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Introduction: Pharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort. Methods: Buffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models' performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites. Results: Overall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model. Discussion: The development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.

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Oxaliplatin, a third-generation platinum derivative, has become one of the main chemotherapeutic treatments for esophagus, gastric and colorectal cancer; however, it is still unclear the potential effectiveness for pancreatic ductal adenocarcinoma (PDAC) with gemcitabine resistance. Here, we observed that PDAC tumors have low level of organic cation transporter 2 (OCT2, also known as SLC22A2) compared with non-tumor tissues and identified that OCT2 expression is positively correlated with oxaliplatin sensitivity in PDAC cells. Treatment of OCT2 inhibitors or knockdown of OCT2 expression significantly decreased the sensitivity to oxaliplatin in PANC-1 cells. In addition, bisulfite sequencing polymerase chain reaction analysis revealed that higher methylation frequency represses OCT2 expression in gemcitabine-resistant PANC-1 (PANC-1/GR) cells. Moreover, we found that treatment of DNA methyltransferase (DNMT) inhibitors, decitabine or 5-azacytidine recover OCT2 expression and oxaliplatin sensitivity in PANC-1/GR cells, and DNMT1 level has inverse correlation with OCT2 expression in PDAC cells and tumors. Our findings jointly suggest that OCT2 expression is a potential and predictive marker for evaluating oxaliplatin sensitivity and developing alternative treatments for PDAC patients with gemcitabine resistance.

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OBJECTIVE@#To investigate the clinical characteristics of lower extremity arterial disease (LEAD) and its risk factors in patients with diabetic foot ulcer (DFU).@*METHODS@#We retrospectively collected the clinical and follow-up data of 650 patients with DFU treated in the Department of Endocrinology and Metabolism of Nanfang Hospital between January, 2017 and December, 2019. We compared the data between patients who had LEAD and those without LEAD and used a multivariate logistic regression model to analyze the risk factors of LEAD in DFU patients.@*RESULTS@#Among the 650 DFU patients, 470 (72.4%) had LEAD. The patients were followed up for a mean of 3.5 months, and the mean healing time of DFU was 2.55 months; healing of DFU occurred in 453 patients and 183 patients received amputation. The patients with LEAD and those without LEAD differed significantly in age, hospitalization costs, diastolic blood pressure (DBP), glycated hemoglobin, blood lipid levels, disease course, ankle brachial index, healing time, smoking history, clinical outcomes, Wagner grade and imaging results (P < 0.05). Multivariate logistic regression analysis identified age (OR=1.070, 95% CI: 1.049-1.091), smoking history (OR= 2.013, 95% CI: 1.268-3.195), and a decreased DBP (OR=0.980, 95% CI: 0.963-0.997) as independent risk factors for LEAD in DFU patients. A prolonged healing time was a prominent clinical feature of DFU complicated by LEAD.@*CONCLUSION@#DFU patients have a high incidence of LEAD, which leads to high rates of disability and mortality and is associated with an advanced age, high smoking rate and longer healing time. A decreased DBP is also a risk factor for LEAD in DFU patients.

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Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a 5-year survival rate of <8%. Therefore, finding new treatment strategies against PDAC cells is an imperative issue. Betulinic acid (BA), a plant-derived natural compound, has shown great potential to combat cancer owing to its versatile physiological functions. In this study, we observed the impacts of BA on the cell viability and migratory ability of PDAC cell lines, and screened differentially expressed proteins (DEPs) by an LC-MS/MS-based proteomics analysis. Our results showed that BA significantly inhibited the viability and migratory ability of PDAC cells under a relatively low dosage without affecting normal pancreatic cells. Moreover, a functional analysis revealed that BA-induced downregulation of protein clusters that participate in mitochondrial complex 1 activity and oxidative phosphorylation, which was related to decreased expressions of RNA polymerase mitochondrial (POLRMT) and translational activator of cytochrome c oxidase (TACO1), suggesting that the influence on mitochondrial function explains the effect of BA on PDAC cell growth and migration. In addition, BA also dramatically increased Apolipoprotein A1 (APOA1) expression and decreased NLR family CARD domain-containing protein 4 (NLRC4) expression, which may be involved in the dampening of PDAC migration. Notably, altered expression patterns of APOA1 and NLRC4 indicated a favorable clinical prognosis of PDAC. Based on these findings, we identified potential proteins and pathways regulated by BA from a proteomics perspective, which provides a therapeutic window for PDAC.

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BACKGROUND: Chloroplasts are important semi-autonomous organelles in plants and algae. Unlike higher plants, the chloroplast genomes of green algal linage have distinct features both in organization and expression. Despite the architecture of chloroplast genome having been extensively studied in higher plants and several model species of algae, little is known about the transcriptional features of green algal chloroplast-encoded genes. RESULTS: Based on full-length cDNA (Iso-Seq) sequencing, we identified widely co-transcribed polycistronic transcriptional units (PTUs) in the green alga Caulerpa lentillifera. In addition to clusters of genes from the same pathway, we identified a series of PTUs of up to nine genes whose function in the plastid is not understood. The RNA data further allowed us to confirm widespread expression of fragmented genes and conserved open reading frames, which are both important features in green algal chloroplast genomes. In addition, a newly fragmented gene specific to C. lentillifera was discovered, which may represent a recent gene fragmentation event in the chloroplast genome. With the newly annotated exon-intron boundary information, gene structural annotation was greatly improved across the siphonous green algae lineages. Our data also revealed a type of non-canonical Group II introns, with a deviant secondary structure and intronic ORFs lacking known splicing or mobility domains. These widespread introns have conserved positions in their genes and are excised precisely despite lacking clear consensus intron boundaries. CONCLUSION: Our study fills important knowledge gaps in chloroplast genome organization and transcription in green algae, and provides new insights into expression of polycistronic transcripts, freestanding ORFs and fragmented genes in algal chloroplast genomes. Moreover, we revealed an unusual type of Group II intron with distinct features and conserved positions in Bryopsidales. Our data represents interesting additions to knowledge of chloroplast intron structure and highlights clusters of uncharacterized genes that probably play important roles in plastids.

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Abstract@#The outbreak of tuberculosis in campus shows a profound impact on academic learning and mental health of students, which might result in more serious social problems. The present editorial addresses weak links in the school tuberculosis prevention and control. Disease prevention and control institutions, medical institutions, education administrative departments and schools need to clarify work responsibilities, strictly implement the school tuberculosis prevention and control laws, regulations and management guidelines, and coordinate with multiple departments, with the aim to strengthen early warning capacity for campus tuberculosis, improve tuberculosis screening and risk assessment of relevant personnel, and implement the health checkup of schools and faculty, as well as the screening, diagnosis, registration, treatment and follow up of students cases. To further improve tuberculosis control across China, strengthening the awareness of tuberculosis prevention and control among institutions and the public, and improving adherence to tuberculosis treatment, as well as moving forward from passive to active tuberculosis monitoring and early prevention, reducing the occurrence of tuberculosis outbreak in school should be prioritized, so as to promote the smooth development of tuberculosis prevention and control work in China.

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Osteoporosis is common in postmenopausal women and elderly people. In this study, the ovariectomized mice were used as an in vivo test to evaluate the effects of 70% ethanolic extracts of Taiwanofungus camphoratus and T. salmoneus (Polyporales, Agaricomycetes) on postmenopausal osteoporosis. Ovariectomized mice had significantly higher body weight and histopathological alterations of the liver were found to have diffused fatty infiltrated vesicles. The bone parameters of the femur were determined by microcomputed tomography. In addition, the relative weight of the uterus is significantly lower and atrophy of the uterine glands was found in histopathological alterations. The results of trabecular bone parameters showed that feeding high doses of T. camphoratus mycelia ethanolic extract to ovariectomized mice had the ability to delay bone loss. The bone density of trabecular bone and cortical bone were also significantly higher than those of ovariectomized mice, indicating that the ethanolic extract of T. camphoratus has the potential to delay the occurrence of osteoporosis.

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Objective: To study on the changes of serum small metabolites in patients with lung cancer and pneumonia, assess the performance of these metabolites on differential diagnosis between lung cancer and pneumonia, and establish diagnostic model. Methods: Liquid chromatography tandem mass spectrometry(LC-MS/MS) was applied to test the serum metabolites, including 13 amino acids and 15 bile acids, of 95 patients with lung cancer, 69 patients with pneumonia and 90 healthy people. T test and Mann-Whitney U test were used to analyze the differences among the three groups. Binary logistic regression was applied to screen valuable indexes and establish diagnostic model. The receiver operating characteristic curve (ROC) was used to compare the differential diagnostic value of single index and diagnostic model. Results: Compared with the control group, 3 kinds of amino acids and 7 kinds of bile acids were decreased significantly, while 1 kind of amino acid and 2 kinds of bile acids were increased significantly in pneumonia patients. 6 kinds of amino acids and 2 kinds of bile acids were decreased significantly, while 2 kinds of amino acids and 4 kinds of bile acids were increased significantly in lung cancer patients. Deoxycholic acid was the most valuable metabolite in differential diagnosis. Citrulline, phenylalanine and deoxycholic acid were screened to establish differential diagnostic model of lung cancer and pneumonia. The area under curve (AUC) of the model was 0.829, and the Cut-Off value was 0.55, while the sensitivity was 76.8%, the specificity was 79.7%, and the coincidence rate was 78.3%. Conclusion: This study revealed that some small metabolites in serum of the patients with pneumonia and lung cancer have changed significantly. The diagnostic model composed of some metabolites has the potential value to assist differential diagnosis of lung cancer and pneumonia.

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Objective@#To investigate the clinical effect of one-stage revision combined with intra-articular injection of antifungal agents in the treatment of chronic periprosthetic fungal infection.@*Methods@#A retrospective analysis of 11 patients(4 hips, 7 knees) admitted with chronic periprosthetic fungal infection at Department of Orthopaedics, First Affiliated Hospital of Xinjiang Medical University from January 2004 to April 2016.There were males and females with an age of 67 years (range:47-77 years). Each patient underwent single-stage revision including aggressive soft-tissue debridement. Liquid samples and tissue samples were immediately sent to the microbiology laboratory for drug sensitivity testing and histological analysis. Removed the infected components and cement thoroughly, pouring powdered vancomycin into the medullary cavity and direct intra-articular injection of fungussensitive antibiotics. The patients with infected hips received an uncemented prosthesis and 0.5 g of gentamicin loaded commercial cement was received by the patients with infected knee.After that, a new prosthesis was implanted.Long-term combination therapy of antibacterial agents and antifungal agents were given after operation. Recurrence of infection and clinical outcomes were evaluated. The follow-up period was 5 years (range: 2-12 years).@*Results@#One patient died of acute heart failure on the eighth postoperative day.Three infection cases were recurred.Eight cases had satisfactory outcomes and required no additional surgical or medical treatment for recurrence of infection. The Harris hip score assessed preoperatively and at latest follow-up was increased from 39.25±5.12 to 79.50±4.79, the difference was statistically significant (t=-11.356, P=0.001).The Hospital for Special Surgery knee score was improved from preoperative 46.25±5.61 to final follow-up 80.50±5.06, and the difference was statistically significant (t=-9.930, P=0.002).@*Conclusion@#Treatment of chronic fungal periprosthetic joint infection with single-stage revision can be fairly effective for achieving acceptable functional outcomes.

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Objective:NRS 2002 nutritoanl risk assessment and PG-SGA scale were used to evaluate the effect of different nutritional treatments on fibula myocutaneous flap reconstruction of mandibular defect postoperative patients,and to find the appropriate timing and method of nutritional support for this kind of patients.Methods:50 cases of fibula myocutaneous flap reconstruction of mandibular defect postoperative patients were divided into two groups according to the nutritional risk assessment and the opinions of the research team including the mixed nutrition support treatment group (SPNS + EN) and the conventional nutrition support treatment group (TEN).The indexes of the patients on the day before surgery and 1,7,13 postoperative days were monitored,including lymphocyte count (LYM),serum albumin (ALB),hemoglobin (HB),potassium (K),sodium (NA),chloride (CL) and nutritional risk screening score (NRS) and other indicators to evaluate therapeutic effect of two groups.Results:The indicators showed no significant differences in the two groups before operation.For K and Na,the levels of the SPN + EN group was higher than that of the TEN group.Hemoglobin (HB) and NRS score on the 13rd day after surgery were statistically different between the two groups (P ＜ 0.05).Besides,Lymphocyte count (LYM) and chloride (CL) on the 1st and 7th after operation showed significant different,too(P ＜ 0.05).Conclusion:By nutritional risk assessment in patients with NRS 2002 before operation,PG-SGA after operation,we corrected the electrolyte and acid-base imbalance,improved stress state of postoperative patients with adjustment of nutritional therapy and intervention to timely and effectively provide plenty of energy and protein.

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Objective Recent evidence points towards a close relationship between dysregulation of long non-coding RNA (lncRNA) and carcinogenesis and progression of various tumors including gastric cancer. The aim of this study was to investigate the expression of lncRNA DGCR5 in the gastric cancer tissue and plasma and its influence on the biological behavior of gastric cancer cells. Methods We collected tumorous and adjacent normal tissues from 96 gastric adenocarcinoma patients as well as plasma samples from 34 gastric cancer patients and another 34 healthy controls. We deter-mined the expression of DGCR5 by real-time fluorescent quantitative PCR,analyzed its correlation with the clinicopathological features of gastric cancer,observed the apoptosis, proliferation and invasiveness of the gastric cancer cells after overexpressing DGCR5, and detected the expressions of epithelial-mesenchymal transition (EMT)-associat-ed genes and proteins by Western blot. Results The expression of DGCR5 was significantly decreased in tumor tissue of the gastric canc-er patients as compared with that in the adjacent normal tissue,which was correlated with the advanced TNM stage and lymph node metastasis, and so was it in the plasma of the patients, which was also correlated with the TNM stage. The area under the ROC curve for the diagnosis of gastric cancer by the expression level of plasma DGCR5 was 0.722. Overexpressed DGCR5 induced significant apoptosis and inhibited the proliferation and invasion of gastric cancer cells,markedly promoted the expression of E-cadherin,and suppressed the expressions of N-cadherin,vimentin and Twist. Conclu-sion The expression of DGCR5 is significantly decreased in the tumor tissue and plasma of gastric cancer patients. The DGCR5 level in the plasma has a certain diagnostic value for gastric cancer. Overexpressed DGCR5 can reduce the proliferation and invasiveness of gastric cancer cells,increase their apoptosis,and inhibit EMT.

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Objective To observe the effect of every-other-day fasting(EODF)on pathology and functional recovery of rats with spinal cord clip-compression injury,and to explore the related mechanism. Methods A total of 36 Sprague-Dawley rats were randomly assigned to groups A(sham operation),B(sham operation and EODF),C(spinal cord injury)and D(spinal cord injury and EODF)with nine rats in each group.The spinal cord injury rat model in T10was established by using medical aneurysm clip in latter two groups.The motor func-tion was assessed by Basso-Beattie-Bresnahan(BBB)score one day before and one day,two,four,six,eight,ten, twelve weeks after operation;and toluidine blue staining was performed for pathological observation at twelve weeks after operation.Another 180 Sprague-Dawley rats were randomly assigned in same way.The level of tu-mor necrosis factor-α(TNF-α)and interleukin-10(IL-10)were detected with ELISA six hours,twelve hours,one day,three days and seven days after operation. Results The BBB score reached lowest on the first day in groups C and D(P<0.05),and gradually increased with time,and were higher in group D than in group C eight weeks,ten weeks and twelve weeks after operation(P<0.05). The pathology in spinal cord was less in group D than in group C.Compared with group A,the level of serum TNF-α increased twelve hours after operation(P<0.05),peaked one day after operation,and returned back seven days after operation;the level of serum IL-10 increased at each time point after operation(P<0.05).Compared with group C,the level of serum TNF-α was lower in group D one day after operation(P<0.05);the level of se-rum IL-10 was not significantly different at each time point after operation(P>0.05). Conclusion Long-term EODF can promote the hind limb motor recovery in rats with spinal cord clip-compression inju-ry,and alleviate pathological damage.EODF might inhibit acute inflammatory reaction at acute stage of spinal cord injury,which may be correlated with its neuroprotective effect.

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<p><b>OBJECTIVE</b>To analyze the characteristics of pathogenic microorganisms in the infected bone tissues in patients with diabetic foot osteomyelitis (DFO) using 16S rRNA high-throughput sequencing to facilitate rapid and accurate detection of pathogens and effective infection control.</p><p><b>METHODS</b>Between September, 2016 and April, 2017, 16 patients with DFO were admitted in our department and infected bone specimens were obtained during debridement. The pathogenic microorganisms in the specimens were identified using both 16S rRNA high-throughput sequencing and automatic blood culture analyzer, and the characteristics of the microflora were analyzed based on 16S rRNA sequencing data in comparison with the results of blood culture.</p><p><b>RESULTS</b>The results of 16S rRNA sequencing showed that bone tissues of DFO contained diverse and uniformly distributed pathogenic organisms, among which 20 (87%) dominant genera were identified with Prevotella as the most abundant pathogen. Both 16S rRNA sequencing and routine culture results suggested the domination of gram-negative bacteria among the pathogens in DFO bone tissues. 16S rRNA sequencing, compared with routine culture, yielded a higher positivity rate (100% vs 88.24%) and detected a greater average number of pathogens (12.56 vs 1.50) and a higher proportion of gram-negative bacteria (67.16% vs 50.00%) in the samples. 16S rRNA sequencing detected nearly all the pathogens identified by routine culture except for Escherichia coli, Serratia marcescens and Enterobacter cloaca, and identified 13 genera that failed to be detected by routine culture, including the obligate or strict anaerobes Anaerococcus, Veillonella, Bacteroides, Fusobacterium, Porphyromonas, Finegoldia, Prevotella, Peptostreptococcus, Parvimonas, Peptoniphilus and Bulleidia. Routine culture did not detect any anaerobes in the samples but identified multidrug-resistant strains in as many as 58.33% of the pathogens.</p><p><b>CONCLUSIONS</b>16S rRNA high-throughput sequencing is capable of demonstrating the diversity and abundance of microflora in DFO bone tissues, where diverse and uniformly distributed pathogens can be detected with a discrete distribution of the dominant genera, most of which are gram-negative. Compared with routine culture method, 16S rRNA sequencing allows more convenient and accurate identification of the pathogens (especially gram-negative bacteria and anaerobes), and can be useful in clinical decision on appropriate treatment of DFO.</p>

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Objective To analyze the causes of poor compliance of elderly patients with diabetes mellitus , and put forward corresponding countermeasures to control blood glucose level and delay the occurrence of complications .Methods A total of 113 elderly patients with type 2 diabetes mellitus aged 60 years and over were recruited in endocrinology department of our hospital.The self-made questionnaire was used to investigate the compliance and the factors that affected the compliance.Results There were 48 patients (42.48%) with good compliance and 65 patients (57.52%) with poor compliance.Univariate analysis showed that the level of education, monthly income, drug types, understanding of diabetes-related knowledge and whether the elderly living alone affected compliance ( P<0.05 ) .Multivariate Logistic regression analysis showed that patients with low education level, poor monthly income, medication types and living alone were the main factors that influence the compliance of elderly patients with diabetes mellitus (P<0.05).And the level of education, monthly income level and the compliance of diabetic medication was positively correlated, medication types and living alone and diabetes compliance were negatively correlated (P<0.05).Conclusion The low level of education, poor monthly income, medication types and living alone are the main factors that affect the compliance of elderly patients with diabetes.The social and family support can effectively improve the compliance of elder patients with diabetes.

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<p><b>OBJECTIVE</b>To investigate foot biomechanics characteristic of patients with type 2 diabetes mellitus.</p><p><b>METHODS</b>This study was conducted among 303 patients with type 2 diabetes. The whole foot was divided into 10 regions, namely the first toe (T1); the second to fifth toes (T2-5); the first, second, third, fourth, and fifth metatarsals (M1, M2, M3, M4, and M5, respectively); midfoot (MF), and the heel medial (HM). Foot arch index, foot angle and maximum peak pressure (MPP) of the 10 regions were measured using a Footscan gait system.</p><p><b>RESULTS</b>The maximum peak pressure of 10 regions decreased in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the left foot, and in the order of M3>M2>HM>M4>HL>M1>M5>T1>ML>T2-5 for the right foot. The MPP in M1 region was higher in the right than in the left foot (P<0.05). The MPP in M3, M4, M5, and MF was higher in the left than in the right foot (P<0.05). The percentage of high-risk foot (defined by a total plantar pressure ≥70 N/cm) was 34% on the left and 17.7% on the right. An increased BMI was associated with a significant increase in high-risk foot, but not for the right foot in underweight patients. Foot flat phase was extended and forefoot push-off phase shortened in stance phase in the patients. Compared with the right foot, the left foot showed a significantly increased foot arch index and increased low and high arch rates with a decreased normal arch rate. Total plantar pressure was higher in of the left high arch foot than in normal arch foot. The foot angle was significantly larger on the right than on the left. The bilateral total plantar pressures were significantly greater in male patients (P<0.05) and increased with age but were not associated with the duration of DM, foot angle, or glycosylated hemoglobin level.</p><p><b>CONCLUSION</b>Diabetic patients have obvious alterations in foot biomechanics with abnormalities of the plantar pressure, and the percentage of high-risk foot increases in overweight and obese patients, suggesting the need of body weight control in these patients when administering offloading treatment for prevention of diabetic foot ulcer.</p>

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Objective To determine normal reference ranges for venous blood count among children aging from 1 year old to 12 years old.Methods These normal reference ranges were defined in a population of 526 healthy children who had no blood system diseases,allergic diseases,respiratory system diseases,urinary system diseases,digestive system disease,rheumatoid disease,thyroid disease,parasitic infections,malignancies and genetic disease,etc.Values of white blood cell count (WBC),red blood cell count (RBC),hemoglobin (Hb)concentration,red blood cell specific volume (Hct),mean corpusular volume(MCV),mean cell hemoglo-bin (MCH),mean corpuscular hemoglobin(MCHC),platelet (PLT),percentage of neutrophil (NE%),percentage of lymphocyte (LY%),percentage of mononuclear cells (MO%),percentage of acidophilic granulocyte (EOS%).Statistical analysis was done on various parameters that we recorded,and then for every parameter,we could get the various reference ranges for different age groups.Results The subjects were divided into 4 groups based on age.Besides the parameters of WBC count and classification of WBC,the rest of parameters were proved to be of no statistical difference between 4 groups..After an integration of the values,we could get the results as follows:RBC(4.02-5.2)×10 1 2/L,HGB 108-144 g/L,Hct 35.2%-40.4%,MCV 74.6-89.9 fL,MCH 20.9-34.7 pg,MCHC 332- 340 g/L,PLT(157 - 409 )× 10 9/L.WBC count did not have statistical difference between the age group 6-<9 and 9-12,but did have between the rest groups.After an integration of the values of WBC count,it could be conclu-ded that WBC count of age group1-<3 was(4.88-13.38)×10 9/L,that of age group 3-<6 was(4.26-1 1.6)×10 9/L and that of age group 6-12 was (4.24-10.24)×10 9/L.WBC classification results were various in different age groups.The values showed as follows:age group 1-<3 NE:29%-32%,LY:58%-61%;age group 3 -<6 NE:43%-46%,LY:43%-46%;age group 6-<9NE:49%-52%,LY:38%-40%;age group 9 to 12NE:5 1% - 58%,LY:33% - 39%.Conclusion WBC classification re-sults and WBC count do have statistical difference in different age groups.Besides the parameters of WBC count and classification of WBC,the rest of parameters are proved to be of no statistically difference in different age groups.The values of WBC count decrea-ses as the age increases.From WBC classification results,the most apparent fact is that the percentage of neutrophil increases as the age increases but the percentage of lymphocyte is just the contrary.As mentioned above,we suggest that we should establish a spe-cific whole blood count normal reference range for each age group during our laboratory testing work.

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<p><b>OBJECTIVE</b>To investigate the role of extracellular signal-regulated kinase (ERK) in apoptosis of human colon cancer (HCT116) cells.</p><p><b>METHODS</b>After the HCT116 cells were pretreated with specific ERK inhibitor (U0126) or specific siRNA and exposed to 10 mmol/L sodium butyrate (NaBT) for 24 h, their apoptosis was detected by flow cytometry, levels of SphK2 and ERK protein were measured by Western blot, and translocation of SphK2 was assayed by immunofluorescence microscopy.</p><p><b>RESULTS</b>The U0126 and siRNAs specific for SphK2 blocked the export of SphK2 from nuclei to cytoplasm and increased the apoptosis of HCT116 cells following NaBT exposure. Over-expression of PKD decreased NaBT-induced apoptosis of HCT116 cells, which was reversed by U0126. Furthermore, transfection of HCT116 cells with constitutively activated PKD plasmids recovered the U0126-blocked export of SphK2.</p><p><b>CONCLUSION</b>ERK regulates the export of SphK2 and apoptosis of HCT116 cells by modulating PKD. Modulation of these molecules may help increase the sensitivity of colon cancer cells to the physiologic anti-colon cancer agent, NaBT.</p>

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<p><b>OBJECTIVE</b>This review focuses on the state-of-the-art of CXCL12/CXCR4 signaling axis in pancreatic cancer and its role in tumor progression.</p><p><b>DATA SOURCES</b>Relevant articles published in English were identified by searching in Pubmed from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer". Important references from selected articles were also retrieved.</p><p><b>STUDY SELECTION</b>Articles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant mechanisms were selected.</p><p><b>RESULTS</b>Pancreatic cancer has been one of the most lethal human malignancies, with median survival less than one year and overall 5-year survival only 6%. Tumor cells from pancreatic cancer express high level of CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces intracellular signaling through several divergent pathways, which are involved in progression and metastasis of pancreatic cancer.</p><p><b>CONCLUSIONS</b>CXCL12/CXCR4 signaling axis may play an important role in the communication between pancreatic cancer cells and their microenvironment, which may have effect on tumor proliferation, invasion, angiogenesis, metastasis and chemoresistance. CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for pancreatic cancer.</p>

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<p><b>OBJECTIVE</b>To analyze the full nucleotide sequence of a null allele of major histocompatibility complex class I chain-related gene (MICA).</p><p><b>METHODS</b>A sequence-based typing method was used to determine the nucleotide sequence of the MICA gene. Potential alleles were identified with a computer program.</p><p><b>RESULTS</b>The identified allele has possessed a sequence similar to that of MICA*027 except for a C→T substitution at position 184 in codon 62 (CAG→TAG) of exon 2. As a stop codon, this may result in a truncated protein.</p><p><b>CONCLUSION</b>A null allele of MICA gene has been identified. The sequence has been submitted to the Genbank nucleotide sequence database (submission No. HWS10011131), which was officially named as MICA*063N by the WHO Nomenclature Committee in October 2010.</p>

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