Proteomic study on CUMS-induced senile depression mice's frontal lobe cortex and the regulating effect of KTLD formula.

OBJECTIVE: The aim of this study was to investigate the protein expression of chronic unpredictable mild stress (CUMS)-induced senile depression in SAMP-8 mice's frontal lobe cortex and the regulating effect of the kidney tonifying and liver dispersing (KTLD) formula. MATERIALS AND METHODS: A total of 15 male SAMP-8 mice were randomly divided into control, CUMS, and KTLD groups. CUMS and KTLD mice were subjected to CUMS for 21 days. Control group mice were kept to normal feeding. At the same time as molding, the herbal gavage (KTLD formula, 19.5 g/kg/d) was given from the beginning of the stress stimulation, while the control group and the CUMS group mice were given the same volume of saline for 21 days. Open-field testing (OFT) was used to assess the mice's depression levels. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify differentially expressed proteins (DEPs) in mice's frontal lobe cortex. Bioinformatics analysis including Gene Ontology (GO); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) networks were utilized to study the DEPs connections. RESULTS: Results revealed that mice with senile depression experienced more anxiety and depression than control mice, whereas KTLD mice had the opposite experience. Biological processes including transport, regulation of transcription, and DNA-templated were identified in both KTLD and CUMS. The KEGG enrichment study of the DEPs in KTLD revealed their involvement in the MAPK signaling pathway, glutamatergic synapse, dopaminergic synapse, axon guidance, and ribosome. KEGG pathway enrichment showed that the mechanism of senile depression and the pathway of KTLD are closely related to axonal conductance and ribosomes. According to the PPI analysis, disease-related proteins regulated by KTLD revealed that some proteins, such as GLOI1 and TRRAP, have potential interactions. This provides fresh insight into how KTLD works to cue senile depression. CONCLUSIONS: KTLD treats senile depression via multiple targets and pathways, which may include regulations of 467 DEPs. Proteomics showed significant changes in protein levels in geriatric depression and after KTLD intervention. Senile depression involves the cross-linking and modulation of signal pathways, presenting a pattern of multiple pathways and multiple targets. According to a protein pathway enrichment and protein interaction model of KTLD in senile depression, KTLD is capable of treating senile depression via multiple pathways and targets.

Photosynthesis in response to salinity and submergence in two Rhizophoraceae mangroves adapted to different tidal elevations.

Mangrove ecosystems are vulnerable to rising sea levels. When the sea level rises, the plants are exposed to increased salinity and tidal submergence. In Taiwan, the mangrove species Kandelia obovata and Rhizophora stylosa grow in different habitats and at different elevations. To understand the response of photosynthesis to salinity and submergence in mangroves adapted to different tidal elevations, gas exchange and chlorophyll fluorescence parameters were measured in K. obovata and R. stylosa under different salinity (20 and 40‰) and submergence treatments. The period of light induction of photosynthesis for the two mangrove species was >60 min. In the induction process, the increase in photosystem efficiency was faster than the increase in stomatal opening, but CO2 fixation efficiency was restricted by stomatal conductance. The constraint of stomatal opening speed is related to the conservative water-use strategy developed in response to mangrove environments. Submergence increased the photosynthetic rate of K. obovata, but not that of R. stylosa. Although R. stylosa was more salt tolerant than K. obovata, R. stylosa was not submergence tolerant in a high-salinity environment, which may be the reason for the higher intertidal elevations observed for R. stylosa in comparison with K. obovata. The photosynthetic rate and energy-dependent quenching (qE) of the two mangroves presented a negative relationship with photoinhibition, and high-salt treatment simultaneously reduced photosynthetic rate and qE. A decrease in the photosynthetic rate increased excess energy, whereas a decrease in qE decreased photoprotection; both increased photoinhibition. As the degree of photoinhibition can be easily measured in the field, it is a useful ecological monitoring index that provides a suitable reference for mangrove restoration, habitat construction and ecological monitoring.

Physicochemical and functional properties of goat milk whey protein and casein obtained during different lactation stages.

During lactation, goat milk contains colostrum, transitional milk, mature milk, and end milk. The protein present in goat milk during different lactation periods has different characteristics. This study aimed to characterize the protein profile of goat milk samples obtained at different lactation stages and to identify changes in the physicochemical and functional properties of whey protein and casein from goat milk collected at 1, 3, 15, 100, and 200 d after calving. The results demonstrated that the lactation period had a great influence on the physicochemical and functional properties of goat milk whey protein and casein, especially the protein properties of colostrum on the first day after delivery. The denaturation temperature, hydrophobicity, and turbidity of whey protein were significantly higher on the first day postpartum than at other lactation periods. Correspondingly, the colostrum whey protein also had better functional properties, such as emulsification, oil holding capacity, and foaming properties on the first day postpartum than at other lactation periods. For casein, the turbidity, particle size, water holding capacity, and foaming properties on the first day after delivery were significantly higher than those at other lactation periods, whereas the denaturation temperature, oil holding capacity, and emulsification followed the opposite trend. For both whey protein and casein, the 2 indicators of emulsifying properties, namely, emulsifying activity index and the emulsion stability, also followed an opposite trend relative to lactation stage, whereas the changes in foaming capacity with the lactation period were completely consistent with the change of foaming stability. These findings could provide useful information for the use of goat milk whey protein and casein obtained during different lactation stages in the dairy industry.

Down-regulation of LINC00667 hinders renal tubular epithelial cell apoptosis and fibrosis through miR-34c.

PURPOSE: This study aimed to down-regulate LINC00667 and inhibit apoptosis and fibrosis of renal tubular epithelial cells through miR-34c. METHODS: Altogether, 98 patients with chronic kidney disease treated in our hospital were selected as the study group, and 67 normal people were selected as the control group. Epithelial cells of proximal convoluted tubules in human renal cortex were purchased. TGF-ß1 was used to induce fibrosis of HK-2 renal tubular epithelial cells. The expression of LINC00667, miR-34c, type I collagen (Col 1) and type III collagen (Col 3) were detected by qRT-PCR and WB. RESULTS: LINC00667 was highly expressed in cancer tissues and HK-2, while miR-34c was poorly expressed. Inhibition of LINC00667 and over-expression of miR-34c could inhibit the proliferation and invasion of chronic kidney disease cells, but increase the apoptosis rate. Down-regulation of LINC00667 could significantly reduce of Col 1 and Col 3 in renal interstitial fibroblasts induced by TGF-ß1, while up-regulation of miR-34c could also achieve this effect. Double luciferase report confirmed that there was a targeted regulatory relationship between LINC00667 and miR-34c. CONCLUSION: LINC00667 could reduce the proliferation and invasion of chronic kidney disease cells, increase the apoptosis rate by regulating miR-34c, and improve renal fibrosis.

[Evaluation of computer-aided diagnosis system for detecting dental approximal caries lesions on periapical radiographs].

Objective: To establish and to evaluate a computer-aided system based on deep-learning for detection and diagnosis of dental approximal caries on periapical radiographs. Methods: One hundred and sixty human premolars and molars extracted for orthodontic or periodontal reasons were obtained from Department of Oral and Maxillofacial Surgery, Affiliated Stomatological Hospital, Fujian Medical University. A total of 160 periapical radiographic images were divided into a training dataset (n=80) and a test dataset (n=80). A deep-learning based computer-aided caries diagnosis system was established and trained. The performances of computer-aided diagnosis system and human observer were compared using receiver operating characteristic (ROC) curves, precision-recall (P-R) curves, the area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The AUC values of human observers and caries diagnosis system was compared by using an online statistical tool (SPSSAU 20.0). Chi-square test was used to analyze the differences between human observers and caries diagnosis system (ɑ=0.05). Results: The AUC values of human observers and caries diagnosis system were 0.729 (95%CI: 0.650-0.808) and 0.762 (95%CI: 0.685-0.839), respectively (P>0.05). No significant differences were found for the specificity, PPV and NPV between the caries diagnosis system and human observers (P all>0.05). The caries diagnosis system was significantly more sensitive in detecting dental proximal caries than human observers (P<0.05). For the diagnosis of level-1 caries (caries limited to outer 1/2 of enamel), the sensitivity of human observers and computer-aided detection system were 27% and 77%, respectively (P<0.05). Conclusions: The computer-aided diagnosis system provided similar accuracy as human observers and significantly better sensitivity than human observers, especially for shallow caries in enamel.

Association of three beta-defensin gene (AvBD4, AvBD5, AvBD14) polymorphisms with carrier-state susceptibility to salmonella in chickens.

1. Chicken salmonellosis is a common zoonotic infectious disease transmitted both vertically and horizontally. Avian beta-defensins (gallinacins) play an important role in the innate defence of the host and provide broad-spectrum immunity against multiple pathogens. 2. To detect the relationship between immune genes and salmonella carrier status and susceptibility to salmonellosis in chickens, polymorphisms with carrier-state susceptibility to salmonella and, hence, developing salmonellosis, were investigated in three avian beta-defensin genes (AvBD4, AvBD5, and AvBD14) in a Chinese local chicken breed, based on a case-control study. 3. Fifteen, twenty and nineteen SNPs were found in AvBD4, AvBD5 and AvBD14, respectively. Among the 54 total SNPs, four resulted in non-synonymous substitution of amino acid changes. Five SNPs in AvBD5 and four SNPs in AvBD14 were significantly associated with salmonellosis susceptibility (P < 0.05). Using the PHASE program, thirteen, ten and twelve major haplotypes were constructed in AvBD4, AvBD5 and AvBD14. Logistic regression analysis revealed that five haplotypes in AvBD5 and six haplotypes in AvBD14 were significantly associated with salmonellosis susceptibility, but no significant haplotype in AvBD4 was detected. A total of six strongly susceptible haplotypes with odds ratio (OR) values greater than 2.0 and four strongly resistant haplotypes with OR value less than 0.5 were revealed in the three genes examined. 4. These results suggested that the AvBD5 and AvBD14 genes may play an important role in the susceptibility to salmonellosis in chickens.

Molecular characteristics of MC1R gene in tile-grey plumage of domestic chicken.

1. Tile-grey plumage is a unique and rare feather type of local chicken breeds in China, but its genetic mechanism and corresponding genes remain unknown. 2. In order to identify the genetic basis and molecular characteristics of tile-grey plumage, this experiment investigated variations of melanocortin 1 receptor (MC1R) gene in Yunnan Piao chickens with typical tile-grey plumage characteristics in contrast with three Yunnan local breeds as well as two standard breeds with different plumage colour, and analysed the association between genic variation and tile-grey plumage. 3. Through sequencing and comparison of the entire coding region of the MC1R gene, a total of 10 SNP loci were detected, of which eight were non-synonymous mutations that cause amino acid changes. The gene frequency and genotype frequency of the MC1R mutation sites in different breeds and different plumage colour groups revealed that C69T, T212C and A274G were significantly associated with tile-grey plumage. Eighteen haplotypes of the MC1R gene were constructed based on 10 nucleotide variations and eight amino acid variations. Haplotype distribution and the median joining network in breeds and plumage colour groups revealed a main haplotype (hap2) for tile-grey plumage. Hap2 is unique to the tile-grey feather of Piao chicken, and the individuals carrying this haplotype account for 62.96% of the whole tile-grey chicken. 4. The results of this study are of significance for further analysis of the molecular basis of tile-grey plumage and the selective breeding of tile-grey plumage.

[Visual-spatial and temporal characteristics related to infectious Tuberculosis epidemics in Guangxi Zhuang Autonomous Region, 2012-2015].

Objective: To study the spatial and temporal mode of infectious TB transmission in Guangxi Zhuang Autonomous Region (Guangxi). Methods: Data related to infectious TB case (Include smear and/or culture positive patients) in Guangxi were collected from the National Notifiable Disease Reported System (NNDRS) from 2010 to 2015. Spatial-temporal analysis and prediction were performed by SaTScan 7.0.2, GeoDa 1.8.12, R program v 3.3.1 and SPSS 19.0 software, using the time series model, Moran's I global and local spatial autocorrelation (Empirical Bayes adjustment). Kulldorff 's space-time scan statistics displayed by R software was used to identify the temporal and spatial trend of TB. Results: The total number of infectious TB cases, collected from NNDRS was 76 151, and showing a decreasing trend on annual incidence (value of Chi-square for Linear trend=3 464.53, P-value=0.000). The forecast value of TB cases in 2016 was 7 764 (4 971-10 557), with peak in March, analyzed through the Winters'multiplicative model. The Moran's I global Statistics was greater than 0 (0.257-0.390). TB cluster seemed to have been existed for several years. The most significant hot spots seemed to be mainly located in the central and western parts of Guangxi, shown by local spatial autocorrelation statistics and the result from space-time scanning.Counties or districts that located in the east parts of Guangxi presented the low-low relation (significant cold spots). The situation of infectious TB seemed migratory. Conclusions: Our data showed an annual decreasing trend of incidence on infectious TB with temporal concentration in spring and summer. Main clusters (hot spots) were found to be located in the central and western parts of Guangxi. Hopefully, our findings can provide clues to uncover the real mode of TB transmission at the molecular-biological level.

MINA controls proliferation and tumorigenesis of glioblastoma by epigenetically regulating cyclins and CDKs via H3K9me3 demethylation.

It is generally known that histone demethylases regulate gene transcription by altering the methylate status on histones, but their roles in cancers and the underlying molecular mechanisms still remain unclear. MYC-induced nuclear antigen (MINA) is reported to be a histone demethylase and highly expressed in many cancers. Here, for the first time, we show that MINA is involved in glioblastoma carcinogenesis and reveal the probable mechanisms of it in cell-cycle control. Kaplan-Meier analysis of progression-free survival showed that high MINA expression was strongly correlated with poor outcome and advancing tumor stage. MINA knockdown significantly repressed the cell proliferation and tumorigenesis abilities of glioblastoma cells in vitro and in vivo that were rescued by overexpressing the full-length MINA afterwards. Microarray analysis after knockdown of MINA revealed that MINA probably regulated glioblastoma carcinogenesis through the predominant cell-cycle pathways. Further investigation showed that MINA deficiency led to a cell-cycle arrest in G1 and G2 phases. And among the downstream genes, we found that cyclins and cyclin-dependent kinases were directly activated by MINA via the demethylation of H3K9me3.

Risks of venous thromboembolism in patients with liver cirrhosis: a nationwide cohort study in Taiwan.

BACKGROUND: The results of various studies attempting to assess the risks of venous thromboembolism in liver cirrhosis have been conflicting. Furthermore, although the incidence of venous thromboembolism is thought to be low in Asians, the relationship between venous thromboembolism and liver cirrhosis has not been investigated in Asian countries. OBJECTIVE: We investigated the risks of venous thromboembolism in cirrhotic patients in Taiwan to evaluate whether the risk is higher than in the general population. METHODS: The data from 1,000,000 National Health Insurance beneficiaries were utilized. All adult beneficiaries were followed from 1 January 2007 to 31 December 2010 to identify those who developed venous thromboembolism. Each identified patient with liver cirrhosis was matched with 10 non-cirrhotic patients on the basis of high-dimensional propensity score. Cox regression models were applied to compare the hazards of venous thromboembolism in the matched cohorts. RESULTS: A total of 757,940 patients were enrolled. After matching, 2223 cirrhotic patients and 22,230 non-cirrhotic patients were selected. The adjusted hazard ratio of venous thromboembolism was significantly increased by having cirrhosis (1.71; 95% confidence interval [CI] 1.05-2.78). A subgroup analysis revealed a much higher hazard ratio of venous thromboembolism in an advanced cirrhosis subgroup (n = 293) than in a matched non-cirrhosis subgroup (n = 2930) (4.36; 95% CI 1.36-14.01). CONCLUSION: The risk of venous thromboembolism may be higher in Asian patients with cirrhosis than in the general Asian population, especially in those with advanced cirrhosis.

STIM1 overexpression promotes colorectal cancer progression, cell motility and COX-2 expression.

Tumor metastasis is the major cause of death among cancer patients, with >90% of cancer-related death attributable to the spreading of metastatic cells to secondary organs. Store-operated Ca(2+) entry (SOCE) is the predominant Ca(2+) entry mechanism in most cancer cells, and stromal interaction molecule 1 (STIM1) is the endoplasmic reticulum (ER) Ca(2+) sensor for store-operated channels. Here we reported that the STIM1 was overexpressed in colorectal cancer (CRC) patients. STIM1 overexpression in CRC was significantly associated with tumor size, depth of invasion, lymph node metastasis status and serum levels of carcinoembryonic antigen. Furthermore, ectopic expression of STIM1 promoted CRC cell motility, while depletion of STIM1 with short hairpin RNA inhibited CRC cell migration. Our data further suggested that STIM1 promoted CRC cell migration through increasing the expression of cyclooxygenase-2 (COX-2) and production of prostaglandin E2 (PGE2). Importantly, ectopically expressed COX-2 or exogenous PGE2 were able to rescue migration defect in STIM1 knockdown CRC cells, and inhibition of COX-2 with ibuprofen and indomethacin abrogated STIM1-mediated CRC cell motility. In short, our data provided clinicopathological significance for STIM1 and SOCE in CRC progression, and implicated a role for COX-2 in STIM1-mediated CRC metastasis. Our studies also suggested a new approach to inhibit STIM1-mediated metastasis with COX-2 inhibitors.

Systematic literature review of the risk factors, comorbidities, and consequences of hypogonadism in men.

The objective of this review was to summarize the literature on the risk factors, comorbidities, and consequences of male hypogonadism, which is defined as a syndrome complex that includes biochemical confirmation of low testosterone (T) and the consistent symptoms and signs associated with low T. A systematic literature search was performed in PubMed/MEDLINE, EMBASE, Cochrane Library for articles published in the last 10 years on risk factors, comorbidities, and consequences of male hypogonadism. Of the 53 relevant studies identified, nine examined potential risk factors, 14 examined potential comorbidities, and 30 examined potential consequences of male hypogonadism. Based on studies conducted in Asia, Australia, Europe, and North & South America, the important factors that predicted and correlated with hypogonadism were advanced age, obesity, a diagnosis of metabolic syndrome (MetS), and a poor general health status. Diabetes mellitus was correlated with hypogonadism in most studies, but was not established as a risk factor. Although diseases, such as coronary heart disease, hypertension, stroke, and peripheral arterial disease did not predict hypogonadism, they did correlate with incident low T. The data reviewed on potential consequences suggest that low T levels may be linked to earlier all-cause and cardiovascular related mortality among men. This literature review suggests that men with certain factors, such as advanced age, obesity, MetS, and poor general health, are more likely to have and develop hypogonadism. Low levels of T may have important long-term negative health consequences.

Inhibitive effects of mulberry leaf-related extracts on cell adhesion and inflammatory response in human aortic endothelial cells.

Effects of mulberry leaf-related extracts (MLREs) on hydrogen peroxide-induced DNA damage in human lymphocytes and on inflammatory signaling pathways in human aortic endothelial cells (HAECs) were studied. The tested MLREs were rich in flavonols, especially bombyx faces tea (BT) in quercetin and kaempferol. Polyphenols, flavonoids, and anthocyanidin also abounded in BT. The best trolox equivalent antioxidant capacity (TEAC) was generated from the acidic methanolic extracts of BT. Acidic methanolic and water extracts of mulberry leaf tea (MT), mulberry leaf (M), and BT significantly inhibited DNA oxidative damage to lymphocytes based on the comet assay as compared to the H2O2-treated group. TNF- α -induced monocyte-endothelial cell adhesion was significantly suppressed by MLREs. Additionally, nuclear factor kappa B (NF- κ B) expression was significantly reduced by BT and MT. Significant reductions were also observed in both NF- κ B and activator protein (AP)-1 DNA binding by MLREs. Significant increases in peroxisome proliferator-activated receptor (PPAR) α and γ DNA binding by MLREs were also detected in M and MT extracts, but no evidence for PPAR α DNA binding in 50 µ g/mL MT extract was found. Apparently, MLREs can provide distinct cytoprotective mechanisms that may contribute to its putative beneficial effects on suppressing endothelial responses to cytokines during inflammation.

Phthalates suppress type I interferon in human plasmacytoid dendritic cells via epigenetic regulation.

BACKGROUND: Exposure to environmental endocrine-disrupting chemicals (EDCs) is associated with allergy, chronic inflammation, and immunodeficiency. Phthalates, the common EDCs used in plastic industry, may act as adjuvants to disrupt immune system and enhance allergy. Plasmacytoid DCs (pDCs) are predominant cells secreting type I interferon (IFN) against infection and are professional antigen-presenting cells in regulating adaptive immunity. However, the effects of phthalates on the function of pDCs are unknown. METHODS: Circulating pDCs were isolated from healthy subjects, were pretreated with diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP), and were stimulated with Toll-like receptor (TLR)-9 agonist CpG. IFN-α/IFN-ß levels, surface markers, and T-cell stimulatory function were investigated using ELISA, flow cytometry, and pDC/T-cell coculture assay. Mechanisms were investigated using receptor antagonists, pathway inhibitors, Western blotting, and chromatin immunoprecipitation. RESULTS: Diethylhexyl phthalate and butyl benzyl phthalate suppressed CpG-induced IFN-α/IFN-ß expression in pDCs, and the effect was reversed by aryl hydrocarbon receptor (AHR) antagonist. Diethylhexyl phthalate suppressed CpG-activated mitogen-activated protein kinase (MAPK)-MEK1/2-ERK-ELK1 and NFκB signaling pathways. Diethylhexyl phthalate suppressed CpG-induced interferon regulatory factor (IRF)-7 expression by suppressing histone H3K4 trimethylation at IRF7 gene promoter region through inhibiting translocation of H3K4-specific trimethyltransferase WDR5 from cytoplasm into nucleus. Butyl benzyl phthalate or diethylhexyl phthalate-treated pDCs suppressed IFN-γ but enhanced IL-13 production by CD4+ T cells. CONCLUSION: Phthalates may interfere with immunity against infection and promote the deviation of Th2 response to increase allergy by acting on human pDCs via suppressing IFN-α/IFN-ß expression and modulating the ability to stimulate T-cell responses.

Differential regulation of collagen, lysyl oxidase and MMP-2 in human periodontal ligament cells by low- and high-level mechanical stretching.

BACKGROUND AND OBJECTIVE: Mechanical stretching modulates extracellular matrix (ECM) protein synthesis by periodontal ligament (PDL) cells. However, the mechanoregulation of lysyl oxidase (LOX), a key enzyme for collagen cross-linking, is not fully understood. In the present study, we hypothesized that low-level and high-level mechanical stretching differentially regulates collagen deposition and the expression of LOX and the enzymes responsible for ECM degradation, such as MMP-2 in PDL cells. MATERIAL AND METHODS: Human PDL cells were cultured on flexible-bottom culture plates and subjected to cyclic mechanical stretching (3% and 10% elongation at 0.1 Hz) for 24 and 48 h in a Flexercell FX-4000 strain unit. The levels of expression of type I collagen alpha 1 (COL1A1), type III collagen alpha 1 (COL3A1), lysyl oxidase (LOX), MMP2 and TIMP2 mRNAs were analyzed using an RT-PCR technique. The cell layer and the culture medium were separately collected and processed for detection of the following ECM-related molecules: (i) total collagen content using a Sircol dye-binding method; (ii) LOX protein expression by western blotting; (iii) LOX activity using a fluorometric assay; and (iv) MMP-2 enzyme activity by gelatin zymography. RESULTS: Low-level (3%) mechanical stretching of PDL cells upregulated the expression of COL1A1, COL3A1 and LOX mRNAs, enhanced the production of collagen and increased the LOX activity but did not change the level of expression of MMP2 or TIMP2 mRNA. The collagen content and LOX activity showed obvious elevation in the medium, but not in the cell layer. High-level (10%) mechanical stretching downregulated COL1A1 mRNA but upregulated COL3A1 mRNA; however, the effect on COL3A1 was smaller, and occurred earlier, compared with the effect on the COL1A1 gene. High-level mechanical stretching upregulated the expression of MMP2 and TIMP2 mRNAs but did not change collagen production or LOX activity. Moreover, high-level mechanical stretching increased the level of pro-MMP-2, especially in the cell layer. CONCLUSIONS: This study substantiates the mechanoregulation of the expression of ECM-related molecules in PDL cells. High-level mechanical stretching upregulated the expression of MMP2 and TIMP2 mRNAs, but did not affect collagen production or LOX activity. In addition to increasing the transcription of COL1A1, COL3A1 and LOX genes, low-level mechanical stretching enhanced total collagen production and LOX activity, which should favor ECM stabilization. As an effective regulator of ECM remodeling, mechanical stretching can be exploited in periodontal regeneration and ligament tissue engineering via application of appropriate mechanical stimulation.

Prospective analysis of KRAS wild-type patients with metastatic colorectal cancer using cetuximab plus FOLFIRI or FOLFOX4 treatment regimens.

Cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, has proven to be efficient in the treatment of metastatic colorectal cancer. We made a prospective study of the efficacy and toxicities of cetuximab-combination first-line (FOLFOX4) versus second/third-line (FOLFIRI) chemotherapy in 98 KRAS wild-type patients who had metastatic colorectal cancer. Wild-type KRAS had been identified by direct sequencing. Associations between clinical response/progression-free survival/overall survival/toxicities and cetuximab-combination chemotherapy timing were evaluated. The overall response rate was significantly higher for first-line treatment than for second/third-line treatment (relative risk = 1.707, 95% confidence interval = 1.121-2.598). Both progression-free survival and overall survival indicated significantly longer survival of first-line treatment than second/third-line treatment patients. This study is a validation of a molecular analysis of KRAS wild-type status for the prediction of response to cetuximab-combination chemotherapy for metastatic colorectal cancer patients; its predictive role was less prominent in the second/third-line than in the first-line treatment patients.

Tomotherapy for neurofibromatosis Type 2: case report and review of the literature.

Neurofibromatosis 2 (NF2) results in multiple central nervous system tumours. In this case report, the patient has one vestibular schwannoma, one trigeminal schwannoma and two meningiomas developed before the age of 30. Aiming to treat three targets at one fraction with minimal interaction and overlapping doses to normal tissue, the sophisticated equipment of tomotherapy was utilised for frameless stereotaxy; tomotherapy delivered intensity-modulated, rotational radiation therapy using a fan-beam delivery. Daily CT scans with the inbuilt CT scanner were also performed as part of the image-guided radiotherapy. The course of fractionated stereotactic radiotherapy consisted of eight fractions given three times per week with an overall treatment time of 17 days. For the meningioma over left parietal vertex, 4.5 Gy per fraction was given at 36 Gy/8 Fr/17 days. For the meningioma over anterior cerebral falx, 4 Gy per fraction was given at 32 Gy/8 Fr/17 days. For the two schwannomas as one target, 5 Gy per fraction was given at 40 Gy/8 Fr/17 days. The acute effect of the treatment was alopecia and mild headache. Subsequent follow-up confirmed clinical improvement. This is the first reported case of clinical experience with tomotherapy in the management of NF2.