Humans ; Infant ; Job Syndrome ; diagnosis ; immunology ; therapy ; Male

Purpose There is no agreement for contrast enhanced ultrasound (CEUS) in differential diagnosis of benign and malignant thyroid nodules. This paper aims to evaluate the diagnostic value of the conventional and contrast-enhanced ultrasonography in the diagnosis of thyroid nodule by meta analysis. Materials and Methods Literature search was performed in PubMed, CNKI and Wanfang databases to identify relevant English and Chinese literatures by using pathological results as the gold standard from January 1990 to September 2014. The quality of each selected study was evaluated by QUADAS. The pooled weighted sensitivity, specificity and the corresponding 95% CI were calculated. Summary receiver operating characteristic curves (SROC), area under curve (AUC) and the Q* index were also calculated. Results A total of 14 literatures (1970 nodules) were included, the pooled weighted sensitivity and specificity of conventional ultrasonography were 0.74 and 0.70; those of contrast-enhanced ultrasonography were 0.86 and 0.82. The AUC by using the two methods were 0.84 and 0.93, respectively, and the Q* index were 0.77 and 0.86, respectively. Conclusion In the diagnosis of thyroid nodule, the accuracy of contrast-enhanced ultrasonography is better than conventional ultrasound; however, both of them have high clinical value in the diagnosis of thyroid nodule, thus they are helpful in avoidance of unnecessary surgical treatment in patients with thyroid disease.

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC₅₀) was 13.8 μmol·L^-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC₅₀: 41.99 μmol·L^-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Objective To evaluate the effects of hyperbaric oxygen on the expressions of hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor-1 receptor (IGF-1R) in the formation of hyperplastic scar in rabbit ears.Methods The ears of 20 New Zealand rabbits were used to construct an animal model for hyperplastic scar by operation.After the establishment of scar models,the rabbits were randomly divided into 4 experimental groups and one control group with 4 mice (48 wound surfaces) in each group.The mice in the 4 experimental groups were treated with hyperbaric oxygen for 7,14,21 and 28 days,respectively,and those in the control group remained in normoxic environment after operation.Scar tissues were resected from all the rabbit ears on day 29 after operation.Hematoxylin and eosin (HE) staining was conducted for the observation of morphological changes and calculation of scar elevation index,and immunohistochemistry to measure the expressions of HIF-1α and IGF-1R.Statistical analysis was carried out by one-way analysis of variance followed by least significant difference t-test.Results HE staining showed that both the number of fibroblasts and amount of collagen fibers were significantly reduced in the experimental groups compared with the control group.Scar elevation index was 4.28 ± 0.22 in the control group,3.64 ± 0.29,3.46 ± 0.21,3.29 ± 0.21,3.16 ± 0.15 in the 7-,14-,21-and 28-day experimental groups respectively,with significant differences among these groups (F =77.70,P ＜ 0.05).The expressions of HIF-1α and IGF-1R were significantly lower in these experimental groups than in the control group (all P ＜ 0.01),lower in the 14-day group than in the 7-day group (P ＜ 0.05),and lower in the 21-day group than in the 14-day group (P ＜ 0.05),with no significant differences between the 28-day group and 21-day group (both P ＞ 0.05).Conclusion Hyperbaric oxygen can effectively down-regulate the expressions of HIF-1α and IGF-1R in scar tissue,and significantly inhibit the formation of hyperplastic scar in rabbit ears.

The contribution of particles to cardiovascular mortality and morbidity has been enlightened by epidemiologic and experimental studies. However, adverse biological effects of the particles with different sizes on cardiovascular cells have not been well recognized. In this study, sub-cultured human umbilical vein endothelial cells (HUVECs) were exposed to increasing concentrations of pure quartz particles (DQ) of three sizes (DQPM1, <1 μm; DQPM3-5, 3-5 μm; DQPM5, 5 μm) and carbon black particles of two sizes (CB0.1, <0.1 μm; CB1, <1 μm) for 24 h. Cytotoxicity was estimated by measuring the activity of lactate dehydrogenase (LDH) and cell viability. Nitric oxide (NO) generation and cytokines (TNF-α and IL-1β) releases were analyzed by using NO assay and enzyme-linked immunoabsorbent assay (ELISA), respectively. It was found that both particles induced adverse biological effects on HUVECs in a dose-dependent manner. The size of particle directly influenced the biological activity. For quartz, the smaller particles induced stronger cytotoxicity and higher levels of cytokine responses than those particles of big size. For carbon black particles, CB0.1 was more capable of inducing adverse responses on HUVECs than CB1 only at lower particle concentrations, in contrast to those at higher concentrations. Meanwhile, our data also revealed that quartz particles performed stronger cell damage and produced higher levels of TNF-α than carbon black particles, even if particles size was similar. In conclusion, particle size as well as particle composition should be both considered in assessing vascular endothelial cells injury and inflammation responses induced by particles.

The aim of this study was to investigate and evaluate the antitumor effects of a novel poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor, YHP-836, in combination with temozolomide (TMZ) for the treatment of glioblastoma (GBM). The cytotoxicity of YHP-836 was tested alone or in combination with TMZ using MTT assay. Immunoblotting and flow cytometry were also employed to assess the combination activity of YHP-836 and TMZ in multiply GBM cell lines. Further, the antitumor activity of YHP-836 and TMZ was evaluated using subcutaneous and orthotopic mice xenograft tumor models. All procedures were approved by the Ethics Committee for Animal Experiments of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and conducted under the Guidelines for Animal Experiments of Peking Union Medical College. The approval number is 00009138. It was demonstrated that the combination of YHP-836 and TMZ increased the cytotoxicity against GBM cells and upregulated histone H2AX phosphorylation (γH2AX) expression levels compared to TMZ treatment alone. The combination also led to the S-phase cell cycle arrest. Moreover, YHP-836 significantly enhanced TMZ antitumor effects without significantly increasing chemotherapy drug toxicity in vivo, whereas YHP-836 alone showed limited therapeutic efficacy against GBM. In conclusion, the novel PARP1/2 inhibitor, YHP-836, sensitizes TMZ and provides a basis for further investigation into its mechanism of action. These findings suggest that YHP-836 may be a potential candidate for combination therapy with TMZ in patients with TMZ resistance.

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

Objective To explore role of 64-slices spiral CT in differetiation of acute chest pains.Methods Thirty six patients with acute chest pains were performed 64-slices spiral CT chest angiography.Two-dimensional and three-dimensional reconstruction was performed in all patients by means of multiplanar reconstruction(MPR)(coronal,sgittal oblique),curved planar reformation(CPR), maximum intensity projection(MIP),and volume rendering(VR).All images were blindly reading by two experienced radiologist.DSA were performed at the same time in 16 cases.Results The coronary artery branches,pulmonary artery and aortic artery in all patients were showed clearly,The acute myocardial infarction were showed in 10 cases,The pulmonary artery embolism in 14 cases,The aortic dissection in 6 cases respectively,The Coronary embolism in One case ,pneumothorax In One case The constrictive pericarditis in 1 case respectively.Normal findings in 4 cases.Conclusion 64-slices spiral CT is a useful and noninvasive examination in acute chest pain.

Objective To investigate the effects of different combinations of vitamin (Vit) C, Vit E and GSH on the biochemical markers and bone mineral density (BMD) in ovariectomized rats. Methods Seventy female SD rats aged 4 months were divided into two groups, 20 rats with sham operation in control group and 50 rats with bilateral oophorectomy in model group. 3 months later, 10 rats in the model group and 10 rats in the control group were randomly selected and their body weight, uterus weight, BMD of the left femurs and lumbar spines,biomeehanical characteristics of the left femurs, serum levels of Ca2+ , creatinine (Cr), alkaline phosphatase (ALP),superoxide dismutase (SOD) , malondialdehyde (MDA) , GSH-peroxidase (GSH-Px) and serum resisting abilities to OH- were determined. Then the rest rats were divided into five groups: A (sham), B (OVX control), C (Vit C +Vit E), D (GSH) and E (Vit C +Vit E +GSH). Vit C, Vit E and GSH were given 750rng/kg, 250 mg/kg, and 125 mg/kg, respectively daily for 3 months. And then the biochemical markers and BMD were measured. Results 3 months after treatment with antioxidants, BMD of left femurs and lumbars spines was increased, while the level of serum ALP was decreased markedly in B, C and D group as compared with that in B group. The serum level of SOD, GSH-Px and serum resisting ability to OH- were increased in D and E groups and the level of MDA decreased in C and D groups as compared with that in B group. Conclusion Vit C, Vit E and GSH increased BMD, prevented the decrease of SOD and GSH-Px and elevated serum resisting ability to OH-in ovariectomized rats.

Objective To investigate the effects of different combinations of antioxidants VitC, VitE and GSH on the biomechanical and biochemical markers in ovariectomized rats, Methods Seventy female SD rats, aged 4 months, were divided into 2 groups (control and model) randomly. Fifty rats in the model group underwent ovariectomy, while the other 20 rats in the control group had sham operations. Three month slater, 10 rats in the model group and 10 rats in the control group were selected randomly to detect their body weight, uterus weight, BMD of the left femur and lumbar vertebra, biomechanical characteristics of the left femur, levels of serum Ca2 +, Cr, ALP, SOD, MDA and GSH-Px and serumal resistance to OH<'->. Then the rest were divided into 5 groups: A (sham), B (model), C (VitC + VitE), D (GSH), and E (VitC + VitE +GSH). VitC, VitE and GSH were given in 750 mg/kg, 250 mg/kg, and 125 mg/kg every day for 3 months,respectively. And then the biomechanical and biochemical markers were measured. Results Three months after ovariectomy, the body weight of the rats in the model group increased markedly compared with the control group, while BMD of the left femur and lumbar vertebra, biomechanical maximal load and uterus weight decreased. The serum levels of Ca<'2+>, ALP and Cr increased. Three months after antioxidant treatment,the biomechanical maximal load and elastic load of the left femur and the maximal load of the 5th lumbar vertebra, the serum levels of SOD, GSH-Px and the serumal resistance to OH<'-> in groups D and E increased markedly, while the serum level of MDA decreased in groups C and D and the level of serum ALP decreased in all the treatment groups. Conclusion GSH and combination of VitC, VitE and GSH play a positive role in treatment of osteoperesis in ovariectomized rats.