Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers

Colorectal cancer(CRC)remains an enormous challenge to human health worldwide.Unfortunately,the mechanism underlying CRC progression is not well understood.Mounting evidence has confirmed that exosomes play a vital role in CRC progression,which has attracted extensive attention among researchers.In addition to acting as messengers between CRC cells,exosomes also participate in the CRC immunomodulatory process and reshape immune function.As stable message carriers and liquid biopsy option under development,exosomes are promising biomarkers in the diagnosis or treatment of CRC.In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC.Moreover,we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC,predict CRC progression,or determine CRC chemoresistance,and described the significance of exosomes in the immunotherapy of CRC.This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.

Dynamic Expression of Hyperpolarization-activated Cyclic Nucleotide-gated Cation Channel 4 Involved in Microwave Induced Pacemaker Cell Injuries

To investigate the mechanisms of microwave induced pacemaker cell injuries, Wistar rats and the primary pacemaker cells of newborn Wistar rats were exposed to microwave at average power density of 50 mW/cm2. Slower spontaneous beating rate, intercellular Ca2＋ aggregation and cell membrane perforation were detected immediately after the exposure. Moreover, hyperpolarizationactivated cyclic nucleotide-gated cation channel 4 （HCN4） was down-regulated immediately after the exposure and up-regulated at 12 h after the exposure. In the sinoatrial node （SAN） of the rats,

Association between ApoE Polymorphism and Type 2 Diabetes: A Meta-Analysis of 59 Studies

Objective To identify the important risk factors for type 2 Diabetes Mellitus(T2 DM) and develop effective strategies to address the problem of T2 DM. Our study aimed to evaluate the association between apolipoprotein E(Apo E) genetic polymorphism and type 2 diabetes, and to provide clues for the etiology of T2 DM.Methods Based on the criteria of inclusion and exclusion, we extracted, pooled, analyzed and assessed the case-control studies of Apo E polymorphism and T2 DM published in Pub Med, Web of Science,Medline, Wan Fang, VIP, and CNKI databases by R soft-ware(version 3.4.3). We used Random-effect models when heterogeneity was present in between-study, and fixed-effect models otherwise.Results We had 59 studies covering 6,872 cases with T2 DM and 8,250 controls, and compared the alleles and genotypes of Apo E between cases and controls. When we conducted a comparison between Apo E ε4 and ε3 alleles, we produced a pooled OR of 1.18(95% CI: 1.09-1.28;P < 0.001). Apo E ε2/ε2 genotype displayed a possible association with T2 DM(OR = 1.46;95% CI: 1.11-1.93;P = 0.007), ε3/ε4 genotype showed a 1.11-fold risk(OR = 1.11;95% CI: 1.01-1.22;P = 0.039) and ε4/ε4 genotype had a1.71-fold risk of developing T2 DM(OR = 1.71;95% CI: 1.33-2.19;P < 0.001) when they were compared with ε3/ε3 genotype.Conclusions There is an association between Apo E polymorphism and T2 DM: allele ε4 and genotypes(ε2/ε2, ε3/ε4, and ε4/ε4) are associated with the increased risk for the development of T2 DM, and they may be risk factors for T2 DM.

Real-time Assessment of Cytosolic, Mitochondrial, and Nuclear Calcium Levels Change in Rat Pheochromocytoma Cells during Pulsed Microwave Exposure Using a Genetically Encoded Calcium Indicator

Little information is available about the effects of exposure to pulsed microwaves on neuronal Ca^2＋ signaling under non-thermal conditions. In this study, rat pheochromocytoma （PC12） cells were exposed to pulsed microwaves for 6 min at a specific absorption rate （SAR） of 4 W/kg to assess possible real-time effects. During microwave exposure, free calcium dynamics in the cytosol, mitochondria, and nucleus of cells were monitored by time-lapse microfluorimetry using a genetically encoded calcium indicator （ratiometric-pericam, ratiometric-10ericam-mt,

Investigation of Mean Glandular Dose in Diagnostic Mammography in China

A survey of 420 exposures of mammography was performed with the parameters recorded. Entrance skin air kerma （ESAK） was measured and the mean glandular dose （MGD） was calculated according to the Dance＇s formula. Correlation analysis showed that several factors could affect the MGD level. Mann-whitney test and Non-parametric ANOVA analyses were used to compare the MGD level grouped by view type and radiographic systems, No significant difference was found in MGD between the craniocaudal （CC） group and the mediolateral oblique （MLO） group. The MGD level was higher in the CR group than in the other two groups. MGD was positively correlated with the compressed breast thickness （CBT）. MGD varied with the half value layer （HVL） and increased first then decreased, The mean MGD level in China is about 1.6 mGy and is lower than the guidance level in the International Basic Safety Standards （IBSS）.

Preliminary Study on the Efficacy of a New Zero-load X-ray Protector for Coronary Intervention

The application of radiation for medical examination and treatment has increased rapidly since the 1980 s.In contrast to other radiation-based imaging and medical treatment,medical staff working in fluoroscopic-based procedures have to suffer radiation exposure.Its harm is well known not only for the deterministic effects causing cataract or dermatitis[1],but also for the stochastic effects with increased risks of chromosomal damage or malignant tumors[2].

A new method for position-sensitive measurement of beta surface contamination

In this paper, we propose a new method for position-sensitive measurement of beta surface contamination. With a position-sensitive detector of enlarged sensitive detection area, accurate information of the contamination distribution can be obtained. The positionsensitive detection is based on a large-area plastic scintillator and the wavelength shifting(WLS) fibers and adopts the ‘‘light center of gravity'' method. Optical transmission of the detector is simulated with a preliminary detector model, and feasibility of the detector design and measurement method is evaluated using an experiment system.The simulation and experiment results at different beta-ray incident points on the scintillator surface show that there is a polynomial relationship between the average amplitude ratio of the output pulses from the two parallel WLS fibers in the same fiber layer and the relative distance from the incident point to the WLS fiber.

Projectile electron loss in collisions of light charged ions with helium

We investigate the single-electron loss processes of light charged ions （Li^1＋,2＋, C^2＋,3＋,5＋, and O^2＋,3＋） in collisions with helium. To better understand the experimental results, we propose a theoretical model to calculate the cross section of projectile electron loss. In this model, an ionization radius of the incident ion was defined under the classical over-barrier model, and we developed ＂strings＂ to explain the processes of projectile electron loss, which is similar with the molecular over-barrier model. Theoretical calculations are in good agreement with the experimental results for the cross section of single-electron loss and the ratio of double-to-single ionization of helium associated with one-electron loss.

Developmental Toxicity in Mice Following Paternal Exposure to Di-N-Butyl-Phthalate (DBP)

Objective The aim of the present study was to investigate the effects of paternal Di‐N‐butyl‐phthalate （DBP） exposure pre‐ and postnatally on F1 generation offspring,and prenatally on F2 generation offspring.Methods Male mice were exposed to either 500 mg/kg or 2 000 mg/kg of DBP for 8 weeks,and mated with non‐exposed females.Three‐quarters of the females were sacrificed a day prior to parturition,and examined for the number of living and dead implantations,and incidence of gross malformations.Pups from the remaining females were assessed for developmental markers,growth parameters,as well as sperm quantity and quality.Results There were no changes in the fertility of parents and in intrauterine development of the offspring.Pups of DBP‐exposed males demonstrated growth‐retardation.Following paternal exposure to 500 mg/kg bw of DBP,there were almost twice the number of males than females born in the F1 generation.F1 generation females had a 2.5‐day delay in vaginal opening.Paternal exposure to 2 000 mg/kg bw of DBP increased the incidence of sperm head malformations in F1 generation males;however,there were no changes in the fertility and viability of foetuses in the F2 generation.Conclusion Paternal DBP exposure may disturb the sex ratio of the offspring,delay female sexual maturation,and deteriorate the sperm quality of F1 generation males.

Lamb’s tripe extract and vitamin B12 capsule plus celecoxib reverses intestinal metaplasia and atrophy:A retrospective cohort study

BACKGROUND Chronic atrophic gastritis(AG)with intestinal metaplasia(IM)significantly increases the risk of gastric cancer.Some medicines have showed definite therapeutic effects in AG and IM regression.AIM To validate the efficacy of Lamb’s tripe extract and vitamin B12 capsule(LTEVB12)initial therapy and celecoxib rescue therapy for IM and AG.METHODS A total of 255 patients were included to receive LTEVB12 initial therapy(2 capsules each time,three times daily for 6 mo)in hospital in this study.The patients with failure of IM regression continued to receive celecoxib rescue therapy(200 mg,once daily for 6 mo).After each therapy finished,the patients underwent endoscopy and biopsy examination.The regression efficiency was assessed by the operative link on gastritis assessment(OLGA)and the operative link on the gastric intestinal metaplasia assessment(OLGIM)staging system.Logistic regression analysis was applied to identify factors associated with the curative effect.RESULTS For LTEVB12 initial therapy,the reversal rates of IM and AG were 52.95%and 48.24%,respectively.Analogously,for celecoxib rescue therapy,the effective rates for IM and AG were 56.25%and 51.56%,respectively.The IM regression rate of complete therapy was up to 85.03%.In different OLGA and OLGIM stages of IM patients,therapeutic efficiency showed a significant difference in each group(P<0.05).For both therapies,patients with high stages(III or IV)of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages(I or II).Among patients with high stages(OLGIM III and IV),the IM regression rate was above 70%for each therapy.Eating habits,fresh vegetable intake,and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy,especially high-salt diet(odds ratio=1.852,P<0.05).CONCLUSION Monotherapy could reverse IM and AG.LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect.IM may not be the point of no return among gastric precancerous lesions.

Efficacy and safety of high-dose esomeprazole–amoxicillin dual therapy for Helicobacter pylori rescue treatment:a multicenter,prospective,randomized,controlled trial

Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H.pylori rescue treatment.Methods:This was a prospective,randomized,multicenter,non-inferiority trial.Patients recruited from eight centers who had failed previous treatment were randomly(1:1)allocated to two eradication groups:HDDT(esomeprazole 40 mg and amoxicillin 1000 mg three times daily;theHDDTgroup)and bismuth-containing quadruple therapy(esomeprazole 40 mg,bismuth potassium citrate 220 mg,and furazolidone 100 mg twice daily,combined with tetracycline 500 mg three times daily;the tetracycline,furazolidone,esomeprazole,and bismuth[TFEB]group)for 14 days.The primary endpoint was the H.pylori eradication rate.The secondary endpoints were adverse effects,symptom improvement rates,and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study.The HDDT group achieved eradication rates of 75.4%(248/329),81.0%(248/306),and 81.3%(248/305)asdetermined by the intention-to-treat(ITT),modified intention-totreat(MITT),and per-protocol(PP)analyses,respectively.The eradication rates were similar to those in the TFEB group:78.1%(257/329),84.2%(257/305),and 85.1%(257/302).The lower 95%confidence interval boundary(9.19%in the ITT analysis,9.21%in the MITT analysis,and9.73%in the PP analysis)was greater than the predefined non-inferiority margin of10%,establishing a non-inferiority of the HDDT group vs.the TFEB group.The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group(11.1%vs.26.8%,P<0.001).Symptom improvement rates and patients’compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy,with fewer adverse effects and good treatment compliance,suggesting HDDT as an alternative for H.pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov,NCT04678492.

Review of the 5·7 Nanjing^(192)Ir source radiological accident

This paper gives a detailed description of a radiological accident of ^(192)Ir source occurring on May 7,2014 in Nanjing,China(the 5⋅7 accident),encompassing a combination of accident overview,emergency response,investigation process and results,dose estimation,medical treatment,experience and lessons learnt.The investigation showed that the accident was mainly caused by insufficient attention to the radiation safety,non-compliance with licensing conditions and employment of untrained temporary radiographer without equipped with alarm dosimeters.Additionally,no area radiation survey meter was used to verify whether the source would have retracted to radiography camera after every exposure.It therefore is the important means to strengthen the management of radioactive source safety and put the strict management measures in place,implement the requirements for personnel qualification management,strengthen regulatory inspection and actively poster safety culture,which are necessary to avoid accidents.This paper aims to provide experience and reference for the emergency response and countermeasure of radiological accidents involving industrial radioactive sources.

MG7-Ag, hTERT, and TFF2 identified high-risk intestinal metaplasia and constituted a prediction model for gastric cancer

To the Editor:Gastric cancer(GC)ranks third in incidence and mortality both worldwide and in China.[1,2]Intestinal metaplasia(IM)significantly increases risk of GC so that identifying high-risk IM patients who will progress to GC is crucial.Currently,the effect of many risk-stratification methods for gastric precancerous lesions(GPLs)was minimal.Monoclonal gastric cancer 7 antigen(MG7-Ag)combined with cyclooxygenase-2 has been shown earlywarning value for the progression of GPLs.[3]The expression of human telomerase reverse transcriptase(hTERT)was proven to be related to state of cell proliferation in IM tissue.[4]Loss expression of trefoil factor family 2(TFF2)from spasmolytic polypeptideexpressing metaplasia to IM may lead to a hyperproliferation and deleterious mutations.[5]We tried to construct and verify a multimolecular prediction model included MG7-Ag and hTERT and TFF2,which could identify high-risk IM patients and have early-warning value for GC.

Risk communication in the post-Fukushima era

In the long-term phases,clear risk communication in the post-Fukushima era is necessary and significant.It is the most urgent in this post-accident phase is for residents to access to all the information available within the scope of current knowledge in order to support their life decisions.For full recovery,authorities,specialists,international organizations,media,and the public will need to work together.The speed of innovation in risk communication should catch up to the development speed of the internet.Long-term communication will be necessary.Learning about the Fukushima nuclear accident experience is essential for the prevention and risk communication of possible accidents in the future.