Risk assessment of malignancy in solitary pulmonary nodules in lung computed tomography: a multivariable predictive model study / 中华医学杂志(英文版)

BACKGROUND@#Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established.@*METHODS@#A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set.@*RESULTS@#The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize.@*CONCLUSIONS@#After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.

Anti-dengue virus activity of natural podocarpane-type diterpenoid in vitro / 药学学报

Dengue virus (DENV) is the most rapidly transmitted mosquito-borne pathogen, which is the main cause of seasonal outbreaks of dengue fever and dengue hemorrhagic fever in tropical and subtropical regions, and may cause serious life-threatening diseases. There is an urgent need to develop effective vaccines or antiviral therapies. In this paper, we found that a podocarpane-type diterpenoid, (3α,5β,10α)-13-methoxypodocarpa-8,11,13-triene-3,12-diol (MPTD), isolated from the stems and leaves of Aleurites moluccana, showed good effect against DENV. The anti-DENV activity of MPTD against four different DENV serotypes was studied by plaque assay. The cytotoxicity of MPTD in Vero and Huh7 cells was tested by MTT assay. qRT-PCR and Western blot assays were used to investigate the anti-DENV activity of MPTD at RNA and protein levels, respectively. The results showed that MPTD greatly reduced the virus titer in DENV infected Vero cells, and its 50% effective concentration (EC50) for DENV (1–4) were 2.72 ± 0.39, 10.99 ± 5.18, 18.72 ± 0.21, and 0.48 ± 0.28 μmol·L-1, respectively. The results showed that MPTD inhibits DENV RNA level and the expression of E protein. In addition, MPTD may inhibit the early stage of DENV replication and exert antiviral activity. Further studies showed that the inhibitory effect of MPTD against DENV infection is not targeting the viral entry stage. Therefore, MPTD has a significant anti-dengue virus effect, and is an anti-DENV compound with potential application value.

RIN1 expression in hepatocellular cancer and the affection on prognosis and tumor invasion ability / 中华外科杂志

<p><b>OBJECTIVE</b>To test the expression of RIN1 in hepatocellular cancer (HCC) and study its clinicopathological significance and mechanism.</p><p><b>METHODS</b>RIN1 mRNA in 36 HCC tissues was analyzed using real-time PCR (RT-PCR). The expression of RIN1 was examined by immunohistochemistry (IHC) in 110 HCC specimens. The relationship between the protein expression and prognosis was analyzed. Transwell was used to test invasion ability of HCC cell lines which were transfected with the expression vector pEGFP-N1-RIN1.</p><p><b>RESULTS</b>RIN1 mRNA expression levels was much lower in tumor tissues than that in their corresponding non-cancerous tissues (χ(2) = 7.430, P = 0.026). RIN1 protein was lowly expressed in liver cancer samples (69.1%) and correlated with poor survival (6.46%) (χ(2) = 13.808, P < 0.05). Transwell assays show that RIN1 overexpression can inhibit invasion ability of HepG2 cells (t = 8.975 and 9.522, both P < 0.05). RIN1 expression and ABL2 and E calcium protein were positively correlated (r = 0.898 and 0.912, P < 0.05), and negatively correlated with MMP-9 (r = -0.933, P = 0.002).</p><p><b>CONCLUSIONS</b>RIN1 expression was down-regulated in HCC and low expression of RIN1 foreshows poor prognosis of HCC patients. RIN1 overexpression can inhibit invasion ability of HepG2 cells.</p>

A new eudesmane sesquiterpenoid lactone from Chloranthus japonicus / 中国天然药物

AIM@#To study the chemical constituents of the whole plant of Chloranthus japonicus.@*METHODS@#Compounds were isolated and purified by column chromatography. Their structures were elucidated on the basis of spectroscopic methods.@*RESULTS@#Six sesquiterpenoids were obtained and their structures were identified as chlojaponilactone A (1), atractylenolide III (2), neolitacumone B (3), 10α-hydroxy-1-oxoeremophila-7(11), 8(9)-diene-8, 12-olide (4), shizukanolide C (5), and shizukanolide H (6).@*CONCLUSION@#Compound 1 is a new eudesmane-type sesquiterpenoid lactone, and compounds 3 and 4 have been isolated from this species for the first time.

Shizukaol F: a new structural type inhibitor of HIV-1 reverse transcriptase RNase H / 药学学报

This study is to investigate the mechanism of action of lindenane disesquiterpenoid shizukaol F on HIV-1 replication. Real time quantity PCR, ELISA assay and fluorescence methods were used to test HIV-1 reverse transcription process, RNA-dependent DNA polymerase activity, and RNase H activity, respectively. It showed that shizukaol F inhibited LTR/Gag production of HIV-1 reverse transcription with an IC50 of 9.11 micromol x L(-1). This result is consistent with its inhibitory effect on HIV-1 replication (IC50 of 6.12 micromol x L(-1)). Mechanism studies showed that compound shizukaol F inhibited HIV-1 RT-RNase H with IC50 of 26.4 micromol x L(-1), but had no effect on HIV-1 RT RNA-dependent DNA polymerase activity. In conclusion, shizukaol F is a new structural type HIV-1 RNase H inhibitor. This discovery will provide a clue for new type of reverse transcriptase inhibitors development.

Role of pigment epithelium-derived factor on proliferation and migration of choroidal capillary endothelium induced by vascular endothelial growth factor in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pigment epithelium-derived factor (PEDF) is expressed in several normal organs and identified as an inhibitor of neovascularization. In the present study, we investigated the effect of PEDF in an in vitro model of ocular choroidal neovascularization.</p><p><b>METHODS</b>Microdissection was used to isolate the human choroidal endothelial cells (CECs), followed by the use of superparamagnetic beads (Dynabeads) coated with the CD31 antibody, which selectively binds to the endothelial cell surface. The mitogenic and motogenic effects of vascular endothelial growth factor (VEGF) on cultured choroidal capillary endothelial cells were examined in the presence or absence of PEDF (1, 10, 100, and 1000 ng/ml) using cell counts and migration assays.</p><p><b>RESULTS</b>Cells bound to the beads were isolated using a magnetic particle concentrator and they were successfully cultured and characterized to be endothelial cells that possessed greater than 95% immunoreactivity to von Willebrand factor. PEDF suppressed the proliferation and migration of VEGF-induced choroidal capillary endothelial cells. However, the concentration of PEDF which we used has little effect on normal CECs.</p><p><b>CONCLUSIONS</b>PEDF played an important role on the growth and migration of VEGF-stimulated choroidal endothelial cell. These findings suggest that PEDF may be an effective approach to the treatment of choroidal neovascular disorders.</p>