The Effect of Blood Lipid Profiles on Chronic Kidney Disease in a Prospective Cohort:Based on a Regression Discontinuity Design

Objective Previous studies on the association between lipid profiles and chronic kidney disease(CKD)have yielded inconsistent results and no defined thresholds for blood lipids.Methods A prospective cohort study including 32,351 subjects who completed baseline and follow-up surveys over 5 years was conducted.Restricted cubic splines and Cox models were used to examine the association between the lipid profiles and CKD.A regression discontinuity design was used to determine the cutoff value of lipid profiles that was significantly associated with increased the risk of CKD.Results Over a median follow-up time of 2.2(0.5,4.2)years,648(2.00%)subjects developed CKD.The lipid profiles that were significantly and linearly related to CKD included total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),TC/HDL-C,and TG/HDL-C,whereas lowdensity lipoprotein cholesterol(LDL-C)and LDL-C/HDL-C were nonlinearly correlated with CKD.TC,TG,TC/HDL-C,and TG/HDL-C showed an upward jump at the cutoff value,increasing the risk of CKD by 0.90%,1.50%,2.30%,and 1.60%,respectively,whereas HDL-C showed a downward jump at the cutoff value,reducing this risk by 1.0%.Female and participants with dyslipidemia had a higher risk of CKD,while the cutoff values for the different characteristics of the population were different.Conclusion There was a significant association between lipid profiles and CKD in a prospective cohort from Northwest China,while TG,TC/HDL-C,and TG/HDL-C showed a stronger risk association.The specific cutoff values of lipid profiles may provide a clinical reference for screening or diagnosing CKD risk.

Epidemiology and natural history of hepatitis C virus infection

Hepatitis C virus(HCV)affects 130-210 million people worldwide and is one of the major risk factors for hepatocellular carcinoma.Globally,at least one third of hepatocellular carcinoma cases are attributed to HCV infection,and 350000 people died from HCV related diseases per year.There is a great geographical variation of HCV infection globally,with risk factors for the HCV infection differing in various countries.The progression of chronic hepatitis C to end-stage liver disease also varies in different study populations.A long-term follow-up cohort enrolling participants with asymptomatic HCV infection is essential for elucidating the natural history of HCV-caused hepatocellular carcinoma,and for exploring potential seromarkers that have high predictability for risk of hepatocellular carcinoma.However,prospective cohorts comprising individuals with HCV infection are still uncommon.The risk evaluation of viral load elevation and associated liver disease/cancer in HCV(REVEAL-HCV)study has followed a cohort of 1095 residents seropositive for antibodies against hepatitis C virus living in seven townships in Taiwan for more than fifteen years.Most of them have acquired HCV infection through iatrogenic transmission routes.As the participants in the REVEALHCV study rarely receive antiviral therapies,it provides a unique opportunity to study the natural history of chronic HCV infection.In this review,the prevalence,risk factors and natural history of HCV infection are comprehensively reviewed.The study cohort,data collection,and findings on liver disease progression of the REVEAL-HCV study are described.

Age-specific causes of upper gastrointestinal bleeding in children

The etiology of upper gastrointestinal bleeding(UGIB)varies by age,from newborns to adolescents,with some of the causes overlapping between age groups.While particular causes such as vitamin K deficiency and cow’s milk protein allergy are limited to specific age groups,occurring only in neonates and infants,others such as erosive esophagitis and gastritis may be identified at all ages.Furthermore,the incidence of UGIB is variable throughout the world and in different hospital settings.In North America and Europe,most UGIBs are nonvariceal,associated with erosive esophagitis,gastritis,and gastric and duodenal ulcers.In recent years,the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries.However,variceal bleeding still predominates in certain parts of the world,especially in South Asia.The most severe hemorrhage arises from variceal bleeding,peptic ulceration,and disseminated intravascular coagulation.Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients.Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings,the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIBincludes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability,followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis inthe pediatric population because some of them are unique to children. Endoscopic techniques are of significantdiagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally,surgical treatment is reserved for the most severe bleeding.

Outcomes of COVID-19 among patients with liver disease

Coronavirus disease 2019(COVID-19)is primarily a respiratory disease with multi-organ involvement,including impaired liver function.It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction,especially those with a more severe disease course.The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2,a cell-surface receptor for cellular entry,that is expressed in the liver.According to previous research,liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients,and elevated liver transaminases were found in about 20%of these patients,alkaline phosphatase in 6.1%,and gamma-glutamyl transferase in 21.1%.COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic liver diseases(CLDs)and also in those without previous liver disorders.The majority of COVID-19 patients who develop liver injury are men,the elderly,and those with a higher body mass index.Compared to the general population,COVID-19 is associated with significant morbidity and mortality in patients with liver disease(cirrhosis and liver transplantation recipients).However,some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.

Hepatic steatosis is associated with an increased risk of carotid atherosclerosis

AIM: Although an association between hepatic steatosis and vascular risk factors has been described, direct relationships between fatty liver and atherosclerosis have not yet been investigated. The aim of the present study has been to investigate those relationships. METHODS: The Study of Health in Pomerania examined a random population sample aged between 20 and 79 years. A study population of 4 222 subjects without hepatitis B and C infections and without liver cirrhosis was available for the present analysis. Hepatic steatosis was defined sonographically and intima-media thickness (IMT) as well as plaque prevalence were estimated by carotid ultrasound. RESULTS: The prevalence rate of hepatic steatosis was 29.9%. Among subjects aged ≥45 years, an association between hepatic steatosis and IMT of the carotid arteries was found in bivariate analysis, but not after adjustment for atherosclerotic risk factors. Individuals with fatty liver had more often carotid plaques than persons without fatty liver (plaque prevalence rate 76.8% vs 66.6%; P<0.001). This association persisted after adjustment for confounding factors and was predominantly present in subjects with no to mild alcohol consumption. CONCLUSION: There is an independent association between hepatic steatosis and carotid atherosclerotic plaques. Metabolic changes due to nonalcoholic fatty liver disease may explain this relationship.

Cost-effectiveness analysis of population-based screening of hepatocellular carcinoma: Comparing ultrasonography with two-stage screening

AIM: To assess the cost-effectiveness of two populationbased hepatocellular carcinoma(HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography(AUS).METHODS: In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per lifeyear gained with a 3% annual discount rate. RESULTS: The results show that the mass screening using AUS was associated with an incremental costeffectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening.CONCLUSION: Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval.

Antiviral activity of Basidiomycete mycelia against influenza type A(serotype H1N1) and herpes simplex virus type 2 in cell culture

In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.

Polymorphisms of some cytokines and chronic hepatitis B and C virus infection

AIM： To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus （HBV） and hepatitis C virus （HCV） infection. METHODS： Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked imrnunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction （PCR）. Hepatocellular injury, as revealed by alanine aminotransferase （ALT） and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-γ＋874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR.RESULTS： Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele. CONCLUSION： These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage.

Relationship between Ambient Fine Particles and Ventricular Repolarization Changes and Heart Rate Variability of Elderly People with Heart Disease in Beijing, China

Objective To explore the effects of particulate matters less than 2.5 μm in aerodynamic diameter （PM2.5） on heart repolarization/depolarization and heart rate variability （HRV）. Methods We conducted a panel study for elderly subjects with heart disease in Beijing from 2007 to 2008. PM2.5 was measured at a fixed station for 20 h continuously each day while electrocardiogram （ECG） indexes of 42 subjects were also recorded repeatedly. Meteorological data was obtained from the China Meteorological Data Sharing Service System. A mixed linear regression model was used to estimate the associations between PMz.s and the ECG indexes. The model was adjusted for age, body mass index, sex, day of the week and meteorology. Results Significant adverse effects of PM2.5 on ECG indexes reflecting HRV were observed statistically and the strongest effect of PM2.s on HRV was on lag i day in our study. However, there were no associations between PM2.5 and ECG indexes reflecting heart repolarization/depolarization. Additionally, the effects of PM2.5 on subjects with hypertension were larger than on the subjects without hypertension. Conclusion This study showed ambient PM2.5could affect cardiac autonomic function of the elderly people with heart disease, and subjects with hypertension appeared to be more susceptive to the autonomic dysfunction induced by PM2.5.

Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression

AIM To detect the mechanisms of Helicobacter pylori(H. pylori) infection in the invasion and metastasis of gastric cancer(GC).METHODS Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase(HPA) and mitogen-activated protein kinase(MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival(OS) and relapse-free survival(RFS) of GC patients were estimated by the KaplanMeier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot. RESULTS H. pylori infection was observed in 70 of 99 patients with GC(70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK(P < 0.05); HPA expression was relevant to MAPK expression(P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing(P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases(P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth. CONCLUSION H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.

Peanut consumption and reduced risk of colorectal cancer in women:A prospective study in Taiwan

AIM： To examine whether peanut consumption is associated with a reduced risk of colorectal cancer in a prospective cohort with a 10-year follow-up. METHODS： In 1990-1992, residents （12026 men and 11917 women aged 30 to 65 years） in 7 townships, Taiwan, were interviewed and recruited into a cancerscreening cohort and annually followed up. Colorectal cancer cases in this cohort were identified from cancer registry and death certificates. Incidence rates of this disease by the end of 2001 were calculated by gender for the primary study variable and covariates. The dietary intake was assessed by means of weekly food frequency measures, including frequently consumed food groups and folk dishes including sweet potato, bean products, peanut products, pickled foodstuffs, nitrated or smoked foodstuffs. RESULTS： During the study period, 107 new colorectal cancer cases （68 men and 39 women） were confirmed. The multivariate Cox＇s proportional hazard model showed that the relative risk （RR） of peanut consumption was 0.73 [95% confidence interval （CI） = 0.44-1.21] for men and 0.42 （95% CI = 0.21-0.84） for women. However, frequent intake of pickled foodstuffs was harmful for women （RR= 2.15, 95% CI=0.99-4.65）. The risk of colorectal cancer was also elevated among cigarette smokers but not significant （P〈 0.05）.CONCLUSION： This study suggests that frequent intake of peanut and its products may reduce colorectal cancer risk in women, demonstrating the anti-proliferating effect of peanut intake.

Generation of Reactive Oxygen Species in Different Fractions of the Coelomocytes of Holothurian Eupentacta fraudatrix in Response to the Thermostable Toxin of Yersinia pseudotuberculosis in Vitro

Pure fraction (92%-95%) of phagocytes (FP) and a mixture of amoebocytes(62%) and morula cells (38 %) FPMC of the holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirota) were obtained by using ficoll verographine step gradient. Basal production of reactive oxygen species (ROS) in FP quantified by using reduction of nitroblue tetrazolium (NBT) was more than twice that in FPMC. Thermostable toxin of Yersinia pseudotuberculosis (TST) at different concentrations ( 0.2; 0.5; 2.5 μg/ml, but not 0.1 μg/ml) stimulated NBT reduction in FPMC after 24 h incubation. In FP, TST at concentrations of 0.1 and 0.2 μg/ml inhibited and at concentrations of 0.5 and 2.5 μg/ml stimulated NBT reduction after 24 h incubation. Maximal effect was observed in FP and FPMC at TST concentrations of 0.5 and 0.2 μg/ml, respectively. Addition of catalase (0.7 μg/ml) to the cells treated with TST (2.5 μg/ml) was followed by a decrease in NBT reduction compared to that under toxin treatment alone. TST stimulated superoxide dismutase activity in concentration dependent manner (maximum at 0.5 μg/ml concentration in FP) after 24 h treatment, and this stimulation was prevented by a commercial catalase. Plant lectin concanavalin A stimulated NBT reduction more than 5 fold in FPMC compared to the control. With addition of TST, lectin stimulated ROS to lesser extent than that with lectin alone. When catalase, TST, and lectin were added into the FPMC simultaneously, ROS increase was similar to that under lectin treatment alone. On the whole, data obtained indicated that ROS generation in holothurian coelomocytes especially occurs in both stimulated and not stimulated phagocytes, and that changes in ROS production by these cells may be one of the mechanisms of antibacterial protection of holothurians.

Modified shock index and mortality rate of emergency patients

BACKGROUND:This study aimed to determine whether modified shock index(MSI)is associated with mortality that is superior to heart rate,blood pressure,or the shock index(SI).in emergency patients.METHODS:A retrospective database review was performed on 22 161 patients who presented to Peking Union Medical College Hospital Emergency Department and received intravenous fluids from January 1 to December 31,2009.We gathered data of the patients on age,gender,vital signs,levels of consciousness,presenting complaints,and SI and MSI were calculated for all patients.RESULTS:Multivariate regression analysis was performed to determine the correlation between risk factors and outcome.There is a significant correlation between emergency patient mortality rate and patient's vital signs obtained at the triage desk(HR>120 beats/min,systolic BP<90 mmHg,diastolic BP<60 mmHg).MSI is a stronger predictor of emergency patient mortality compared to heart rate and blood pressure alone,whereas SI does not have a significant correlation with emergency patient mortality rate.CONCLUSION:MSI is a clinically significant predictor of mortality in emergency patients.It may be better than using heart rate and blood pressure alone.SI is not significantly correlated with the mortality rate of the emergency patient.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Effects of Outdoor Temperature on Blood Pressure in a Prospective Cohort of Northwest China

Objective The relationship between outdoor temperature and blood pressure(BP) has been inconclusive. We analyzed data from a prospective cohort study in northwestern China to investigate the effect of outdoor temperature on BP and effect modification by season.Methods A total of 32,710 individuals who participated in both the baseline survey and the first follow-up in 2011–2015 were included in the study. A linear mixed-effect model and generalized additive mixed model(GAMM) were applied to estimate the association between outdoor temperature and BP after adjusting for confounding variables.Results The mean differences in systolic blood pressure(SBP) and diastolic blood pressure(DBP)between summer and winter were 3.5 mm Hg and 2.75 mm Hg, respectively. After adjusting for individual characteristics, meteorological factors and air pollutants, a significant increase in SBP and DBP was observed for lag 06 day and lag 04 day, a 0.28 mm Hg(95% CI: 0.27–0.30) per 1 °C decrease in average temperature for SBP and a 0.16 mm Hg(95% CI: 0.15–0.17) per 1 °C decrease in average temperature for DBP, respectively. The effects of the average temperature on both SBP and DBP were stronger in summer than in other seasons. The effects of the average temperature on BP were also greater if individuals were older, male, overweight or obese, a smoker or drinker, or had cardiovascular diseases(CVDs), hypertension, and diabetes.Conclusions This study demonstrated a significant negative association between outdoor temperature and BP in a high-altitude environment of northwest China. Moreover, BP showed a significant seasonal variation. The association between BP and temperature differed by season and individuals' demographic characteristics(age, gender, BMI), unhealthy behaviors(smoking and alcohol consumption), and chronic disease status(CVDs, hypertension, and diabetes).

Enteroaggregative Escherichia aoliisolated from Chinese diarrhea patients with high-pathogenicity island of Yersinia'xs involved in synthesis of siderophore yersiniabactin

AIM: To investigate the distribution of 12 high-pathogenicity island (HPI) genes and the relation between HPI genes and expression of yersiniabactin (Ybt) in enteroaggregative E.coli(EAggEC) isolated from Chinese diarrhea patients.METHODS: The distribution of 12 HPI genes was investigated by PCR and DNA hybridization in two prototype strains of EAggEC, EAggEC 17-2, EAggEC O42, and 6 clinical EAggEC isolates from China. The production of siderophore Ybt in HPI-positive strains was detected by reporter gene bioassay to determine the relation between HPI genes and expression of Ybt. Flow cytometry was used to detect fluorescent signal of the reporter strain that could designate production of Ybt.RESULTS: Seven strains were HPI-positive and one strain was HPI-negative. Six of the seven HPI-positive strains were inserted into asnT-tRNA site. Moreover, seven EAggEC HPI-positive strains revealed enhanced fluorescence signal but the EAggEC HPI-negative strain did not. However, there was a difference in Ybt expression condition and level among these seven EAggEC HPI-positive strains. Although UFT073 strain, the prototype strain of uropathogenic E.coli(UPEC), carried the complete HPI core part, we did not detect the expression of Ybt in it.CONCLUSION: EAggEC HPI-positive strains can express the Ybt system, but the presence of HPI core part does not mean the functional expression of Ybt.

Pup Vaccination Practices in India Leave People to the Risk of Rabies — Lessons from Investigation of Rabies Deaths Due to Scratch/Bite by Pups in Remote Hilly Villages of Himachal Pradesh, India

Rabies, a zoonotic disease, kills 55,000 persons every year globally and 20,000 persons in India. Two years back, we learnt of two deaths due to Rabies in remote village Shiv Shankar Garh of Arki block of District Solan and decided to investigate the deaths. Method: A rapid response team was constituted to investigate the deaths. We interviewed the villagers & family to conduct verbal autopsy. A line list of entire population of village and household contacts of the patients, who died, were made along with the line list of dogs and cattle. Results & Discussion: A-month-old stray pup brought home by the family and had caused an abrasion with its toes on the hands of both the deceased on June 2, 2011 while playing. The lady developed paralysis of the arm on July 3, 2011 and 3 days later developed symptoms of hydrophobia. She died on July 9, 2011. Her son had developed hydrophobia 10 days after that and died on July 19, 2011. Assumption that bite or abrasion by a small pup of one month cannot be fatal proved otherwise. Lack of awareness regarding the fatality of even a scratch and lack of knowledge regarding local treatment of the wound & vaccination of both human and pups, were the main reasons for the deaths. While such incidents keep on happening, and the veterinarians in India are refusing to vaccinate pups before three months of age, as pups may not develop immunity before that age, leaving unsuspecting people to the risk of rabies. Conclusions: Humans can be exposed to rabies even by pups below 3 months of age. Recommendation: Pup vaccination schedule in rabies endemic countries like India need revision. Veterinarians and public health experts need to strongly consider vaccinating pups at first contact with humans even if they are less than 3 months of age. A booster to the pup can be given at three months of age with subsequent yearly boosters.

Metal Exposure and Risk of Diabetes and Prediabetes among Chinese Occupational Workers

Objective To study the association between metal exposure and risk of diabetes and prediabetes among Chinese workers exposed to metals.Methods We used data obtained from the baseline survey of the Jinchang Cohort Study of workers in Jinchang Industry,the largest nickel production company in China.A total of 42,122 workers ≥20 years of age were included in the study.A standardized,structured questionnaire was used to collect epidemiological information.Physical examinations and laboratory tests were conducted to evaluate the health status of the participants and to measure various biomarkers including blood sugar,lipids,and urinary metal concentrations.Logistic regression was used to study the association between occupational groups categorized according to the measured metal levels(office workers,low-level;mining/production workers,mid-level;and smelting/refining workers,high-level)and risk of diabetes and prediabetes.Results The overall prevalence of diabetes and prediabetes was 7.5% and 16.8%,respectively.The adjusted odds ratios for diabetes among mining/production workers and smelting/refining workers compared to office workers were 1.5(95% CI:1.3,1.7)and 3.8(95% CI:3.4,4.3),respectively.No association was observed between these occupational groups and prediabetes in this study.Conclusion Occupations associated with higher levels of metal exposure were associated with an increased risk of diabetes in this cohort.More studies are needed to confirm this observed association.

Gene-modified leucoconcentrate for personalized ex vivo gene therapy in a mini pig model of moderate spinal cord injury

We previously demonstrated that gene-modified umbilical cord blood mononuclear cells overexpressing a combination of recombinant neurotrophic factors are a promising therapeutic approach for cell-mediated gene therapy for neurodegenerative diseases,neurotrauma,and stroke.In this study,using a mini pig model of spinal cord injury,we proposed for the first time the use of gene-modified leucoconcentrate prepared from peripheral blood in the plastic blood bag for personalized ex vivo gene therapy.Leucoconcentrate obtained from mini pig peripheral blood was transduced with a chimeric adenoviral vector(Ad5/35 F)that carried an enhanced green fluorescent protein(EGFP)reporter gene in the plastic blood bag.The day after blood donation,the mini pigs were subjected to moderate SCI and four hours post-surgery they were intravenously autoinfused with gene-modified leucoconcentrate.A week after gene-modified leucoconcentrate therapy,fluorescent microscopy revealed EGFP-expressing leucocytes in spinal cord at the site of contusion injury.In the spleen the groups of EGFP-positive cells located in the lymphoid follicles were observed.In vitro flow cytometry and fluorescent microscopy studies of the gene-modified leucoconcentrate samples also confirmed the production of EGFP by leucocytes.Thus,the efficacy of leucocytes transduction in the plastic blood bag and their migratory potential suggest their use for temporary production of recombinant biologically active molecules to correct certain pathological conditions.This paper presents a proof-of-concept of simple,safe and effective approach for personalized ex vivo gene therapy based on gene-modified leucoconcentrate autoinfusion.The animal protocols were approved by the Kazan State Medical University Animal Care and Use Committee(approval No.5)on May 27,2014.

Estimation Study of New Cancer Cases and Deaths in Wuwei, Hexi Corridor Region, China, 2018

Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends（＋2.63% per year; P 〈 0.05 and ＋1.9% per year; P 〈 0.05）. This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.