在真核生物细胞中,各细胞器间物质和信息的交流是细胞生命活动的基本保证,而囊泡转运是细胞器之间物质和信息交流的主要方式。大多数的囊泡融合过程是由可溶性的N-乙基马来酰亚胺敏感因子连接物复合体(Soluble N-ethyl-maleimide-sensit...在真核生物细胞中,各细胞器间物质和信息的交流是细胞生命活动的基本保证,而囊泡转运是细胞器之间物质和信息交流的主要方式。大多数的囊泡融合过程是由可溶性的N-乙基马来酰亚胺敏感因子连接物复合体(Soluble N-ethyl-maleimide-sensitive fusion protein attachment protein receptors,SNAREs)介导的,物种间的SNAREs具有高度保守的特性。与其他真核生物相比,植物的基因组编码更多的SNAREs。研究证明,植物的SNAREs是一个多功能的蛋白家族,在植物的许多生理过程中都有着重要的作用。本文对植物SNAREs作用的分子机理及生物学功能的最新研究进展做一概述。展开更多
Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. Ho...Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.展开更多
Current guidelines recommend cold snare polypectomy for polyps less than 10 mm in size.Conversely,endoscopic mucosal resection is still the preferred technique for larger polyps.Concerns regarding cold snare polypecto...Current guidelines recommend cold snare polypectomy for polyps less than 10 mm in size.Conversely,endoscopic mucosal resection is still the preferred technique for larger polyps.Concerns regarding cold snare polypectomy for larger polyps revolve around the difficulty in conducting en-bloc resection(resulting in piecemeal removal),and the potential for local residual polyp tissue and a high rate of recurrence.On the other hand,cold snare technique has the advantages of shortening procedure time,reducing delayed bleeding risks and lowering cost of treatment.Numerous ongoing and recent studies are focused on evaluating the risks and benefits of this technique for polyps larger than 10 mm,with the goal of providing clear guidelines in the near future.The aim of this editorial is to provide our readers with an overview regarding this subject and the latest developments surrounding it.展开更多
BACKGROUND Pleomorphic leiomyosarcomas make up around 8.6%of all leiomyosarcomas.They behave aggressively and often have poor prognoses.They can affect the gastrointestinal tract and retroperitoneum.To date,pleomorphi...BACKGROUND Pleomorphic leiomyosarcomas make up around 8.6%of all leiomyosarcomas.They behave aggressively and often have poor prognoses.They can affect the gastrointestinal tract and retroperitoneum.To date,pleomorphic leiomyosarcoma involving the mesocolon have been reported in nine patients.CASE SUMMARY The patient was a 44-year-old man with a history of pleomorphic leiomyosarcoma of the left maxilla with metastasis to the lung and liver.His most recent positron emission tomography-computed tomography(PET-CT)scan showed uptake in the ascending and transverse colons.A colonoscopy revealed a 5.0 cm×3.5 cm×3.0 cm pedunculated polyp in the ascending colon.The polyp was removed using hot snare polypectomy technique and retrieved with Rothnet.Histopathologic examination of the polyp showed a metastatic pleomorphic leiomyosarcoma.CONCLUSION Uptake(s)on PET-CT in a patient with pleomorphic leiomyosarcoma should raise suspicion for metastasis.展开更多
BACKGROUND Esophageal foreign bodies are common around the world.Newer approaches,such as cap-assisted endoscopy,have been introduced as an alternative to conventional methods.Therefore,we performed a meta-analysis on...BACKGROUND Esophageal foreign bodies are common around the world.Newer approaches,such as cap-assisted endoscopy,have been introduced as an alternative to conventional methods.Therefore,we performed a meta-analysis ono cap-assisted endoscopy versus conventional endoscopy for removal of esophageal foreign bodies.AIM To investigated the effectiveness of cap-assisted endoscopy with conventional endoscopy.METHODS An extensive literature search was performed(December 2021).For esophageal foreign body removal,cap-assisted endoscopy was compared to conventional endoscopy for procedure time,technical success of the procedure,time of foreign body retrieval,en bloc removal,and adverse event rate using odds ratio and mean difference.RESULTS Six studies met the inclusion criteria(n=1305).Higher odds of technical success(P=0.002)and en bloc removal(P<0.01)and lower odds of adverse events(P=0.02)and foreign body removal time(P<0.01)were observed with cap-assisted endoscopy as compared to conventional techniques.CONCLUSION For esophageal foreign bodies,the technique of cap-assisted endoscopy demonstrated increased en bloc removal and technical success with decreased time and adverse events as compared to conventional techniques.展开更多
Rectal neuroendocrine tumours represent a rare colorectal tumour with a 10 fold increased prevalence due to incidental detection in the era of colorectal screening.Patient outcomes with early diagnosis are excellent.H...Rectal neuroendocrine tumours represent a rare colorectal tumour with a 10 fold increased prevalence due to incidental detection in the era of colorectal screening.Patient outcomes with early diagnosis are excellent.However endoscopic recognition of this lesion is variable and misdiagnosis can result in suboptimal endoscopic resection with subsequent uncertainty in relation to optimal long-term management.Endoscopic techniques have shown particular utility in managing this under-recognized neuroendocrine tumour.展开更多
Due to the high risk of morbidity and mortality associated with surgical resection in this tract,endoscopic resection(ER)has taken the place of surgical resection as the first line treatment for non-ampullary duodenal...Due to the high risk of morbidity and mortality associated with surgical resection in this tract,endoscopic resection(ER)has taken the place of surgical resection as the first line treatment for non-ampullary duodenal adenomas.However,due to the anatomical characteristics of this area,which enhance the risk of post-ER problems,ER in the duodenum is particularly difficult.Due to a lack of data,no ER technique for superficial non-ampullary duodenal epithelial tumours(SNADETs)has yet been backed by strong,high-quality evidence;yet,traditional hot snare-based techniques are still regarded as the standard treatment.Despite having a favourable efficiency profile,adverse events during duodenal hot snare polypectomy(HSP)and hot endoscopic mucosal resection,such as delayed bleeding and perforation,have been reported to be frequent.These events are primarily caused by electrocautery-induced damage.Thus,ER techniques with a better safety profile are needed to overcome these shortcomings.Cold snare polypectomy,which has already been shown as a safer,equally effective pro-cedure compared to HSP for treatment of small colorectal polyps,is being increasingly evaluated as a potential therapeutic option for non-ampullary duodenal adenomas.The aim of this review is to report and discuss the early outcomes of the first experiences with cold snaring for SNADETs.展开更多
BACKGROUND Although endoscopic submucosal dissection(ESD)is becoming more common for early gastric cancer,it requires more advanced techniques and a longer treatment duration than endoscopic mucosal resection.Hybrid E...BACKGROUND Although endoscopic submucosal dissection(ESD)is becoming more common for early gastric cancer,it requires more advanced techniques and a longer treatment duration than endoscopic mucosal resection.Hybrid ESD using a multifunctional snare(SOUTEN)has been reported to be effective for colorectal lesions,as it can reduce treatment duration.Endoscopic suturing of post-ESD mucosal defects has been reported to reduce the incidence of ESD-related complications.CASE SUMMARY This study reports outpatient hybrid ESD for early gastric cancer using SOUTEN,followed by endoscopic suturing of post-ESD mucosal defects in an 86-year-old man.On referral for ESD,a 10-mm flat,depressed lesion was found on the posterior wall of the gastric antrum,the depth of which was expected to be mucosal.Given his history of delirium,we performed outpatient endoscopic treatment.The procedure used was hybrid ESD using SOUTEN to reduce the duration of treatment and endoscopic suturing of post-ESD mucosal ESD defects to reduce complications.The procedure time was 62 min and the lesion was completely resected based on histopathological examination,with no reported postoperative complications.CONCLUSION This safe and useful procedure may be especially important for outpatient endoscopic treatment.展开更多
文摘在真核生物细胞中,各细胞器间物质和信息的交流是细胞生命活动的基本保证,而囊泡转运是细胞器之间物质和信息交流的主要方式。大多数的囊泡融合过程是由可溶性的N-乙基马来酰亚胺敏感因子连接物复合体(Soluble N-ethyl-maleimide-sensitive fusion protein attachment protein receptors,SNAREs)介导的,物种间的SNAREs具有高度保守的特性。与其他真核生物相比,植物的基因组编码更多的SNAREs。研究证明,植物的SNAREs是一个多功能的蛋白家族,在植物的许多生理过程中都有着重要的作用。本文对植物SNAREs作用的分子机理及生物学功能的最新研究进展做一概述。
基金supported by the National Natural Science Foundation of China(Grant No:81903643)the“Young Talent Support Plan”of Xi'an Jiaotong University,the Shaanxi Province Science and Technology Development Plan Project(Grant No.:2022ZDLSF05-05)+1 种基金the Project of Shaanxi Provincial Administration of Traditional Chinese Medicine(Project No.:2021-03-ZZ-002)the Shaanxi Province Science Fund for Distinguished Young Scholars(Grant No:2023-JC-JQ-59).
文摘Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.
文摘Current guidelines recommend cold snare polypectomy for polyps less than 10 mm in size.Conversely,endoscopic mucosal resection is still the preferred technique for larger polyps.Concerns regarding cold snare polypectomy for larger polyps revolve around the difficulty in conducting en-bloc resection(resulting in piecemeal removal),and the potential for local residual polyp tissue and a high rate of recurrence.On the other hand,cold snare technique has the advantages of shortening procedure time,reducing delayed bleeding risks and lowering cost of treatment.Numerous ongoing and recent studies are focused on evaluating the risks and benefits of this technique for polyps larger than 10 mm,with the goal of providing clear guidelines in the near future.The aim of this editorial is to provide our readers with an overview regarding this subject and the latest developments surrounding it.
文摘BACKGROUND Pleomorphic leiomyosarcomas make up around 8.6%of all leiomyosarcomas.They behave aggressively and often have poor prognoses.They can affect the gastrointestinal tract and retroperitoneum.To date,pleomorphic leiomyosarcoma involving the mesocolon have been reported in nine patients.CASE SUMMARY The patient was a 44-year-old man with a history of pleomorphic leiomyosarcoma of the left maxilla with metastasis to the lung and liver.His most recent positron emission tomography-computed tomography(PET-CT)scan showed uptake in the ascending and transverse colons.A colonoscopy revealed a 5.0 cm×3.5 cm×3.0 cm pedunculated polyp in the ascending colon.The polyp was removed using hot snare polypectomy technique and retrieved with Rothnet.Histopathologic examination of the polyp showed a metastatic pleomorphic leiomyosarcoma.CONCLUSION Uptake(s)on PET-CT in a patient with pleomorphic leiomyosarcoma should raise suspicion for metastasis.
文摘BACKGROUND Esophageal foreign bodies are common around the world.Newer approaches,such as cap-assisted endoscopy,have been introduced as an alternative to conventional methods.Therefore,we performed a meta-analysis ono cap-assisted endoscopy versus conventional endoscopy for removal of esophageal foreign bodies.AIM To investigated the effectiveness of cap-assisted endoscopy with conventional endoscopy.METHODS An extensive literature search was performed(December 2021).For esophageal foreign body removal,cap-assisted endoscopy was compared to conventional endoscopy for procedure time,technical success of the procedure,time of foreign body retrieval,en bloc removal,and adverse event rate using odds ratio and mean difference.RESULTS Six studies met the inclusion criteria(n=1305).Higher odds of technical success(P=0.002)and en bloc removal(P<0.01)and lower odds of adverse events(P=0.02)and foreign body removal time(P<0.01)were observed with cap-assisted endoscopy as compared to conventional techniques.CONCLUSION For esophageal foreign bodies,the technique of cap-assisted endoscopy demonstrated increased en bloc removal and technical success with decreased time and adverse events as compared to conventional techniques.
文摘Rectal neuroendocrine tumours represent a rare colorectal tumour with a 10 fold increased prevalence due to incidental detection in the era of colorectal screening.Patient outcomes with early diagnosis are excellent.However endoscopic recognition of this lesion is variable and misdiagnosis can result in suboptimal endoscopic resection with subsequent uncertainty in relation to optimal long-term management.Endoscopic techniques have shown particular utility in managing this under-recognized neuroendocrine tumour.
文摘Due to the high risk of morbidity and mortality associated with surgical resection in this tract,endoscopic resection(ER)has taken the place of surgical resection as the first line treatment for non-ampullary duodenal adenomas.However,due to the anatomical characteristics of this area,which enhance the risk of post-ER problems,ER in the duodenum is particularly difficult.Due to a lack of data,no ER technique for superficial non-ampullary duodenal epithelial tumours(SNADETs)has yet been backed by strong,high-quality evidence;yet,traditional hot snare-based techniques are still regarded as the standard treatment.Despite having a favourable efficiency profile,adverse events during duodenal hot snare polypectomy(HSP)and hot endoscopic mucosal resection,such as delayed bleeding and perforation,have been reported to be frequent.These events are primarily caused by electrocautery-induced damage.Thus,ER techniques with a better safety profile are needed to overcome these shortcomings.Cold snare polypectomy,which has already been shown as a safer,equally effective pro-cedure compared to HSP for treatment of small colorectal polyps,is being increasingly evaluated as a potential therapeutic option for non-ampullary duodenal adenomas.The aim of this review is to report and discuss the early outcomes of the first experiences with cold snaring for SNADETs.
文摘BACKGROUND Although endoscopic submucosal dissection(ESD)is becoming more common for early gastric cancer,it requires more advanced techniques and a longer treatment duration than endoscopic mucosal resection.Hybrid ESD using a multifunctional snare(SOUTEN)has been reported to be effective for colorectal lesions,as it can reduce treatment duration.Endoscopic suturing of post-ESD mucosal defects has been reported to reduce the incidence of ESD-related complications.CASE SUMMARY This study reports outpatient hybrid ESD for early gastric cancer using SOUTEN,followed by endoscopic suturing of post-ESD mucosal defects in an 86-year-old man.On referral for ESD,a 10-mm flat,depressed lesion was found on the posterior wall of the gastric antrum,the depth of which was expected to be mucosal.Given his history of delirium,we performed outpatient endoscopic treatment.The procedure used was hybrid ESD using SOUTEN to reduce the duration of treatment and endoscopic suturing of post-ESD mucosal ESD defects to reduce complications.The procedure time was 62 min and the lesion was completely resected based on histopathological examination,with no reported postoperative complications.CONCLUSION This safe and useful procedure may be especially important for outpatient endoscopic treatment.
基金This work was supported by the National Natural Science Foundation of China (No. 30170302 39470238+3 种基金 39070323 39860249)the Climbing Project of Ministry of Science and Technology of China (No. P8505) the National Basic Research Priorities Programmeof China (No. G19999054000) and the Basic Research Program of Shanghai Municipal Commission for Science and Technology (No.O2JC14011).
