To explore the predictive value of nutrition risk screening score 2002 (NRS-2002) and L3 skeletal muscle index (L3-SMI) for mortality within 90 days in patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF).Methods:A retrospective analysis was conducted on 162 cases with HBV-ACLF who were diagnosed and treated at the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2023. Patients were divided into a survival and death group according to the 90-day survival status following diagnosis, and the clinical data between the two groups were compared. Binary logistic regression analysis was used to screen out the influencing factors related to the occurrence of mortality events. The receiver operating characteristic (ROC) curve was plotted to compare the predictive value of NRS-2002 and L3-SMI for mortality within 90 days in patients with HBV-ACLF.Results:There were statistically significant differences in lymphocyte count (LY), platelet (PLT), total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, international normalized ratio (INR), total bilirubin (TBil), urea, model for end-stage liver disease (MELD) score, NRS-2002 score, and L3-SMI between the death and the survival group ( P<0.05). Multivariate analysis showed that higher levels of INR [odds ratio ( OR)=4.412, 95% confidence interval ( CI): 1.974-9.959, P<0.001], TBil ( OR=1.004, 95% CI: 1.001-1.007, P<0.05), MELD score ( OR=1.148, 95% CI: 1.071-1.232, P<0.001), NRS-2002 score ( OR=1.526, 95% CI: 1.194-1.950, P<0.05), and lower levels of LY ( OR=0.351, 95% CI: 0.103-0.755, P<0.01), and L3-SMI ( OR=0.902, 95% CI: 0.854-0.953, P<0.001) were independent risk factors for 90-day mortality in patients with HBV-ACLF. The ROC curve showed that AUCL3-SMI was 0.706 and AUCNRS-2002 was 0.712. Multivariate logistic analysis showed that the optimal cutoff point for the prediction of 90-day mortality was 0.5. The area under the ROC curve was 0.841 (95% CI: 0.763-0.926), which was significantly higher than the single application of the MELD, NRS-2002, and L3-SMI indicators. Conclusion:The 90-day mortality risk has a correlation with low L3-SMI and high NRS-2002 scores in patients with HBV-ACLF. The SNM model has a certain predictive value for mortality within 90 days in patients with HBV-ACLF.
3.Advances in albicidin.
Lilan CHEN ; Haibin HUANG ; Runtian BIAN ; Zuhu DENG ; Sanji GAO ; Huili ZHANG
Chinese Journal of Biotechnology 2022;38(8):2738-2753
Xanthomonas albilineans (Ashby) Downson is a quarantine pest for importing plants to China that causes leaf scald bacterial disease on sugarcane. X. albilineans produces a potent phytotoxin/antibiotic called albicidin. As a pathogenic factor, albicidin causes typical white leaf stripes by inhibiting plastid DNA gyrase and disturbing chloroplast differentiation. Meanwhile, the antibacterial activity of albicidin gives X. albilineans a competitive advantage against rival bacteria during their colonization. Furthermore, albicidin has a rapid bactericidal activity against a variety of Gram-positive and Gram-negative pathogenic bacteria of human species at nanomolar concentrations, making it a potential antimicrobial drug for clinical application. This article reviews the advances of albicidin from the aspects of its molecular structure, traditional extraction methods, mechanism of action, biosynthetic genes and processes, chemical synthesis method and improvement, in order to provide insights into the prevention and treatment of the sugarcane leaf scald disease, and the development of new antibiotics.
Anti-Bacterial Agents/pharmacology*
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China
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Humans
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Organic Chemicals
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Xanthomonas/genetics*
4.Viral load and cytokines in the pathogenesis of severe fever with thrombocytopenia syndrome
Yaping HAN ; Li DONG ; Lianhua KONG ; Lili ZHANG ; Ning LIU ; Nian CHEN ; Ke JIN ; Qian WANG ; Zuhu HUANG ; Jun LI
Chinese Journal of Infectious Diseases 2014;(9):538-544
Objective To observe the relationship of viral load,serum cytokines and tissue damage after severe fever with thrombocytopenia syndrome virus (SFTSV)infection,and to explore the impact of SFTSV levels on tissue injury and prognosis.Methods Twenty-four ambulatory and hospitalized patients who were infected with SFTSV were enrolled between May 2011 and July 2012 at Department of Infectious Disease, First Affiliated Hospital with Nanjiang Medical University. According to their prognosis,they were divided into cure and death group,while 32 healthy blood donators were also enrolled from center blood station in Nanjing as control.The serum SFTSV load was detected using fluorescence quantitative polymerase chain reaction (PCR).The serum T helper (Th)1/Th2/Th17 cytokines in patients with severe fever with thrombocytopenia syndrome (SFTS)were determined dynamically and quantitatively by flow cytometry.The relationships between viral load,cytokines and serum enzymes, white blood cell (WBC),platelet (PLT)counts were analyzed.Comparisons among groups were achieved by rank sum test and correlation analysis among serum cytokines,blood cell counts and tissue damage was done by Spearman correlation test.Results All of the 24 patients showed a positive reaction to SFTSV RNA.The SFTSV loads of 21 cured cases,those of 2 were > 7.0 lg copy/mL,and those of 3 death patients were 6.7 lg copy/mL,8.8 lg copy/mL and 9.8 lg copy/mL,respectively.Serum level of interleukin (IL)-6 (21 .76 pg/mL in day 5 and 7.12 pg/mL in day 7)and IL-10 (14.33 pg/mL in day 5 , 14.13 pg/mL in day 7 and 3.01 pg/mL in day 9)of cured patients were significantly higher than those of healthy controls (IL-6:2.82 pg/mL and IL-10:1 .56 pg/mL)(P <0.05 ).At day 7 and day 9,serum levels of IL-6 of death cases were 137.61 pg/mL and 1 450.83 pg/mL,respectively and serum levels of IL-10 were 50.26 pg/mL and 49.43 pg/mL,respectively.Both of the indicators in the death group were significantly higher than those of cure group (P <0.05 ).However,serum levels of IL-2 and IL-4 were significantly lower than those in healthy control group (P <0.05 ).In the cure group,WBC and PLT counts were lowest during the early course of the disease,and serum alamine aminotransferase (ALT), aspartate aminotransferase (AST ), lactic dehydrogenase (LDH ) and creatine kinase (CK ) were significantly higher than their upper limits of normal.The correlation analysis showed that serum IL-6, IL-10 levels were negatively correlated with PLT count (r=-0.390 and -0.608,respectively;both P <0.01),and positively correlated with SFTSV load (r=0.560 and 0.758,respectively),ALT (r=0.412 and 0.390,respectively),AST (r = 0.686 and 0.764,respectively),LDH (r = 0.633 and 0.677, respectively)and CK (r =0.527 and 0.636,respectively)(all P <0.01 ).Conclusions SFTSV load, IL-6,IL-10 and serum enzyme levels are closely related to the severity of the disease.The inflammatory and anti-inflammatory cytokine storm after SFTSV infection may be involved in the immune pathological injury in patients with SFTS.
5.Dynamic changes of peripheral blood lymphocyte subsets in fever with thrombocytopenia syndrome patients
Yaping HAN ; Donghui ZHOU ; Yali WENG ; Li DONG ; Nian CHEN ; Dongyue ZHANG ; Yuan LIU ; Longfeng JIANG ; Shuang LI ; Zuhu HUANG ; Jun LI
Chinese Journal of Laboratory Medicine 2012;35(9):826-831
Objective The aim of this study is to dynamically investigate peripheral blood lymphocyte subsets in fever with thrombocytopenia syndrome (SFTS) patients at different stages,to evaluate the influence of these changes in the infection process.Methods Case-control study was used in the research.Twelveconfirmedthrombocytopeniasyndromevirus ( SFTSV ) infectedpatientswere enrolled.According to SFTS prevention guide issued by Chinese Ministry of Health,these patients were divided into two groups,recovery group and death group.For each group,dynamic profiles of the CD3 + T cells,CD4 + helper T cells,CD8 + cytotoxic T cell and CD3 - CD16 + CD56 + natural killer cells were tested by flow cytometry.Meanwhile, the relationshipsbetween these dynamicchanges and liver function,leukocytes,and platelets were analyzed respectively.Two independent-samples t test was used to compare the difference of the peripheral blood lymphocyte subsets count between the SFTS patients and healthy control.Small sample was analyzed by Mann-Whitney U test.Results In the early stage of infection,Th cells in peripheral blood of recovery group were significantly reduced and Th/Tc ratio was reversed.On day 5,7,9 of post infection,Th cell counts in peripheral blood were (740.9 ± 6.4),(836.2 ± 272.3 ) and ( 1083.6 ± 319.7 ) cells/μl respectively,which were significantly lower than health control ( 1351.4 ± 295.1 ) cells/μl ( t value was -2.883,-4.235,-2.145 respectively,all P <0.05).Tc cell counts were significantly more than healthy controls (690.1 ± 194.8) cells/μl through the course,which were ( 1006.3 ±356.5),(1166.4±242.4),(1102.4±245.9),(991.3±205.1) and (886.5±154.5) cells/μl on day 7,9,11,13,15 of the course (t value was 3.312,5.661,4.574,3.874,2.382,all P<0.05).NK cells were decreased significantly from the ninth day of the course.Associated with abnormal changes of cell subsets,WBC and PLT decreased significantly,and serum ALT,AST,LDH and CK etc.were higher than normal level.With the disease recovery,the abnormality above was gradually improved.In contrast,death cases showed significant decrease in T and Th cells compared with health control (P < 0.05).On day 7,8,9 of the course,the counts of total T cell were (735.9 ± 359.9),(724.9 ± 125.9),(845.3 ± 389.3) cells/μl and the counts of Th cell were ( 533.2 ± 246.9 ),( 532.1 ± 105.7 ),( 551.7 ± 86.9 ) cells/μl,significantly lower than healthy control ( 1727.9 ± 230.2 ) cells/μl and ( 1351.4 ± 295.1 ) cells/μl,with statistically differences (z value was - 2.828, - 2.342,- 2.342 and - 2.828, - 2.342, - 2.342,all P < 0.05 ).On day 7,8,9 of the course,the numbers of NK cell in death group were ( 1141.8 ± 415.5),( 1047.2 ±68.4),( 1276.3 ±545.3) cells/μl,which were significantly more than health group (470.7 ± 242.2) cells/μl,with statistically differences (z value was - 2.180,- 2.335,- 2.258,all P <0.05).Conclusions SFTSV infection can induce cell immunity damage.The changes of lymphocyte subsets are associated with clinical classification and prognosis.Significant reduction of T cell and CD4 +cell in peripheral blood are accompanied with significant increase of NK cell,which may be a pivotal indicator of poor prognosis and play an important role in making appropriate strategy in clinical treatment.( Chin J Lab Med,2012,35:826-831 )
6.Expression of HERG1 potassium channel and its effect on cell migration and proliferation in pancreatic cancer cell line(PANC1)
Linhua YAO ; Jin FENG ; Bo HAO ; Zekuan XU ; Zuhu HUANG ; Guoxin ZHANG
Chinese Journal of Pancreatology 2009;9(3):174-177
0 (P<0.01).Conclusions HERG1 was over expressed in PANC1 cells and tissues of human pancreatic cancer.The HERG1 K+ channel was related to the proliferation,migration and invasion of PANC1.
7.The mechanism of quinolone resistance in Pseudomonas aeruginosa
Ke JIN ; Yaping HAN ; Jun LI ; Yinghui LIU ; Yaning MEI ; Yi WEN ; Zuhu HUANG
Chinese Journal of Clinical Infectious Diseases 2009;2(2):74-77
Objective To investigate the mechanism of quinolone resistance in Psendomonas aeruginosa.Methods The minimum inhibitory concentrations (MICs)of ciprofloxacin and levofloxacin with and without carbonylcyainde-m-chlorophenylhydrazone(CCCP)were determined by agar dilution method.Polymerase chain reaction(PCR)and DNA sequencing were used to study the mutations in quinolone resistance-determining region of gyrA and parC genes.The strains were genotyped by enterbacterial repetitive intergenie consensus-PCR(ERIC-PCR).Results Sixteen quinolones-resistant Pseudomonas aeruginosa strains were obtained.The MICs of ciprofloxacin and levofloxacin were not reduced significantly by adding CCCP.Thr-83→Ile of gyrA and Ser-87→Leu of parC were found simultaneously in 16 strains of resistant Pseudomonas aeruginosa.Analysis of ERIC-PCR products indicated that 16 quinolone-resistant strains had an identical band pattern which was different from that seen in the sensitive strains.Conclusion Mutations in gyrA and parC may be the main mechanism of quinolone resistance in clinical isolates of Pseudomonas aeruginosa.
8.The association between antigen-specific cytotoxic lymphocytes response and different clinical status in patients with hepatitis B
Yufeng WAN ; Yaping HAN ; Jun LI ; Lianhua KONG ; Shuang LI ; Li DONG ; Nian CHEN ; Yuan LIU ; Zuhu HUANG
Chinese Journal of Infectious Diseases 2009;27(5):287-291
Objective To analyze human leucocyte antigen (HLA)-A0201 restricted antigen-specific cytotoxic lymphocytes (CTL), and to investigate the difference of T cell response to specific antigen epitopes between patients with acute phase of acute hepatitis B and active phase of chronic hepatitis B. Methods Peripheral blood mononuclear cells (PBMC) from 5 patients with acute phase of acute hepatitis B and 6 patients with active phase of chronic hepatitis B were isolated. The numbers and functions of CD8+ T-lymphocyte epitope peptide specific CTL were detected using enzyme-linked immunosorbent spot (ELISPOT) assay, and the 3 peptides were from HBV polymerase region (Pol575-583), envelope region (Env348-357) and core region (Core18-27), respectively. The data were analyzed using t test. Results The spot formation cell counts (SFC) of Pol575-583, Env348-357 and Core18-27 stimulations in patients with acute phase of acute hepatitis B were 110±13, 165±17 and 185±20, respectively; and those in patients with active phase of chronic hepatitis B were 22±4, 23±5 and 30±5, respectively; the differences were all significant (t=10.9, 15.2 and 8.0, respectively, all P<0.05). The CTL responses to the three peptides in patients with acute phase of acute hepatitis B were Pol575-583
10.Humoral and cellular immunogenecity of nucleic acid vaccine of hepatitis B core antigen in rhesus monkeys
Zuhu HUANG ; Hui ZHUANG ; Renhua GUO
Chinese Journal of Infectious Diseases 2001;0(03):-
Objective To observe humoral and cellular immunogenecity of nucleic acid vaccine of hepatitis B core antigen (HBcAg) in rhesus monkeys. Methods Rhesus monkeys of the experimental group and the control group received intramuscular injections of a HBcAg nucleic acid vaccine(pJW4303/HBc) and a control plasmid (pJW4303), respectively. Anti HBc titers, isotypes of anti HBc IgG in sera of the rhesus monkeys pre and post vaccinations, and IFN ? as well as IL 4 levels in the culture supernatant of PBMC isolated from the monkeys were detected by an enzyme linked immunoabsorbent assay. HBcAg specific proliferation activities of PBMC in the monkeys were measured by 3H TdR incorporation assay. Results It was observed in rhesus monkeys of experimental group an obvious anti HBc response after immunization with HBcAg nucleic acid vaccine. The major isotypes of anti HBc IgG was IgG2 and IFN ? was predominant compared with IL 4 in the culture supernatant of rhesus monkeys' PBMC, both indicating Th1 type of immune responses. HBcAg specific proliferation activities of PBMC in the experimental group were significantly stronger than those in the control group. Conclusions The nucleic acid vaccine based on HBcAg shows a good humoral and cellular immunogenecity in rhesus monkeys.

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