1.Introduction Irreversible electroporation(IRE)has emerged as a promising non-thermal ablation technique for the treatment of malignant tumors.^([1-3])By applying high-voltage electrical pulses to tumor tissue,IRE cr...1.Introduction Irreversible electroporation(IRE)has emerged as a promising non-thermal ablation technique for the treatment of malignant tumors.^([1-3])By applying high-voltage electrical pulses to tumor tissue,IRE creates irrecoverable pores in the cell membrane,thus disrupting the balance between the intracellular and extracellular environments,and ultimately causing cell death.^([1])展开更多
BACKGROUND Duodenal mucosal ablation(DMA)using irreversible electroporation(IRE)with a glucagon-like peptide-1 receptor agonist has been clinically shown to reduce liver lipid deposition in non-alcoholic fatty liver d...BACKGROUND Duodenal mucosal ablation(DMA)using irreversible electroporation(IRE)with a glucagon-like peptide-1 receptor agonist has been clinically shown to reduce liver lipid deposition in non-alcoholic fatty liver disease(NAFLD).However,the specific metabolic contributions of DMA using IRE in NAFLD remain unclear.AIM To assess the feasibility and effectiveness of DMA using IRE in NAFLD rat models.METHODS Seven-week-old male Sprague-Dawley rats underwent DMA using IRE after 8 weeks on a high-fat diet.Two weeks post-treatment,duodenal and liver tissues and blood samples were collected.We evaluated differences in the duodenal wall structure,liver lipid deposition,enteroendocrine,claudin,and zonula ocludens-1 in the duodenal mucosa.RESULTS DMA using IRE could be safely performed in rats with NAFLD without duodenal bleeding,perforation,or stenosis.The duodenum healed well 2 weeks after DMA and was characterized by slimmer villi,narrower and shallower crypts,and thicker myenterons compared with the sham-control setting.Liver lipid deposition was reduced and serum lipid index parameters were considerably improved in the DMA setting.However,these improvements were independent of food intake and weight loss.In addition,enteroendocrine parameters,such as claudin,and zonula ocludens-1 levels in the duodenal mucosa,differed between the different settings in the DMA group.CONCLUSION By altering enteroendocrine and duodenal permeability,simple DMA using IRE ameliorated liver lipid deposition and improved serum lipid parameters in NAFLD rats.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com...BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.展开更多
Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper...Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.展开更多
Objective:To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis(VVC)caused by Candida albicans.Methods:Temperature-sensitive in situ gels(IS...Objective:To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis(VVC)caused by Candida albicans.Methods:Temperature-sensitive in situ gels(ISG)were prepared using poloxamers 407 and 188 as matrices.The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29℃ and gelation time of 2.5 min.Results:Electroporation increased the transmucosal permeability of the model drug,doxorubicin and improved the antifungal effects of curcumin.In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG.In vivo pharmacodynamic experiments showed that,compared to the model group,curcumin ISG with electroporation inhibited the growth of C.albicans,alleviated vaginal mucosal edema,and reduced the inflammatory response.Conclusion:Curcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.展开更多
BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about ...BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about this phenomenon.AIM To investigate the reasons of hypertension and tachycardia and appropriate preventive measures.METHODS IRE was performed under general anesthesia and neuromuscular blockade.Systolic blood pressures,diastolic blood pressures,heart rate,and the distance of the electrode from abdominal aorta and adrenal gland during IRE were recorded.RESULTS All of 78 patients underwent 96 IRE sessions,44(56.4%)patients occurred hypertension when the electrode was close to the abdominal aorta(<2.0 cm).The median systolic blood pressures and diastolic blood pressures was 194 and 108 mmHg.Furthermore,11(14.1%)patients occurred tachycardia when the electrode was close to the adrenal gland(<1.3 cm).The median heart rate of patients with tachycardia was 114 beats per minute.Furthermore,hypertension and tachycardia can be prevented with nicardipine and esmolol before treatment.CONCLUSION Intraoperative hypertension and tachycardia occur because electrodes close to the abdominal aorta(<2.0 cm)and adrenal glands(<1.3 cm),which can be prevented by preoperative treatment of vasoactive drugs.展开更多
One of the main causes of liver fibrosis and cancer,non-alcoholic fatty liver disease(NAFLD)is becoming more common every year.The novel work by Yu et al,which evaluates the viability and efficacy of duodenal mucosal ...One of the main causes of liver fibrosis and cancer,non-alcoholic fatty liver disease(NAFLD)is becoming more common every year.The novel work by Yu et al,which evaluates the viability and efficacy of duodenal mucosal ablation(DMA)with irreversible electroporation(IRE)in NAFLD rat models,is examined in this article.When DMA was used with IRE to small rodents,the study found that the duodenum healed successfully two weeks later and had thicker myenterons,narrower and shallower crypts,and slimmer villi than in the sham-control group.When DMA with IRE were used,liver lipid deposition and serum lipid index values decreased;these improvements occurred regardless of food consumption or weight loss.Furthermore,the DMA group's enteroendocrine parameters varied among the various duodenal areas,including claudin and zonula ocludens-1 Levels in the duodenal mucosa.As a result,DMA with IRE in rodents demonstrated no duodenal bleeding or perforation following ablation,providing a promising path for more advanced NAFLD treatment approaches.In order to improve approach outcomes,this paper addresses the implications of extending the study length and animal size,analyzing inflammatory marker studies,and measuring intestinal lipid indexes and endocrine parameters on a weekly basis.展开更多
We read with great interest the recent article by Xing et al,which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model.The study of...We read with great interest the recent article by Xing et al,which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model.The study offers valuable mechanistic insights into local ablation,enhancing the efficacy of immune checkpoint blockade.However,critical methodological limitations and an overstatement of mechanistic conclusions warrant cautious interpretation.We recommend clarifying experimental details,optimizing murine models,applying more robust statistical analyses,and tempering conclusions to reflect the correlative nature of the findings.Further work should investigate immune mechanisms,durability of response,and safety in clinically relevant models to maximize translational potential.These refinements will strengthen the study’s impact in advancing ablation-immunotherapy strategies in hepatocellular carcinoma.展开更多
BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate t...BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.展开更多
Metallothionein gene (MT) has been transferred into mushroom protoplasts by electroporation. It is a low molecular weight, cysteine-rich and metal-binding protein. MT can bind metals. Its synthesis is induced by Zn io...Metallothionein gene (MT) has been transferred into mushroom protoplasts by electroporation. It is a low molecular weight, cysteine-rich and metal-binding protein. MT can bind metals. Its synthesis is induced by Zn ion. Thus the expression of MT gene in mushroom can improve the accumulation of Zn in this fungus. This transgenic mushroom, consumed as a kind of vegetable, can supply the necessary Zn to people who are short of the element. When protoplasts were prepared, the concentration (C) of protoplasts is 6.745 x 10(6) /mL. After protoplast electroporation, the transformation rate of protoplasts is 0.01 %. Polymerase chain reaction (PCR) analysis showed that the gene had been integrated into the mushroom chromosome, SDS-PAGE, Western blot analysis indicated that the MT gene had been expressed in the transgenic mushroom. The expressing level, detected by ELISA, is 0.6 % - 0.8 %. Tested for metal resistance, the wild-type mushroom growth was inhibited on die medium containing 1.0 - 1.2 mmoL/L ZnSO4. While the transgenic mushroom was inhibited on the medium containing 1. 5 - 2.0 mmol/L ZnSO4. The mycelium can develop into hymenophore in the medium of rice bran: sawdust = 1: 3, and not in the medium of rice bran: sawdust = 1: 4.展开更多
Green fluorescent protein ( GFP ) gene was expressed transiently in 2-3 d old rice embryos by electroporation with the aid of a specially designed loading net. Under suitable conditions (500 μF capacitance, 300 V/c...Green fluorescent protein ( GFP ) gene was expressed transiently in 2-3 d old rice embryos by electroporation with the aid of a specially designed loading net. Under suitable conditions (500 μF capacitance, 300 V/cm Voltage, 100 μg/mL plasmid DNA), the percentage of embryos expressing GFP was up to 35%. The highest electroporation efficiency (40%) was obtained at pH 5.8 of the electroporation buffer. The GFP gene driven by the Ubi promoter produced the highest efficiency. Thus, on the basis of optimizing electroporation conditions, a transformation system has been developed for young embryos in rice. The electroporated 4-6 d old embryos regenerated plantlets under the controlled cultural conditions. Fluorescence microscopic observations indicated that GFP gene expressed in their calli and R0 plantlets.展开更多
Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepato...Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching Pub Med and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients(0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.展开更多
Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a me...Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.展开更多
BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after stan...BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.展开更多
Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior m...Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior mesenteric artery(SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature.A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma.IRE procedure was applied to the patient during laparotomy under general anesthesia.After finishing the procedure,an acute intestinal ischemia was detected.A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained.It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor.展开更多
AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic...AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.展开更多
Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (EPs) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. I...Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (EPs) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. In vitro, with scan electromicroscope (SEM) and Trypan blue staining examination, the best parameter of EPs of electroporation is studied by the S-180 cells exposed to EP with various voltages, pulses , capacitance. The best parameter of EP of electroporation is 600V/cm, 6 pulses, 10 μF. In the in vivo study, ECT is studied with the Cytoxan (CTX) injected directly into the tumor followed immediately by a local EP at the tumor site. Four parameters, which include the tumor inhibitory ratio, the curing ratio and the vas capillare of tumor, the tumor’s histopathological characteristics are determined and compared among the ECT group, the control group, the EP-only group and the drug-only group. The results indicate that the antitumor effect of CTX is significantly enhanced by electroporation.展开更多
To obtain a suitable condition for electroporation transformation in indica rice, the 10-day-old immature embryos were selected for optimization experiments. The results showed that one pulse at 850 V/cm, 950μF capac...To obtain a suitable condition for electroporation transformation in indica rice, the 10-day-old immature embryos were selected for optimization experiments. The results showed that one pulse at 850 V/cm, 950μF capacitance, 200 μL electroporation buffer with 70 mmol/L sodium glutamate, 100 μg/mL plasmid, 50μg/mL carrier DNA, 20 embryos per cuvette, 0℃ treatment and CC medium were the best parameters, which not only improved the transformation efficiency to 30.89%, but also ameliorated the embryo survival ratio to 95.92%. To further verify the practicability of this condition, the embryos from another indica rice variety and a rice type Ⅱ metallothionein-like gene （OsMT2bL） promotec：mgfp5：：gusA construct were tested, and specific GUS expression on the embryos was visualized by histochemical staining. The results showed that the GUS expression on the embryos activated by the OsMT2bL promoter was mainly concentrated on the apical point of the plumule whereas the expression driven by CaMV35S promoter was distributed on nearly all areas of the electroporated tissues. These results indicated that the optimized embryo electroporation conditions could be used not only in genetic transformation of indica rice but also in assay of gene regulation on embryos.展开更多
Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locall...Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locally advanced pancreatic cancer. Drain removal and discharge of the patient from the hospital were scheduled on postoperative day(POD) 7; however, a magnetic resonance imaging scan revealed the presence of PVT. We suspected postoperative inflammation in the pancreas as the main cause of PVT. However, the patient did not undergo any medical treatment because she did not have any clinical symptoms, and she was discharged on POD 8.展开更多
Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4...Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.展开更多
文摘1.Introduction Irreversible electroporation(IRE)has emerged as a promising non-thermal ablation technique for the treatment of malignant tumors.^([1-3])By applying high-voltage electrical pulses to tumor tissue,IRE creates irrecoverable pores in the cell membrane,thus disrupting the balance between the intracellular and extracellular environments,and ultimately causing cell death.^([1])
基金Supported by the National Key Research and Development Program,No.2023YFF0713700 and No.2023YFF0713705Common Technology R&D Platform of Shaanxi Province,No.2023GXJS-01-1-2the Cyrus Tang Foundation Chung Ying Young Scholars Program.
文摘BACKGROUND Duodenal mucosal ablation(DMA)using irreversible electroporation(IRE)with a glucagon-like peptide-1 receptor agonist has been clinically shown to reduce liver lipid deposition in non-alcoholic fatty liver disease(NAFLD).However,the specific metabolic contributions of DMA using IRE in NAFLD remain unclear.AIM To assess the feasibility and effectiveness of DMA using IRE in NAFLD rat models.METHODS Seven-week-old male Sprague-Dawley rats underwent DMA using IRE after 8 weeks on a high-fat diet.Two weeks post-treatment,duodenal and liver tissues and blood samples were collected.We evaluated differences in the duodenal wall structure,liver lipid deposition,enteroendocrine,claudin,and zonula ocludens-1 in the duodenal mucosa.RESULTS DMA using IRE could be safely performed in rats with NAFLD without duodenal bleeding,perforation,or stenosis.The duodenum healed well 2 weeks after DMA and was characterized by slimmer villi,narrower and shallower crypts,and thicker myenterons compared with the sham-control setting.Liver lipid deposition was reduced and serum lipid index parameters were considerably improved in the DMA setting.However,these improvements were independent of food intake and weight loss.In addition,enteroendocrine parameters,such as claudin,and zonula ocludens-1 levels in the duodenal mucosa,differed between the different settings in the DMA group.CONCLUSION By altering enteroendocrine and duodenal permeability,simple DMA using IRE ameliorated liver lipid deposition and improved serum lipid parameters in NAFLD rats.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer.
基金Supported by Department of Biotechnology,Government of India,No.RLS/BT/Re-entry/05/2012.
文摘Irreversible electroporation is a promising non-thermal ablation method that has been shown to increase overall survival in locally advanced pancreatic cancer in some studies.However,higher quality studies with proper controls and randomization are required to establish its superiority when added with neoadjuvant chemotherapy over the current management of choice,which is chemotherapy alone.Further studies are required before establishment of any survival benefit in metastatic pancreatic carcinoma,and such evidence is lacking at present.
基金supported by the Beijing Natural Science Foundation(L222126).
文摘Objective:To observed the effect of a curcumin-based vaginal gel combined with electroporation for the treatment of vulvovaginal candidiasis(VVC)caused by Candida albicans.Methods:Temperature-sensitive in situ gels(ISG)were prepared using poloxamers 407 and 188 as matrices.The mass ratio of poloxamer 407 and poloxamer 188 was 7:1 with a gelation temperature of approximately 29℃ and gelation time of 2.5 min.Results:Electroporation increased the transmucosal permeability of the model drug,doxorubicin and improved the antifungal effects of curcumin.In vitro antifungal experiments showed that the number of fungal colonies in curcumin ISG combined with electroporation was lower than that in pure curcumin ISG.In vivo pharmacodynamic experiments showed that,compared to the model group,curcumin ISG with electroporation inhibited the growth of C.albicans,alleviated vaginal mucosal edema,and reduced the inflammatory response.Conclusion:Curcumin ISG combined with electroporation has substantial potential for the efficient clinical treatment of VVC.
基金Supported by International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2022-MS-02.
文摘BACKGROUND Irreversible electroporation(IRE)is a novel non-thermal ablation technology for unresectable tumors.Hypertension and tachycardia usually occur during the IRE.To date,there has been little explanation about this phenomenon.AIM To investigate the reasons of hypertension and tachycardia and appropriate preventive measures.METHODS IRE was performed under general anesthesia and neuromuscular blockade.Systolic blood pressures,diastolic blood pressures,heart rate,and the distance of the electrode from abdominal aorta and adrenal gland during IRE were recorded.RESULTS All of 78 patients underwent 96 IRE sessions,44(56.4%)patients occurred hypertension when the electrode was close to the abdominal aorta(<2.0 cm).The median systolic blood pressures and diastolic blood pressures was 194 and 108 mmHg.Furthermore,11(14.1%)patients occurred tachycardia when the electrode was close to the adrenal gland(<1.3 cm).The median heart rate of patients with tachycardia was 114 beats per minute.Furthermore,hypertension and tachycardia can be prevented with nicardipine and esmolol before treatment.CONCLUSION Intraoperative hypertension and tachycardia occur because electrodes close to the abdominal aorta(<2.0 cm)and adrenal glands(<1.3 cm),which can be prevented by preoperative treatment of vasoactive drugs.
文摘One of the main causes of liver fibrosis and cancer,non-alcoholic fatty liver disease(NAFLD)is becoming more common every year.The novel work by Yu et al,which evaluates the viability and efficacy of duodenal mucosal ablation(DMA)with irreversible electroporation(IRE)in NAFLD rat models,is examined in this article.When DMA was used with IRE to small rodents,the study found that the duodenum healed successfully two weeks later and had thicker myenterons,narrower and shallower crypts,and slimmer villi than in the sham-control group.When DMA with IRE were used,liver lipid deposition and serum lipid index values decreased;these improvements occurred regardless of food consumption or weight loss.Furthermore,the DMA group's enteroendocrine parameters varied among the various duodenal areas,including claudin and zonula ocludens-1 Levels in the duodenal mucosa.As a result,DMA with IRE in rodents demonstrated no duodenal bleeding or perforation following ablation,providing a promising path for more advanced NAFLD treatment approaches.In order to improve approach outcomes,this paper addresses the implications of extending the study length and animal size,analyzing inflammatory marker studies,and measuring intestinal lipid indexes and endocrine parameters on a weekly basis.
文摘We read with great interest the recent article by Xing et al,which describes the synergy between irreversible electroporation and anti-programmed death-1 therapy in a murine hepatocellular carcinoma model.The study offers valuable mechanistic insights into local ablation,enhancing the efficacy of immune checkpoint blockade.However,critical methodological limitations and an overstatement of mechanistic conclusions warrant cautious interpretation.We recommend clarifying experimental details,optimizing murine models,applying more robust statistical analyses,and tempering conclusions to reflect the correlative nature of the findings.Further work should investigate immune mechanisms,durability of response,and safety in clinically relevant models to maximize translational potential.These refinements will strengthen the study’s impact in advancing ablation-immunotherapy strategies in hepatocellular carcinoma.
基金Supported by the Science and Technology Program of Guangzhou,No.202201020024.
文摘BACKGROUND Irreversible electroporation(IRE)represents an innovative localized technique for tumor ablation,possessing the capacity to activate the immune response of the host.However,this method alone is inadequate to halt cancer progression,necessitating the integration of additional strategies to achieve effective immuno-therapy.AIM To investigate the effects and underlying mechanisms of antitumor immunity derived from the synergistic application of IRE and anti-programmed cell death protein 1(PD-1)therapy within a murine model of hepatocellular carcinoma.METHODS C57BL-6 mice with tumor growth were divided into four separate cohorts:Control group;IRE group;Anti-PD-1 group;And IRE+anti-PD-1 group.The infiltration levels of T,B,and natural killer cells within the tumors,as well as the plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-β),were evaluated.Real-time polymerase chain reaction was utilized to quantify the expression of cluster of differentiation(CD)8(a marker indicative of CD8+T cells)in the tumor specimens of the mice at various temporal intervals.Tumor growth trajectories were charted.RESULTS The results indicated that the IRE+anti-PD-1 group exhibited significantly heightened percentages of T lymphocyte infiltration,particularly CD4+and CD8+T cells,when compared to the control cohort.Additionally,this group displayed increased infiltration of natural killer and B cells,augmented cytokine levels,and elevated CD8 messenger RNA expression.A marked decrease in tumor volume was noted in the IRE+anti-PD-1 group,indicating enhanced therapeutic efficacy.CONCLUSION The combined application of IRE and checkpoint blockade elicits an antitumor immune response,leading to a more substantial reduction in tumor volume and improved therapeutic outcomes,thereby establishing a novel avenue for the ablation and immunotherapy of hepatocellular carcinoma.
文摘Metallothionein gene (MT) has been transferred into mushroom protoplasts by electroporation. It is a low molecular weight, cysteine-rich and metal-binding protein. MT can bind metals. Its synthesis is induced by Zn ion. Thus the expression of MT gene in mushroom can improve the accumulation of Zn in this fungus. This transgenic mushroom, consumed as a kind of vegetable, can supply the necessary Zn to people who are short of the element. When protoplasts were prepared, the concentration (C) of protoplasts is 6.745 x 10(6) /mL. After protoplast electroporation, the transformation rate of protoplasts is 0.01 %. Polymerase chain reaction (PCR) analysis showed that the gene had been integrated into the mushroom chromosome, SDS-PAGE, Western blot analysis indicated that the MT gene had been expressed in the transgenic mushroom. The expressing level, detected by ELISA, is 0.6 % - 0.8 %. Tested for metal resistance, the wild-type mushroom growth was inhibited on die medium containing 1.0 - 1.2 mmoL/L ZnSO4. While the transgenic mushroom was inhibited on the medium containing 1. 5 - 2.0 mmol/L ZnSO4. The mycelium can develop into hymenophore in the medium of rice bran: sawdust = 1: 3, and not in the medium of rice bran: sawdust = 1: 4.
文摘Green fluorescent protein ( GFP ) gene was expressed transiently in 2-3 d old rice embryos by electroporation with the aid of a specially designed loading net. Under suitable conditions (500 μF capacitance, 300 V/cm Voltage, 100 μg/mL plasmid DNA), the percentage of embryos expressing GFP was up to 35%. The highest electroporation efficiency (40%) was obtained at pH 5.8 of the electroporation buffer. The GFP gene driven by the Ubi promoter produced the highest efficiency. Thus, on the basis of optimizing electroporation conditions, a transformation system has been developed for young embryos in rice. The electroporated 4-6 d old embryos regenerated plantlets under the controlled cultural conditions. Fluorescence microscopic observations indicated that GFP gene expressed in their calli and R0 plantlets.
基金supported by grants from the Traditional Chinese Medicine Scientific Research Fund Project of Zhejiang province(No.2017ZA079)the Key Research Development Program of Zhejiang province(No.2018C03018)+1 种基金the Key Science and Tech-nology Program of Zhejiang Provience(No.WKJ-ZJ-1923)the National S&T Major Project of China(No.2018ZX10301201)
文摘Background: Irreversible electroporation(IRE) is a novel ablative technique for hepatobiliary and pancreatic cancers. This review summarizes the data regarding the safety and efficacy of IRE in the treatment of hepatobiliary and pancreatic cancers. Data sources: Studies were identified by searching Pub Med and Embase for articles published in English from database inception through July 31, 2017. For inclusion, each clinical study had to report morbidity and survival data on hepatobiliary and pancreatic cancers treated with IRE and contain at least 10 patients. Studies that met these criteria were included for analysis. Two authors assessed each clinical study for data extraction. The controversial parts were resolved through discussion with seniors. Results: A total of 24 clinical studies were included. Fourteen focused on hepatic ablation with IRE comprising 437 patients with 666 lesions of different tumor types. Two patients(0.5%) died after the IRE procedure. Morbidity of hepatic ablation with IRE ranged from 7% to 35%. Most complications were mild. Complete response for hepatic tumors was reported as 57%–97%. Ten studies with 455 patients focused on pancreatic IRE. The overall mortality of IRE in pancreatic cancer was 2%. Overall severe morbidity of IRE in pancreatic cancer ranged from 0 to 20%. The median overall survival after IRE ranged from 7 to 23 months. Patients treated with IRE combined with surgical resection showed a longer overall survival. Conclusions: IRE significantly improves the prognosis of advanced hepatobiliary and pancreatic malignances, and companied with less complications. Hence, IRE is a relatively safe and effective non-thermal ablation strategy and potentially recommended as an option for therapy of patients with hepatobiliary and pancreatic malignances.
文摘Pancreatic cancer is currently the seventh leading cause of cancer death(4.5%of all cancer deaths)while 80%-90%of the patients suffer from unresectable disease at the time of diagnosis.Prognosis remains poor,with a mean survival up to 15 mo following systemic chemotherapy.Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures,which can lead to severe adverse events.Irreversible electroporation,a promising novel non-thermal ablative modality,has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option.Experimental and initial clinical data are optimistic.This review will focus on the basic principles of IRE technology,currently available data,and future directions.
基金Supported by International Science Foundation of Affiliated Fuda Cancer Hospital,Jinan University,No.Y2018-ZD-01.
文摘BACKGROUND Locally advanced pancreatic cancer(LAPC)is a common malignant digestive system tumor that ranks as the fourth leading cause of cancer-related death in the world.The prognosis of LAPC is poor even after standard treatment.Irreversible electroporation(IRE)is a novel ablative strategy for LAPC.Several studies have confirmed the safety of IRE.To date,no prospective studies have been performed to investigate the therapeutic efficacy of conventional gemcitabine(GEM)plus concurrent IRE.AIM To compare the therapeutic efficacy between conventional GEM plus concurrent IRE and GEM alone for LAPC.METHODS From February 2016 to September 2017,a total of 68 LAPC patients were treated with GEM plus concurrent IRE(n=33)or GEM alone(n=35).Overall survival(OS),progression free survival(PFS),and procedure-related complications were compared between the two groups.Multivariate analyses were performed to identify any prognostic factors.RESULTS There were no treatment-related deaths.The technical success rate of IRE ablation was 100%.The GEM+IRE group had a significantly longer OS from the time of diagnosis of LAPC(19.8 mo vs 9.3 mo,P<0.0001)than the GEM alone group.The GEM+IRE group had a significantly longer PFS(8.3 mo vs 4.7 mo,P<0.0001)than the GEM alone group.Tumor volume less than 37 cm3 and GEM plus concurrent IRE were identified as significant favorable factors for both the OS and PFS.CONCLUSION Gemcitabine plus concurrent IRE is an effective treatment for patients with LAPC.
文摘Irreversible electroporation(IRE) is a non-thermal ablation technique used especially in locally advanced pancreatic carcinomas that are considered surgically unresectable.We present the first case of acute superior mesenteric artery(SMA) occlusion secondary to pancreatic IRE procedure that has not been reported before in the literature.A 66-year-old man underwent neoadjuvant chemoradiotherapy for locally advanced pancreatic ductal adenocarcinoma.IRE procedure was applied to the patient during laparotomy under general anesthesia.After finishing the procedure,an acute intestinal ischemia was detected.A conventional vascular angiography was performed and a metallic stent was successfully placed to the SMA and blood flow was maintained.It is important to be careful in such cases of tumor involvement of SMA when evaluating for IRE procedure of pancreatic tumor.
基金Supported by Yigan Biological Products Co.,Ltd.of Guangzhou Pharmaceutical Holdings Ltd.(GPC,Guangzhou,China)Guangdong Provincial Sci.&Tech.Project,No.2012A080204009+2 种基金Guangdong Provincial Natural Science Fund,No.2014A030313 770Guangdong Provincial Public Benefit Foundation,No.2015A010107011National Key Program for Management of AIDS and Viral Hepatitis during the China "11~(th) 5-Year Plan" Period,No.2008ZX10002-003
文摘AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.
文摘Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (EPs) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. In vitro, with scan electromicroscope (SEM) and Trypan blue staining examination, the best parameter of EPs of electroporation is studied by the S-180 cells exposed to EP with various voltages, pulses , capacitance. The best parameter of EP of electroporation is 600V/cm, 6 pulses, 10 μF. In the in vivo study, ECT is studied with the Cytoxan (CTX) injected directly into the tumor followed immediately by a local EP at the tumor site. Four parameters, which include the tumor inhibitory ratio, the curing ratio and the vas capillare of tumor, the tumor’s histopathological characteristics are determined and compared among the ECT group, the control group, the EP-only group and the drug-only group. The results indicate that the antitumor effect of CTX is significantly enhanced by electroporation.
基金This project was supported by the National Natural Science Foundation of China(Grant No.30570103)the Key Grant Project of Chinese Ministry of Education(Grant No.307018).
文摘To obtain a suitable condition for electroporation transformation in indica rice, the 10-day-old immature embryos were selected for optimization experiments. The results showed that one pulse at 850 V/cm, 950μF capacitance, 200 μL electroporation buffer with 70 mmol/L sodium glutamate, 100 μg/mL plasmid, 50μg/mL carrier DNA, 20 embryos per cuvette, 0℃ treatment and CC medium were the best parameters, which not only improved the transformation efficiency to 30.89%, but also ameliorated the embryo survival ratio to 95.92%. To further verify the practicability of this condition, the embryos from another indica rice variety and a rice type Ⅱ metallothionein-like gene （OsMT2bL） promotec：mgfp5：：gusA construct were tested, and specific GUS expression on the embryos was visualized by histochemical staining. The results showed that the GUS expression on the embryos activated by the OsMT2bL promoter was mainly concentrated on the apical point of the plumule whereas the expression driven by CaMV35S promoter was distributed on nearly all areas of the electroporated tissues. These results indicated that the optimized embryo electroporation conditions could be used not only in genetic transformation of indica rice but also in assay of gene regulation on embryos.
文摘Portal vein thrombosis(PVT) is a rare but serious postoperative complication associated with irreversible electroporation(IRE). We report a case of postoperative PVT in a 54-year-old woman who underwent IRE for locally advanced pancreatic cancer. Drain removal and discharge of the patient from the hospital were scheduled on postoperative day(POD) 7; however, a magnetic resonance imaging scan revealed the presence of PVT. We suspected postoperative inflammation in the pancreas as the main cause of PVT. However, the patient did not undergo any medical treatment because she did not have any clinical symptoms, and she was discharged on POD 8.
基金supported by the National Natural Science Foundation of China (81772172, 81471957, 81671971, U1602223)
文摘Dengue fever, caused by dengue viruses(DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate(pV-D4 ME) expressing prM-E protein of DENV serotype 4(DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4 ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4 ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4 ME could provide stable protection(100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4 ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.
