Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric...Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.展开更多
Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer-related deaths worldwide.Dendritic cells(DCs)constitute a heterogeneous group of antigen-presenting cells that are important...Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer-related deaths worldwide.Dendritic cells(DCs)constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses.As a crucial component of the immune system,DCs have a pivotal role in the pathogenesis and clinical treatment of CRC.DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response.However,the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment.This review systematically elucidates the specific characteristics and functions of different DC subsets,as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment.Moreover,how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed,which will provide new perspectives and approaches for immunotherapy in patients with CRC.展开更多
Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophag...Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter(LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents(herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.展开更多
To explore the influence and significance of the ischemia reperfusion on the hepatic neoplasm, the hepatic VX2 neoplasm model of rabbits was established under the guide of ultrasonography; and ischemia was caused by u...To explore the influence and significance of the ischemia reperfusion on the hepatic neoplasm, the hepatic VX2 neoplasm model of rabbits was established under the guide of ultrasonography; and ischemia was caused by using a non-traumatic vascular clamp to block the branches distributing in the left-middle lobe of the hepatic artery for 60 min, and subsequently the clamp was removed and the reperfusion injury of hepatic neoplasm occurred. At different time-points, the normal and hepatic neoplasm tissues of the animal models were taken out to detect the superoxide dismutase (SOD) and malondialdehyde (MDA) respectively.The results show that the products and injurious effects of oxygen free radical (OFR) of the neoplasm tissues are more serious than those of the normal hepatic tissues.展开更多
AIM： To investigate the role of IFN-T inducible protein -10 （IP-10） and regulated upon activation, normal T cell expressed and secreted （RANTES） protein in acute pancreatic allograft rejection in rats. METHODS： ...AIM： To investigate the role of IFN-T inducible protein -10 （IP-10） and regulated upon activation, normal T cell expressed and secreted （RANTES） protein in acute pancreatic allograft rejection in rats. METHODS： An experimental model was established using pancreas transplantation diabetic SD rats as the recipient, induced by applying streptozocin （STZ）. Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group （group A, n = 24） and allograft group （group B, n = 24） in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry. RESULTS： In group B （allograft group）, the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A （isograft group）. CONCLUSION： Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.展开更多
Although approximately one million sudden cardiac deaths occur yearly in the US and Europe,cardiac arrest (CA)remains a clinical condition still characterized by a poor prognosis.In an effort to improve the cardio- pu...Although approximately one million sudden cardiac deaths occur yearly in the US and Europe,cardiac arrest (CA)remains a clinical condition still characterized by a poor prognosis.In an effort to improve the cardio- pulmonary resuscitation(CPR)technique,the 2005 American Heart Association(AHA)Guidelines for CPR gave the impedance threshold device(ITD)a Class IIa recommendation.The AHA recommendation means that there is strong evidence to demonstrate that ITD enhances circulation,improves hemodynamics and increases the likelihood of resuscitation in patients in CA.During standard CPR,venous blood return to the heart relies on the natural elastic recoil of the chest which creates a transient decrease in intrathoracic pressure.The ITD further decreases intrathoracic pressure by preventing respiratory gases from entering the lungs during the decompression phase of CPR. Thus,although ITD is placed into the respiratory circuit it works as a circulatory enhancer device that provides its therapeutic benefit with each chest decompression. The ease of use of this device,its ability to be incor- porated into a mask and other airway devices,the absence of device-related adverse effects and few requirements in additional training,suggest that ITD may be a favorable new device for improving CPR efficiency.Since the literature is short of studies with clinically meaningful outcomes such as neurological outcome and long term survival,further evidence is still needed.展开更多
Objective:To study the effect of reactive oxygen species of inducing apoptosis on the heptocacinoma tissues following ischemia and reperfusion and perfusion hyperoxia liquid of hepatocarcinoma. Methods: The hepatocarc...Objective:To study the effect of reactive oxygen species of inducing apoptosis on the heptocacinoma tissues following ischemia and reperfusion and perfusion hyperoxia liquid of hepatocarcinoma. Methods: The hepatocarcinoma animal models ware established by implantation of VX2 tumor constitution mass into the left middle lobe of liver of rabbits. The animals were subjected to 60 min clamp-induced ischemia of hepatic artery distributing in the left middle lobe followed by reperfusion at 1 h, 1 d, 3 d and 7 d, respectively, and perfusion hyperoxia liquid (partial pressure of oxygen, PO2>80 kPa) at the same time with reperfusion beginning. The concentration of MDA and NO ware tested. Apoptotic changes in the hepatocarcinoma and normal hepatic tissues were observed by means of HE staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Results:The concentration of MDA in normal hepatic tissues and hepatocarcinoma tissue increased followed ischemia and reperfusion especially for reperfusion 1 h (4.61±0.40, 3.10±0.23) and restored to normal level at reperfusion 7 d in normal hepatic tissues but still kept high concentration in the hepatocarcinoma tissue. Even though concentration of MDA in normal hepatic tissues is higher than that of before ischemia and reperfusion, no difference have been found after perfusion of hyperoxia liquid, and in the hepatocarcinoma tissue, the increasing of concentration of MDA was obvious after simply ischemia and reperfusion at reperfusion 1 d (4.25±0.45). The concentration of NO in normal hepatic tissues increased for reperfusion 3 d and 7 d(18.17±0.13, 17.45±0.23),while that of hepatocarcinoma tissue decreased at reperfusion 3 d(15.95±043). After perfusion of hyperoxia liquid, the concentration of NO in normal hepatic tissues kept increasing and that decreased in the hepatocarcinoma tissues in all time point and reached the lowest level at reperfusion 1 d(14.62±0.45).The result demonstrated the changes of concentration of NO and MDA in the hepatocarcinoma tissues ware more obvious than that of normal hepatic tissues(P<0.01). Conclusion:Perfusion of hyperoxia liquid from hepatic portal vein can intensify ischemia and reperfusion injury but less so for normal hepatic tissues.展开更多
Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making...Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making the models of ischemia and reperfusion by clamping superior mesenteric artery, the concentration of NO and SOD in the blood was examined before clamping the artery and reperfusion for 0, 30, 60 min, 1, 3, and 7 d. The expression of Bax, Bal-2, and p53 in myocardial cell was studied by means of immunohistochemical SP method and the microstructure damage was observed under electron microscopy. Results: After clamping the superior mesenteric artery and reperfusion the concentration of NO increased continuously and reached a peak for reperfusion 7 d (P<0.01) but that of SOD decreased from 30 min to 7 d. The expression of Bax, p53 and Bcl-2 also increased obviously especially for reperfusion 30 min and 7 d following ischemia and reperfusion. After reperfusion for 30 min the positive cell rate of Bax, p53 and Bcl-2 was 53.6%, 45.9% and 67.9%, for reperfusion 7 d it was 52.4%, 43.4% and 31.9% respectively, but the positive cell rate of Bax and p53 was higher than that of Bcl-2. The result of electron microscopy observation showed mfofiliments breaked, dissolved and chromatin condensed. Conclusion: Intestinal ischemia and reperfusion of rat can induced the changes of oxygen free radical and the expression of apoptotic gene and second injury of myocardial cells.展开更多
Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularizatio...Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.展开更多
AIM: To examine whether the social desirability response has an effect on the structure validity of 16 PF. After controlling for the effect of social desirability,it can improve the predictive validity of 16 PF and ac...AIM: To examine whether the social desirability response has an effect on the structure validity of 16 PF. After controlling for the effect of social desirability,it can improve the predictive validity of 16 PF and accuracy of different selection decision. METHODS: A total of 1224 subjects were tested for two times and the interval was 7 months. The 16 PF and the "Social Desirability Scale in Context of Psychological Screening",were used to verify and clarify the social desirability response to the structure of 16 PF and its impact on the secondary factor structure theory model. RESULTS: The social desirability response had a significant effect on the 16 PF root traits,structure validity and the theoretical model of the secondary factors,but the influence was small and the influence was not significant. CONCLUSION:The structure validity of the 16 PF is not significantly affected by the test motivation or social desirability,and the social desirability response in the psychological test of the military academy students will not have a significant impact on the structure validity of the personality test.展开更多
A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is...A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is still a major concern. Therefore, the process of liver regeneration has been a constant theme of study in order to optimize this process. Erythropoietin, a hormone produced by the kidney and involved in protecting organs like heart, liver and kidney itself against injuries can be one of these factors that could accelerate the liver regeneration. This study aims to observe if erythropoietin can accelerate the process of liver regeneration after partial hepatectomy in pigs. Methods: 8 pigs were classified into 2 groups of 4 pigs each: the control group and the test group. The animals in the first group underwent an application of saline solution subcutaneous on the day before the hepatectomy. Instead of saline solution, the test groups received a subcutaneous injection of 200 UI/lg of recombinant erythropoietin also on the day before the surgical procedure. After 7 days since the hepatectomy, in each animal the liver was biopsied in two regions, one next to the hepatectomy section and other far from it. The liver regeneration was analyzed using Ki-67. Results: Pigs from control group presented the following results: Control pig I: 30% of regeneration in the hepatectomy section and 10% in the region far from it;control pig II 24% and 4%;control pig III 27% and 7%. The test group presented no significant liver regeneration since Ki-67 could not identify cell proliferation in neither the biopsied areas. Conclusion: Since the number of pigs was not statistically significant, we could not conclude any further hypothesis. We strong believe that enhancing the number of pigs and testing different doses, we will be able to reach further conclusions.展开更多
Literature data on glioblastoma ongoingly underline the link between metabolism and cancer stemness,the latter is one responsible for potentiating the resistance to treatment,inter alia due to increased invasiveness.I...Literature data on glioblastoma ongoingly underline the link between metabolism and cancer stemness,the latter is one responsible for potentiating the resistance to treatment,inter alia due to increased invasiveness.In recent years,glioblastoma stemness research has bashfully introduced a key aspect of cytoskeletal rearrangements,whereas the impact of the cytoskeleton on invasiveness is well known.Although non-stem glioblastoma cells are less invasive than glioblastoma stem cells(GSCs),these cells also acquire stemness with greater ease if characterized as invasive cells and not tumor core cells.This suggests that glioblastoma stemness should be further investigated for any phenomena related to the cytoskeleton and metabolism,as they may provide new invasion-related insights.Previously,we proved that interplay between metabolism and cytoskeleton existed in glioblastoma.Despite searching for cytoskeleton-related processes in which the investigated genes might have been involved,not only did we stumble across the relation to metabolism but also reported genes that were found to be implicated in stemness.Thus,dedicated research on these genes in GSCs seems justifiable and might reveal novel directions and/or biomarkers that could be utilized in the future.Herein,we review the previously identified cytoskeleton/metabolism-related genes through the prism of glioblastoma stemness.展开更多
AIM: To evaluate if canine models are appropriate for teaching endoscopy fellows the techniques of endoscopic submucosal dissection (ESD). METHODS: ESD was performed in 10 canine models under general anesthesia, on ar...AIM: To evaluate if canine models are appropriate for teaching endoscopy fellows the techniques of endoscopic submucosal dissection (ESD). METHODS: ESD was performed in 10 canine models under general anesthesia, on artificial lesions of the esophagus or stomach marked with coagulation points. After ESD, each canine model was euthanized and surgical resection of the esophagus or stomach was carried out according to "The Principles of Humane Experimental Technique, Russel and Burch". The ESD specimens were fixed with needles on cork submerged in a formol solution with the esophagus or stomach, and delivered to the pathology department to be analyzed. RESULTS: ESD was completed without complications using the Hook-knife in five esophageal areas, with a procedural duration of 124 ± 19 min, a length of 27.4 ± 2.6 mm and a width of 21 ± 2.4 mm. ESD was also completed without complications using the IT-knife2 in five gastric areas, with a procedural duration of 92.6 ± 19 min, a length of 32 ± 2.5 mm and a width of 18 ± 3.7 mm. CONCLUSION: ESD is feasible in the normal esopha- gus and stomach of canine models, which are appropriate for teaching this technique.展开更多
Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in ...Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in additional treatment morbidity and even threaten the lives of patients.Thus,designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge.Herein,a series of injectable pH-responsive selfhealing adhesive hydrogels based on acryloyl-6-aminocaproic acid(AA)and AA-g-N-hydroxysuccinimide(AA-NHS)were developed,and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model.The hydrogels showed a suitable gelation time,an autonomous and efficient self-healing capacity,hemostatic properties,and good biocompatibility.With the introduction of AA-NHS as a micro-cross-linker,the hydrogels exhibited enhanced adhesive strength.A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding.A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition,α-SMA expression,and blood vessel formation.These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.展开更多
Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease that affects the left ventricle. HCM can appear at any age, with the majority of the patients remaining clinically stable. When patients com...Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease that affects the left ventricle. HCM can appear at any age, with the majority of the patients remaining clinically stable. When patients complain of symptoms, these include: dyspnea, dizziness, syncope and angina. HCM can lead to sudden cardiac death (SCD), mainly due to ventricular tachyarrhythmia or ventricular tachycardia. High-risk patients benefit from implantable cardioverter-defibrillators. Left ventricular outflow tract obstruction is not a rare feature in HCM, especially in symptomatic patients, and procedures that abolish that obstruction provide positive and consistent results that can improve longterm survival. HCM is the most common cause of sudden death in young competitive athletes and preparticipation screening programs have to be implemented to avoid these tragic fatalities. The structure of these programs is a matter of large debate. Worldwide registries are necessary to identify the full extent of HCMrelated SCD.展开更多
AIM： Hydrodynamics based transfection （HBT）, the injection of a large volume of naked plasmid DNA in a short time is a relatively simple, efficient and safe method for in vivo transfection of liver cells. Though us...AIM： Hydrodynamics based transfection （HBT）, the injection of a large volume of naked plasmid DNA in a short time is a relatively simple, efficient and safe method for in vivo transfection of liver cells. Though used for quite some time, the mechanism of gene transfection has not yet been elucidated. METHODS： A lucJferase encoding plasmid was injected using the hydrodynamics based procedure into normal and thioacetamide-induced fibrotic Sprague Dawley rats. Scanning and transmission electron microscopy images were taken. The consequence of a dual injection of Ringer solution and luciferase pDNA was followed. Halofuginone, an anti collagen type I inhibitor was used to reduce ECM load in fibrotic rats prior to the hydrodynamic injection. RESULTS： Large endothelial gaps formed as soon as 10＇ following hydrodynamic injection; these gradually returned to normal 10 d post injection. Hydrodynamic administration of Ringer 10 or 30 m prior to moderate injection of plasmid did not result in efficient transfection suggesting that endothelial gaps by themselves are not sufficient for gene expression. Gene transfection following hydrodynamic injection in thioacetamide induced fibrotic rats was diminished coinciding with the level of fibrosis. Halofuginone, a specific collagen type I inhibitor, alleviated this effect. CONCLUSION： The hydrodynamic pressure formed following HBT results in the formation of large endothelial gaps. These gaps, though important in the transfer of DNA molecules from the blood to the space of Disse are not enough to provide the appropriate conditions for hepatocyte transfection. Hydrodynamics based injection is applicable in fibrotic rats provided that ECM load is reduced.展开更多
<b>Background:</b> Peripheral block techniques for total hip arthroplasty have been used as an analgesic strategy, only a few studies described it as an anesthetic technique, so the perioperative performan...<b>Background:</b> Peripheral block techniques for total hip arthroplasty have been used as an analgesic strategy, only a few studies described it as an anesthetic technique, so the perioperative performance and safety are poorly studied. <b>Methods:</b> 78 total hip arthroplasties were prospectively observed in our hospital. Divided into 2 groups: 1) General anesthesia;and 2) Lumbar sacral plexus block anesthesia. Variables measured in both groups were: demographics, conversion to general anesthesia, total opioid doses, surgical time, blood loss, postoperative pain, use and total dose of vasopressors drugs, transfusion and ICU transfer needs, postoperative ambulation time, and length of hospital stay. T student and chi-square tests were used upon the case. A significant difference was considered when a value of p < 0.05 was obtained. Descriptive statistics were performed in frequency, percentages, variance and standard deviation. <b>Results:</b> 3 patients (7.3%) anesthetized with combined lumbar sacral plexus block were converted to general anesthesia. When comparing peripheral nerve block and general anesthesia, less intraoperative (p = 0.000) and postoperative (p = 0.002) opioid consumption were noted, less postoperative pain in PACU (p = 0.002) and in the first 24 hours (p = 0.005), as well as earlier onset of ambulation (p = 0.008) and shorter hospital stay (p = 0.031). <b>Conclusions:</b> In our study, the lumbar and sacral plexus block anesthesia technique provided anesthetic conditions to perform hip joint arthroplasty and it was proved to be advantageous in comparison to general anesthesia.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82201621(to LS),31930048(to QY)and 81720108016(to QY),and 81971225(to CG)the Key Research and Development Project of Shaanxi Province,No.2022SF-189(to XS)the Tangdu Hospital Supporting Foundation,Nos.2021ZTXM-006(to LS)and 2021JSZH-006(to CG)。
文摘Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury.Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury.Thus,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease.To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,respectively.Using bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting proteins.Interactions between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in vitro.Our data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory effects.Taken together,our findings show that mitochondrial transplantation protects against the deleterious effects of ischemic stroke by suppressing pyroptosis and promoting neurogenesis,and that S100A9 plays a vital role in promoting internalization of exogenous mitochondria.
基金This study was supported by grants from the National Natural Science Foundation of China(Grant Nos.82222058,82073197,82273142,and 82173256).
文摘Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer-related deaths worldwide.Dendritic cells(DCs)constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses.As a crucial component of the immune system,DCs have a pivotal role in the pathogenesis and clinical treatment of CRC.DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response.However,the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment.This review systematically elucidates the specific characteristics and functions of different DC subsets,as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment.Moreover,how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed,which will provide new perspectives and approaches for immunotherapy in patients with CRC.
文摘Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter(LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents(herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.
文摘To explore the influence and significance of the ischemia reperfusion on the hepatic neoplasm, the hepatic VX2 neoplasm model of rabbits was established under the guide of ultrasonography; and ischemia was caused by using a non-traumatic vascular clamp to block the branches distributing in the left-middle lobe of the hepatic artery for 60 min, and subsequently the clamp was removed and the reperfusion injury of hepatic neoplasm occurred. At different time-points, the normal and hepatic neoplasm tissues of the animal models were taken out to detect the superoxide dismutase (SOD) and malondialdehyde (MDA) respectively.The results show that the products and injurious effects of oxygen free radical (OFR) of the neoplasm tissues are more serious than those of the normal hepatic tissues.
基金Supported by a grant from the "135" Foundation of Jiangsu Province, No. 2003-19
文摘AIM： To investigate the role of IFN-T inducible protein -10 （IP-10） and regulated upon activation, normal T cell expressed and secreted （RANTES） protein in acute pancreatic allograft rejection in rats. METHODS： An experimental model was established using pancreas transplantation diabetic SD rats as the recipient, induced by applying streptozocin （STZ）. Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group （group A, n = 24） and allograft group （group B, n = 24） in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry. RESULTS： In group B （allograft group）, the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A （isograft group）. CONCLUSION： Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.
文摘Although approximately one million sudden cardiac deaths occur yearly in the US and Europe,cardiac arrest (CA)remains a clinical condition still characterized by a poor prognosis.In an effort to improve the cardio- pulmonary resuscitation(CPR)technique,the 2005 American Heart Association(AHA)Guidelines for CPR gave the impedance threshold device(ITD)a Class IIa recommendation.The AHA recommendation means that there is strong evidence to demonstrate that ITD enhances circulation,improves hemodynamics and increases the likelihood of resuscitation in patients in CA.During standard CPR,venous blood return to the heart relies on the natural elastic recoil of the chest which creates a transient decrease in intrathoracic pressure.The ITD further decreases intrathoracic pressure by preventing respiratory gases from entering the lungs during the decompression phase of CPR. Thus,although ITD is placed into the respiratory circuit it works as a circulatory enhancer device that provides its therapeutic benefit with each chest decompression. The ease of use of this device,its ability to be incor- porated into a mask and other airway devices,the absence of device-related adverse effects and few requirements in additional training,suggest that ITD may be a favorable new device for improving CPR efficiency.Since the literature is short of studies with clinically meaningful outcomes such as neurological outcome and long term survival,further evidence is still needed.
文摘Objective:To study the effect of reactive oxygen species of inducing apoptosis on the heptocacinoma tissues following ischemia and reperfusion and perfusion hyperoxia liquid of hepatocarcinoma. Methods: The hepatocarcinoma animal models ware established by implantation of VX2 tumor constitution mass into the left middle lobe of liver of rabbits. The animals were subjected to 60 min clamp-induced ischemia of hepatic artery distributing in the left middle lobe followed by reperfusion at 1 h, 1 d, 3 d and 7 d, respectively, and perfusion hyperoxia liquid (partial pressure of oxygen, PO2>80 kPa) at the same time with reperfusion beginning. The concentration of MDA and NO ware tested. Apoptotic changes in the hepatocarcinoma and normal hepatic tissues were observed by means of HE staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). Results:The concentration of MDA in normal hepatic tissues and hepatocarcinoma tissue increased followed ischemia and reperfusion especially for reperfusion 1 h (4.61±0.40, 3.10±0.23) and restored to normal level at reperfusion 7 d in normal hepatic tissues but still kept high concentration in the hepatocarcinoma tissue. Even though concentration of MDA in normal hepatic tissues is higher than that of before ischemia and reperfusion, no difference have been found after perfusion of hyperoxia liquid, and in the hepatocarcinoma tissue, the increasing of concentration of MDA was obvious after simply ischemia and reperfusion at reperfusion 1 d (4.25±0.45). The concentration of NO in normal hepatic tissues increased for reperfusion 3 d and 7 d(18.17±0.13, 17.45±0.23),while that of hepatocarcinoma tissue decreased at reperfusion 3 d(15.95±043). After perfusion of hyperoxia liquid, the concentration of NO in normal hepatic tissues kept increasing and that decreased in the hepatocarcinoma tissues in all time point and reached the lowest level at reperfusion 1 d(14.62±0.45).The result demonstrated the changes of concentration of NO and MDA in the hepatocarcinoma tissues ware more obvious than that of normal hepatic tissues(P<0.01). Conclusion:Perfusion of hyperoxia liquid from hepatic portal vein can intensify ischemia and reperfusion injury but less so for normal hepatic tissues.
文摘Objective: To study the changes of oxygen free radical, expression of apoptotic gene, ultrastructure of myocardial cell and second injury of the heart following the intestinal ischemia and reperfusion. Methods: Making the models of ischemia and reperfusion by clamping superior mesenteric artery, the concentration of NO and SOD in the blood was examined before clamping the artery and reperfusion for 0, 30, 60 min, 1, 3, and 7 d. The expression of Bax, Bal-2, and p53 in myocardial cell was studied by means of immunohistochemical SP method and the microstructure damage was observed under electron microscopy. Results: After clamping the superior mesenteric artery and reperfusion the concentration of NO increased continuously and reached a peak for reperfusion 7 d (P<0.01) but that of SOD decreased from 30 min to 7 d. The expression of Bax, p53 and Bcl-2 also increased obviously especially for reperfusion 30 min and 7 d following ischemia and reperfusion. After reperfusion for 30 min the positive cell rate of Bax, p53 and Bcl-2 was 53.6%, 45.9% and 67.9%, for reperfusion 7 d it was 52.4%, 43.4% and 31.9% respectively, but the positive cell rate of Bax and p53 was higher than that of Bcl-2. The result of electron microscopy observation showed mfofiliments breaked, dissolved and chromatin condensed. Conclusion: Intestinal ischemia and reperfusion of rat can induced the changes of oxygen free radical and the expression of apoptotic gene and second injury of myocardial cells.
文摘Critical limb ischemia is a medical condition that decreases blood flow and limb oxygen supply;this disease in its late stages of progression leads to only two possible options: either surgical bypass revascularization or limb amputation. We investigated a novel method using autologous transplantation of progenitor cells derived from mobilized peripheral blood bone marrow mononuclear cells to evaluate its long-term effect as a cell therapy to induce neo-angiogenesis and restore blood flow in the affected ischemic limbs. A total of 20 ischemic limbs from critical limb ischemia diagnosed patients, non candidates to surgical revascularization were transplanted with autologous progenitor cells by either intramuscular combined with intravenous (group A) or intramuscular (group B) procedure. Patients were monitored during 31 months. Treatment efficacy was evaluated according to the following parameters: ankle brachial index which increased at a range of 0.29-1.0 in group A and 0.40-0.90 in group B;pain-free walking distance which increased at a range of 50-600 m in group A and 50-300 m in group B;and blood perfusion (measured by Laser Doppler) which increased at a range of 48-299 in group A and 135-225 in group B. We achieved 90% treated ischemic limbs free of amputation in both transplanted groups. Results here described provide a safe, efficient and minimally invasive therapy with progenitor cells to induce angiogenesis and preserve limbs from amputation in CLI diagnosed patients.
文摘AIM: To examine whether the social desirability response has an effect on the structure validity of 16 PF. After controlling for the effect of social desirability,it can improve the predictive validity of 16 PF and accuracy of different selection decision. METHODS: A total of 1224 subjects were tested for two times and the interval was 7 months. The 16 PF and the "Social Desirability Scale in Context of Psychological Screening",were used to verify and clarify the social desirability response to the structure of 16 PF and its impact on the secondary factor structure theory model. RESULTS: The social desirability response had a significant effect on the 16 PF root traits,structure validity and the theoretical model of the secondary factors,but the influence was small and the influence was not significant. CONCLUSION:The structure validity of the 16 PF is not significantly affected by the test motivation or social desirability,and the social desirability response in the psychological test of the military academy students will not have a significant impact on the structure validity of the personality test.
文摘A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is still a major concern. Therefore, the process of liver regeneration has been a constant theme of study in order to optimize this process. Erythropoietin, a hormone produced by the kidney and involved in protecting organs like heart, liver and kidney itself against injuries can be one of these factors that could accelerate the liver regeneration. This study aims to observe if erythropoietin can accelerate the process of liver regeneration after partial hepatectomy in pigs. Methods: 8 pigs were classified into 2 groups of 4 pigs each: the control group and the test group. The animals in the first group underwent an application of saline solution subcutaneous on the day before the hepatectomy. Instead of saline solution, the test groups received a subcutaneous injection of 200 UI/lg of recombinant erythropoietin also on the day before the surgical procedure. After 7 days since the hepatectomy, in each animal the liver was biopsied in two regions, one next to the hepatectomy section and other far from it. The liver regeneration was analyzed using Ki-67. Results: Pigs from control group presented the following results: Control pig I: 30% of regeneration in the hepatectomy section and 10% in the region far from it;control pig II 24% and 4%;control pig III 27% and 7%. The test group presented no significant liver regeneration since Ki-67 could not identify cell proliferation in neither the biopsied areas. Conclusion: Since the number of pigs was not statistically significant, we could not conclude any further hypothesis. We strong believe that enhancing the number of pigs and testing different doses, we will be able to reach further conclusions.
文摘Literature data on glioblastoma ongoingly underline the link between metabolism and cancer stemness,the latter is one responsible for potentiating the resistance to treatment,inter alia due to increased invasiveness.In recent years,glioblastoma stemness research has bashfully introduced a key aspect of cytoskeletal rearrangements,whereas the impact of the cytoskeleton on invasiveness is well known.Although non-stem glioblastoma cells are less invasive than glioblastoma stem cells(GSCs),these cells also acquire stemness with greater ease if characterized as invasive cells and not tumor core cells.This suggests that glioblastoma stemness should be further investigated for any phenomena related to the cytoskeleton and metabolism,as they may provide new invasion-related insights.Previously,we proved that interplay between metabolism and cytoskeleton existed in glioblastoma.Despite searching for cytoskeleton-related processes in which the investigated genes might have been involved,not only did we stumble across the relation to metabolism but also reported genes that were found to be implicated in stemness.Thus,dedicated research on these genes in GSCs seems justifiable and might reveal novel directions and/or biomarkers that could be utilized in the future.Herein,we review the previously identified cytoskeleton/metabolism-related genes through the prism of glioblastoma stemness.
文摘AIM: To evaluate if canine models are appropriate for teaching endoscopy fellows the techniques of endoscopic submucosal dissection (ESD). METHODS: ESD was performed in 10 canine models under general anesthesia, on artificial lesions of the esophagus or stomach marked with coagulation points. After ESD, each canine model was euthanized and surgical resection of the esophagus or stomach was carried out according to "The Principles of Humane Experimental Technique, Russel and Burch". The ESD specimens were fixed with needles on cork submerged in a formol solution with the esophagus or stomach, and delivered to the pathology department to be analyzed. RESULTS: ESD was completed without complications using the Hook-knife in five esophageal areas, with a procedural duration of 124 ± 19 min, a length of 27.4 ± 2.6 mm and a width of 21 ± 2.4 mm. ESD was also completed without complications using the IT-knife2 in five gastric areas, with a procedural duration of 92.6 ± 19 min, a length of 32 ± 2.5 mm and a width of 18 ± 3.7 mm. CONCLUSION: ESD is feasible in the normal esopha- gus and stomach of canine models, which are appropriate for teaching this technique.
基金This work was jointly supported by the National Natural Science Foundation of China(grant Nos.:51973172,51673155,81201927,82002957 and 81672460)the National Key Research and Development Plan of China(No.2018YFC0115300)+5 种基金the State Key Laboratory for Mechanical Behavior of Materials,the World-Class Universities(Disciplines)the Characteristic Development Guidance Funds for the Central Universities,the Natural Science Foundation of Shaanxi Province(No.2020JC-03 and 2019TD-020)the Innovation Talent Promotion Plan of Shaanxi(No.2017KJXX-07)the Key Research and Development Program of Shaanxi Province(No.2019SF-012)the Opening Project of Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University(No.2019LHM-KFKT008)Fundamental Research Funds for the Central Universities of China(No.xjj2018090).
文摘Endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD)are well-established therapeutics for gastrointestinal neoplasias,but complications after EMR/ESD,including bleeding and perforation,result in additional treatment morbidity and even threaten the lives of patients.Thus,designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge.Herein,a series of injectable pH-responsive selfhealing adhesive hydrogels based on acryloyl-6-aminocaproic acid(AA)and AA-g-N-hydroxysuccinimide(AA-NHS)were developed,and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model.The hydrogels showed a suitable gelation time,an autonomous and efficient self-healing capacity,hemostatic properties,and good biocompatibility.With the introduction of AA-NHS as a micro-cross-linker,the hydrogels exhibited enhanced adhesive strength.A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding.A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition,α-SMA expression,and blood vessel formation.These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.
文摘Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease that affects the left ventricle. HCM can appear at any age, with the majority of the patients remaining clinically stable. When patients complain of symptoms, these include: dyspnea, dizziness, syncope and angina. HCM can lead to sudden cardiac death (SCD), mainly due to ventricular tachyarrhythmia or ventricular tachycardia. High-risk patients benefit from implantable cardioverter-defibrillators. Left ventricular outflow tract obstruction is not a rare feature in HCM, especially in symptomatic patients, and procedures that abolish that obstruction provide positive and consistent results that can improve longterm survival. HCM is the most common cause of sudden death in young competitive athletes and preparticipation screening programs have to be implemented to avoid these tragic fatalities. The structure of these programs is a matter of large debate. Worldwide registries are necessary to identify the full extent of HCMrelated SCD.
基金Supported by the Israel Science Foundation, No. 537/01, the C. Rosenblantt Cancer Research Fund and the Rappaport Institute Fund
文摘AIM： Hydrodynamics based transfection （HBT）, the injection of a large volume of naked plasmid DNA in a short time is a relatively simple, efficient and safe method for in vivo transfection of liver cells. Though used for quite some time, the mechanism of gene transfection has not yet been elucidated. METHODS： A lucJferase encoding plasmid was injected using the hydrodynamics based procedure into normal and thioacetamide-induced fibrotic Sprague Dawley rats. Scanning and transmission electron microscopy images were taken. The consequence of a dual injection of Ringer solution and luciferase pDNA was followed. Halofuginone, an anti collagen type I inhibitor was used to reduce ECM load in fibrotic rats prior to the hydrodynamic injection. RESULTS： Large endothelial gaps formed as soon as 10＇ following hydrodynamic injection; these gradually returned to normal 10 d post injection. Hydrodynamic administration of Ringer 10 or 30 m prior to moderate injection of plasmid did not result in efficient transfection suggesting that endothelial gaps by themselves are not sufficient for gene expression. Gene transfection following hydrodynamic injection in thioacetamide induced fibrotic rats was diminished coinciding with the level of fibrosis. Halofuginone, a specific collagen type I inhibitor, alleviated this effect. CONCLUSION： The hydrodynamic pressure formed following HBT results in the formation of large endothelial gaps. These gaps, though important in the transfer of DNA molecules from the blood to the space of Disse are not enough to provide the appropriate conditions for hepatocyte transfection. Hydrodynamics based injection is applicable in fibrotic rats provided that ECM load is reduced.
文摘<b>Background:</b> Peripheral block techniques for total hip arthroplasty have been used as an analgesic strategy, only a few studies described it as an anesthetic technique, so the perioperative performance and safety are poorly studied. <b>Methods:</b> 78 total hip arthroplasties were prospectively observed in our hospital. Divided into 2 groups: 1) General anesthesia;and 2) Lumbar sacral plexus block anesthesia. Variables measured in both groups were: demographics, conversion to general anesthesia, total opioid doses, surgical time, blood loss, postoperative pain, use and total dose of vasopressors drugs, transfusion and ICU transfer needs, postoperative ambulation time, and length of hospital stay. T student and chi-square tests were used upon the case. A significant difference was considered when a value of p < 0.05 was obtained. Descriptive statistics were performed in frequency, percentages, variance and standard deviation. <b>Results:</b> 3 patients (7.3%) anesthetized with combined lumbar sacral plexus block were converted to general anesthesia. When comparing peripheral nerve block and general anesthesia, less intraoperative (p = 0.000) and postoperative (p = 0.002) opioid consumption were noted, less postoperative pain in PACU (p = 0.002) and in the first 24 hours (p = 0.005), as well as earlier onset of ambulation (p = 0.008) and shorter hospital stay (p = 0.031). <b>Conclusions:</b> In our study, the lumbar and sacral plexus block anesthesia technique provided anesthetic conditions to perform hip joint arthroplasty and it was proved to be advantageous in comparison to general anesthesia.
