Quantitative and Qualitative Analysis of Atherosclerotic Stenosis in the Middle Cerebral Artery Using High-Resolution Magnetic Resonance Imaging.

PURPOSE: We analyzed and compared the imaging characteristics of the vessel wall of the middle cerebral artery (MCA) in symptomatic and asymptomatic patients using a 3.0-T high-resolution magnetic resonance imaging (HR-MRI) protocol, including a 3-dimensional T1-sampling perfection with application-optimized contrasts using different flip angle evolutions sequence. METHODS: Fifty-three patients with atherosclerotic stenosis of the MCA underwent 3.0-T HR-MRI examinations. The characteristics of atherosclerotic plaques in 53 patients (28 symptomatic, 25 asymptomatic) were analyzed, including plaque distribution and signal intensity. Plaque burden (PB), stenosis degree, and the remodeling index were measured and compared between symptomatic and asymptomatic patients. RESULTS: The PB of the symptomatic group was significantly higher than that of the asymptomatic group (P = .006), and moderate-severe stenosis was more common (P = .01). The remodeling index of the symptomatic group was also lower (P = .015) and negative remodeling (NR) was more common (P = .043). Binary logistic regression analysis showed that stenosis degree was a risk factor in symptomatic patients (odds ratio = 135, P = .023). CONCLUSION: There is a trend that some characteristics of plaques and vessels, including the moderate-severe stenosis, larger PB, and NR, were observed more frequently among patients with symptomatic atherosclerotic stenosis of the MCA than among asymptomatic patients.

A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.

Cannabinoid receptors in osteoporosis and osteoporotic pain: a narrative update of review.

OBJECTIVE: Osteoporosis is a skeletal disease with decreased bone mass and alteration in microarchitecture of bone tissue, and these changes put patients in risk of bone fracture. As a common symptom of osteoporosis and complication of osteoporotic fracture, chronic pain is a headache for clinicians. Nonsteroidal anti-inflammatory drugs (NSAIDs), selective COX-2 inhibitors and opioid drugs can temporarily reduce osteoporotic pain but have relevant side effects, such as addiction, tolerability and safety. The review summarized the recent advancements in the study of CB receptors in osteoporosis and osteoporotic pain and related mechanisms. KEY FINDINGS: Recent studies indicated the two nociceptive receptors, cannabinoid receptor (CB) and transient receptor potential vanilloid type 1 (TRPV1) channel, are co-expressed in bone cells and play important role in the metabolism of bone cells, suggesting that dualtargeting these 2 receptors/channel may provide a novel approach for osteoporotic pain. In addition, both CB receptor and TRPV1 channel are found to be expressed in the glial cells which play vital role in mediating inflammation, chronic pain and metabolism of bone cells, suggesting a role of glial cells inosteoporotic pain. SUMMARY: Multiple-targeting against glial cells, CB receptors and TRPV1 channel may be one effective therapeutic strategy for osteoporotic pain in the future, following the elucidation of the complicated mechanism.

[The inhibitory effect of paclitaxel nanoparticles on ovarian cancer xenografts and lymphatic targeting].

OBJECTIVE: To develop a polymeric drug delivery system for paclitaxel and determine whether paclitaxel can inhibit the growth of ovarian carcinoma xenografts in F344 rats by intraperitoneal administration. METHODS: Paclitaxel loading nanoparticles (PLA) were synthesized by ultrasonic emulsification; rat ovarian carcinoma cells were injected into the peritoneal cavity of F344 rats. The antitumor effect of paclitaxel nanoparticles in vivo has been evaluated by measuring tumor weight and ascite volume. At the end of the procedure the rats were killed, tumors were excised and processed for PCNA staining, tissue terminal deoxynucleotide transferase-mediated dUTP nick and labeling (TUNEL) assay. Paclitaxel concentration in plasma, pelvic lymph nodes, liver, heart were determined by high-performance liquid chromatography (HPLC). RESULTS: In the implanted carcinoma cells, paclitaxel nanoparticles significantly reduced tumor weight [(4.55 +/- 0.11) g vs (10.13 +/- 0.52) g]and ascites volume [(3.55 +/- 0.50) mL vs (30.45 +/- 1.55) mL], and induced apoptosis of tumor cells [(105 +/- 15) vs (55 +/- 10)]. The paclitaxel concentration of pelvic lymph nodes in PLA treated animals was significantly higher than that of free PTX treated animals 48 h after intraperitoneal administration [(0.75 +/- 0.05) microg/g vs (0.188 +/- 0.045) microg/g]. CONCLUSION: The intraperitoneal administration of paclitaxel nanoparticles can significantly inhibit the progression of ovarian carcinoma in peritoneal cavity of female F344 rats. The paclitaxel nanoparticle is safe and lymphatic targeting.

A periplasmic glutamate/aspartate binding protein from Shigella flexneri: Gene cloning, over-expression, purification and preliminary crystallographic studies of the recombinant protein.

Periplasmic substrate binding proteins (PSBPs) are essential components of the bacterial periplasmic transport system, which transports a wide variety of nutrients from the periplasmic space to the cytoplasm. The glutamate/aspartate binding protein SfGlu/AspBP is a unique PSBP consisting of 279 amino acid residues. The SfGlu/AspBP gene was cloned, over-expressed, and purified by immobilized metal ion affinity chromatography and size-exclusion chromatography. The recombinant protein SfGlu/AspBP has been crystallized by the hanging-drop vapor-diffusion method and its X-ray diffraction data were collected at an atomic resolution of 1.15 A. The crystals belong to the space group P2(1) with unit cell parameters: a = 48.41 A, b = 68.18 A, c = 80.21 A and beta = 98.78 degrees. There are two molecules per asymmetric unit.

Purification and preliminary crystallographic studies of CutC, a novel copper homeostasis protein from Shigella flexneri.

CutC is a novel copper homeostasis protein containing 248 amino acids. Here we report the cloning, expression, purification, crystallization and preliminary X-ray crystallographic studies of CutC from Shigella flexneri 2a. Purification of CutC and its selenomethionine (SeMet) derivate were done using immobilized metal ion affinity chromatography, size-exclusion and ion-exchange chromatography. The purified proteins were crystallized using the hanging drop vapor diffusion method. The diffraction data for the native and SeMet CutC, respectively, have been collected with resolution of 1.7 A and 2.1 A. They belong to the space group C2221 and similar cell dimension. The native protein crystals have cell parameters: a=75.3267, b=97.6718, c=132.6910.

[The role of adhesion molecules in the pathogenic mechanisms of hypertension in obstructive sleep apnea-hypopnea syndrome].

OBJECTIVE: To explore the role of adhesion molecules in the pathogenesis of hypertension in obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: The levels of serum soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and L-selectin in 30 OSAHS patients accompanied by hypertension, 30 normotensive OSAHS patients and 30 healthy controls were measured by enzyme-linked immunosorbent assay (ELISA) method. The relationship of the concentration of ICAM-1, VCAM-1 and L-selectin with the polysomnogram (PSG) parameters was analyzed. RESULTS: The levels of serum soluble ICAM-1 [(601 +/- 406) microg/L, (513 +/- 244) microg/L, respectively] and VCAM-1 [(578 +/- 176) microg/L, (480 +/- 144) microg/L, respectively] were significantly higher in OSAHS accompanied by hypertension and normotensive OSAHS than those in the healthy controls [(355 +/- 119) microg/L, (310 +/- 163) microg/L, q = 4.78, 3.07; 9.09, 5.76, P < 0.01, respectively]. But the levels of serum L-selectin was not significantly different among the three groups (P > 0.05). The levels of serum VCAM-1 were significantly higher in OSAHS accompanied by hypertension than those in the normotensive OSAHS (q = 3.32, P < 0.05). The was not significantly different between the two groups (P > 0.05). There was a significantly positive correlation between the concentration of ICAM-1 and the apnea hyponea index (AHI) as well as microarousal index in all the 60 OSAHS patients with and without hypertension (r = 0.465, P < 0.01, r = 0.226, P < 0.05). There was a significantly negative correlation between the concentration of ICAM-1 and the lowest oxygen desaturation in all the 60 OSAHS patients with and without hypertension (r = -0.368, P < 0.01). CONCLUSION: The high level of serum VCAM-1 and ICAM-1 is an important risk factor for the development of hypertension in OSAHS patients.

[Evaluation of the serum endothelin-1 level and sleep architecture change in patients with obstructive sleep apnea hypopnea syndrome accompanied hypertension].

OBJECTIVE: To explore the role of endothelin-1 (ET-1) in the pathogenesis of hypertension in obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The levels of serum ET-1 in 30 OSAHS patients accompanied by hypertension, 30 normotensive OSAHS patients and 30 healthy controls were measured by ET-1 enzyme immunoassay kit. Meanwhile the correlation about the concentration of ET-1 in OSAHS patients with the clinic, polysomnography (PSG) parameters was analyzed. RESULTS: OSAHS patients with or without hypertension compared with snoring group and normal people, the sleep structure was significantly disturbed. The time percentages of awake and stage I sleep were increased, while stage II sleep decreased significantly in OSAHS patients than those in snoring group (P < 0.01, respectively). There were no significantly difference about the sleep structure in the two OSAHS groups. The levels of serum ET-1 (mean +/- s) were significantly higher in OSAHS patients accompanied by hypertension and normotensive OSAHS patients(42.5 +/- 8.4) ng/L and (38.6 +/- 4.7) ng/L respectively than those in the healthy controls(33.1 +/- 5.4) ng/L (P < 0.01, respectively). In the two OSAHS groups, the levels of serum ET-1 were significantly higher in OSAHS patients accompanied by hypertension than those in the normotensive OSAHS patients (P < 0.05). There were positive correlations between the concentration of ET-1 and the apnea hypopnea index (AHI) in all the 60 OSAHS patients with and without hypertension (r = 0.334, P < 0.01). There were negative correlations between the concentration of ET-1 and the lowest oxygen desaturation in all the 60 OSAHS patients with and without hypertension (r = -0.230, P < 0.05). CONCLUSION: These results indicate that the sleep disordered breathing and hypoxia may contribute to the elevation of ET-1 in the OSAHS patients and OSAHS patients accompanied by hypertension. ET-1 may play an important role in the pathogenesis of OSAHS-induced hypertension.

[Epidemiological study of human caliciviruses among children with acute diarrhea in Lulong county, 1999 - 2001].

OBJECTIVE: To investigate the epidemiological characteristus of human caliciviruses (HuCVs) among children under 5 years of age with acute diarrhea and to estimate the disease burden in Lulong county. METHODS: HuCVs were detected by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Some PCR amplicons were cloned and sequenced. Phylogenetic tree was constructed for strain characterization. The rate of HuCVs-attributed hospitalization was estimated according to the positive rate of HuCVs detection in fecal specimens collected from hospitalized diarrhea patients. RESULTS: Between July 1999 and June 2001, 708 fecal specimens were collected, of which 393 rotavirus-negative and 5 rotavirus-positive specimens were detected for HuCVs. Thirty-one point six percentage of fecal specimens from patients with diarrhea was HuCVs positive. Among inpatients, HuCVs positive rate was 17.5%. HuCVs detection was mainly distributed in 3 - 17 mouth-old children, in winter. All 11 strains belonged to NLV GII in which 6 strains GII-3, 2 strains GII-4 and 3 strains GII-7, and they shared 55.1% - 100% nucleotide identity. NLV GII-4 and GII-7 were identified in 2000, while NLV GII-3 and GII-7 in 2001. The preliminary estimate of HuCVs-attributed hospitalization rate was 3.6 per thousand. CONCLUSION: Human caliciviruses with different genotypes circulated among children in Lulong county with GII NLVs were the prevalent strains. The disease burden of HuCVs was second to rotavirus.