BACKGROUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a pro...BACKGROUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a problem, interpreting when it is appropriate to intervene, recognizing personal responsibility to intervene, and knowing how to intervene. Using virtual reality (VR) to simulate emergencies such as sudden cardiac arrest (SCA) can be used to study these stages. METHODS: In a secondary analysis of an observational cohort study, we analyzed bystander self-effi cacy for stages of BI before and after simulated SCA. Each subject participated in a singleplayer, immersive, VR SCA scenario. Subjects interacted with simulated bystanders through voice commands (“call 911”,“get an AED”). Actions taken in scenario, like performing CPR, were documented. Scenario BI actions were compared based on dichotomized comfort/discomfort. RESULTS: From June 2016 to June 2017, 119 subjects participated. Average age was 37±14 years, 44% were female and 46% reported CPR training within 2 years. During the scenario, 98%“noticed the event” and “interpreted it as a problem”, 78%“took responsibility”, and 54%“possessed the necessary skills”. Self-effi cacy increased from pre- to post-scenario: noticing the event increased from 80% to 96%;interpreting as a problem increased from 86% to 97%;taking responsibility increased from 56% to 93%;possessing necessary skills increased from 47% to 63%(P<0.001). CONCLUSION: Self-efficacy to respond to an SCA event increased pre- to post-scenario. Bystanders who reported feeling comfortable “taking responsibility to intervene” during an emergency were more likely to take action during a simulated emergency.展开更多
In the past 20 years, the classic paradigm in radiobiology recognizing DNA as the main target for the action of radiation has changed. The new paradigm assumes that both targeted and non-targeted effects of radiation ...In the past 20 years, the classic paradigm in radiobiology recognizing DNA as the main target for the action of radiation has changed. The new paradigm assumes that both targeted and non-targeted effects of radiation determine the final outcome of irradiation. Radiotherapy is one of the main modality treatments of neoplastic diseases with intent to cure, or sometimes to palliate only, thus radiation-induced non-targeted effect, commonly referred to as the radiation-induced bystander effect (RIBE) may have a share in cancer treatment. RIBE is mediated by molecular signaling from radiation targeted cells to their non-irradiated neighbors, and comprises such phenomena as bystander effect, genomic instability, adaptive response and abscopal effect. Whereas first three phenomena may appear both in vitro and in vivo, an abscopal effect is closely related to partial body irradiation and is a systemic effect mediated by immunologic system which synergizes with radiotherapy. From the clinical point of view abscopal effect is particularly interesting due to both its possible valuable contribution to the treatment of metastases, and the potential harmful effects as induction of genetic instability and carcinogenesis. This review summarized the main results of investigations of non-targeted effects coming from in vitro monolayer cultures, 3-dimentional models of tissues, preclinical studies on rodents and clinically observed beneficial abscopal effects with particular emphasis on participation of immunotherapy in the creation of abscopal effects.展开更多
BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect a...BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.展开更多
We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient ...We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.展开更多
This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the...This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the kinetics model proposed by (McMahon et al. 2013) for in vivo conditions coupled with a hypothesis called “Layer-limited bystander signaling (LLBS)” to demonstrate 1) an enhancement in TCP (i.e. Enhanced TCP or ETCP) due to bystander signals, 2) the development of nonequilibrium of RIBE under steep dose gradient regions and 3) the reduction in ETCP in the surface of Clinical Target Volume (CTV) due to the non-equilibrium of RIBE. We incorporated the elements of RIBE directly in the existing Poisson LQ model available in Pinnacle3 TPS (Version 9.10.0) to compute the percentage reduction of ETCP in the tumor surface due to nonequilibrium of RIBE. The percentage improvement in TCP obtained in tumor surface by accounting for RIBE is about 46% lower than that obtained in the interior of the tumor. This suggests that relatively more number of cancerous cells might survive in the vicinity of tumor surface. The result obtained from the study is indicative of an additional uncertainty component associated with radiation treatment. Hence, this paper suggests that the radiation treatments employing steep dose gradients could be biophysically different in many ways.展开更多
Radiation-induced bystander effect is the phenomenon that the cells which are not directly exposed to radiation have identical or similar biological reactions with the cells of direct exposure to radiation. It is a co...Radiation-induced bystander effect is the phenomenon that the cells which are not directly exposed to radiation have identical or similar biological reactions with the cells of direct exposure to radiation. It is a common second reaction of radiotherapy and has a strong impact on cancer patients. Here we review and synthesize its studies in vitro and in vivo, its time effect and the mechanism. And the existing problems and its research significance are also discussed.展开更多
Since the first report by Nagasawa et al.[1] in 1992, which demonstrates evidences that non-irradiated bystandercells also showed damage of sister chromatid exchange in samples irradiated with low-dose α particles, r...Since the first report by Nagasawa et al.[1] in 1992, which demonstrates evidences that non-irradiated bystandercells also showed damage of sister chromatid exchange in samples irradiated with low-dose α particles, radiationinduced bystander effect (RIBE) has been studied for more than decades and many publications showed that RIBEswere found after treatment of both low and high-LET radiations. However, there are also some reports showingcontrary facts that no obvious bystander effects can be found, for example Fournier et al.[2] reported that theyobserved no early cytogenetic damage in the bystander cells after heavy ion microbeam irradiation. RIBE is ofgreat interest in radiotherapy using X-ray radiation or high-LET heavy ions because of RIBE-related cell killing andcarcinogenesis in neighboring normal cells[3]. In this work, we investigated the damage in bystander cells exposedto medium from cells irradiated with X-ray and carbon beam.展开更多
Genomic instability after radiation is the main reason of the increase of malignancy degree and normal tissuetransformation[1]. Previous study indicated that bystander cells show more long-term genomic instability aft...Genomic instability after radiation is the main reason of the increase of malignancy degree and normal tissuetransformation[1]. Previous study indicated that bystander cells show more long-term genomic instability afterradiation[2].In this study, non-small cell lung cancer cell line (A549) was radiated with X-rays (30 kV of 2 Gy), and theconditioned medium was transferred to bystander cells. The fast and slowly proliferating populations in bystandercells were isolated by the colony formation assay. After one month, the chromosome number (Table 1, Fig. 1),drug resistance ability (Fig. 2) and cancer stem-like cell enrichment (Fig. 3) were investigated in fast and slowlyproliferating cells, respectively.展开更多
Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke trea...Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.展开更多
Aim:We aimed to investigate the association between bystander cardiopulmonary resuscitation(CPR)and survival of patients with out-of-hospital cardiac arrests(OHCA)in Beiing.Methods:This observational study analyzed ad...Aim:We aimed to investigate the association between bystander cardiopulmonary resuscitation(CPR)and survival of patients with out-of-hospital cardiac arrests(OHCA)in Beiing.Methods:This observational study analyzed adult patients with OHCA treated by the Beiing emergency medical service(EMS)from January 2013 to December 2017.Data were collected in a Utstein style with a 1-year follow-up and a primary outcome 01 survival to hospital discharge.Secondary outcomes were return of spontaneous circulation(ROSC),survival to admission,favorable neurological outcome at hospital discharge,and survival and favorable neurological outcomes of up to 1 year.Results:A total of 5016 patients with OHCA from Beiing's urban area were recorded by EMS,wherein 765 patients(15.25%)underwent bystander CPR.The data were propensity score-matched forage,sex,location,witness,aetiology,initial rhythm,and call to EMS arrival to compare the difference between the occurrence and nonoccurrence of bystander CPR.The survival upon the discharge of patients who experienced bystander CPR was superior to that of patients who did not receive bystander CPR(3.7%vs 1.2%,respectively;P<0.001).Moreover,patients with OHCA resuscitated with bystander CPR achieved better outcomes of ROSC,survival to admission,favorable neurological outcome at hospital discharge,survival and favorable neurological outcome after 1 year compared with those who were not resuscitated with bystander CPR.Conclusion:Survival and neu rological outcome of patients who underwent bystander CPR was better than those who underwent nonbystander CPR in Beiing.However,the rate of bystander CPR was low.展开更多
Radiation-induced bystander effect(RIBE)and abscopal effect(RIAE)are non-target cellular responses outside the radiation field.It has been recognized that these effects are of great significance to both radiation prot...Radiation-induced bystander effect(RIBE)and abscopal effect(RIAE)are non-target cellular responses outside the radiation field.It has been recognized that these effects are of great significance to both radiation protection of environmental low-dose radiation and clinical radiotherapy in which the anti-tumor abscopal effect is even beneficial to patients.However,the mechanisms of them are still obscure.This review briefly introduced the inflammatory signaling factors and immune regulation in RIBE in vitro and RIAE on normal tissues and organisms,and emphasized the genetic consequences of RIAE.Based on a large number of investigation results,we suggest that it’s time to incorporate RIBE and RIAE into the concept of“classic”radiation biology.展开更多
Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation bystander effect. In
Purpose: Ionizing radiation is a well known human carcinogen. It has been generally accepted that direct damage to nuclear DNA is the main caused to induce genotoxicity
We report resuscitation of a near-drowning child by a bystander in a rural south China township.Resuscitation was performed on a 6-year-old,otherwise healthy boy who was witnessed drowning in a river,with submersion f...We report resuscitation of a near-drowning child by a bystander in a rural south China township.Resuscitation was performed on a 6-year-old,otherwise healthy boy who was witnessed drowning in a river,with submersion for approximately 12 min.Following several resuscitation attempts,spontaneous breathing was established at the scene and the boy was transferred to a nearby hospital.He developed pneumonia but recovered completely on the ward and was discharged without any neurologic disabilities.This case shows that early bystander resuscitation is an important factor for survival after submersion.The search for an ideal approach to resuscitation must continue,and all members of society must work together towards this goal.展开更多
A public debate on the bystander effect,prompted by a viral video of a fatal traffic accident,has highlighted continued gaps in China’s'Good Samaritan'laws—legal protections for those who volunteer to help v...A public debate on the bystander effect,prompted by a viral video of a fatal traffic accident,has highlighted continued gaps in China’s'Good Samaritan'laws—legal protections for those who volunteer to help victims.The 94-second video from Zhumadian,Henan,recorded in April but circulated in mid-June,showed a展开更多
Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-ca...Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-called "bystander effect" mediated by thymidine kinase (TK) suicide gene therapy on PCa cells is not of significance and to explore the role of GJIC in PCa carcinogenesis. mRNA and protein expression of Cx43 in a PCa cell line PC-3m was detected by re- verse-transcription polymerase chain reaction (RT-PCR) and strapt-avidin-biotin-enzyme complex (SABC) immunohistochemical staining, and inherent GJIC of PC-3m cells was assayed by scrape-loading and dye transfer (SLDT) assay. The expression of Cx43 in human normal and malig- nant prostate tissues was determined by SABC immunohistochemistry as well. It was found that Cx43 mRNA and protein expression in PC-3m cells was slightly reduced as compared with positive controls and the location of Cx43 protein was aberrant in cytoplasm rather than on membrane. As- sessment of paraffin sections demonstrated that the expression of Cx43 protein in PCa cells was ab- normally located and markedly diminished as compared with normal prostatic epithelial ones, dis- playing a negative correlation to the pathological grade (χ2=4.025, P<0.05). Additionally, capacity of inherent GJIC in PC-3m cells was disrupted, which was semi-quantified as (+) or (-). It was indi- cated that both down-regulated expression of Cx43 mRNA and aberrant location of Cx43 protein par- ticipated in the mechanisms leading to deficient GJIC in PC-3m cells. Lack of efficient GJIC is a molecular event, which may contribute not only to limited extent of "bystander effect", but also to initiation and progression of prostatic neoplasm.展开更多
Background: Since 2004, the number of installed Automated External Defibrillator (AED) has been increased in Japan annually, the cumulative number of sold AED more than 600,000 units by 2016. Despite there have been a...Background: Since 2004, the number of installed Automated External Defibrillator (AED) has been increased in Japan annually, the cumulative number of sold AED more than 600,000 units by 2016. Despite there have been about 130,000 out of hospital cardiac arrest annually, there have only 1302 cases delivered defibrillation by bystanders at the scene. Therefore, we investigate that number of AED installation and usage rate for Out of Hospital Cardiac Arrest (OHCA) patients. Methods: Retrospective metropolitan wide cohort study. Subject: Total 13,364 OHCA patients in the Tokyo Metropolitan area from Jan. 1 through Dec. 31 in 2012 were eligible for theses analyses. Also, OHCA occurrence place and AED usage rate were studied. Results: 82.8% of OHCA occurred at residences, 10% at outdoors, 6.4% at indoors, only 0.7% at schools. In the other hand, highest bystander’s CPR rates were found in sports facilities and schools (71.4%). The installation rate of AEDs in residences was 9.6%, instead of highest incidence for OHCA patients, school and sports institute made up 21.4% of AED installations, but only 1.0% of the incidences of cardiac arrest. We found that there is a mismatch between incidence sites of cardiac arrest and locations of installed AED. Discussion: It is essential to increase the number of AED installations. Furthermore, it is desirable to install AEDs in locations where cardiac arrest is liable to occur following guidelines for the proper placement of AEDs, and important to further spread BLS education among the general citizens.展开更多
Objective: To study the induction of sensitivity toganciclovir (GCV) or acyclovir (ACV) in humanhepatocellular carcinoma (HCC) cell line trans-ferred by an Epstein-Barr virus (EBV)-based repli-con expression vector ca...Objective: To study the induction of sensitivity toganciclovir (GCV) or acyclovir (ACV) in humanhepatocellular carcinoma (HCC) cell line trans-ferred by an Epstein-Barr virus (EBV)-based repli-con expression vector carrying the herpes simplex vi-rus thymidine kinase (HSV-tk) gene, including kill-ing and "bystander" effect, and also the gene delive-ry procedure and route of gene therapy in vivo forHCC.Methods: Liposome-entrapped plasmid pDR2/tk wastransferred into HCC cells, and then different con-centrations of GCV or ACV were added. The trans-ferred cells were mixed with untransferred HCC cellsin different proportion and 200 μmol/L GCV wasthen added into each well. After 72 hours, all sam-ples were measured by MTT colorimetric assay. AnEBV-based plasmid eukarotic expression vector car-rying IL-2 cDNA was used. Three models of gene di-rect injection in the local liver, injection through theportal vein, and injection through the embolized he-patic artery were established in closed Wister rats.For each model, two subgroups, injected either na-ked plasmid DNA or lipofectin-plasmid complex wereincluded. The expression of the IL-2 gene was regu-larly examined immunohistochemically.Results: GCV or ACV could apparently kill thetransferred HCC cells at a concentration of 0. 2μmol/L. The inhibition rate was changed with dif-ferent drug concentrations. The "bystander" effectwas obviously induced at a transferred to untrans-ferred HCC cells ratio of 1:5. IL-2 gene expressionwas observed in liver cells of all animals on day 3,which reached peak within 3-7 days, and declined af-ter day 7. Injection of naked plasmid DNA throughthe hepatic artery plus embolization obtained a bestexpression.Conclusions: EBV-based vector is suitable for carry-ing suicide gene therapy for hepatocellular carcino-ma. Gene direct delivery in vivo combined with in-terventional surgery can be used to treat hepatocellu-lar carcinoma.展开更多
BACKGROUND: To evaluate the outcome of cardiopulmonary resuscitation(CPR) in out-ofhospital cardiac arrests(OHCA) in India and factors infl uencing the outcome.METHODS: The outcome and related factors like demographic...BACKGROUND: To evaluate the outcome of cardiopulmonary resuscitation(CPR) in out-ofhospital cardiac arrests(OHCA) in India and factors infl uencing the outcome.METHODS: The outcome and related factors like demographics, aspects of the OHCA event, return of spontaneous circulation(ROSC) and survival to discharge, among the 80 adult patients presenting to emergency department experiencing OHCA considered for resuscitation between January 2014 to April 2015, were analyzed, according to the guidelines of the Utstein consensus conference.RESULTS: The survival rate to hospital admission was 32.5%, the survival rate to hospital discharge was 8.8% and with good cerebral performance category(CPC1) neurological status was 3.8%. Majority of OHCA was seen in elderly individuals between 51 to 60 years, predominately in males. Majority of OHCA were witnessed arrests(56.5%) with 1.3% bystander CPR rate, 92.5% arrests occurred at home, 96% presented with initial non-shockable rhythm and 92.5% with presumed cardiac etiology but survival was better in those who experienced OHCA at public place, in witnessed arrests, in patients who had shockable presenting rhythm and in those where CPR duration was ≤20 minutes.CONCLUSION: Witnessed arrests, early initiation of CPR by bystanders, CPR duration ≤20 minutes, initial presenting shockable rhythm, OHCA with non-cardiac etiology are associated with a good outcome. To improve the outcome of CPR and the low survival rates after an OHCA event in India, focused strategies should be designed to set up an emergency medical system(EMS), to boost the rates of bystander CPR and education of the lay public in basic CPR.展开更多
BACKGROUND: Few studies have examined the association of layperson characteristics with cardiopulmonary resuscitation(CPR) provision. Previous studies suggested provider characteristics, including age and gender, were...BACKGROUND: Few studies have examined the association of layperson characteristics with cardiopulmonary resuscitation(CPR) provision. Previous studies suggested provider characteristics, including age and gender, were associated with CPR quality, particularly chest compression(CC) depth. We sought to determine the association of subject characteristics, including age and gender with layperson CPR quality during an unannounced simulated CPR event. We hypothesized shallower CC depth in females, and older-aged subjects.METHODS: As part of a larger multicenter randomized controlled trial of CPR training for cardiac patients' caregivers, CPR skills were assessed 6 months after training. We analyzed associations between subject characteristics and CC rate, CC depth and no-? ow time. Each variable was analyzed independently; signi? cant predictors determined via univariate analysis were assessed in a multivariate regression model.RESULTS: A total of 521 laypersons completed a 6-month CPR skills assessment and were included in the analysis. Mean age was 51.8±13.7 years, 75% were female, 57% were Caucasian. Overall, mean CC rate was 88.5±25.0 per minute, CC depth was 50.9±2.0 mm, and mean no-flow time was 15.9±2.7 sec/min. CC depth decreased signi? cantly in subjects >62 years(P<0.001). Male subjects performed deeper CCs than female subjects(47.5±1.7 vs. 41.9±0.6, P<0.001).CONCLUSION: We found that layperson age >62 years and female gender are associated with shallower CC depth.展开更多
基金supported by the Medtronic Foundationthe Laerdal Foundation
文摘BACKGROUND: Understanding bystander reactions to an emergency is an important component of effective training. Four stages of bystander intervention (BI) have been previously described: noticing the situation as a problem, interpreting when it is appropriate to intervene, recognizing personal responsibility to intervene, and knowing how to intervene. Using virtual reality (VR) to simulate emergencies such as sudden cardiac arrest (SCA) can be used to study these stages. METHODS: In a secondary analysis of an observational cohort study, we analyzed bystander self-effi cacy for stages of BI before and after simulated SCA. Each subject participated in a singleplayer, immersive, VR SCA scenario. Subjects interacted with simulated bystanders through voice commands (“call 911”,“get an AED”). Actions taken in scenario, like performing CPR, were documented. Scenario BI actions were compared based on dichotomized comfort/discomfort. RESULTS: From June 2016 to June 2017, 119 subjects participated. Average age was 37±14 years, 44% were female and 46% reported CPR training within 2 years. During the scenario, 98%“noticed the event” and “interpreted it as a problem”, 78%“took responsibility”, and 54%“possessed the necessary skills”. Self-effi cacy increased from pre- to post-scenario: noticing the event increased from 80% to 96%;interpreting as a problem increased from 86% to 97%;taking responsibility increased from 56% to 93%;possessing necessary skills increased from 47% to 63%(P<0.001). CONCLUSION: Self-efficacy to respond to an SCA event increased pre- to post-scenario. Bystanders who reported feeling comfortable “taking responsibility to intervene” during an emergency were more likely to take action during a simulated emergency.
文摘In the past 20 years, the classic paradigm in radiobiology recognizing DNA as the main target for the action of radiation has changed. The new paradigm assumes that both targeted and non-targeted effects of radiation determine the final outcome of irradiation. Radiotherapy is one of the main modality treatments of neoplastic diseases with intent to cure, or sometimes to palliate only, thus radiation-induced non-targeted effect, commonly referred to as the radiation-induced bystander effect (RIBE) may have a share in cancer treatment. RIBE is mediated by molecular signaling from radiation targeted cells to their non-irradiated neighbors, and comprises such phenomena as bystander effect, genomic instability, adaptive response and abscopal effect. Whereas first three phenomena may appear both in vitro and in vivo, an abscopal effect is closely related to partial body irradiation and is a systemic effect mediated by immunologic system which synergizes with radiotherapy. From the clinical point of view abscopal effect is particularly interesting due to both its possible valuable contribution to the treatment of metastases, and the potential harmful effects as induction of genetic instability and carcinogenesis. This review summarized the main results of investigations of non-targeted effects coming from in vitro monolayer cultures, 3-dimentional models of tissues, preclinical studies on rodents and clinically observed beneficial abscopal effects with particular emphasis on participation of immunotherapy in the creation of abscopal effects.
基金Supported by Key R&D Plan of Science and Technology Program of Gansu Province,China,No.19YF3FH001.
文摘BACKGROUND Although the bystander effect and abscopal effect are familiar in medicine,they are relatively rare in clinical practice.Herein,we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma.CASE SUMMARY A 44-year-old female presented with shortness of breath.Eleven years prior,she was diagnosed with athymic tumor located in the anterosuperior mediastinum.She underwent extensive tumor resection,and the postoperative pathologic diagnosis was thymic carcinoma.She was administered 50 Gy/25 Fx of postoperative radiation.In 2019,she was diagnosed with a recurrence of thymic carcinoma,with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity,the largest of which was in the diaphragm pleura proximal to the pericardium,with a size of 6.7 cm×5.3 cm×4.8 cm.She received carbonion radiotherapy.After carbon-ion radiotherapy treatment,the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging.We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case.CONCLUSION This report is the first of obvious abscopal and bystander effects following carbonion irradiation in a human patient,and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.
文摘We previously reported a serendipitous finding from a patient with refractory severe aplastic anemia who had gotten an unexpected hematological response to treatment with gut-cleansing preparations(GCPs).This patient experienced three recurrences over the ensuing one year of intermittent GCP treatments,with each recurrence occurring 7-8 wk from a GCP.After his third recurrence,he was prescribed successive treatment with rifampicin,berberine,and monthly administered GCP for 4 mo,and he developed an erythroid proliferative neoplasma and an overwhelming enteropathy,and eventually died of septic shock.Laboratory investigations had validated the resolution of myelosuppression and the appearance of malignant clonal hematopoiesis.From the treatment process and laboratory investigations,it is reasonably inferred that the engagement of gut inflammation is critically required in sustaining the overall pathophysiology of acquired aplastic anemia probably by creating a chronic inflammatory state.Incorporation of rifampicin,berberine,and monthly GCP into cyclosporine can enhance the immunosuppressive effect.In a subgroup of acquired aplastic anemia patients whose pathogenesis is associated with genotoxic exposure,the suppressed normal hematopoiesis may result from the bystander insult that is mediated by the soluble inflammatory cytokines generated in response to the immunogenic products of damaged hematopoietic cells in the context of chronic inflammatory state and may offer a protective antineoplastic mechanism against malignant proliferation.
文摘This work aims to theoretically show the development of a nonequilibrium of radiation-induced bystander effect (RIBE) under steep dose gradient regions that typically occur in the field edges of a beam. We applied the kinetics model proposed by (McMahon et al. 2013) for in vivo conditions coupled with a hypothesis called “Layer-limited bystander signaling (LLBS)” to demonstrate 1) an enhancement in TCP (i.e. Enhanced TCP or ETCP) due to bystander signals, 2) the development of nonequilibrium of RIBE under steep dose gradient regions and 3) the reduction in ETCP in the surface of Clinical Target Volume (CTV) due to the non-equilibrium of RIBE. We incorporated the elements of RIBE directly in the existing Poisson LQ model available in Pinnacle3 TPS (Version 9.10.0) to compute the percentage reduction of ETCP in the tumor surface due to nonequilibrium of RIBE. The percentage improvement in TCP obtained in tumor surface by accounting for RIBE is about 46% lower than that obtained in the interior of the tumor. This suggests that relatively more number of cancerous cells might survive in the vicinity of tumor surface. The result obtained from the study is indicative of an additional uncertainty component associated with radiation treatment. Hence, this paper suggests that the radiation treatments employing steep dose gradients could be biophysically different in many ways.
基金the National Natural Science Foundation of China (81460695, 81760836).
文摘Radiation-induced bystander effect is the phenomenon that the cells which are not directly exposed to radiation have identical or similar biological reactions with the cells of direct exposure to radiation. It is a common second reaction of radiotherapy and has a strong impact on cancer patients. Here we review and synthesize its studies in vitro and in vivo, its time effect and the mechanism. And the existing problems and its research significance are also discussed.
文摘Since the first report by Nagasawa et al.[1] in 1992, which demonstrates evidences that non-irradiated bystandercells also showed damage of sister chromatid exchange in samples irradiated with low-dose α particles, radiationinduced bystander effect (RIBE) has been studied for more than decades and many publications showed that RIBEswere found after treatment of both low and high-LET radiations. However, there are also some reports showingcontrary facts that no obvious bystander effects can be found, for example Fournier et al.[2] reported that theyobserved no early cytogenetic damage in the bystander cells after heavy ion microbeam irradiation. RIBE is ofgreat interest in radiotherapy using X-ray radiation or high-LET heavy ions because of RIBE-related cell killing andcarcinogenesis in neighboring normal cells[3]. In this work, we investigated the damage in bystander cells exposedto medium from cells irradiated with X-ray and carbon beam.
文摘Genomic instability after radiation is the main reason of the increase of malignancy degree and normal tissuetransformation[1]. Previous study indicated that bystander cells show more long-term genomic instability afterradiation[2].In this study, non-small cell lung cancer cell line (A549) was radiated with X-rays (30 kV of 2 Gy), and theconditioned medium was transferred to bystander cells. The fast and slowly proliferating populations in bystandercells were isolated by the colony formation assay. After one month, the chromosome number (Table 1, Fig. 1),drug resistance ability (Fig. 2) and cancer stem-like cell enrichment (Fig. 3) were investigated in fast and slowlyproliferating cells, respectively.
基金supported by the National Natural Science Foundation of China,No.81971105(to ZNG)the Science and Technology Department of Jilin Province,No.YDZJ202201ZYTS677(to ZNG)+3 种基金Talent Reserve Program of the First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)Science and Technology Department of Jilin Province,Nos.YDZJ202302CXJD061,20220303002SF(to YY)Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY).
文摘Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
基金the Beiing Municipal Administration of Hospitals Clinical Medicine Development(XMLX201313)National Science&Technology Fundamental Resource Investigation Programme of China(No.2018FY 100600,2018FY 100602)。
文摘Aim:We aimed to investigate the association between bystander cardiopulmonary resuscitation(CPR)and survival of patients with out-of-hospital cardiac arrests(OHCA)in Beiing.Methods:This observational study analyzed adult patients with OHCA treated by the Beiing emergency medical service(EMS)from January 2013 to December 2017.Data were collected in a Utstein style with a 1-year follow-up and a primary outcome 01 survival to hospital discharge.Secondary outcomes were return of spontaneous circulation(ROSC),survival to admission,favorable neurological outcome at hospital discharge,and survival and favorable neurological outcomes of up to 1 year.Results:A total of 5016 patients with OHCA from Beiing's urban area were recorded by EMS,wherein 765 patients(15.25%)underwent bystander CPR.The data were propensity score-matched forage,sex,location,witness,aetiology,initial rhythm,and call to EMS arrival to compare the difference between the occurrence and nonoccurrence of bystander CPR.The survival upon the discharge of patients who experienced bystander CPR was superior to that of patients who did not receive bystander CPR(3.7%vs 1.2%,respectively;P<0.001).Moreover,patients with OHCA resuscitated with bystander CPR achieved better outcomes of ROSC,survival to admission,favorable neurological outcome at hospital discharge,survival and favorable neurological outcome after 1 year compared with those who were not resuscitated with bystander CPR.Conclusion:Survival and neu rological outcome of patients who underwent bystander CPR was better than those who underwent nonbystander CPR in Beiing.However,the rate of bystander CPR was low.
文摘Radiation-induced bystander effect(RIBE)and abscopal effect(RIAE)are non-target cellular responses outside the radiation field.It has been recognized that these effects are of great significance to both radiation protection of environmental low-dose radiation and clinical radiotherapy in which the anti-tumor abscopal effect is even beneficial to patients.However,the mechanisms of them are still obscure.This review briefly introduced the inflammatory signaling factors and immune regulation in RIBE in vitro and RIAE on normal tissues and organisms,and emphasized the genetic consequences of RIAE.Based on a large number of investigation results,we suggest that it’s time to incorporate RIBE and RIAE into the concept of“classic”radiation biology.
文摘Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation bystander effect. In
文摘Purpose: Ionizing radiation is a well known human carcinogen. It has been generally accepted that direct damage to nuclear DNA is the main caused to induce genotoxicity
文摘We report resuscitation of a near-drowning child by a bystander in a rural south China township.Resuscitation was performed on a 6-year-old,otherwise healthy boy who was witnessed drowning in a river,with submersion for approximately 12 min.Following several resuscitation attempts,spontaneous breathing was established at the scene and the boy was transferred to a nearby hospital.He developed pneumonia but recovered completely on the ward and was discharged without any neurologic disabilities.This case shows that early bystander resuscitation is an important factor for survival after submersion.The search for an ideal approach to resuscitation must continue,and all members of society must work together towards this goal.
文摘A public debate on the bystander effect,prompted by a viral video of a fatal traffic accident,has highlighted continued gaps in China’s'Good Samaritan'laws—legal protections for those who volunteer to help victims.The 94-second video from Zhumadian,Henan,recorded in April but circulated in mid-June,showed a
文摘Connexin-43 (Cx43) expression in prostate cancer (PCa) cells and the potency of gap junctional intercellular communication (GJIC) in the cells were investigated, with an attempt to elu- cidate the reason why the so-called "bystander effect" mediated by thymidine kinase (TK) suicide gene therapy on PCa cells is not of significance and to explore the role of GJIC in PCa carcinogenesis. mRNA and protein expression of Cx43 in a PCa cell line PC-3m was detected by re- verse-transcription polymerase chain reaction (RT-PCR) and strapt-avidin-biotin-enzyme complex (SABC) immunohistochemical staining, and inherent GJIC of PC-3m cells was assayed by scrape-loading and dye transfer (SLDT) assay. The expression of Cx43 in human normal and malig- nant prostate tissues was determined by SABC immunohistochemistry as well. It was found that Cx43 mRNA and protein expression in PC-3m cells was slightly reduced as compared with positive controls and the location of Cx43 protein was aberrant in cytoplasm rather than on membrane. As- sessment of paraffin sections demonstrated that the expression of Cx43 protein in PCa cells was ab- normally located and markedly diminished as compared with normal prostatic epithelial ones, dis- playing a negative correlation to the pathological grade (χ2=4.025, P<0.05). Additionally, capacity of inherent GJIC in PC-3m cells was disrupted, which was semi-quantified as (+) or (-). It was indi- cated that both down-regulated expression of Cx43 mRNA and aberrant location of Cx43 protein par- ticipated in the mechanisms leading to deficient GJIC in PC-3m cells. Lack of efficient GJIC is a molecular event, which may contribute not only to limited extent of "bystander effect", but also to initiation and progression of prostatic neoplasm.
文摘Background: Since 2004, the number of installed Automated External Defibrillator (AED) has been increased in Japan annually, the cumulative number of sold AED more than 600,000 units by 2016. Despite there have been about 130,000 out of hospital cardiac arrest annually, there have only 1302 cases delivered defibrillation by bystanders at the scene. Therefore, we investigate that number of AED installation and usage rate for Out of Hospital Cardiac Arrest (OHCA) patients. Methods: Retrospective metropolitan wide cohort study. Subject: Total 13,364 OHCA patients in the Tokyo Metropolitan area from Jan. 1 through Dec. 31 in 2012 were eligible for theses analyses. Also, OHCA occurrence place and AED usage rate were studied. Results: 82.8% of OHCA occurred at residences, 10% at outdoors, 6.4% at indoors, only 0.7% at schools. In the other hand, highest bystander’s CPR rates were found in sports facilities and schools (71.4%). The installation rate of AEDs in residences was 9.6%, instead of highest incidence for OHCA patients, school and sports institute made up 21.4% of AED installations, but only 1.0% of the incidences of cardiac arrest. We found that there is a mismatch between incidence sites of cardiac arrest and locations of installed AED. Discussion: It is essential to increase the number of AED installations. Furthermore, it is desirable to install AEDs in locations where cardiac arrest is liable to occur following guidelines for the proper placement of AEDs, and important to further spread BLS education among the general citizens.
文摘Objective: To study the induction of sensitivity toganciclovir (GCV) or acyclovir (ACV) in humanhepatocellular carcinoma (HCC) cell line trans-ferred by an Epstein-Barr virus (EBV)-based repli-con expression vector carrying the herpes simplex vi-rus thymidine kinase (HSV-tk) gene, including kill-ing and "bystander" effect, and also the gene delive-ry procedure and route of gene therapy in vivo forHCC.Methods: Liposome-entrapped plasmid pDR2/tk wastransferred into HCC cells, and then different con-centrations of GCV or ACV were added. The trans-ferred cells were mixed with untransferred HCC cellsin different proportion and 200 μmol/L GCV wasthen added into each well. After 72 hours, all sam-ples were measured by MTT colorimetric assay. AnEBV-based plasmid eukarotic expression vector car-rying IL-2 cDNA was used. Three models of gene di-rect injection in the local liver, injection through theportal vein, and injection through the embolized he-patic artery were established in closed Wister rats.For each model, two subgroups, injected either na-ked plasmid DNA or lipofectin-plasmid complex wereincluded. The expression of the IL-2 gene was regu-larly examined immunohistochemically.Results: GCV or ACV could apparently kill thetransferred HCC cells at a concentration of 0. 2μmol/L. The inhibition rate was changed with dif-ferent drug concentrations. The "bystander" effectwas obviously induced at a transferred to untrans-ferred HCC cells ratio of 1:5. IL-2 gene expressionwas observed in liver cells of all animals on day 3,which reached peak within 3-7 days, and declined af-ter day 7. Injection of naked plasmid DNA throughthe hepatic artery plus embolization obtained a bestexpression.Conclusions: EBV-based vector is suitable for carry-ing suicide gene therapy for hepatocellular carcino-ma. Gene direct delivery in vivo combined with in-terventional surgery can be used to treat hepatocellu-lar carcinoma.
基金partially supported by Moolch and Medcity,New Delhi,India
文摘BACKGROUND: To evaluate the outcome of cardiopulmonary resuscitation(CPR) in out-ofhospital cardiac arrests(OHCA) in India and factors infl uencing the outcome.METHODS: The outcome and related factors like demographics, aspects of the OHCA event, return of spontaneous circulation(ROSC) and survival to discharge, among the 80 adult patients presenting to emergency department experiencing OHCA considered for resuscitation between January 2014 to April 2015, were analyzed, according to the guidelines of the Utstein consensus conference.RESULTS: The survival rate to hospital admission was 32.5%, the survival rate to hospital discharge was 8.8% and with good cerebral performance category(CPC1) neurological status was 3.8%. Majority of OHCA was seen in elderly individuals between 51 to 60 years, predominately in males. Majority of OHCA were witnessed arrests(56.5%) with 1.3% bystander CPR rate, 92.5% arrests occurred at home, 96% presented with initial non-shockable rhythm and 92.5% with presumed cardiac etiology but survival was better in those who experienced OHCA at public place, in witnessed arrests, in patients who had shockable presenting rhythm and in those where CPR duration was ≤20 minutes.CONCLUSION: Witnessed arrests, early initiation of CPR by bystanders, CPR duration ≤20 minutes, initial presenting shockable rhythm, OHCA with non-cardiac etiology are associated with a good outcome. To improve the outcome of CPR and the low survival rates after an OHCA event in India, focused strategies should be designed to set up an emergency medical system(EMS), to boost the rates of bystander CPR and education of the lay public in basic CPR.
文摘BACKGROUND: Few studies have examined the association of layperson characteristics with cardiopulmonary resuscitation(CPR) provision. Previous studies suggested provider characteristics, including age and gender, were associated with CPR quality, particularly chest compression(CC) depth. We sought to determine the association of subject characteristics, including age and gender with layperson CPR quality during an unannounced simulated CPR event. We hypothesized shallower CC depth in females, and older-aged subjects.METHODS: As part of a larger multicenter randomized controlled trial of CPR training for cardiac patients' caregivers, CPR skills were assessed 6 months after training. We analyzed associations between subject characteristics and CC rate, CC depth and no-? ow time. Each variable was analyzed independently; signi? cant predictors determined via univariate analysis were assessed in a multivariate regression model.RESULTS: A total of 521 laypersons completed a 6-month CPR skills assessment and were included in the analysis. Mean age was 51.8±13.7 years, 75% were female, 57% were Caucasian. Overall, mean CC rate was 88.5±25.0 per minute, CC depth was 50.9±2.0 mm, and mean no-flow time was 15.9±2.7 sec/min. CC depth decreased signi? cantly in subjects >62 years(P<0.001). Male subjects performed deeper CCs than female subjects(47.5±1.7 vs. 41.9±0.6, P<0.001).CONCLUSION: We found that layperson age >62 years and female gender are associated with shallower CC depth.
