Value of peripheral blood PCT, CRP, FIB and D-D levels for early diagnosing PTB complicated with bacterial pneumonia / 中国热带医学

@#Abstract: Objective　To investigate the early diagnostic value of peripheral blood procalcitonin (PCT), C-reactive protein (CRP), fibrinogen (FIB) and D-dimer (D-D) levels in patients with pulmonary tuberculosis (PTB) complicated with bacterial pneumonia. Methods　A total of 102 patients who admitted to Department of Tuberculosis of Affiliated Nantong Hospital of Shanghai University from Jan 2021 to May 2022 were enrolled in this study and divided into a group (52 cases) with pulmonary tuberculosis (PTB) patients and a group (50 cases) with PTB patients complicated with bacterial pneumonia. The levels of PCT, CRP, FIB and D-D in the peripheral blood were measured, the differences and correlations in all indicators were compared among two groups. The sensitivity and specificity of these indicators in the early diagnosis of PTB complicated with bacterial pneumonia were analyzed by receiver operating characteristic (ROC) curve. Results　The levels of PCT, CRP, FIB and D-D in the peripheral blood from the PTB complicated with bacterial pneumonia group were 0.06 (0.04, 0.16) ng/mL, 38.00 (3.88, 96.10) mg/L, 4.51 (3.02, 6.07) g/L, and 0.59 (0.34, 1.88) mg/L, respectively, which were significantly higher than corresponding 0.04 (0.03, 0.04) ng/mL, 3.20 (0.84, 7.22) mg/L, 2.96 (2.48, 3.77) g/L, and 0.27 (0.17, 0.36) mg/L in the PTB group (Z=-4.784, -5.233, -3.853, -4.199, all P<0.001). Furthermore, the levels of CRP and FIB in the PTB complicated by bacterial pneumonia group were highly positively correlated (r=0.855, P<0.001). The area under the ROC curve (AUC) of PCT, CRP, FIB and D-D for early diagnosis of PTB complicated with bacterial pneumonia were 0.757, 0.794, 0.747 and 0.764, respectively. In addition, the AUC obtained by simultaneous measurement of PCT, CRP, FIB and D-D was as high as 0.916, and the sensitivity and specificity of diagnosing PTB complicated with bacterial pneumonia were increased to 85.7% and 96.9%, respectively, which were higher than those of individual indicators. Conclusions　Levels of peripheral blood PCT, CRP, FIB, and D-D all show varying degrees of increase in patients with PTB complicated with bacterial pneumonia, and detecting the levels of all four markers, rather than any single marker, can assist in early monitoring whether the tuberculosis patients are complicated with bacterial pneumonia.

Research progress of active probes targeting specific aminoacids / 药学学报

Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Phosphoproteomic analysis of human umbilical venous endothelial cells with DENV-2 infection / 南方医科大学学报

OBJECTIVE@#To analyze the differentially phosphorylated proteins in DENV-2-infected human umbilical venous endothelial cells (HUVECs) and explore the possible pathogenic mechanism of DENV-2 infection.@*METHODS@#The total proteins were extracted from DENV-2-infected HUVECs and blank control HUVEC using SDT lysis method. The phosphorylated proteins were qualitatively and quantitatively analyzed using tandem mass spectrometry (TMT). The identified differentially phosphorylated proteins were analyzed by bioinformatics analyses such as subcellular localization analysis, GO enrichment analysis, KEGG pathway analysis and protein-protein interaction (PPI) analysis. Western blotting was used to detect the expressions of phosphorylated Jun, map2k2 and AKT1 proteins in DENV-2-infected HUVECs.@*RESULTS@#A total of 2918 modified peptides on 1385 different proteins were detected, and among them 1346 were significantly upregulated (FC > 1.2, P < 0.05) and 1572 were significantly downregulated (FC < 0.83, P < 0.05). A total of 49 phosphorylated conserved motifs were obtained by amino acid conservative motif analysis. The most abundant differentially phosphorylated peptides in protein domain analysis included RNA recognition motif, protein kinase domain and PH domain. Subcellular localization analysis showed that the differentially modified peptides were mainly localized in the nucleus and cytoplasm. GO enrichment and KEGG pathway analysis showed that the differential peptides were mainly enriched in the regulation of stimulation response, biosynthesis of small molecules containing nuclear bases, and migration of phagosomes and leukocytes across the endothelium. PPI and KEGG joint analysis showed that the up-regulated and down-regulated differentially phosphorylated proteins were enriched in 15 pathways. In DENV-2-infected HUVECs, Western blotting detected differential expressions of phosphorylated proteins related with the autophagy pathway, namely JUN, MAP2K2 and AKT1, and among them p-JUN was significantly down-regulated and p-AKT1 and p-MAP2K2 were significantly upregulated (P < 0.01).@*CONCLUSION@#DENV-2 infected HUVECs show numerous differentially expressed proteins. The downregulation of p-JUN and upregulation of p-MAP2K2 and p-AKT1 suggest their potential roles in regulating autophagy, which is probably involved in the mechanism of DENV-2 infection.

Correlation analysis of hepatic steatosis, blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B / 公共卫生与预防医学

Objective To analyze the correlation of hepatic steatosis with blood lipids and uric acid metabolism in elderly patients with chronic hepatitis B (CHB). Methods The clinical data of 120 patients with CHB admitted to the hospital from January to December 2021 were retrospectively analyzed. According to the presence or absence of hepatic steatosis, the patients were divided into steatosis group (n=35) and non-steatosis group (n=85). The general clinical data, serological indicators of hepatitis B virus, blood lipid and uric acid levels were compared between the two groups. The correlation of hepatic steatosis grading with blood lipids and uric acid metabolism was analyzed. Results The inflammation and fibrosis degree of liver tissues were significantly different in the two groups (P0.05). Pearson correlation analysis found that the grade of hepatic steatosis in patients with CHB was negatively correlated with liver tissue inflammation, fibrosis degree and HDL-C level (P<0.05), and positively correlated with TG and TC levels (P<0.05). Conclusion Elderly patients with CHB and hepatic steatosis have abnormal blood lipid metabolism. Hepatic steatosis will exacerbate abnormal blood lipid metabolism but not liver tissue inflammation or fibrosis degree. Clinically, attention should be paid to blood lipid monitoring of elderly patients with CHB.

Identification of a novel bombesin bioactive peptide QUB2995 and its insulin secreting activity / 中华内分泌代谢杂志

Objective:To identify a novel bombesin bioactive peptide from the skin secretion of Hylarana Latouchii, and to explore its effect on insulin secretion in islet cells.Methods:The skin secretion from Hylarana Latouchii was extracted by electrical stimulation, and the single chain of bombesin peptide was cloned and sequenced. The peptide QUB2995 was synthesized via solid-phase synthesis, then purified using reversed-phase high performance liquid chromatography (HPLC). Matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF) was applied to validate. QPCR and ELISA were used to probe the effect of QUB2995 on insulin secretion in MIN6 and INS-1 cells.Results:A novel bombesin peptide named QUB2995 (GAFGDFLKGAAKA GALKILSIAQCKLSGTC) was found in the skin secretion of Hylarana Latouchii through molecular cloning. The bioactive peptide could significantly promote the proliferation and insulin secretion from mouse islet MIN6 cells and rat islet INS-1 cells. The effect reached a climax at the concentration of 10 -5 mol/L. Conclusion:A novel bombesin bioactive peptide named QUB2995 was found from Hylarana Latouchii. It could significantly promote insulin secretion in MIN6 cells of mouse islets and INS-1 cells of rat islets, indicating its potential in the treatment of diabetes.

Recent advances in G protein coupled receptor 119 agonists / 药学学报

G protein-coupled receptor 119 (GPR119) has been a promising target for the treatment of type 2 diabetes. It can not only directly promote insulin secretion, but also indirectly increase insulin secretion by stimulating the release of glucose-dependent GIP/CLP-1 without causing hypoglycemia. The remarkable advantages of small molecule GPR119 agonists make it one of the research hotspots for the development of type 2 diabetes drugs. This article reviews the anti-diabetic small molecules based on the GPR119 target in the past five years.

Concentration-dependent effects of nitric oxide on tumors and chemosensitivity / 药学学报

The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.

Acetoacetate extract of pleione bulbocodioides (franch. ) rolfe induces apoptosis of human leukemia thp-1cells through a mitochondria-regulated intrinsic apoptotic pathway / Extrato de acetoacetato de Pleione bulbocodioides (Franch. ) Rolfe induz a apoptose de células THP-1 de leucemia humana através de uma via apoptótica intrínseca regulada por mitocôndrias

The tubers of three orchidaceous plants, includingPleione bulbocodioides (Franch.) Rolfe, have been used as 'Shan-Ci-Gu' in traditional Chinese medicine for the treatment of bacterial infections and cancers for thousands of years. In this study, the effects of an acetoacetate (EtOAc) extract of P. bulbocodioides on the cell viability and apoptosis of THP-1 (human acute monocytic leukemia cell line) cells and its interaction with possible apoptotic pathways were investigated. THP-1 cells were treated with the EtOAc extract of P. bulbocodioides at different concentrations. The results showed that THP-1 cell viability was significantly inhibited by the EtOAc extract ofP. bulbocodioides with an IC50 of 51.37±2.68 µ g/ mL at 24 h. The examination of cytotoxic effects on healthy cells showed that the EtOAc extract of P. bulbocodioidesdid not show any effect on healthy Vero cells. Selectivity indexes were greater than 15.57, suggesting that the EtOAc extract of P. bulbocodioides had selective toxicity against THP-1 cells. The results of annexin V-FITC/PI and DAPI staining showed that the EtOAc extract of P. bulbocodioides induced cell apoptosis in a dose-dependent manner. The apoptotic rate was increased in the treatment groups compared with that in the control group (P<0.05). The distribution of cells in the G2 phase of the cell cycle increased along with typical cell apoptosis-induced morphological changes. The levels of the pro-apoptotic proteins Bax, cleaved PARP and cleaved caspase-3 increased with increasing concentration of acetoacetate extract of P. bulbocodioides, while the anti-apoptosis protein Bcl-2 was downregulated. Cyt c and AIF, which are characteristic proteins of the mitochondria-regulated intrinsic apoptosis pathway, also increased in the cytosol with increasing concentrations of the EtOAc extract of P. bulbocodioides. These results showed that the EtOAc extract of P. bulbocodioidessignificantly inhibits cell viability and induces cell apoptosis in the human leukemia cell line THP-1 through a mitochondria-regulated intrinsic apoptotic pathway

Os tubérculos de três plantas orquidáceas, incluindo Pleione bulbocodioides (Franch.) Rolfe, têm sido usados como "Shan-Ci-Gu" na medicina tradicional chinesa para o tratamento de infecções bacterianas e cânceres por milhares de anos. Neste estudo, os efeitos de um extrato de acetoacetato (EtOAc) de P. bulbocodioides na viabilidade celular e apoptose de células THP-1 (linhagem celular de leucemia monocítica aguda humana) e sua interação com possíveis vias apoptóticas foram investigados. As células THP-1 foram tratadas com o extrato EtOAc de P. bulbocodioides em diferentes concentrações. Os resultados mostraram que a viabilidade das células THP-1 foi significativamente inibida pelo extrato EtOAc de P. bulbocodioides com IC50 de 51,37 ± 2,68 µ g/mL às 24 h. O exame dos efeitos citotóxicos em células saudáveis mostrou que oextrato de EtOAc de P. bulbocodioides não mostrou nenhum efeito sobre células Vero saudáveis. Os índices de seletividade foram maiores que 15,57, sugerindo que o extrato de EtOAc de P. bulbocodioides teve toxicidade seletiva contra as células THP-1. Os resultados da coloração da anexina V-FITC/PI e DAPI mostraram que o extrato de EtOAc de P. bulbocodioides induziu a apoptose celular de maneira dose-dependente. A taxa de apoptose foi aumentada nos grupos de tratamento em comparação com o grupo controle (P <0,05). A distribuição de células na fase G2 do ciclo celular aumentou juntamente com alterações morfológicas típicas induzidas pela apoptose celular. Os níveis das proteínas pró-apoptóticas Bax, PARP clivada e caspase-3 clivada aumentaram com o aumento da concentração do extrato acetoacetato de P. bulbocodioides, enquanto a proteína anti-apoptose Bcl-2 foi regulada negativamente. Cyt c e AIF, que são proteínas características da via de apoptose intrínseca regulada por mitocôndrias, também aumentaram no citosol com concentrações crescentes do extrato de EtOAc de P. bulbocodioides. Estes resultados mostraram que o extrato de EtOAc de P. bulbocodioides inibe significativamente a viabilidade celular e induz a apoptose na linha celular de leucemia humana THP-1 através de uma via apoptótica intrínseca regulada por mitocôndrias.

Effect of loureirin A against Candida albicans biofilms / 中国天然药物

Loureirin A is a major active component of Draconis sanguis, a traditional Chinese medicine. This work aimed to investigate the activity of loureirin A against Candida albicans biofilms. 2, 3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)reduction assay and scanning electron microscopy were used to investigate the anti-biofilm effect. Minimal inhibitory concentration testing and time-kill curve assay were used to evaluate fungicidal activity. Cell surface hydrophobicity (CSH) assay and hyphal formation experiment were respectively carried out to investigate adhesion and morphological transition, two virulence traits of C. albicans. Real-time RT-PCR was used to investigate gene expression. Galleria mellonella-C. albicans and Caenorhabditis elegans-C. albicans infection models were used to evaluate the in-vivo antifungal effect. Human umbilical vein endothelial cells and C. elegans nematodes were used to evaluate the toxicity ofloureirin A. Our data indicated that loureirin A had a significant effect on inhibiting C. albicans biofilms, decreasing CSH, and suppressing hyphal formation. Consistently, loureirin A down-regulated the expression of some adhesion-related genes and hypha/biofilm-related genes. Moreover, loureirin A prolonged the survival of Galleria mellonella and Caenorhabditis elegans in C. albicans infection models and exhibited low toxicity. Collectively, loureirin A inhibits fungal biofilms, and this effect may be associated with the suppression of pathogenic traits, adhesion and hyphal formation.

Preparation and <italic>in vitro</italic> evaluation of phospholipid-coated silver-graphene quantum dot multifunctional nanoparticles / 药学学报

@#In this paper, multifunctional silver-graphene quantum dot nanoparticles coated with phospholipids (ADG-DDPC) were prepared and their properties were evaluated <italic>in vitro</italic>. Cationic phospholipids 1,2-diolefinoxy-3-trimethy-laminopropane (DOTAP) was absorbed first onto the surface of the core of silver nanoparticle (AgNPs) through the mutual attraction between the positive and negative charge. Based on the principle of phase transformation and hydrophobic interaction, dstearyl-phosphatidylglycolamine-polyethylene-glycol-cyclic-cRGD peptide (DSPE-PEG₂₀₀₀-cRGD) self-assembled onto the outlayer of DOTAP of AgNPs. A stable multifunctional nano-preparation was formed and its ultraviolet absorption, particle size distribution, morphology,<italic>in vitro</italic> release behavior, ability to kill cancer cells and cell uptake were studied. The maximum UV absorption of the synthesized nanometer preparation was about 400 nm. Malvern particle size meter and transmission electron microscope showed that the particle size of the nano- preparation was about 30-40 nm and its particle size distribution was uniform. The <italic>in vitro</italic> release of nano-preparation was positively correlated with the concentration of H₂O₂. The IC₅₀ value of AgNPs for tumor cells was (347.78 ± 0.06) ng·mL^-1, and the IC₅₀ value of ADG-DDPC for tumor cells was (209.68 ± 0.09) ng·mL^-1, indicating that ADG-DDPC possessed a stronger cytotoxicity than that of AgNPs. Cell uptake experiment showed that ADG-DDPC could be absorbed by tumor cells and exhibited fluoresce inside those cells. In conclusion, ADG-DDPC was successfully prepared, and <italic>in vitro</italic>characterization study pointed to that the nano-preparation exhibits a higher antitumor activity than AgNPs.

Ethyl acetate extract of Pleione bulbocodioides(Franch.)Rolfe induces apoptosis of human leukemia K562 and HL-60 cells through intrinsic mi-tochondrial apoptosis pathway / 中国病理生理杂志

AIM:To investigate the effects of ethyl acetate(EtOAc)extract of Pleione bulbocodioides (Franch.)Rolfe on proliferation and apoptosis of human leukemia K 562 and HL-60 cells and the possible apoptosis path-way.METHODS:Human leukemia cell lines were treated with EtOAc extract of Pleione bulbocodioides at different con-centrations.XTT method was used to evaluate the viability of K 562 cells and HL-60 cells.The cell growth inhibition was calculated by Trypan blue exclusion test.The percentage of apoptotic cells was determined by flow cytometry,and 4,,6-dia-midino-2-phenylindole(DAPI)was used to observe morphological changes of the cells.The cell cycle was observed by pro-pidium iodide(PI)staining.The protein expression of Bcl-2, Bax, cleaved poly(ADP-ribose)polymerase(PARP), cleaved caspase-3,cytochrome C and apoptosis-inducing factor(AIF)wase determined by Western blot.RESULTS:The cell viability and proliferation were inhibited by EtOAc extract of Pleione bulbocodioides with IC50of(42.14 ±2.54)mg/L for HL-60 cells and(51.28 ±3.12)mg/L for K562 cells at 24 h.The results of Annexin V-FITC/PI and DAPI staining showed that EtOAc extract of Pleione bulbocodioides induced cell apoptosis in a dose-dependent manner.The apoptotic rate was increased compared with control group(P<0.05).The G2phase increased with typical cell apoptosis-induced mor-phological changes.The levels of pro-apoptotic proteins Bax,cleaved PARP and cleaved caspase-3 were increased, while Bcl-2 was down-regulated(P<0.05).Cytochrome C and AIF in cytosol,characteristic proteins of intrinsic mitochondrial apoptosis pathway,also increased with the concentration of EtOAc extract of Pleione bulbocodioides increasing(P<0.05). CONCLUSION:EtOAc extract of Pleione bulbocodioides significantly inhibits cell proliferation and induces cell apoptosis in human leukemia cell lines HL-60 and K562 through intrinsic mitochondrial apoptosis pathway.

Effects of FEA from Polygonum hydropiper L. on Biochemical Indexes and Inflammatory Cytokines in Mice with Endotoxemia Induced by Lipopolysaccharide / 中国中医药信息杂志

Objective To observe the effect of flavonoids ethyl acetate(FEA)from Polygonum hydropiper L.on biochemical indexes and inflammatory cytokines in mice with endotoxemia; To expore the mechanism. Methods Total flavonoids in the whole plant of Polygonum hydropiperum L. were extracted by enzymolysis-ultrasonic coupling method. The FEA part were obtained by extracting and separating, followed with macroporous resin purification and enrichment. The animal model of endotoxemia was established by stimulation of lipopolysaccharide (LPS) in mice. Experimental mice were divided into blank group, model group, FEA high-, medium-, and low-dose groups. Each administration group was given the corresponding concentration of herb liquor. The concentration of malondialdehyde (MDA) and myeloperoxidase (MPO) in intestinal tissue, total antioxidant capacity (T-AOC), superoxide dismutase (T-SOD) activity and glutathione peroxidase (GSH-Px) activity in liver tissue, glutathione (GSH), lysozyme (LZM) and acid phosphatase (ACP) in serum were determined. The contents of tumor necrosis factor-α (TNF-α), interferon (IFN)-α, IFN-γ and interleukin-2 (IL-2) in lung tissue were detected by RT-PCR. Results Compared with blank group,the levels of MDA, MPO in intestinal tissue and serum ACP of model mice were increased, while T-AOC, T-SOD, GSH-Px in liver tissue, serum GSH and LZM levels were decreased; TNF-α in serum, intestinal and liver tissues were increased, the expressions of TNF-α, IFN-α, IFN-γ and IL-2 mRNA in lung tissue were increased. Compared with the model group, the levels of MDA, MPO in intestinal tissue and serum ACP were decreased in all dose of FEA groups;The levels of T-AOC, T-SOD, GSH-Px in liver tissue, serum GSH and LZM of FEA medium and high-dose groups were increased. The content of TNF-α in mice serum, intestinal and liver tissues of all dose of FEA groups were significantly reduced, and the expressions of TNF-α, IFN-α, IFN-γ and IL-2 mRNA in lung tissues were significantly decreased. The pathological morphology of mice lung, ileum and colon tissues of FEA high-dose group were significantly ameliorated than model group. Conclusion FEA can attenuate inflammation injury of endotoxemia mice induced by LPS, which has protective effects for organism.

Multidisciplinary decision on a rectal cancer patient with multiple synchronous pulmo-nary metastasis / 中国肿瘤临床

Lungs are the second most common distant metastatic organs of colorectal cancer, following the liver. However, clinical re-searches on lung metastasis are insufficient comparing with that on liver metastasis due to its low occurrence and relatively mild bio-logical behavior. This paper aims to investigate the clinicopathological characteristics and prognostic factors of rectal cancer patients with multiple synchronous lung metastases. The patient was from the Second Affiliated Hospital of Zhejiang University, School of Medi-cine underwent multi-disciplinary diagnosis and treatment. Moreover, this article aims to discuss the related existing consensus and controversies on this issue.

LNA-modified isothermal oligonucleotide microarray for differentiating bacilli of similar origin.

Oligonucleotide microarray has been one of the most powerful tools in the ‘Post-Genome Era’ for its high sensitivity, high throughput and parallel processing capability. To achieve high detection specificity, we fabricated an isothermal microarray using locked nucleic acid (LNA)-modified oligonucleotide probes, since LNA has demonstrated the advanced ability to enhance the binding affinity toward their complementary nucleotides. After designing the nucleotide sequences of these oligonucleotide probes for gram-positive bacilli of similar origin (Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus megaterium and Bacillus circulans), we unified the melting temperatures of these oligonucleotide probes by modifying some nucleotides using LNA. Furthermore, we optimized the experimental procedures of hydrating microarray slides, blocking side surface as well as labelling the PCR products. Experimental results revealed that KOD Dash DNA polymerase could efficiently incorporate Cy3-dCTP into the PCR products, and the LNA-isothermal oligonucleotide microarray were able to distinguish the bacilli of similar origin with a high degree of accuracy and specificity under the optimized experimental condition.

Research progress of the natural small molecular products synergistically with antifungal agents to inhibit drug-resistant fungi / 药学学报

The incidence of systemic fungal infections have increased dramatically, moreover, drug resistance including either primary (intrinsic) or secondary (acquired) resistance, becomes one of the main reasons accounting for the failure of treating invasive fungal infections in the past decades. Nowadays, clinically available antifungal drugs are limited and their combination in antifungal therapy was not effective. It is expected to be a new strategy to synergistically sensitize antifungal drugs against drug-resistant fungi by using new small molecules. Based on the study in our research group and the reported work of others, we reviewed the research of the natural products which have synergistic effect with the antifungal agents against drug-resistant fungi. This review focused on the resource, structure, pharmacological activity, and action mechanism of the compounds, as well as somewhat in common, and would provide theoretical base for seeking new drug against drug-resistance fungi.

Derivatization of berberine based on its synergistic antifungal activity with fluconazole against fluconazole-resistant Candida albicans / 药学学报

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

Prevalence of human cytomegalovirus infection and analysis of its plasma neutralizing antibody level in hypertension patients / 第二军医大学学报

Objective: To determine the prevalence of human cytomegalovirus (HCMV) infection and plasma level of its neutralizing antibody in hypertension patients, so as to discuss the association between HCMV infection and hypertension. Methods: A total of 51 anti-coagulated blood samples were collected from hypertension patients and the 50 control samples were obtained from age- and sex-matched healthy controls in the Second People's Hospital of Anhui Province from Jan. 2013 to Apr. 2013. Neutralizing antibody level was analyzed by rapid fluorescence micro-neutralization; plasma anti-HCMV IgG and anti-HCMV IgM were determined by enzyme-linked immuno sorbent assay (ELISA), and HCMV UL93 DNA was detected by nested PCR. Results: The positive rates of HCMV UL93 DNA and anti-HCMV IgG in hypertension patients were significantly higher than those in healthy controls (72.55% vs 56.00% for UL93 DNA and 70.59% vs 50.00% for IgG, P0.05). The geometric mean titer of HCMV neutralizing antibody was 38.56 ±20.42 in hypertension patients, which was significantly lower than that in healthy controls (60.12 ± 25.38, P = 0.0326). Conclusion: HCMV positive rate is higher in hypertension patients than in healthy controls; however, the specific neutralizing antibody level of HCMV is greatly lower than that in healthy controls, suggesting that the humoral immune status is declined in hypertension patients and there is a correlation between HCMV infection and hypertension.

Seroepidemiology and genetic characterization of hepatitis E virus in western Yunnan Province

OBJECTIVE@#To investigate the seroepidemiology and genetic characterization of hepatitis E virus (HEV) in western Yunnan Province.@*METHODS@#Questionnaire survey was conducted among 1638 residents in western Yunnan Province using stratified sampling method. Enzyme-linked immunosorbent assay was used to detect serum anti-HEV IgG and IgM. HEV RNA was extracted from patients with serum anti-HEV IgM positive. The open reading flame 2 (ORF2) of HEV that was amplified by nested RT-PCR was sequenced and compared with standard HEV genotypes 1-4.@*RESULTS@#Serum anti-HEV positive was found in 13.92% (228/1638) residents. The HEV infection rate in males was significantly higher than that in females with a ratio of 1.47 (P<0.01). 20-30 and 30-40 years old young men showed the highest incidence, 20.57% and 20.78%, respectively. While 10-20 and 20-30 years old young women exhibited the highest infection rate, 11.85% and 15.60%, respectively. According to occupation, the highest HEV infection rate was observed in farmers (20.35%) and migrants (16.50%). We isolated 10 individual HEV isolates from 31 patients with serum anti-HEV IgM positive. Homology analysis and phylogenetic analysis indicated that these 10 HEV isolates belonged to HEV genotype 4 with the homology of 78.65%-94.71%.@*CONCLUSIONS@#The HEV infection rate is high in western Yunnan Province. HEV genotype 4 is the leading cause of HEV infection and young farmers and migrants are the main infected population.

Seroepidemiology and genetic characterization of hepatitis E virus in western Yunnan Province

Objective: To investigate the seroepidemiology and genetic characterization of hepatitis E virus (HEV) in western Yunnan Province. Methods: Questionnaire survey was conducted among 1638 residents in western Yunnan Province using stratified sampling method. Enzyme-linked immunosorbent assay was used to detect serum anti-HEV IgG and IgM. HEV RNA was extracted from patients with serum anti-HEV IgM positive. The open reading flame 2 (ORF2) of HEV that was amplified by nested RT-PCR was sequenced and compared with standard HEV genotypes 1-4. Results: Serum anti-HEV positive was found in 13.92% (228/1638) residents. The HEV infection rate in males was significantly higher than that in females with a ratio of 1.47 (. P<0.01). 20-30 and 30-40 years old young men showed the highest incidence, 20.57% and 20.78%, respectively. While 10-20 and 20-30 years old young women exhibited the highest infection rate, 11.85% and 15.60%, respectively. According to occupation, the highest HEV infection rate was observed in farmers (20.35%) and migrants (16.50%). We isolated 10 individual HEV isolates from 31 patients with serum anti-HEV IgM positive. Homology analysis and phylogenetic analysis indicated that these 10 HEV isolates belonged to HEV genotype 4 with the homology of 78.65%-94.71%. Conclusions: The HEV infection rate is high in western Yunnan Province. HEV genotype 4 is the leading cause of HEV infection and young farmers and migrants are the main infected population.