Expression Profiles of TRAIL Receptors and Their Clinical Significance in Human Hepatocellular Carcinoma

Objective To investigate the expression profiles and their clinical significance of TRAIL receptors (TRAILR) in human hepatocellular carcinoma (HCC). Methods The expression profiles of TRAILR were determined in 60 samples from hepatocellular carcinoma, 20 from normal liver tissue and two HCC cell lines HepG2, SMMC-7721 by in situ hybridization. Results Both DR4 and DR5 were present in all HCC tissues as well as normal hepatic tissues. In contrast, 54 HCC tissues did not express DcR1 and 25 did not express DcR2. But both DcR were detectable in all of the normal liver tissues. The expression patterns of DR and DcR in HCC samples (higher DR expression level and lower DcR expression level) were quite different from those in normal tissue. DR5, DR4, and DcR2 expressed in both cell lines, while no DcR1 expression was detected. The expression level of DR was correlated with HCC differentiation and stage. The weaker expression was more commonly found in HCC with poor differentiation and late stage, while the stronger expression was more common in HCC with middle to high-differentiation and early stage. No relationship was found between DR and gender, age, negative or positive HBsAg, tumor size, grade or metastasis. Multidrug resistance cell lines expressed lower level DR. Conclusion TRAILR expression was prevalent and discrepancy of receptor types was exited in HCC. Loss of DcR1 may contribute for TRAIL therapy for HCC. Key words TRAILR - apoptosis - hepatocellular carcinoma Supported by the Major Fundation of Ministry of Health, NO. 2001–2003

Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes

The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a ＇social＇ dimension to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane nanotube formation between neighbouring T cells. This is critically dependent on Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and cytosolic elements including active caspases can be observed to occur via these nanotubes. Nanotube formation and intercellular exchanges of death signals are defective in T lymphocytes from patients with autoimmune iymphoproliferative syndrome harbouring mutations in the Fas receptor. We conclude that nanotuhemediated exchanges constitute a novel form of intercellular communication that augments the propagation of death signalling between neighbouring T cells.

REDUCED GROWTH IN HYBRID TILAPIA (OREOCHROMIS MOSSAMBICUS×O. NILOTICUS) AT INTERMEDIATE STOCKING DENSITY

Hybrid tilapia were reared at densities of 1, 5 or 10 fish per tank for four weeks. Mortality was 0 at 1 and 10 fish per tank, but was 25% at 5 fish per tank. Specific growth rate was highest at 1 fish per tank, and lowest at 5 fish per tank. The lower growth rate at the intermediate stocking density was associated with reduced feed efficiency, but there was no reduction in feed intake or digestibility. The results suggested increased metabolic cost caused by aggressive behaviour at intermediate stocking density, which can be suppressed by a further increase in density.

Exposure Work Commuting： Case Study among Commuting Accidents in Klang Valley, Malaysia

Traffic accidents caused the most accidental deaths at work in Malaysia. The SOCSO （Social Security Organization） reported that the number of deaths due to commuting accidents was 760, nearly two times more than deaths caused by accidents that happened at the workplace （471 deaths）. The aim of this study is to investigate the relationship of socio-demographic background and the risk exposure of the drivers during their work commuting trips. The study was based on compensation claims to SOCSO where data were extracted from ＂Form 21＂ provided by SOCSO. A total of 377 respondents were selected through systematic random sampling method from a list of SOCSO claimants. It was found that majority of the traffic accidents （83%） involved males and most of them （92.2%） were on motorcycles. Male drivers have an average driving experience of 10.7 years and 8.6 years for females. The estimation of the travelled distance for the sample from home to the workplace is 0.65-131 km. Mean accident occurrence time was 23 rain whilst mean distance was 11.6 km. The multiple regression analysis showed that the accident distance was affected by the age of driver, actual travel distance, travel objective and speed.

Genetic polymorphisms predict response to anti-tumor necrosis factor treatment in Crohn's disease

To investigate genetic factors that might help define which Crohn’s disease (CD) patients are likely to benefit from anti-tumor necrosis factor (TNF) therapy. METHODSThis was a prospective cohort study. Patients were recruited from a university digestive disease practice database. We included CD patients who received anti-TNF therapy, had available medical records (with information on treatment duration and efficacy) and who consented to participation. Patients with allergic reactions were excluded. Patients were grouped as ever-responders or non-responders. Genomic DNA was extracted from peripheral blood, and 7 single nucleotide polymorphisms (SNPs) were assessed. The main outcome measure (following exposure to the drug) was response to therapy. The patient genotypes were assessed as the predictors of outcome. Possible confounders and effect modifiers included age, gender, race, and socioeconomic status disease, as well as disease characteristics (such as Montreal criteria). RESULTS121 patients were included. Twenty-one were non-responders, and 100 were ever-responders. Fas ligand SNP (rs763110) genotype frequencies, TNF gene -308 SNP (rs1800629) genotype frequencies, and their combination, were significantly different between groups on multivariable analysis controlling for Montreal disease behavior and perianal disease. The odds of a patient with a Fas ligand CC genotype being a non-responder were four-fold higher as compared to a TC or TT genotype (P = 0.009, OR = 4.30, 95%CI: 1.45-12.80). The presence of the A (minor) TNF gene -308 allele correlated with three-fold higher odds of being a non-responder (P = 0.049, OR = 2.88, 95%CI: 1.01-8.22). Patients with the combination of the Fas ligand CC genotype and the TNF -308 A allele had nearly five-fold higher odds of being a non-responder (P = 0.015, OR = 4.76, 95%CI: 1.35-16.77). No difference was seen for the remaining SNPs. CONCLUSIONThe Fas-ligand SNP and TNF gene -308 SNP are associated with anti-TNF treatment response in CD and may help select patients likely to benefit from therapy.

顾盼留情

曾听过这样一个故事:一只小白兔,很小的时候与父母失散了,幸好一只灰免子路过,始终不离弃地陪伴着它,让它不孤单。

Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding

The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature rhythm.Time-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many diseases.The potential side effects of TRF remain unknown.Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality.Nearly half of the mice died at 21℃,and all mice died at 18℃during 4-h TRF.This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis.Remarkably,disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF.Analysis of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in thermoregulation.Together,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process.Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.

Study on the Treatment of Acute Cerebral Infarction by Xuanzhong(GB 39)Toward Sanyinjiao(SP 6)Acupuncture as Main Therapy

Objective： To investigate the effects of acupuncture therapy on acute cerebral infarction. Methods： Eighty patients with acute cerebral infarction were randomly divided into a treatment group of 40 cases and a control group of 40 cases. Xuanzhong（GB 39）-throughSanyinjiao（SP 6） acupuncture was performed as a main treatment. The curative effects were compared between the two groups and the sizes of cerebral infarct, between pretreatment and posttreatment after one course of treatment. Results. The total recovery rate was 88.5% in the treatment group and 57.5% in the control group after one course of treatment. There was a significant difference between the two（P〈 0.05）. The rate of change in the infarct for the better was significantly higher in the treatment group than in the control group. There was also a significant difference（P〈 0.05）, Conclusion： This treatment is an effective method for lowering the rate of apoplectic disability and raising the cure rate,

Dynamics of Entanglement for a Two-Parameter Class of States in a Qubit-Qutrit System

We investigate the dynamics of entanglement for a two-parameter class of states in a hybrid qubit-qutrit system under the influence of various dissipative channels. Our results show that entanglement sudden death （ESD） is a general phenomenon and it usually takes place in a qubit-qutrit system interacting with various noisy channels, not only the ease with dephasing and depolarizing channels observed by others. ESD can only be avoided for some initially entangled states under some particular noisy channels. Moreover, the environment affects the entanglement and the coherence of the system in very different ways.

Epidemiological characteristics of fatal pedestrian ac- cidents in Fars Province of Iran： a community-based survey

Objective： To determine the epidemio logical characteristics of fatal pedestrian accidents in Fats Province of Iran. Methods： This crosssectional study was conducted in Fats Province of Iran during a 29month period from March 2009 to July 2011. The data were from the Fats Forensic Medi cine Registry, In 4 923 recorded road traffic accident fatalities, 971 deaths were due to pedestrian accidents. The demographic and accidentrelated information were analyzed by SPSS ver sion 11.5. P value less than 0.05 was considered significant. Results： The mean age of decedents was （47.2±26.2） years, ranging from 6 months to 103 years old. Males ac counted for 69.8% of all deaths. Fatal accidents were mostcommon in September; 56.1% of the fatal injuries occurred on intracity roads and 33.1% on extracity roads. Fatal head injuries were present in 60.54% of cases. Evaluation of the injury site and the cause of death found that they were significantly associated with age, interval between injury and death. Besides, the type of roads played an important role in mortality. Conclusion： Although the clinical management of trauma patients has been improved in our country in the recent decade, decreasing the burden of injuries needs co ordination among trauma system organizations.

Time analysis of fatal traffic accidents in Fars Province of Iran

Objective： To analyze the time factor in road traffic accidents （RTAs） in Fats Province of Iran. Methods： This study was conducted in Fars Province, Iran from November 22, 2009 to November 21,2011. Victims＇ information consisted of age, sex, death toll involving dri- vers or passengers of cars, motorcycles and pedestrians, and site of injury etc. Accidents were analyzed in relation to hour of the day, season of the year, lighting condition in- cluding sunrise, sunset, daytime and nighttime. Results： Atotal of 3 642 deaths （78.3% were males, and the ratio of males to females was about 3.6：1） were studied regarding their autopsy records. There was a steady in- crease in fatal accidents occurring at midnight to 15：59. The risk of being involved in a fatal traffic accident was higherfor those injured between 4：00 to 7：59 than at other times （OR=2.13, 95% C11.85-2.44）. The greatest number of fatal RTAs took place in summer. Mortalities due to RTA during spring and summer were more pronounced at 20：00 to 23：59 and midnight to 3：59, whereas mortalities in fall and winter were more pronounced from 12：00 to 15：59. Conclusion： The high mortality rate ofRTAis a major public health problem in Fars Province. Our results indicate that the time is an important factor which contributes to road traffic deaths.

Formation and repair of DNA-protein crosslink damage

DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks(DPCs)—the covalent linkage of proteins with a DNA strand—are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated degradation.Nucleotide excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.

Road traffic deaths in Kashan region, Iran： An eight-year study （2006-2013）

Purpose： The aim of this study was to analyze the trend of road traffic fatalities in Kashan Region, lran, in a period of eight years. Methods： Through a cross-sectional study, all road traffic deaths classified under the VO1-V99 codes according to ICD-10 in Kashan region, central Iran, from March 2006 to March 2013 and population data were collected from the registration system of Kashan University of Medical Sciences. Years of lost life （YLL） and mortality rates were calculated regarding age, gender and year of the accident. Generalized linear model （GLM） with Poisson log-linear link was used to evaluate the effects of the mentioned variables on mortality rate. Results： During the period of the study （8 years）, 928 people （767 men） died due to road traffic injuries （RTIs）. The total YLL was 20,818. The mortality rate due to RTIs has been declined constantly from 43.1 in March 2006 to 21.1 per 100,000 in March 2013. The highest mortality rate was found in the age group of over 60 years old and the lowest in the age group of 0-14 years old. Both mortality rate and YLL was greater in men than in women. Poisson regression showed that age, gender and year of the accidents had a significant effect on mortality rate （p 〈 0.001 ）. Conclusion： Although there has been a constant decline of mortality rate in Kashan area within the study period, the value remains higher than the mean level of Eastern Mediterranean region and the global average, which is a notable fact for policymakers and authorities.

Epidemiology of road traffic mortality and injuries in Yazd, Iran during 2003-2008

Objective： Road traffic crashes （RTCs） are considered to be the second highest cause of mortality in Iran. The purpose of this study was to describe the morbidity and mortality of RTC during 2003-2008.Methods： Data were got from national health sources of Iran. These data included population, the number of RTCs,consequent fatalities, cause and place of death from 2003 to 2008.Results： RTC incidence rate increased from 868.5 per 100 000 population in the year 2003 to 1 643.6 in 2008. A total of 2 565 deaths from RTC were recorded in Yazd from 2003 to 2008. RTC mortality rate increased from 46.1 per 100 000 population in 2003 to 46.9 in 2006, then declined to 38.8 in 2008. During this time period, overall traffic injury incidence per 100 000 population increased from 368.8 in 2003 to 647.9 in 2006, then declined to 527.9 in 2008. Head injuries were the most common cause of road traffic-related mortality from 2003 to 2008. Following road traffic accidents, most of the deaths occurred before arriving hospital.Conclusions： Road traffic crash-related mortality and morbidity in Yazd in the recent six years are increased, but decreased in the last two years. This decline is most probably the result of a variety of interventions, including laws,police enforcement, improvements in traffic and transport,health care resources and media and public education.

Road traffic fatalities among pedestrians, bicyclists and motor vehicle occupants in Sirjan, Kerman, Iran

Objective： To analyze the crash and injury data in forensic medicine for years of 2004-2007. Methods： A sample of over 567 accident cases （9 pedestrians, 116 bicyclists, and 442 motor vehicle occupants） was considered from the Department of Forensic Medicine, Shahid Bahonar University of Kerman, involving drivers of all ages and covering a four-year period. Results： The male fatality rates were significantly higher than female ones. The groups at 15-30 years old and at 30-55 years old had the first and second highest numbers of deaths （40% and 34%, respectively）. There were substantial differences in distribution of injuries in motor vehicle occupants and pedestrians and bicyclists. Among motor vehicle occupants, there were more head injuries, such as skull fracture, brain contusion, subdural haemorrhage, and epidural haemorrhage. Nearly 77% of fatalities occurred during 08：00-22：00 in Sirjan. Internal bleeding was also higher in motor vehicle occupants. Pedestrians and bicyclists also had head injuries frequently. Conclusions： In spite of reduction of road traffic fatalities in Sirjan in 2007, it is still one of the cities with high road traffic fatality in the world. These results underline the importance of preventive strategies in transportation, suggesting that different methods are necessary to reduce fatalities of various traffic participants.

Epidemiology of traffic crash mortality in west of Iran in a 9 year period

Purpose： In Iran, the most common cause of injuries and the second leading cause of deaths are traffic accidents, and those problems impose a substantial financial burden on the society. This study aims to determine traffic accident mortality trends and their epidemiologic characteristics in the Kermanshah province, west of lran. Methods： In a cross sectional study, road traffic fatality data from 2004 to 2013 were analyzed to determine the epidemiological pattern of traffic accident mortality. Trend assessment was performed to ascertain the decreasing or increasing status. Chi-square and one-way analysis of variance （ANOVA） tests, as well as Poisson regression were used to determine the significance of the data in time. Data were analyzed using Excel and statistical package of SPSS version 19. Results： Out of 5110 people that died in traffic accidents, 4024 （78.7%） were males. The state of accidents indicated that 404 （43.8%） female pedestrians died as a result of car crashes, and 1330 （41.4%） males died because of car collisions. 1554 （31.9%） deaths happened to pedestrians and 1556 （32.1%） to vehicle drivers, and the rest belonged to vehicle passengers. Head trauma was the cause of death for as much as 3400 （69.9%） cases. Fatal crashes in which pedestrians were involved mostly occurred between the hours 13：00 to 15：00, while the time for vehicle drivers was between 16：00 to 18：00. 2882 people （59.1%） died before reaching to health care facilities. Traffic crash mortality trend for pedestrians follows a linear pattern with a gentle downward slope, but the trend shows various swings when it comes to vehicle drivers. Conclusion： The number of traffic crash deaths from 2004 to 2013 indicates a decreasing trend in two groups of road users： vehicle drivers and car occupants. This can be due to some interventions such as modification of traffic rules and enhancement of police control which has been implemented in recent years. Moreover, more attention should be paid to promote the optimal health care services to save the lives of the injured from traffic accidents.

Road traffic crashes in rural setting： an experience of a middle-income country

Objective： To date, there has been little information published on the death of rural road accident deaths. This study uses burden of injury method to explore a more accurate estimate of years of life lost due to road traffic crashes occurring over a four-year period in Guilan province, northern Iran. Methods： Rural road accident deaths from 2009 to 2013 were extracted from Iran＇s Forensic Medicine System, Death Registry System and Road Trauma Research center database. Results： During the study period, the average years of life lost due to motor vehicle crashes was 13.8 per 1 000 persons, ranging from 11.9 during March 2011- 2012 to 15.8 per 1 000 persons during March 2012-2013. Conclusion： Road accident deaths in 2013 remained at the same high level as in 2009. The information obtained from this study provides a new perspective on fatal road traffic crash victims in rural settings and show us that more attention is needed in this area.