A Prediction Model for Cognitive Impairment Risk in Colorectal Cancer after Chemotherapy Treatment.

BACKGROUND: A prediction model can be developed to predict the risk of cancer-related cognitive impairment in colorectal cancer patients after chemotherapy. METHODS: A regression analysis was performed on 386 colorectal cancer patients who had undergone chemotherapy. Three prediction models (random forest, logistic regression, and support vector machine models) were constructed using collected clinical and pathological data of the patients. Calibration and ROC curves and C-indexes were used to evaluate the selected models. A decision curve analysis (DCA) was used to determine the clinical utility of the line graph. RESULTS: Three prediction models including a random forest, a logistic regression, and a support vector machine were constructed. The logistic regression model had the strongest predictive power with an area under the curve (AUC) of 0.799. Age, BMI, colostomy, complications, CRA, depression, diabetes, QLQ-C30 score, exercise, hypercholesterolemia, diet, marital status, education level, and pathological stage were included in the nomogram. The C-index (0.826) and calibration curve showed that the nomogram had good predictive ability and the DCA curves indicated that the model had strong clinical utility. CONCLUSIONS: A prediction model with good predictive ability and practical clinical value can be developed for predicting the risk of cognitive impairment in colorectal cancer after chemotherapy.

Three-dimensional cone beam computed tomography analysis of temporomandibular joint response to the Twin-block functional appliance.

OBJECTIVE: To propose a three-dimensional (3D) method for evaluating temporomandibular joint (TMJ) changes during Twin-block treatment. METHODS: Seventeen patients with Class II division 1 malocclusion treated using Twin-block and nine untreated patients with a similar malocclusion were included in this research. We collected their cone beam computed tomography (CBCT) data from before and 8 months after treatment. Segmentations were constructed using ITK-SNAP. Condylar volume and superficial area were measured using 3D Slicer. The 3D landmarks were identified on CBCT images by using Dolphin software to assess the condylar positional relationship. 3D models of the mandible and glenoid fossa of the patients were constructed and registered via voxel-based superimposition using 3D Slicer. Thereafter, skeletal changes could be visualized using 3DMeshMetric in any direction of the superimposition on a color-coded map. All the superimpositions were measured using the same scale on the distance color-coded map, in which red color represents overgrowth and blue color represents resorption. RESULTS: Significant differences were observed in condylar volume, superficial area, and condylar position in both groups after 8 months. Compared with the control group (CG), the Twin-block group exhibited more obvious condyle-fossa modifications and joint positional changes. Moreover, on the color-coded map, more obvious condyle-fossa modifications could be observed in the posterior and superior directions in the Twin-block group than in the CG. CONCLUSIONS: We successfully established a 3D method for measuring and evaluating TMJ changes caused by Twin-block treatment. The treatment produced a larger condylar size and caused condylar positional changes.

Synthesis of ß-acetoxy alcohols by PhI(OAc)2-mediated metal-free diastereoselective ß-acetoxylation of alcohols.

ß-Acetoxy alcohols can be synthesized in good yields with excellent diastereoselectivity from tertiary alcohols through PhI(OAc)2-mediated metal-free ß-acetoxylation. Mechanistic studies showed that the ß-acetoxylation process might undergo dehydration and sequential highly regioselective and diastereoseletive dioxygenation. Gram scale and diverse useful scaffolds could be prepared via this ß-acetoxylation process.

L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating Heme oxygenase-1 in lipopolysaccharide-treated mice.

Microglia activation-induced neuroinflammation contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglia activation and reduction of major neurotoxic cytokines have been becoming a therapeutic strategy for neurodegenerative diseases. L-3-n-Butylphthalide (L-NBP) has shown the potent neuroprotective effects in stroke and Alzheimer's disease animal models. The present study investigated the immune modulatory effects of L-NBP on pro-inflammatory cytokines and microglia activation in brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Our results showed that systemic LPS treatment induced microglia activation in the brain. L-NBP treatment significantly suppressed the expression of proinflammatory cytokines, such as tumor necrosis factor (TNFα), interlukin-1ß (IL-1ß), interlukin-6 (IL-6), and interlukin-10 (IL-10) in LPS-treated mice. At the meantime, L-NBP treatment decreased the morphological activation of microglia. In addition, the phosphorylation level of JNK MAP kinase-signaling pathway was also inhibited by L-NBP in LPS-treated mice. Furthermore, L-NBP upregulated the expression of heme oxygenase (HO)-1, a key element in the anti-inflammation and anti-oxidative stress. These results suggested that L-NBP might be a promising candidate in delaying and reversing the progress of neurodegenerative diseases by inhibiting microglia activation.

Therapeutic Effect of Chenodeoxycholic Acid in an Experimental Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile. However, the therapeutic effect of CDCA on OA severity was largely unknown. The purpose of this study was to evaluate the therapeutic effect of intra-articular injection of CDCA in a rabbit OA model. OA was induced in experimental rabbits by anterior cruciate ligament transection (ACLT) and then rabbits were intra-articularly injected with CDCA (10 mg/kg or 50 mg/kg) once per week for 5 weeks. The results showed that CDCA significantly decreased cartilage degradation on the surface of femoral condyles, reducing the pathological changes of articular cartilage and synovial membrane by macroscopic and histological analysis. CDCA also significantly decreased bone destruction and erosion of joint evaluated by micro-CT. Furthermore, CDCA could markedly reduce the release of matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3), interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2) in synovial fluid. These observations highlight CDCA might be a potential therapeutic agent for OA.

[Role of Nrf2 in neurodegenerative diseases and recent progress of its activators].

The nuclear factor erythroid 2 related factor 2 (Nrf2) is a key protein of endogenous antioxidant defense systems in the body. In response to oxidative stress, Nrf2 translocates to nucleus and binds to antioxidant response elements (ARE), regulating the expression of a large amounts of antioxidant genes and maintaining a proper redox balance. The pathological processes of neurodegenerative diseases are associated with generation of reactive oxygen species, which cause oxidative stress. Oxidative stress plays a cardinal role in the onset and progression of neurodegenerative diseases. Nrf2-inducer compounds can reduce oxidant stress and have shown therapeutic efficacy in many neurodegenerative disease models. How to activate the Nrf2 signaling pathway effectively has been received much attention. Here we provided an overview of specific mechanism of Nrf2-ARE pathway and the protective effects of Nrf2 in different neurodegenerative diseases, and summarized the Nrf2 activators recently in preclinical study.

[Three-dimensional localization and assessment of maxillary palatal impacted canines with cone-beam computed tomography].

PURPOSE: To evaluate the location of maxillary palatal impacted canines and resorption of neighboring incisors with cone-beam computed tomography (CBCT). METHODS: Twenty-two healthy adolescent patients who had received orthodontic treatments at Stomatological Hospital of Nanjing Medical University were selected and scanned by CBCT. Palatal impacted maxillary canines were reconstructed by Dolphin imaging 11.0 software. The impactions, spatial relationships and classification relative to adjacent structures and incisor resorption were assessed. RESULTS: Most of the maxillary palatal impacted canines inclinated mesially and palatally. Mesial malpositions were more significantly prevalent in Class I and IV, and the prevalence rates were 30.8% and 38.5% respectively. Mesial inclinations of the impacted canines to occlusal plane were mostly between 53.8° and 68.5°, and the distances from the impacted canines to median sagittal plane were between 5.4 and 8.4 mm. Older the patient was, further the impacted canines mesiopalatal displaced and mesial inclined. The roots of 84.6% of lateral incisors and 19.2% of central incisors contacted impacted canines; Root resorption occurred in 50% of lateral incisors and 15.4% of central incisors, which predominantly located in apical third of the lateral incisors and middle third of the central incisors. A inverse correlation was found between the resorption rates of adjacent incisors and minimum distances from impacted canines to adjacent incisors. CONCLUSIONS: CBCT allows three dimensional evaluation of impaction and spatial relationships relative to adjacent structures. In addition, 3 dimensional measurement contributes to more accurate exhibition of the adjacent root resorptions, inclinations and depths of the impacted canines, which leads to more efficient guidance of maxillary palatal impacted canines treatment.

l-3-n-Butylphthalide attenuates ß-amyloid-induced toxicity in neuroblastoma SH-SY5Y cells through regulating mitochondrion-mediated apoptosis and MAPK signaling.

Alzheimer's disease (AD) is a progressive neurodegenerative disease. Amyloid-ß protein (Aß), the hallmark of AD, invokes a cascade of mitochondrial dysfunction and eventually leads to neuronal death. l-3-n-Butylphthalide (l-NBP) has shown the potent neuroprotective effects in stroke and AD animal models. The present study is to evaluate the neuroprotective effect of l-NBP on Aß25-35-induced neuronal injury and the possible mechanism in the human neuroblastoma SH-SY5Y cells. Our results showed that l-NBP significantly attenuated Aß25-35-induced cell death and reduced neuronal apoptosis. l-NBP significantly inhibited Aß25-35-induced mitochondrial dysfunction, including mitochondrial membrane potential reduction, and reactive oxygen species production. Furthermore, l-NBP could partially reverse the elevations of Aß25-35-induced active caspase-3, caspase-9, and cytochrome c expressions, and the downregulation of anti-apoptosis protein Bcl-2. Moreover, l-NBP markedly inhibited the activations of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway. These results demonstrated that l-NBP was capable of protecting neuronal cells from Aß25-35-induced toxicity through a mitochondrial-dependent apoptotic pathway. Thus, l-NBP shows promising candidate of multi-target neuronal protective agent for the treatment of AD.

Glomerxanthones A-C, three xanthonolignoid C-glycosides from Polygala glomerata Lour.

Three novel xanthonolignoid C-glycosides, glomexanthones A-C, with a trans-dihydrobenzofuran on B ring and a 2-hydroxymethyl-5-hydroxyl-2-pentenoic acid moiety in the sugar chain were isolated from an ethanol extract of Polygala glomerata. Their structures and absolute configurations were characterized by extensive NMR, MS, and CD spectroscopic studies. Screening results indicated that compounds 1-3 showed moderate neuroprotective effects on L-Glutamic acid-induced cellular damage in human neuroblastoma SK-N-SH cells.

[Three dimensional measurement and analysis of maxillary protraction treatment in skeletal Class III malocclusion].

PURPOSE: To study the three-dimensional mechanism of maxillary protraction in skeletal Class III malocclusion by cone-beam CT (CBCT). METHODS: Fourteen patients (6 males and 8 females with a mean age of 10.9 years) of early permanent dentition with skeletal Class III malocclusion were treated with maxillary protraction. CBCT was used to obtain the Dicom data both before and after treatment, and then digitized with the software Dolphin 11.0 was used to reconstruct and establish the tridimensional coordinate system. 23 landmarks were chosen for measurement and analysis. The data was analyzed using SPSS 17.0 software package. RESULTS: After maxillary protraction, A- coronal plane distance, SNA and ANB increased significantly (P<0.01); A- horizontal plane distance, ANS-PNS increased significantly (P<0.05), suggest maxillary growth was forward and downward. Po-S-N increased significantly (P<0.01), while SNB decreased significantly (P<0.05), suggesting that the chin was rotated downward and backward, and mandibular growth was inhibited. U1j - the coronal plane distance increased significantly (P<0.01), suggesting that the upper incisor moved forward; U1-SN angle increased significantly (P<0.05), suggesting anterior teeth inclined labially. The distance between U6j- horizontal plane and U6j- the coronal plane increased significantly (P<0.05), suggesting that maxillary molar elongated and moved mesially. Frontomaxillary suture changed on the three-dimensional direction, but without significant difference (P<0.05). CONCLUSIONS: Three-dimensional measurements confirm that growth and remodeling of bone suture (such as pterygopalatine suture) play an important role in maxilla development. The maxilla and maxillary teeth move forward and downward, while the mandibular growth is inhibited after maxillary protraction.

[Role of DNA-associated autoantibodies to cell membrane in the diagnosis of juvenile systemic lupus erythematosus].

OBJECTIVE: To establish a method of indirect immunofluorescence (IIF) to measure DNA (mDNA)-associated autoantibodies to cell membrane, and to evaluate diagnostic value of the anti-mDNA antibodies in patients with juvenile systemic lupus erythematosus (SLE) in comparison with anti-dsDNA antibody. METHODS: Forty-four children with SLE were enrolled in this study. As a control group, 30 children with other rheumatic diseases were also enrolled. Anti-mDNA and anti-dsDNA antibodies were measured by IIF. Anti-smooth muscle (Sm) antibodies were measured by immuno-double diffusion (ID) and IIF. RESULTS: Out of 44 juvenile SLE patients, 34 (77.27%) were seropositive for anti-mDNA, which was significantly higher than that of patients with other rheumatic diseases (20.00%, P<0.05). The sensitivity and specificity of anti-mDNA for juvenile SLE diagnosis were 77.27% and 80.00%, respectively. The positive predictive value and negative predictive value were 85.00% and 70.59%, respectively. The positive rate of anti-mDNA in SLE lacking of anti-dsDNA and anti-Sm antibodies were 68.00% (17/25) and 79.49% (31/39), respectively. CONCLUSION: The detection of anti-mDNA antibodies is useful for diagnosis of juvenile SLE, especially in patients who are negative for anti-dsDNA antibodies and anti-Sm antibodies.

The novel inhibitory effect of Pangdahai on fatty acid synthase.

Recently, animal fatty acid synthase (FASN) is reported as a potential therapeutic target for obesity and cancer. Considerable interest has been developed in searching for novel inhibitors of this enzyme. An extract from Pangdahai has been found to inhibit FASN in both reversible and irreversible manners, with an IC(50) of 3.5 microg/ml and an apparent inactivation rate constant of k(obs) of 2.2 x 10(-3)/min. The kinetic study showed that the Pangdahai extract inhibited the overall FASN reaction uncompetitively with acetyl-CoA, but it presented in a mixed manner both with NADPH and with malonyl-CoA. Its major reacting site on this enzyme, as compared between two IC(50) values, is not in the beta-ketoacyl reduction domain. A weight reducing experiment in rats showed that the extract significantly reduced the adipose and food intake, but in view of statistics (P < 0.05), a correlation between the reductions in the adipose and in the food consumption and the inhibition of hepatic FASN could not be established. Three known flavonoid compounds were isolated from the extract and the structure-activity relationship was discussed.

[Studies on chemical constituents from leaves of Sapium sebiferum].

OBJECTIVE: To study the chemical constituents from leaves of Sapium sebiferum. METHOD: The compounds were isolated and purified by silic gel column chromatography and preparative HPLC. The structures were identified by various spectral evidence. RESULT: Nine compounds were obtained and they were shikimic acid (1), kaempferol (2), quercetin (3), isoquercein (4), hyperin (5), kaempferol-3-O-beta-D-glucopyranoside (6), kaempferol-3-O-beta-D-glueopyranoside (7), gallic acid (8), rutin (9). CONCLUSION: Compounds 1, 5, 6 and 7 are isolated from this genus for the first time and compound 9 is isolated from this plant for the first time.