Development and Validation of a Diagnostic Model for Identifying Clear Cell Renal Cell Carcinoma in Small Renal Masses Based on CT Radiological Features: A Multicenter Study.

RATIONALE AND OBJECTIVES: This study aimed to develop a diagnostic model based on clinical and CT features for identifying clear cell renal cell carcinoma (ccRCC) in small renal masses (SRMs). MATERIAL AND METHODS: This retrospective multi-centre study enroled patients with pathologically confirmed SRMs. Data from three centres were used as training set (n = 229), with data from one centre serving as an independent test set (n = 81). Univariate and multivariate logistic regression analyses were utilised to screen independent risk factors for ccRCC and build the classification and regression tree (CART) diagnostic model. The area under the curve (AUC) was used to evaluate the performance of the model. To demonstrate the clinical utility of the model, three radiologists were asked to diagnose the SRMs in the test set based on professional experience and re-evaluated with the aid of the CART model. RESULTS: There were 310 SRMs in 309 patients and 71% (220/310) were ccRCC. In the testing cohort, the AUC of the CART model was 0.90 (95% CI: 0.81, 0.97). For the radiologists' assessment, the AUC of the three radiologists based on the clinical experience were 0.78 (95% CI:0.66,0.89), 0.65 (95% CI:0.53,0.76), and 0.68 (95% CI:0.57,0.79). With the CART model support, the AUC of the three radiologists were 0.93 (95% CI:0.86,0.97), 0.87 (95% CI:0.78,0.95) and 0.87 (95% CI:0.78,0.95). Interobserver agreement was improved with the CART model aids (0.323 vs 0.654, P < 0.001). CONCLUSION: The CART model can identify ccRCC with better diagnostic efficacy than that of experienced radiologists and improve diagnostic performance, potentially reducing the number of unnecessary biopsies.

Correction: The attenuated hepatocellular carcinoma-specific Listeria vaccine Lmdd-MPFG prevents tumor occurrence through immune regulation of dendritic cells.

[This corrects the article DOI: 10.18632/oncotarget.3558.].

[Effect of electroacupuncture at "Shenmen"(HT7) and "Sanyinjiao"(SP6) on energy metabolism in paraventricular nucleus of hypothalamus of insomnia rats].

OBJECTIVE: To observe the effect of electroacupuncture(EA) at "Shenmen"(HT7) and "Sanyinjiao"(SP6)on energy metabolism in paraventricular nucleus (PVN) of hypothalamus in insomnia rats, so as to explore its mechanism underlying improvement of insomnia. METHODS: A total of 66 SD rats (half male and half female) were randomized into 3 groups：normal control, model and EA groups(n＝22 per group). The insomnia model was established by binding the rat for at least 4 h (step increase of 30 min per day), once daily for 15 days. EA (5 Hz /25 Hz, 0.5－1.0 mA) was applied to unilateral HT7 and SP6 for 15 min, once daily for 5 days. The rats' spontaneous activities during day and night were recorded by using the ClockLab Data Collection and Analysis System, and the duration of exhausted swimming was detected by using load-bearing endurance swimming test. The expression of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) of PVN tissue was assayed by Western blot, and the contents of acetyl coenzyme A (Ac-CoA) and Na＋-K＋adenosine triphosphatase (Na＋-K＋-ATPase) in the PVN tissue, and corticosterone (CORT) in plasma were assayed by ELISA. Changes of the ultrastructure of PVN cells were observed by transmission electron microscope. RESULTS: After modeling, the rats' daytime and nocturnal locomotor activities were significantly increased and decreased, respectively (P<0.05), and the duration of exhausted swimming was considerably shortened in the model group compared with that of the normal control group (P<0.05). The expression level of AMPK protein in the PVN was obviously up-regulated (P<0.05), and the contents of Ac-CoA and Na＋-K＋-ATPase in PVN and CORT in plasma were markedly decreased in the model control group relevant to the normal group (P<0.05). After EA intervention, the increased daytime locomotion and the decreased nocturnal activities, the shortened duration of exhausted swimming, the up-regulated expression of AMPK, and the decreased Ac-CoA, Na＋-K＋-ATPase and CORT contents were all reversed in the EA treated rats relevant to those of the insomnia rats (all P<0.05). Moreover, ultrastructural observation showed mitochondrial swelling and disappearance of partial ribosomes in the plasma of PVN cells in the model group, while in the EA group, only mild swelling of some mitochondria was found, being with basically normal nuclear membrane, mitochondria, rough endoplasmic reticulum, Golgi complex and ribosomes. CONCLUSION: EA at HT7 and SP6 has a positive effect in improving insomnia and insomnia-induced fatigue in insomnia rats, which may be associated with its effects in restraining the expression of AMPK protein, and up-regulating the contents of Ac-CoA and Na＋-K＋-ATPase in PVN and CORT in plasma.

Transcriptome sequencing of neurologic diseases associated genes in HHV-6A infected human astrocyte.

Human Herpesvirus 6 (HHV-6) has been involved in the development of several central nervous system (CNS) diseases, such as Alzheimer's disease, multiple sclerosis and glioma. In order to identify the pathogenic mechanism of HHV-6A infection, we carried out mRNA-seq study of human astrocyte HA1800 cell with HHV-6A GS infection. Using mRNA-seq analysis of HA1800-control cells with HA1800-HHV-6A GS cells, we identified 249 differentially expressed genes. After investigating these candidate genes, we found seven genes associated with two or more CNS diseases: CTSS, PTX3, CHI3L1, Mx1, CXCL16, BIRC3, and BST2. This is the first transcriptome sequencing study which showed the significant association of these genes between HHV-6A infection and neurologic diseases. We believe that our findings can provide a new perspective to understand the pathogenic mechanism of HHV-6A infection and neurologic diseases.

CD24 promotes HCC progression via triggering Notch-related EMT and modulation of tumor microenvironment.

CD24 is known as a cell surface molecule in hematopoiesis and also described as a diagnostic marker for tumors. Previous studies suggested the important role of CD24 in hepatocellular carcinoma (HCC) pathogenesis. However, precise functions of CD24 in HCC are still unknown. Here, we found that CD24 is highly expressed in HCC both in mRNA and protein levels. Further, the epithelial-mesenchymal transition (EMT) and Notch1 signaling activations mediated by CD24 were elucidated as potential mechanisms of HCC promotion in Hepa1-6/Hepa1-6-CD24 cell models. Additionally, possible systemic immune reaction was explored through immune cells and Hepa1-6/Hepa1-6-CD24 cell co-culture. We demonstrated that the EMT process of HCC cell was effectively induced by CD24; also, the tumor immune microenvironment was changed by facilitating Notch-related EMT in vivo. These results reveal the underlying link between the HCC processes mediated by CD24. Moreover, as a clear tumor promoter, CD24 is considered a potential new target for HCC treatment.

S100A4 hypomethylation affects epithelial-mesenchymal transition partially induced by LMP2A in nasopharyngeal carcinoma.

To identify cellular target genes involved in NPC cell invasion and metastasis, gene expression profiles of CNE-1 cells with or without ectopic LMP2A expression were compared by using the metastatic gene array. S100 calcium binding protein A4 (S100A4) was the highest increased one among these genes both in mRNA and protein levels of NPC cells. Moreover, S100A4 was upregulated in LMP2A-positive NPC tissues. We found that CNE-1-S100A4 showed significantly increased invasion ability as compared to the controls both in vitro and in vivo, which indicated that S100A4 induced EMT occurrence and promoted metastasis. Notably, the DNA hypomethylation of S100A4 was found in LMP2A-positive NPC tissues. Besides, inhibition of DNA methyltransferases via 5-Aza-dC stimulated the expression of S100A4 in the cells without ectopic LMP2A expression. The methylation changes were confirmed by methylation specific PCR (MSP), suggesting that LMP2A ectopic expression led to the demethylation of S100A4 promoter. These results demonstrated that LMP2A-induced hypomethylation participated in regulating S100A4 expression in NPC. Our findings provide an evidence for the emerging notion that hypomethylation and activation of correlated genes are crucial for metastasis progression in cancer. © 2015 Wiley Periodicals, Inc.

Novel Ge-Ga-Te-CsBr glass system with ultrahigh resolvability of halide.

CO2 molecule, one of the main molecules to create new life, should be probed accurately to detect the existence of life in exoplanets. The primary signature of CO2 molecule is approximately 15 µm, and traditional S- and Se-based glass fibers are unsuitable. Thus, Te-based glass is the only ideal candidate glass for far-infrared detection. In this study, a new kind of Te-based chalcohalide glass system was discovered with relatively stable and large optical band gap. A traditional melt-quenching method was adopted to prepare a series of (Ge15Ga10Te75)100-x (CsBr)x chalcogenide glass samples. Experiment results indicate that the glass-forming ability and thermal properties of glass samples were improved when CsBr was added in the host of Ge-Ga-Te glass. Ge-Ga-Te glass could remarkably dissolve CsBr content as much as 85 at.%, which is the highest halide content in all reports for Te-based chalcohalide glasses. Moreover, ΔT values of these glass samples were all above 100 °C. The glass sample (Ge15Ga10Te75)65 (CsBr)35 with ΔT of 119 °C was the largest, which was 7 °C larger than that of Ge15Ga10Te75 host glass. The infrared transmission spectra of these glasses show that the far-infrared cut-off wavelengths of (Ge15Ga10Te75)100-x (CsBr)x chalcogenide glasses were all beyond 25 µm. In conclusion, (Ge15Ga10Te75)100-x (CsBr)x chalcogenide glasses are potential materials for far-infrared optical application.

The attenuated hepatocellular carcinoma-specific Listeria vaccine Lmdd-MPFG prevents tumor occurrence through immune regulation of dendritic cells.

Immunotherapy is a promising treatment for liver cancer. Here, we tested the ability of the attenuated hepatocellular carcinoma-specific Listeria vaccine (Lmdd-MPFG) to treat hepatocellular carcinoma (HCC) in a mouse model. Immunization with the vaccine caused a strong anti-tumor response, especially in mice reinfused with dendritic cells (DCs). In mice that were also administered DCs, tumor suppression was accompanied by the strongest cytotoxic T lymphocyte response of all treatment groups and by induced differentiation of CD4+ T cells, especially Th17 cells. Additionally, the Lmdd-MPFG vaccine caused maturation of DCs in vitro. We demonstrated the synergistic effect of TLR4 and NLRP3 or NOD1 signaling pathways in LM-induced DC activation. These results suggest that the Lmdd-MPFG vaccine is a feasible strategy for preventing HCC.

[Discussion on the constructing principle of syndrome differentiation system according to meridian and collateral theories].

According to the meridian and collateral theories in the Internal Classic, the authors proposed that the construction of the syndrome differentiation system with science characteristics of acupuncture and moxibustion should follow the principle of systemic structure and physiological function. The establishment of the whole frame structure of syndrome differentiation system according to meridian and collateral theories should base on the principle of systemic structure and the establishment of symptom of each syndrome should base on the principle of physiological function.

[Effect of electroacupuncture at Shenshu (BL 23) and Zusanli (ST 36) on the event-related potentials of chronic fatigue syndrome].

OBJECTIVE: To observe the effective mechanism of electroacupuncture for chronic fatigue syndrome (CFS). METHODS: The dynamic detection of chronobiology was used to test the event-related potentials in 20 healthy subjects and 20 CFS patients. P3a and P3b latencies at 4 equidistant time points (8:00, 14:00, 20:00, 2:00) within 24 hours were collected and analyzed. RESULTS: (1) Latency of P3a in CFS group was obviously prolonged at 14:00 compared to health group with statistical significance (P < 0.05), latency of P3b was decreased at 14:00 after electroacupuncture treatment with statistical significance compared to that of pre-treatment (P < 0.01). (2) There were obviously circadian rhythm in latency of P3a and P3b in health group (P < 0.05), which were not seen in CFS group (P > 0.05); the circadian rhythm latency of P3b restored after treatment (P < 0.05). (3) The latency acrophase of P3a and P3b pre-treatment obviously shifted backward compared to that of healthy subjects (P < 0.05), shifted forward after electroacupuncture treatment (P < 0.05). CONCLUSION: The event-related potential circadian rhythms are lost in CFS patients. Electroacupuncture at Shenshu (BL 23) and Zusanli (ST 36) can regulate the circadian rhythm of P3a and P3b latency and improve the cognition of the patients in daytime.

Levels and value of platelet activity in patients with severe internal carotid artery stenosis.

BACKGROUND: Turbulent blood flow caused by arterial stenosis can induce platelet activation and aggregation, which subsequently participate in arterial thromboembolic events. OBJECTIVE: To test the hypothesis that platelet activation (expressed by CD62p) is enhanced in cerebral vs systemic circulation in patients with severe internal carotid artery (ICA) stenosis. METHODS: Platelet CD62p expression was prospectively measured using flow cytometry in 35 consecutive symptomatic patients with severe ICA stenosis and in 20 at-risk control subjects who underwent both coronary and cerebral angiographic studies due to angina pectoris and suspicious vertebral artery or intracranial artery stenosis. The CD62p expression was also evaluated in 20 healthy subjects. Blood samples were first drawn from the right internal jugular vein (cerebral circulation) and right femoral vein (systemic circulation) before extra- and intracerebral angiographic examination of both patients and at-risk control subjects and again at 40 minutes after ICA stenting. Clopidogrel was administered to the patients following the second blood sampling. RESULTS: Systemic CD62p expression was higher in patients than in both the healthy and at-risk control subjects (both p < 0.0001). Additionally, cerebral CD62p expression was higher in patients than in at-risk control subjects (p < 0.0001) prior to intervention. Moreover, CD62p expression was higher in cerebral circulation than in systemic circulation in the patients (p < 0.0001) before ICA stenting. However, CD62p expression was less enhanced in cerebral circulation than in systemic circulation after ICA stenting (p < 0.0001). Furthermore, CD62p expression was decreased after 3 months of follow-up (p < 0.0001). CONCLUSIONS: Compared to systemic CD62p expression, cerebral CD62p expression was more enhanced prior to ICA stenting and was less enhanced after ICA stenting in patients with severe ICA stenosis.