Due to the limitations of current anti-HBV therapies, the HBV core (HBc or HBcAg) protein assembly modulators (CpAMs) are believed to be potential anti-HBV agents. Therefore, discovering safe and efficient CpAMs is of great value. In this study, we established a HiBiT-based high-throughput screening system targeting HBc and screened novel CpAMs from an in-house marine chemicals library. A novel lead compound 8a, a derivative of the marine natural product naamidine J, has been successfully screened for potential anti-HBV activity. Bioactivity-driven synthesis was then conducted, and the structure‒activity relationship was analyzed, resulting in the discovery of the most effective compound 11a (IC₅₀ = 0.24 μmol/L). Furthermore, 11a was found to significantly inhibit HBV replication in multiple cell models and exhibit a synergistic effect with tenofovir disoproxil fumarate (TDF) and IFNa2 in vitro for anti-HBV activity. Treatment with 11a in a hydrodynamic-injection mouse model demonstrated significant anti-HBV activity without apparent hepatotoxicity. These findings suggest that the naamidine J derivative 11a could be used as the HBV core protein assembly modulator to develop safe and effective anti-HBV therapies.

Objective:To analyze the role of preoperative circulating tumor cell(CTC) and circulating tumor vascular endothelial cells (CTEC) in the diagnosis of gastric cancer and its correlation with the clinicopathological characteristics of gastric cancer.Methods:Sixty-two gastric cancer patients and 11 patients of benign gastric diseases were enrolled. Subtraction enrichment (SE) and immunofluorescence staining-chromosome fluorescence in situ hybridization (i·FISH) were used to integrate the unique SE-i ·FISH technology platform detecting patients′ CTC and CTEC.Results:The number of CTC in the gastric cancer group was significantly higher than that in the control group ( t=2.693, P=0.009); the number of CTEC in the gastric cancer group was higher than the control group ( t=2.015, P=0.048). With the cut-off value being set at 9 cells/6 ml in blood, the sensitivity of CTC in the diagnosis of gastric cancer is 84%, and the specificity is 82% (AUC=0.876, 95% CI, 0.792-0.963, P<0.01); When set at 6 cells/6 ml, the sensitivity of CTEC in the diagnosis of gastric cancer is 50%, and the specificity is 100%(AUC=0.727, 95% CI, 0.603-0.851, P=0.02). CTC positive is closely related to tumor location(χ 2=4.292, P=0.038 ) and TNM stage(CTC≥10, χ 2=4.848, P=0.028; CTC≥11, χ 2=6.234, P=0.013). CTEC positive is closely related to serum CA19-9(χ 2=4.858, P=0.028) and serum CA724 (χ 2=4.108, P=0.043 ) . Conclusion:SE-i·FISH technology has high sensitivity and specificity in the detection of CTC and CTEC of gastric cancer.

DNA barcode technology was used to establish a rapid identification method of Chrysanthemum indicum and Ch. morifolium based on psbA-trn H,mat K and trn L sequences. The total DNA was extracted from 21 samples collected,and the psbA-trn H,mat K,trn L sequences were amplified by PCR and sequenced. The information of these sequences were obtained. We aligned all 63 sequences,calculated the intraspecific and interspecific distances,analysed the SNPs distribution of psbA-trn H+mat K+trn L combination sequences and constructed the Neighbor-joining( NJ) Tree,using MEGA 7. 0. The results showed that the genetic distances of Ch. indicum,Ch. indicum( Juhuanao)and Ch. morifolium were overlapped. The SNPs analysis of psbA-trn H+mat K+trn L combination sequences showed that there were 19 nucleotide polymorphism loci( SNPs) and nine parsim-informative sites in the combination sequences. In addition,Ch. indicum showed more obvious sequence polymorphism than those of Ch. indicum( Juhuanao) and Ch. morifolium. The psbA-trn H sequences showed obvious length variation.The NJ Tree showed that Ch. morifolium numbered C2-C5 were clustered into a single subbranch with a bootstrap value of 62%,and Ch.morifolium could be distinguished from Ch. indicum and Ch. indicum( Juhuanao). Moreover,Ch. indicum numbered Z9 and Z10 collected from Gansu province were singly clustered into one branch with a bootstrap value of 77%. It was also found that the changes of psbA-trn H and trn L sequences information of Ch. indicum samples from the northwest were obviously related to the geography and environment. Moreover,Ch.indicum and Ch. indicum( Juhuanao) had obvious differentiation,were also regarded as the evolutionary sources of Ch. morifolium. Therefore,psbA-trn H+mat K+trn L combination sequences as DNA barcode can identify Ch. indicum and Ch. morifolium accurately and rapidly,which provides an important basis for germplasm resources identification and species identification.
Chrysanthemum ; DNA Barcoding, Taxonomic ; DNA, Plant ; Phylogeny ; Trees

By exploring additional phylogenetic information hidden in ITS2 secondary structure,the possibility of identifying Chrysanthemum indicum and its related species with DNA barcode of ITS2 nucleic acid sequence and its structure information were discussed.The genomic DNA was extracted from 12 samples. The ITS2 fragments were amplified by PCR and sequenced bidirectionally to obtain ITS2 sequence information. 28 sequences of related species for Ch. indicum were downloaded from Gen Bank. Until all 40 ITS2 sequences were aligned,ITS2 secondary structure prediction and structure comparison were finished. Then ITS2 secondary structure information was coded. After comparing ITS2 structure information and nucleic acid information,MP phylogenetic trees were built. The results showed that the secondary structures of ITS2 shared the same structure model--a four-fingered hand. They not only have the common characteristics of ITS2 secondary structures in plants,but also have many other conservative sequences,and their overall conservativeness is high. Among all species used in this study,their ITS2 secondary structures had obvious difference. In addition,the number of mutation sites in the joint matrix compared with the nucleic acid sequences increased by nearly 90%,which greatly enriched the number of mutation sites. This method of information analysis distinguished Ch. indicum from its related species. At the same time,the support rate of the branches of evolutionary trees and the identification rate of species were significantly improved. Although there was no distinction between Ch. zawadskii and Ch. morifolium,it effectively distinguished the three species,namely,Ch. hypargyrum,Ch.oreastrum,and Ch. dichrum. Therefore,the authors suggest that the ITS2 sequence combined with its structural data information should be applied to the identification of Ch. indicum and its related species,and be widely applied to DNA barcode research.
Chrysanthemum ; DNA Barcoding, Taxonomic ; DNA, Plant ; DNA, Ribosomal Spacer ; Phylogeny ; Plants

Female ; Glomerulonephritis, IGA ; metabolism ; pathology ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; metabolism ; pathology ; Humans ; Kidney ; metabolism ; pathology ; Male ; Renal Insufficiency, Chronic ; metabolism ; pathology

BACKGROUNDAtopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczema/AD and to propose Chinese diagnostic criteria for adult/adolescent AD.

METHODSA hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software.

RESULTSA total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients.

CONCLUSIONLate-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD.

Adolescent ; Adult ; Dermatitis, Atopic ; diagnosis ; immunology ; Eczema ; diagnosis ; Female ; Humans ; Immunoglobulin E ; blood ; Male ; Middle Aged ; Retrospective Studies ; Surveys and Questionnaires

BACKGROUNDVentricular septal rupture (VSR) remains an infrequent but devastating complication of acute myocardial infarction (AMI). The best time to undergo surgical repair is controversial and there is currently no risk stratification for patients with VSR to guide treatment. The purpose of this study was to review the clinical outcomes of 70 patients with VSR, to analyze the short-term prognosis factors of VSR following AMI, and to make a risk stratification for patients with VSR.

METHODSA total of 70 consecutive VSR patients following AMI treated in our hospital from January 2002 to October 2010 were enrolled in this study retrospectively. The difference of clinical characteristics were observed between patients with VSR who survived ≤30 days and survived >30 days. We analyzed the short-term prognosis factors of VSR and established the short-term prognosis index of VSR (SPIV) based on the Logistic regression analysis to stratify patients with VSR.

RESULTSAmong 12 354 patients with acute ST-segment elevation myocardial infarction, 70 (0.57%) patients (33 males and 37 females) were found to have VSR. The average age was (68.1±8.5) years. Fifty-four (77.1%) patients were diagnosed with an acute anterior infarction. Patients with VSR selected for surgical repair had better outcomes than patients treated conservatively; 1-year mortality 9.5% versus 87.8%, P < 0.005. Logistic regression analysis revealed that female (P = 0.013), anterior AMI (P = 0.023), non-ventricular aneurysm (P = 0.023), non-diabetes (P = 0.009), Killip class 3 or 4 (P = 0.022) and time from AMI to VSR less than 4 days (P = 0.027) were independent risk determinants for shortterm mortality. SPIV ≥9 indicates a high risk as the 30-day mortality is 77.4%; SPIV <8 indicates a low risk as the 30-day mortality is 28.6%; SPIV between 8 and 9 indicates a moderate risk.

CONCLUSIONSVSR remains a rare but devastating complication of AMI. The independent risk determinants for short-term mortality of VSR were female gender, anterior AMI, non-ventricular aneurysm, non-diabetes, Killip class 3 or 4, and the time from AMI to VSR less than 4 days. It is reasonable to take more active treatments for the patients at high risk to save more lives.

Aged ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; complications ; physiopathology ; Ventricular Septal Rupture ; diagnosis ; etiology

BACKGROUNDSpontaneous attack of variant angina (VA) is a unique component of coronary artery disease (CAD), and associated with severe cardiac events. However, no data are available regarding sex differences in Chinese patients with spontaneous attacks of VA. Accordingly, the present retrospective study was initiated to evaluate the Clinical characteristics of Chinese female patients with spontaneous attacks of VA.

METHODSFrom January 2003 to January 2008, a total of 209 patients were diagnosed to have had a spontaneous attack of VA at Fu Wai Hospital. Of them, 27 were female, and their clinical findings were collected and compared with male patients for aspects of risk factors, clinical features and angiographical findings.

RESULTSSpontaneous attacks of VA was relatively uncommon in female (12.9%) compared with male patients. The female patients were less likely to have a history of smoking (14.8% vs. 79.7%, P < 0.001), more likely to have a family history of CAD (33.3% vs. 11.0%, P < 0.01), and to have had a greater incidence of ventricular fibrillation during attack (11.1% vs. 2.2%, P < 0.05). There were no significant differences in other characteristics between the two groups.

CONCLUSIONChinese female patients who experienced a spontaneous attack of VA had the characteristics of less smoking history, more family history of CAD and higher occurrence of ventricular fibrillation than male patients.

Adult ; Angina Pectoris, Variant ; pathology ; Asian Continental Ancestry Group ; Coronary Angiography ; Electrocardiography ; Female ; Humans ; Male ; Middle Aged ; Sex Factors

OBJECTIVETo investigate the oxidative damage to lung tissue and peripherial blood in PM2.5-treated rats.

METHODSPM2.5 samples were collected using an auto-sampling instrument in summer and winter. Treated samples were endotracheally instilled into rats. Activity of reduced glutathione peroxidase (GSH-Px) and concentration of malondialdehyde (MDA) were used as oxidative damage biomarkers of lung tissue and peripheral blood detected with the biochemical method. DNA migration length (microm) and rate of tail were used as DNA damage biomarkers of lung tissue and peripheral blood detected with the biochemical method.

RESULTSThe activity of GSH-Px and the concentration of MDA in lung tissue significantly decreased after exposure to PM2.5 for 7-14 days. In peripheral blood, the concentration of MDA decreased, but the activity of GSH-Px increased 7 and 14 days after experiments. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood. The DNA migration length (microm) and rate of tail in lung tissue and peripheral blood significantly increased 7 and 14 days after exposure to PM2.5. The two indicators had a dose-effect relation and similar changing tendency in lung tissue and peripheral blood.

CONCLUSIONPM2.5 has a definite oxidative effect on lung tissue and peripheral blood. The activity of GSH-Px and the concentration of MDA are valuable biomarkers of oxidative lung tissue damage induced by PM2.5. The DNA migration length (microm) and rate of tail are simple and valuable biomarkers of PM2.5-induced DNA damage in lung tissues and peripheral blood. The degree of DNA damage in peripheral blood can predict the degree of DNA damage in lung tissue.

Animals ; DNA Damage ; drug effects ; Drug Administration Routes ; Drug Administration Schedule ; Lung ; drug effects ; pathology ; Lung Diseases ; blood ; chemically induced ; pathology ; Male ; Oxidative Stress ; Particle Size ; Particulate Matter ; administration & dosage ; toxicity ; Rats ; Rats, Wistar ; Seasons

Laser techniques are widely applied in medical research and military affairs. The characters of laser make it the best way to evoke pain.Pain induced by laser stimuli is influenced by laser parameters such as wavelength, pulse duration and stimulus area in addition to the properties of skin such as the distance from the brain, type and color of skin. In this review,both laser evoked pain and factors influencing it are discussed.