Development and validation of a clinical prediction model for the risk of distal metastasis in intrahepatic cholangiocarcinoma: a real-world study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant and easily metastatic bile duct tumor with poor prognosis. We aimed at studying the associated risk factors affecting distal metastasis of CCA and using nomogram to guide clinicians in predicting distal metastasis of CCA. METHODS: Based on inclusion and exclusion criteria, 345 patients with CCA were selected from the Fifth Medical Center of Chinese PLA General Hospital and were divided into distal metastases (N = 21) and non-distal metastases (N = 324). LASSO regression models were used to screen for relevant parameters and to compare basic clinical information between the two groups of patients. Risk factors for distal metastasis were identified based on the results of univariate and multivariate logistic regression analyses. The nomogram was established based on the results of multivariate logistic regression, and we drawn the corresponding correlation heat map. The predictive accuracy of the nomogram was evaluated by receiver operating characteristic (ROC) curves and calibration plots. The utility of the model in clinical applications was illustrated by applying decision curve analysis (DCA), and overall survival(OS) analysis was performed using the method of Kaplan-meier. RESULTS: This study identified 4 independent risk factors for distal metastasis of CCA, including CA199, cholesterol, hypertension and margin invasion, and developed the nomogram based on this. The result of validation showed that the model had significant accuracy for diagnosis with the area under ROC (AUC) of 0.882 (95% CI: 0.843-0.914). Calibration plots and DCA showed that the model had high clinical utility. CONCLUSIONS: This study established and validated a model of nomogram for predicting distal metastasis in patients with CCA. Based on this, it could guide clinicians to make better decisions and provide more accurate prognosis and treatment for patients with CCA.

Genetic and phenotypic frequency distribution of ACE, ADRB1, AGTR1, CYP2C9*3, CYP2D6*10, CYP3A5*3, NPPA and factors associated with hypertension in Chinese Han hypertensive patients.

We analyzed the polymorphisms of 7 antihypertensive drugs-related genes and the factors associated with hypertension in hypertensive patients of Han ethnicity in Qingyang, China. A total of 354 hypertensive patients of Han ethnicity were enrolled from Qingyang, China. The ACE (I/D), ADRB1 (1165G > C), AGTR1 (1166A > C), CYP2C9*3, CYP2D6*10, CYP3A5*3 and NPPA (T2238C) polymorphisms were assessed. Clinical data of patients was also obtained. The influencing factors of hypertension were evaluated. The genotype frequencies of ACE, ADRB1, AGTR1, CYP2C9, CYP3A5 and NPPA loci were in Hardy-Weinberg equilibrium, with mutation frequencies of 39.27%, 74.29%, 6.21%, 4.80%, 72.46% and 0.71%, respectively. CYP2D6 locus was not in Hardy-Weinberg equilibrium. There was no statistical difference in allele frequencies between different genders (P > .05). There was significant difference in the frequencies of ACE (I/D) and NPPA (T2238C) loci among different regions of China (P < .05). Gender, ACE (I/D) and ADRB1 (1165G > C) gene polymorphism, smoking, homocysteine and HDL levels were associated hypertension. The mutation frequencies of ADRB1 (1165G > C) and CYP3A5*3 were high in hypertensive patients of Han ethnicity in Qingyang, suggesting these patients may be more sensitive to beta-blockers and calcium ion antagonists. Meanwhile, hypertension was associated with gender, ACE (I/D) and ADRB1 (1165G > C) gene polymorphisms, smoking, homocysteine and HDL levels.

Recent Research Progress of Mn4+-Doped A2MF6 (A = Li, Na, K, Cs, or Rb; M = Si, Ti, Ge, or Sn) Red Phosphors Based on a Core-Shell Structure.

White light emitting diodes (WLEDs) are widely used due to their advantages of high efficiency, low electricity consumption, long service life, quick response time, environmental protection, and so on. The addition of red phosphor is beneficial to further improve the quality of WLEDs. The search for novel red phosphors has focused mainly on Eu2+ ion- and Mn4+ ion-doped compounds. Both of them have emissions in the red region, absorption in blue region, and similar quantum yields. Eu2+-doped phosphors possess a rather broad-band emission with a tail in the deep red spectral range, where the sensitivity of the human eye is significantly reduced, resulting in a decrease in luminous efficacy of WLEDs. Mn4+ ions provide a narrow emission band ~670 nm in oxide hosts, which is still almost unrecognizable to the human eye. Mn4+-doped fluoride phosphors have become one of the research hotspots in recent years due to their excellent fluorescent properties, thermal stability, and low cost. They possess broad absorption in the blue region, and a series of narrow red emission bands at around 630 nm, which are suitable to serve as red emitting components of WLEDs. However, the problem of easy hydrolysis in humid environments limits their application. Recent studies have shown that constructing a core-shell structure can effectively improve the water resistance of Mn4+-doped fluorides. This paper outlines the research progress of Mn4+-doped fluoride A2MF6 (A = Li, Na, K, Cs, or Rb; M = Si, Ti, Ge or Sn), which has been based on the core-shell structure in recent years. From the viewpoint of the core-shell structure, this paper mainly emphasizes the shell layer classification, synthesis methods, luminescent mechanism, the effect on luminescent properties, and water resistance, and it also gives some applications in terms of WLEDs. Moreover, it proposes challenges and developments in the future.

Integrated Transcriptomic Analysis of the miRNA-mRNA Interaction Network in Thin Endometrium.

Although the thin endometrium (TE) has been widely recognized as a critical factor in implantation failure, the contribution of miRNA-mRNA regulatory network to the development of disease etiology remains to be further elucidated. This study performed an integrative analysis of the miRNA-mRNA expression profiles in the thin and adjacent normal endometrium of eight patients with intrauterine adhesion to construct the transcriptomic regulatory networks. A total of 1,093 differentially expressed genes (DEGs) and 72 differentially expressed miRNAs (DEMs) were identified in the thin adhesive endometrium of the TE group compared with the control adjacent normal endometrial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of DEM were significantly enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway. Multiple hub genes (CAV1, MET, MAL2, has-mir-138, ARHGAP6, CLIC4, RRAS, AGFG1, has-mir-200, and has-mir-429) were identified by constructing the miRNA-mRNA regulatory networks. Furthermore, a miRNA-mRNA pathway function analysis was conducted, and the hub genes were enriched in the FoxO signaling pathway, cell growth regulation, inflammatory response regulation, and regulation of autophagy pathways. Our study is the first to perform integrated mRNA-seq and miRNA-seq analyses in the thin adhesive endometrium and the control adjacent normal endometrial cells. This study provides new insights into the molecular mechanisms underlying the formation of thin endometrium.

[Real-Time Stability Monitoring of Photonic Crystal Sensing System Based on Guided-Mode Resonance Effect].

The detection limit of antibody content has reached level of nanograms per milliliter due to high sensitivity and extremely narrow band of photonic crystal (PC) filter. The PC filter based on guided-mode resonance (GIR) effect can also be applied to detecting the molecular interactions. As the transducing element, one-dimensional PC filters transform biological information to photoelectric signal on optical spectrum analyzer (OSA). The main sensing performance is the change of peak-wavelength of PC filter. The sensing system using PC filter is restricted to the system stability which determines the effectiveness of detecting data. So in this paper, a detecting system we designed is briefly addressed. The morphology and the spectrum of PC filter we fabricated are tested. Considering the coupling light loss and integration of the system, noise signal in spectrum is going to affect the detecting results. To monitor the influence, realization of real-time monitoring the changes of the peak wavelength of PC filter is mainly illustrated. The monitoring is realized by transferring detecting data to computer in time and the results can represent the stability of the system. The program is compiled by Lab VIEW. In our experiment, the shift of 0. 25 nm of the peak wavelength caused by vibration of platform or unsteadiness of light source is within the sensitivity of the PC filter obtained by simulation, so we proposed this system we mentioned can be used in sensing most kind of bulk reagents.

Delivery of AP-2α siRNA into cultured bovine trophoblast cells by electroporation repressed key placenta-specific gene expression.

Binucleate trophoblast giant cells (BNC) characteristically appear early in gestation in the bovine placenta. They secret pivotal hormones and cytokines for feto-maternal communication, for example, expression of placental lactogens (CSH1), prolactin-related protein 1 (PRP1) and pregnancy-associated glycoprotein 1 (PAG1) are necessary for pregnancy establishment in bovine. These genes transcription are regulated in a temporal and spatial manner, however, molecular mechanisms by which these gene transcriptions are regulated in this manner have not been firmly elucidated. In this study, a cell culture model for bovine trophoblast cells was initially established, small interfering RNA duplexes against Activator Protein-2α (TFAP2A) was transfected into the cells by electroporation, and transcripts of CSH1, PRP1 and PAG1 were measured by qPCR. The results showed that trophoblast giant cells were confluent for 90% after cultured for 10 days, and BNC constituted of a population of more than 45% of the total cells. Using a fluorescein-labeled non-silencing siRNA duplex, an electroporation protocol yielding routinely >93% positive cells could be established, and siRNA duplex transfection demonstrated an efficient knockdown of cellular AP-2α mRNA level by 72.30 ± 3.28% in electroporated cells. Finally, CSH1, PRP1 and PAG1 genes expression were effectively down-regulated by 65.45 ± 6.38% (P<0.01), 40.73±11.72% (P<0.01) and 11.59 ± 1.88% (P<0.05), respectively. It was therefore suggested that electroporating siRNA into bovine trophoblast cells could be an efficient method to manipulate BNC function and to study the regulation mechanism of specific gene transcription without the use of chemical transfection reagents. It was suggested that AP-2α could be at least involved in the regulation of expression CSH1 and PRP1 transcripts.

Effects of microRNA-143 in the differentiation and proliferation of bovine intramuscular preadipocytes.

MicroRNAs (miRNAs) are short non-coding RNA that post-transcriptionally regulates gene expression. miRNA-143 has been proposed to play a role in the differentiation of preadipocytes. However, effects and mechanism of miRNA-143 in the differentiation of mammals intramuscular adipocytes is unknown. In this study, the fibroblast-like preadipocytes were cultured from the marbling muscle tissue of holstein steers by the ceiling culture method. The in vitro studies showed that the fibroblast-like preadipocytes could differentiated into mature adipocytes with up-regulated expression of miRNA-143. Furthermore, the transfection of the fibroblast-like preadipocytes with miRNA-143 antisense inhibitor induced a significant suppression of differentiation, and indicated by decreased storage of lipid droplets and down-regulated expression of key adipocytes regulatory genes such as CCAAT/enhancer-binding protein-α (C/EBPα) and fatty acid binding proteins-4 (FABP-4). On the contrary, cells proliferation were increased with miRNA-143 inhibitor transfection. Taken together, our study provide the first evidence for stimulation of endogenous miRNA-143 in the differentiation of bovine intramuscular fat, which in part contribute to the regulated expression of adipocyte genes.

Changes in proteins within germinating seeds of transgenic wheat with an antisense construct directed against the thioredoxin.

Thioredoxin h is closely related to germination of cereal seeds. The mechanism of transgenic wheat seeds with antisense trxs gene, which is responsible for low germination rate was studied through analyzing the changes in proteins of wheat seeds during germination. The antisense trxs could weaken the metabolism of wheat seeds by decreasing the quantity of proteins involved in metabolism, while chloroform-methanol (CM) protein fraction consisted mostly of some low molecular weight proteins (<20 kD). Compared with wild-type wheat seeds, the folding of glutenin in transgenic wheat ones was affected during the wheat maturating. Big glutenin macropolymers could be formed more easily in transgenic wheat seeds than in wild-type wheat ones. Therefore, the degradation speed of glutenin in transgenic wheat seeds was slower than that in wild-type wheat ones during seed germination. In addition, the degradation of some proteins in transgenic wheat embryos was also delayed during germination.

L-carnitine inhibits apoptotic DNA fragmentation induced by a new spin-labeled derivative of podophyllotoxin via caspase-3 in Raji cells.

L-carnitine (beta-hydroxy-trimethylaminobutyric acid) plays an essential metabolic role that consists of transferring the long chain fatty acids through the mitochondrial barrier, thus allowing their energy-yielding oxidation. GP7 (4-[4''-(2'', 2'', 6'', 6''-tetramethyl-l''-piperidinyloxy) amino] -4'-demethyl-epipodophyllotoxin) is a new spin-labeled derivative of podophyllotoxin semi-synthesized by our university. In this study, we examined the activity of L-carnitine in GP7-induced apoptosis in Burkitt's lymphoma cell line, Raji. GP7 induced time- and dose-dependent apoptotic DNA fragmentation accompanied by caspase-3 activation in Raji cells, and the kinetics of caspase-3 activation induced by GP7 was well correlated with that of apoptotic DNA fragmentation. L-carnitine treatment prevented GP7-induced caspase-3 activation, suppressed caspase-3 cleavage and abrogated GP7-induced apoptotic DNA fragmentation in Raji cells. Our findings suggest that L-carnitine is a potent anti-apoptotic agent to human lymphoma cells and may exert its anti-apoptotic effect via inhibition of caspase-3 activity in GP7-treated Raji cells.