Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders ...Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders the clinical application of CR-PDT.Here,we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether(HMME)and a radiation energy amplifier Eu^(3+),named HMME-Eu@LEV.Colloidal Eu^(3+)convertsγ-radiation and CR from radioisotopes into fluorescence to enhance antitumor effects.Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical^(18)F-fluorodeoxyglucose(FDG)at the tumor site,triggering enhanced CR-PDT and immunogenic cell death.Our observations indicated that luminescence resonance energy transfer between Eu^(3+)and HMME was efficient,and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone.As a result,abundant ROS were generated,and macrophages in the tumor microenvironment were polarized from M2 to M1.In addition,the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes.The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases.Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.展开更多
Objective:To evaluate the efficacy and safety of balloon occlusion of the abdominal aorta for the treatment of pernicious placenta previa with placenta accreta.Methods:The clinical data of 623 patients with pernicious...Objective:To evaluate the efficacy and safety of balloon occlusion of the abdominal aorta for the treatment of pernicious placenta previa with placenta accreta.Methods:The clinical data of 623 patients with pernicious placenta previa combined with placenta accrete,who were admitted to our hospital from January 2013 to January 2019 were retrospectively analyzed.All patients underwent abdominal aortic balloon occlusion combined with cesarean section,and 78 patients underwent sequential bilateral uterine artery embolization.We analyzed the operation time,intraoperative blood loss,blood transfusion volume,intraoperative and postoperative complications,fetal radiation exposure time and dose,and the Apgar score of the newborns.We also performed other evaluations to ascertain the efficacy and safety of abdominal aortic balloon occlusion treatment for dangerous placenta previa with placenta accrete.Results:Of the 623 patients,545 underwent only abdominal aortic balloon occlusion,and 78 underwent uterine artery embolization due to intraoperative or postoperative bleeding.The uterus was successfully preserved in all patients.Except for five cases of right lower extremity arterial thrombosis,the remaining patients did not have postoperative lower extremity arteriovenous thrombosis,renal insufficiency,late postpartum hemorrhage,ectopic embolism,spinal cord or peripheral nerve damage,pelvic infection,or other serious complications.The mean operative time was 65.3(±14.5)min.The mean intraoperative blood loss was620(±570)ml.Ninety-six patients(15.4%,96/623)were treated with blood transfusion,and the average amount of blood transfused was 750(±400)ml.The average number of hospitalization days was 6.8(±3.4)days,the average time of fetal ray exposure was 5.2(±1.6)s,and the average radiation dose was 4.1(±2.7)m Gy.The neonatal Apgar score,was 8.4(±0.6)points at 1 min,and 9.6(±0.4)points at 5 min.In the follow-up to May 31,2019,29 patients were lost to follow-up,96 were lactating,and 498 were menstruating.Except for the cases lost to follow-up,the remaining 596 surviving newborns(including 2 twins)showed no abnormalities at the 42-day postnatal outpatient follow-up examination.Conclusion:Balloon occlusion of the abdominal aorta is a safe and effective method for the treatment of pernicious placenta previa with placenta accreta.展开更多
Objective:This study aimed to investigate the clinical effects of abdominal aortic balloon occlusion followed by uterine artery embolization for the treatment of pernicious placenta previa complicated with placenta ac...Objective:This study aimed to investigate the clinical effects of abdominal aortic balloon occlusion followed by uterine artery embolization for the treatment of pernicious placenta previa complicated with placenta accreta during cesarean section.Methods:We performed a retrospective analysis of the clinical data for 623 patients who experienced pernicious placenta previa complicated with placenta accreta and received treatment in our hospital from January 2013 to January 2019.All patients underwent abdominal aortic balloon occlusion before their cesarean section.Seventyeight patients received bilateral uterine artery embolization,and among them,placenta accreta was found at the opening of the cervix in 13 patients.Due to suturing difficulty after the removal of the placenta,gauze packing was used to temporarily compress the hemorrhage.As soon as the uterus was sutured,emergent bilateral uterine artery embolization was performed.Active bleeding was noted in the remaining 65 patients when the lower part of the uterus was pressed after the placenta was removed and the uterus was sutured,therefor,bilateral uterine artery embolization was performed urgently.Results:Of the 623 patients,545 patients underwent only abdominal aortic balloon occlusion and 78 patients underwent additional emergent bilateral uterine artery embolization due to hemorrhaging during or after their cesarean section.No hysterectomies were performed.In the 78 patients,the amount of bleeding was 800-3,200 ml with an average of 1,650 ml during the operation;the volume of blood transfused was 360-1,750 ml(average:960 ml).The fetal fluoroscopy time was 3–8 s(average:5 s).The dose of radiation exposure was(4.2±2.9) m Gy.Fetal appearance,pulse,grimace,activity,and respiration(Apgar) score were normal.No serious complications were observed during or after the operation in the follow-up visits.Conclusion:For patients with pernicious placenta previa complicated with placenta accreta who experience active bleeding after cesarean section and abdominal aortic balloon occlusion,bilateral uterine artery embolization can effectively reduce blood loss and requirement of blood transfusion during the operation,and lowers the risk of hysterectomy.展开更多
Purpose: Descending necrotizing mediastinitis(DNM) is a lethal and acute suppurative disease. This report aimed to summarize our experience in the treatment of DNM with continuous negative pressure catheter drainage a...Purpose: Descending necrotizing mediastinitis(DNM) is a lethal and acute suppurative disease. This report aimed to summarize our experience in the treatment of DNM with continuous negative pressure catheter drainage and transnasal jejunal feeding by interventional techniques. Materials and Methods: We retrospectively analyzed relevant clinical data of patients with DNM who underwent continuous negative pressure catheter drainage and transnasal jejunal feeding. All drainage catheters and jejunal feeding tubes were inserte d by interventional techniques. Results: In total, 21 patients were diagnosed with DNM by esophagography and computed tomography(CT). Catheters for the drainage of mediastinal abscesses as well as transnasal jejunal feeding tubes were successfully placed in all patients, indicating a 100% success rate. Of all patients, 13 underwent insertion of abscess drainage catheters through percutaneous puncture under DynaCT guidance, while eight had drainage catheter insertion through fistula orifices in the posterior nasopharyngeal wall or esophagus under fluoroscopic guidance. In total, 26 drainage tubes were inserted. One patient with diabetes died of sepsis and diabetic ketoacidosis 5 days postoperatively, while the remaining 20 patients showed good recovery with successful removal of the drainage catheters. Durations of catheterization were 45.2±50.44 days. The overall clinical success rate was 95.2%. Conclusion: The above described methods are non-surgical, minimally invasive and efficacious, and may be alternative therapeutic tools for patients who are not eligible for surgical operation, have a high postoperative risk, or are more likely to choose minimally invasive techniques.展开更多
Background:Patients who survive initial esophagogastric variceal bleeding(EVB)are at an increased risk of recurrent bleeding and death;however,a reliable predictive model is lacking.We aimed to develop a model for reb...Background:Patients who survive initial esophagogastric variceal bleeding(EVB)are at an increased risk of recurrent bleeding and death;however,a reliable predictive model is lacking.We aimed to develop a model for rebleeding prediction in patients with EVB after modified percutaneous transhepatic variceal embolization(PTVE)with cyanoacrylate.Methods:A total of 122 patients with EVB who underwent PTVE from January 2015 to November 2020 were enrolled.Multivariate logistic analyses were conducted to determine independent risk factors for nomogram construction.The discrimination,calibration,and clinical utility of the nomogram were compared with the Model for End-stage Liver Disease score(MELD)and the Child–Pugh model.Risk stratification was performed according to the nomogram.Results:Rebleeding within 3 months of PTVE occurred in 32 patients(26.2%).Independent rebleeding indicators included prior history of endoscopic therapy,Child–Pugh score,partial splenic embolization,and creatinine level.The nomogram incorporating these four predictors achieved excellent calibration and discriminatory abilities,with a concordance index of 0.85,which was confirmed to be 0.83 through bootstrapping validation.The nomogram demonstrated superior discrimination and clinical applicability than the MELD and Child–Pugh models.As shown in the Kaplan–Meier curves,high-risk patients had a high probability of rebleeding(P<0.001).Conclusions:The creatinine-based nomogram had a superior ability to predict rebleeding after PTVE in patients with EVB.Risk stratification may help identify high-risk patients and lead to the earlier implementation of aggressive treatments and formulation of intensive follow-up plans.展开更多
Objective: To evaluate the efficacy and safety of patient-controlled analgesia(PCA) with hydromorphone as perioperative analgesia during uterine artery embolization(UAE) via the right radial artery.Patients and method...Objective: To evaluate the efficacy and safety of patient-controlled analgesia(PCA) with hydromorphone as perioperative analgesia during uterine artery embolization(UAE) via the right radial artery.Patients and methods: A total of 33 patients with uterine fibroids, who underwent UAE at the authors’ hospital between June 2021 and March 2022, were selected. Hydromorphone(10 mg) was dispensed into a 100 ml PCA pump with normal saline. Pump administration was initiated 15 min before the start of the procedure, and the intraoperative dose was adjusted according to patient pain level. A numerical rating scale was used to evaluate pain immediately after embolization, 5 min after embolization, at the end of the procedure, and 6, 12, 24, 48, and 72 h after the procedure. Side effects were also observed.Results: Thirty-three patients underwent uterine artery embolization via the right radial artery. Patient pain was well controlled at all time points surveyed, and patients reported satisfaction with analgesia. The median length of hospital stay was 5 days. There were 7 cases of adverse reactions, but no serious side effects were observed.Conclusion: Patients reported positive experiences with arterial embolization of uterine fibroids via the right radial artery. Hydromorphone PCA effectively controlled pain. The PCA pump is easy to operate, has a low incidence of adverse reactions, and offers economic benefits at the patient and institutional levels.展开更多
Gastric varices are a major complication of portal hypertension in patients with liver cirrhosis and are associated with more massive bleeding events and higher mortality rate.Transjugular intrahepatic portosystemic s...Gastric varices are a major complication of portal hypertension in patients with liver cirrhosis and are associated with more massive bleeding events and higher mortality rate.Transjugular intrahepatic portosystemic shunt(TIPS)and balloon-occluded retrograde transvenous obliteration(BRTO)have been well documented as effective therapies for portal hypertensive gastric variceal bleeding.In China,TIPS are well accepted but BRTO is not well recieved due to the increase risk of complications associated with traditional BRTO.However,modified-BRTO,known as coil-assisted and plug-assisted retrograde transvenous obliteration(CARTO and PARTO,respectively),is receiving increased attention due to devoid of BRTO’s shortcomings.No CARTO case from China has been reported in literature thus far.Here,we present a Chinese case of CARTO to treat gastric varices bleeding.展开更多
Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms ...Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers,termed inflammaging.This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases.Thymic involution,naïve/memory cell ratio imbalance,dysregulated metabolism,and epigenetic alterations are striking features of immunosenescence.Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells,and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging.Although the underlying molecular mechanisms remain to be addressed,it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence.Potential counteractive measures will be discussed,including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence.In recent years,immunosenescence has attracted increasing attention for its role in tumor development.As a result of the limited participation of elderly patients,the impact of immunosenescence on cancer immunotherapy is unclear.Despite some surprising results from clinical trials and drugs,it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.展开更多
The cascade of metastasis in tumor cells,exhibiting organ-specific tendencies,may occur at numerous phases of the disease and progress under intense evolutionary pressures.Organ-specific metastasis relies on the forma...The cascade of metastasis in tumor cells,exhibiting organ-specific tendencies,may occur at numerous phases of the disease and progress under intense evolutionary pressures.Organ-specific metastasis relies on the formation of pre-metastatic niche(PMN),with diverse cell types and complex cell interactions contributing to this concept,adding a new dimension to the traditional metastasis cascade.Prior to metastatic dissemination,as orchestrators of PMN formation,primary tumor-derived extracellular vesicles prepare a fertile microenvironment for the settlement and colonization of circulating tumor cells at distant secondary sites,significantly impacting cancer progression and outcomes.Obviously,solely intervening in cancer metastatic sites passively after macrometastasis is often insufficient.Early prediction of metastasis and holistic,macro-level control represent the future directions in cancer therapy.This review emphasizes the dynamic and intricate systematic alterations that occur as cancer progresses,illustrates the immunological landscape of organ-specific PMN creation,and deepens understanding of treatment modalities pertinent to metastasis,thereby identifying some prognostic and predictive biomarkers favorable to early predict the occurrence of metastasis and design appropriate treatment combinations.展开更多
Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adeno...Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adenocarcinoma(LUAD)accounts for approximately 40%of all lung cancer cases.1 Due to the heterogeneity of LUAD,accurate categorization is required to create a treatment plan for LUAD patients,while the existing paradigm does not adequately capture the enormously heterogeneous characteristics of LUAD.The rise of epigenetics has brought new perspectives for tumor heterogeneity exploration.Epigenetic modifications,such as aberrant DNA methylation and microRNA(miRNA),are essential in controlling gene expression,heterogeneity,and clinical implication.2 Meanwhile,epigenetic disruptions contribute to lung cancer tumorigenesis,the generation of a malignant phenotype and aggression,and chemoresistance,which could serve as credible biomarkers for lung cancer molecular categorization,early diagnosis,prognosis classification,and treatment efficacy prediction.3 Through integrative clustering of the gene expression profiles regulated by epigenetics,we determined and validated four lung adenocarcinoma epigenetic subtypes(LAESs)with distinct prognoses and biological peculiarities from four independent multi-center lung adenocarcinoma cohorts.展开更多
The interaction of lactate metabolism with immunity plays a crucial role in the remodeling of the immune microenvironment and even in the heterogeneous progression of hepatocellular carcinoma(HCC).The intratumor-accum...The interaction of lactate metabolism with immunity plays a crucial role in the remodeling of the immune microenvironment and even in the heterogeneous progression of hepatocellular carcinoma(HCC).The intratumor-accumulated lactate served a vital role in the inefficacy of antitumor immune responses,the aggressiveness of tumor cells,and immunotherapy.1 Furthermore,lactate generated from the tumor microenvironment can be used as fuel for the proliferation and infiltration of immunosuppressive cells.2 Previous studies regarding the taxonomies of HCC,solely from the perspective of lactate3 or tumor immune microenvironment4 may introduce the potential for bias in the comprehension of HCC heterogeneity.Thus,deciphering the crosstalk properties between lactate and immune is imperative.展开更多
Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites,influencing both physiological and pathological states.In individuals with a ...Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites,influencing both physiological and pathological states.In individuals with a genetic predisposition,disruptions to the“innate immunity‒microbiota”axis appear to rewire immune responses within the tumor microenvironment(TME),thereby driving cancer pathogenesis.This review summarizes the intricate crosstalk between the microbiota and innate immunity in both healthy and cancerous states,focusing on the modulation of immune recognition and polarization during tumor progression,including immune escape,barrier disruption,chronic inflammatory transformation,and angiogenesis in the initiation phase,as well as the regulation of local invasion,vascular invasion,and pre-metastatic ecological niche formation involved in the metastatic phase.This review also highlights recent advances and challenges in leveraging microbiota for cancer immunotherapy,covering innovations in bacteriophages,genetically engineered probiotics,and bioinformatic applications.Moreover,this review proposes potential approaches to enhance therapeutic efficacy by targeting innate immunity‒microbiota interactions.Further mechanistic insights into these interactions may pave the way for developing innovative microbiota-based cancer immunotherapies.展开更多
Copper,one of the essential nutrients for the human body,acts as an electron relay in multiple pathways due to its redox properties.Both deficiencies and excesses of copper lead to cellular fragility.Therefore,it can ...Copper,one of the essential nutrients for the human body,acts as an electron relay in multiple pathways due to its redox properties.Both deficiencies and excesses of copper lead to cellular fragility.Therefore,it can manifest pro-and anti-cancer properties in tumors.Therefore,it is crucial to clarify the copper activity within the cell.We have thoughtfully summarized the metabolic activi-ties of copper from a macro and micro perspective.Cuproptosis,as well as other forms of cell death,is directly or indirectly interfered with by Cu2+,causing cancer cell death.Meanwhile,we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes.In addition,copper has been found to be involved in multiple pathways within the metastasis of cancer cells.Given the complexity of copper’s role,we are compelled to ask:is copper a friend or a foe?Up to now,copper has been used in various clinical applications,including protocols for measurement of copper concentration and bioimaging of radioactive 64Cu.But therapeutically it is still a continuation of the old medicine,and new possibilities need to be explored,such as the use of nanomaterials.Some studies have also shown that copper has considerable interventional power in metabolic cancers,which provides the great applications potential of copper therapy in specific cancer types.This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress,cell death,and tumor metastasis,and points out the value of its application in specific can-cer types,summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs,and emphasizes the prospects for the application of nano-copper.展开更多
Gastroesophageal reflux disease(GERD)is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus,which leads to a series of symptoms.[1]The incidence of GERD in East Asi...Gastroesophageal reflux disease(GERD)is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus,which leads to a series of symptoms.[1]The incidence of GERD in East Asia ranges from 2.5%to 7.8%.[2]Hiatal hernia(HH)refers to the upper part of the stomach protruding into the chest through the esophageal hiatus.HH is closely related to GERD and can play a role in the development and increased incidence of GERD.[3]The surgical treatment of patients with GERD and HH includes HH repair and Nissen,Toupet,or Dor fundoplication(DF).However,post-operative complications have been associated with fundoplication,including dysphagia and abdominal distension,which reduce the benefit of fundoplication.展开更多
Anti-inflammatory and antihyperplasia activities are essential requirements for the successful use of airway stents.In this work,silver nanoparticles(AgNPs)and cisplatin(DDP)were combined in a synergistic modification...Anti-inflammatory and antihyperplasia activities are essential requirements for the successful use of airway stents.In this work,silver nanoparticles(AgNPs)and cisplatin(DDP)were combined in a synergistic modification strategy to improve the surface function of airway stents.Using polycaprolactone(PCL)as a drug carrier,a dual-functional PCL-AgNPs-DDP fiber film-coated airway stent was fabricated by electrospinning.The physicochemical and biological properties of the obtained fiber films were examined.The ATR-FTIR,XPS,SEM-EDS and TEM results suggested that AgNPs and DDP could be successfully immobilized onto the airway stent surface.The drug release and surface degradation results revealed that AgNPs and DDP can undergo sustained release from films for 30 d,and the weight loss was approximately 50%after 35 d.In addition,the dual-functional fiber film suppressed human embryonic lung fibroblast growth and exhibited excellent antibacterial activity against Staphylococcus aureus,Pseudomonas aeruginosa and Candida albicans.Furthermore,the effectiveness of the dual-functional fiber film-coated airway stent was evaluated by application to the trachea of New Zealand rabbits.The in vivo results indicated that PCL-AgNPs-DDP fiber film-coated airway stent can significantly inhibit granulation tissue formation and collagen deposition,reduced the expression of IL-8,TNF-α,IL-1α,PCNA,α-SMA and CD68,and ultimately achieved anti-inflammatory and antihyperplasia effects.Hence,this study provides a dual-functional surface-coated airway stent to address the clinical complications associated with respiratory tract inflammation and granulation tissue hyperplasia,thus inhibiting tracheal stenosis.展开更多
This randomized,prospective,multicenter(12 centers in China)phase III trial(Chinese Clinical Trial Registry#ChiCTR2000041170)compared drug-eluting bead transarterial chemoembolization(DEB-TACE)combined with apatinib a...This randomized,prospective,multicenter(12 centers in China)phase III trial(Chinese Clinical Trial Registry#ChiCTR2000041170)compared drug-eluting bead transarterial chemoembolization(DEB-TACE)combined with apatinib and DEB-TACE monotherapy for patients with unresectable hepatocellular carcinoma(uHCC).Progression-free survival(PFS)was the primary endpoint.Overall survival(OS),mRECIST-based objective response rates(ORR)and disease control rates(DCR),and treatment-related adverse events(TRAEs)were secondary endpoints.Totally 243 cases were randomized,with 122 and 121 in the DEB-TACE+apatinib and DEBTACE groups,respectively.Cases administered DEB-TACE+apatinib displayed markedly improved median PFS(7.1 months[95%CI 6.6-8.3]vs.5.2 months[95%CI 5.0-5.9])and OS(23.3 months[95%CI 20.7-29.6]vs.18.9 months[95%CI 17.9-20.1]compared with those treated with DEB-TACE(both p<0.001).Additionally,patients administered DEB-TACE+apatinib had elevated ORR(56.6%vs.38.8%)and DCR(89.3%vs.80.2%)versus the DEB-TACE group(both p<0.001).Majority of TRAEs were mild and manageable.Regarding DEB-TACE-related TRAEs,the rates of hepatic artery thinning and spasms were elevated during the second DEB-TACE in cases administered DEB-TACE+apatinib vs.DEB-TACE.The commonest apatinib-related TRAEs in the DEB-TACE+apatinib group included hypertension,hand-foot syndrome,fatigue,and diarrhea.In conclusion,DEB-TACE plus apatinib demonstrates superior PFS versus DEB-TACE monotherapy in uHCC cases,maintaining a favorable safety profile with similar occurrences of AEs.展开更多
Innovative biomedical applications have high requirements for biomedical materials.Herein,a series of biocompatible,antibacterial and hemostatic sponges were successfully fabricated for the treatment of acute upper ga...Innovative biomedical applications have high requirements for biomedical materials.Herein,a series of biocompatible,antibacterial and hemostatic sponges were successfully fabricated for the treatment of acute upper gastrointestinal bleeding(AUGB).Quaternized chitosan(QC)and soy protein isolate(SPI)were chemically cross-linked to obtain porous SPI/QC sponges(named SQS-n,with n¼30,40,50 or 60 corresponding to the weight percentage of the QC content).The chemical composition,physical properties and biological activity of SQS-n were investigated.SQS-n could support the adhesion and proliferation of L929 cells while triggering no obvious blood toxicity.Meanwhile,SQS-n exhibited good broad-spectrum antibacterial activity against both grampositive bacteria(Staphylococcus aureus)and gram-negative bacteria(Escherichia coli).The in vivo hemostatic effect of SQS-n was evaluated using three different bleeding models.The results revealed that SQS-50 performed best in reducing blood loss and hemostatic time.The overall hemostatic effect of SQS-50 was comparable to that of a commercial gelatin sponge.The enhanced antibacterial and hemostatic activities of SQS-n were mainly attributed to the QC component.In conclusion,this work developed a QC-functionalized hemostatic sponge that is highly desirable for innovative biomedical applications,such as AUGB.展开更多
基金supported by the Major Science and Technology Special Projects in Henan Province(No.221100310100)co-construction Project of Henan Medical Science and Technology(LHGJ20230286).
文摘Cerenkov radiation(CR)can serve as a source of internal light to overcome the limited tissue penetration of external light in conventional photodynamic therapy(PDT).However,insufficient luminescence intensity hinders the clinical application of CR-PDT.Here,we developed a glutathione-responsive biomimetic nanoplatform by fusing cancer cell membranes and liposomes loaded with photosensitizer hematoporphyrin monomethyl ether(HMME)and a radiation energy amplifier Eu^(3+),named HMME-Eu@LEV.Colloidal Eu^(3+)convertsγ-radiation and CR from radioisotopes into fluorescence to enhance antitumor effects.Sequential administration ensures co-localization of HMME-Eu@LEV and radiopharmaceutical^(18)F-fluorodeoxyglucose(FDG)at the tumor site,triggering enhanced CR-PDT and immunogenic cell death.Our observations indicated that luminescence resonance energy transfer between Eu^(3+)and HMME was efficient,and Cerenkov luminescence from Eu@LEV+FDG was approximately 5.6-fold higher in intensity than that from FDG alone.As a result,abundant ROS were generated,and macrophages in the tumor microenvironment were polarized from M2 to M1.In addition,the immunosuppressive tumor microenvironment could be reversed by promoting the maturation of dendritic cells and infiltration of cytotoxic T lymphocytes.The activated immune system effectively inhibited the growth of primary tumors and spread of distant metastases.Our work demonstrates the feasibility of CR-PDT without an external light source and the critical role of nanomaterials in personalized medicine.
文摘Objective:To evaluate the efficacy and safety of balloon occlusion of the abdominal aorta for the treatment of pernicious placenta previa with placenta accreta.Methods:The clinical data of 623 patients with pernicious placenta previa combined with placenta accrete,who were admitted to our hospital from January 2013 to January 2019 were retrospectively analyzed.All patients underwent abdominal aortic balloon occlusion combined with cesarean section,and 78 patients underwent sequential bilateral uterine artery embolization.We analyzed the operation time,intraoperative blood loss,blood transfusion volume,intraoperative and postoperative complications,fetal radiation exposure time and dose,and the Apgar score of the newborns.We also performed other evaluations to ascertain the efficacy and safety of abdominal aortic balloon occlusion treatment for dangerous placenta previa with placenta accrete.Results:Of the 623 patients,545 underwent only abdominal aortic balloon occlusion,and 78 underwent uterine artery embolization due to intraoperative or postoperative bleeding.The uterus was successfully preserved in all patients.Except for five cases of right lower extremity arterial thrombosis,the remaining patients did not have postoperative lower extremity arteriovenous thrombosis,renal insufficiency,late postpartum hemorrhage,ectopic embolism,spinal cord or peripheral nerve damage,pelvic infection,or other serious complications.The mean operative time was 65.3(±14.5)min.The mean intraoperative blood loss was620(±570)ml.Ninety-six patients(15.4%,96/623)were treated with blood transfusion,and the average amount of blood transfused was 750(±400)ml.The average number of hospitalization days was 6.8(±3.4)days,the average time of fetal ray exposure was 5.2(±1.6)s,and the average radiation dose was 4.1(±2.7)m Gy.The neonatal Apgar score,was 8.4(±0.6)points at 1 min,and 9.6(±0.4)points at 5 min.In the follow-up to May 31,2019,29 patients were lost to follow-up,96 were lactating,and 498 were menstruating.Except for the cases lost to follow-up,the remaining 596 surviving newborns(including 2 twins)showed no abnormalities at the 42-day postnatal outpatient follow-up examination.Conclusion:Balloon occlusion of the abdominal aorta is a safe and effective method for the treatment of pernicious placenta previa with placenta accreta.
文摘Objective:This study aimed to investigate the clinical effects of abdominal aortic balloon occlusion followed by uterine artery embolization for the treatment of pernicious placenta previa complicated with placenta accreta during cesarean section.Methods:We performed a retrospective analysis of the clinical data for 623 patients who experienced pernicious placenta previa complicated with placenta accreta and received treatment in our hospital from January 2013 to January 2019.All patients underwent abdominal aortic balloon occlusion before their cesarean section.Seventyeight patients received bilateral uterine artery embolization,and among them,placenta accreta was found at the opening of the cervix in 13 patients.Due to suturing difficulty after the removal of the placenta,gauze packing was used to temporarily compress the hemorrhage.As soon as the uterus was sutured,emergent bilateral uterine artery embolization was performed.Active bleeding was noted in the remaining 65 patients when the lower part of the uterus was pressed after the placenta was removed and the uterus was sutured,therefor,bilateral uterine artery embolization was performed urgently.Results:Of the 623 patients,545 patients underwent only abdominal aortic balloon occlusion and 78 patients underwent additional emergent bilateral uterine artery embolization due to hemorrhaging during or after their cesarean section.No hysterectomies were performed.In the 78 patients,the amount of bleeding was 800-3,200 ml with an average of 1,650 ml during the operation;the volume of blood transfused was 360-1,750 ml(average:960 ml).The fetal fluoroscopy time was 3–8 s(average:5 s).The dose of radiation exposure was(4.2±2.9) m Gy.Fetal appearance,pulse,grimace,activity,and respiration(Apgar) score were normal.No serious complications were observed during or after the operation in the follow-up visits.Conclusion:For patients with pernicious placenta previa complicated with placenta accreta who experience active bleeding after cesarean section and abdominal aortic balloon occlusion,bilateral uterine artery embolization can effectively reduce blood loss and requirement of blood transfusion during the operation,and lowers the risk of hysterectomy.
文摘Purpose: Descending necrotizing mediastinitis(DNM) is a lethal and acute suppurative disease. This report aimed to summarize our experience in the treatment of DNM with continuous negative pressure catheter drainage and transnasal jejunal feeding by interventional techniques. Materials and Methods: We retrospectively analyzed relevant clinical data of patients with DNM who underwent continuous negative pressure catheter drainage and transnasal jejunal feeding. All drainage catheters and jejunal feeding tubes were inserte d by interventional techniques. Results: In total, 21 patients were diagnosed with DNM by esophagography and computed tomography(CT). Catheters for the drainage of mediastinal abscesses as well as transnasal jejunal feeding tubes were successfully placed in all patients, indicating a 100% success rate. Of all patients, 13 underwent insertion of abscess drainage catheters through percutaneous puncture under DynaCT guidance, while eight had drainage catheter insertion through fistula orifices in the posterior nasopharyngeal wall or esophagus under fluoroscopic guidance. In total, 26 drainage tubes were inserted. One patient with diabetes died of sepsis and diabetic ketoacidosis 5 days postoperatively, while the remaining 20 patients showed good recovery with successful removal of the drainage catheters. Durations of catheterization were 45.2±50.44 days. The overall clinical success rate was 95.2%. Conclusion: The above described methods are non-surgical, minimally invasive and efficacious, and may be alternative therapeutic tools for patients who are not eligible for surgical operation, have a high postoperative risk, or are more likely to choose minimally invasive techniques.
基金the Key Scientific Research Project of Colleges and Universities in Henan Province,China(grant number 17A320011)。
文摘Background:Patients who survive initial esophagogastric variceal bleeding(EVB)are at an increased risk of recurrent bleeding and death;however,a reliable predictive model is lacking.We aimed to develop a model for rebleeding prediction in patients with EVB after modified percutaneous transhepatic variceal embolization(PTVE)with cyanoacrylate.Methods:A total of 122 patients with EVB who underwent PTVE from January 2015 to November 2020 were enrolled.Multivariate logistic analyses were conducted to determine independent risk factors for nomogram construction.The discrimination,calibration,and clinical utility of the nomogram were compared with the Model for End-stage Liver Disease score(MELD)and the Child–Pugh model.Risk stratification was performed according to the nomogram.Results:Rebleeding within 3 months of PTVE occurred in 32 patients(26.2%).Independent rebleeding indicators included prior history of endoscopic therapy,Child–Pugh score,partial splenic embolization,and creatinine level.The nomogram incorporating these four predictors achieved excellent calibration and discriminatory abilities,with a concordance index of 0.85,which was confirmed to be 0.83 through bootstrapping validation.The nomogram demonstrated superior discrimination and clinical applicability than the MELD and Child–Pugh models.As shown in the Kaplan–Meier curves,high-risk patients had a high probability of rebleeding(P<0.001).Conclusions:The creatinine-based nomogram had a superior ability to predict rebleeding after PTVE in patients with EVB.Risk stratification may help identify high-risk patients and lead to the earlier implementation of aggressive treatments and formulation of intensive follow-up plans.
文摘Objective: To evaluate the efficacy and safety of patient-controlled analgesia(PCA) with hydromorphone as perioperative analgesia during uterine artery embolization(UAE) via the right radial artery.Patients and methods: A total of 33 patients with uterine fibroids, who underwent UAE at the authors’ hospital between June 2021 and March 2022, were selected. Hydromorphone(10 mg) was dispensed into a 100 ml PCA pump with normal saline. Pump administration was initiated 15 min before the start of the procedure, and the intraoperative dose was adjusted according to patient pain level. A numerical rating scale was used to evaluate pain immediately after embolization, 5 min after embolization, at the end of the procedure, and 6, 12, 24, 48, and 72 h after the procedure. Side effects were also observed.Results: Thirty-three patients underwent uterine artery embolization via the right radial artery. Patient pain was well controlled at all time points surveyed, and patients reported satisfaction with analgesia. The median length of hospital stay was 5 days. There were 7 cases of adverse reactions, but no serious side effects were observed.Conclusion: Patients reported positive experiences with arterial embolization of uterine fibroids via the right radial artery. Hydromorphone PCA effectively controlled pain. The PCA pump is easy to operate, has a low incidence of adverse reactions, and offers economic benefits at the patient and institutional levels.
文摘Gastric varices are a major complication of portal hypertension in patients with liver cirrhosis and are associated with more massive bleeding events and higher mortality rate.Transjugular intrahepatic portosystemic shunt(TIPS)and balloon-occluded retrograde transvenous obliteration(BRTO)have been well documented as effective therapies for portal hypertensive gastric variceal bleeding.In China,TIPS are well accepted but BRTO is not well recieved due to the increase risk of complications associated with traditional BRTO.However,modified-BRTO,known as coil-assisted and plug-assisted retrograde transvenous obliteration(CARTO and PARTO,respectively),is receiving increased attention due to devoid of BRTO’s shortcomings.No CARTO case from China has been reported in literature thus far.Here,we present a Chinese case of CARTO to treat gastric varices bleeding.
文摘Infection susceptibility,poor vaccination efficacy,age-related disease onset,and neoplasms are linked to innate and adaptive immune dysfunction that accompanies aging(known as immunosenescence).During aging,organisms tend to develop a characteristic inflammatory state that expresses high levels of pro-inflammatory markers,termed inflammaging.This chronic inflammation is a typical phenomenon linked to immunosenescence and it is considered the major risk factor for age-related diseases.Thymic involution,naïve/memory cell ratio imbalance,dysregulated metabolism,and epigenetic alterations are striking features of immunosenescence.Disturbed T-cell pools and chronic antigen stimulation mediate premature senescence of immune cells,and senescent immune cells develop a proinflammatory senescence-associated secretory phenotype that exacerbates inflammaging.Although the underlying molecular mechanisms remain to be addressed,it is well documented that senescent T cells and inflammaging might be major driving forces in immunosenescence.Potential counteractive measures will be discussed,including intervention of cellular senescence and metabolic-epigenetic axes to mitigate immunosenescence.In recent years,immunosenescence has attracted increasing attention for its role in tumor development.As a result of the limited participation of elderly patients,the impact of immunosenescence on cancer immunotherapy is unclear.Despite some surprising results from clinical trials and drugs,it is necessary to investigate the role of immunosenescence in cancer and other age-related diseases.
基金supported by the Major Science and Technology projects of Henan Province(Grant no.221100310100).
文摘The cascade of metastasis in tumor cells,exhibiting organ-specific tendencies,may occur at numerous phases of the disease and progress under intense evolutionary pressures.Organ-specific metastasis relies on the formation of pre-metastatic niche(PMN),with diverse cell types and complex cell interactions contributing to this concept,adding a new dimension to the traditional metastasis cascade.Prior to metastatic dissemination,as orchestrators of PMN formation,primary tumor-derived extracellular vesicles prepare a fertile microenvironment for the settlement and colonization of circulating tumor cells at distant secondary sites,significantly impacting cancer progression and outcomes.Obviously,solely intervening in cancer metastatic sites passively after macrometastasis is often insufficient.Early prediction of metastasis and holistic,macro-level control represent the future directions in cancer therapy.This review emphasizes the dynamic and intricate systematic alterations that occur as cancer progresses,illustrates the immunological landscape of organ-specific PMN creation,and deepens understanding of treatment modalities pertinent to metastasis,thereby identifying some prognostic and predictive biomarkers favorable to early predict the occurrence of metastasis and design appropriate treatment combinations.
基金supported by Henan Provincial Key Laboratory of Medicine and Henan Provincial Clinical Medical Research Center for Respiratory Diseases.
文摘Lung cancer is the leading cause of cancer-related mortality globally,including small-cell lung cancer and non-small-cell lung cancer.As the most prevalent histological subtype of non-small-cell lung cancer,lung adenocarcinoma(LUAD)accounts for approximately 40%of all lung cancer cases.1 Due to the heterogeneity of LUAD,accurate categorization is required to create a treatment plan for LUAD patients,while the existing paradigm does not adequately capture the enormously heterogeneous characteristics of LUAD.The rise of epigenetics has brought new perspectives for tumor heterogeneity exploration.Epigenetic modifications,such as aberrant DNA methylation and microRNA(miRNA),are essential in controlling gene expression,heterogeneity,and clinical implication.2 Meanwhile,epigenetic disruptions contribute to lung cancer tumorigenesis,the generation of a malignant phenotype and aggression,and chemoresistance,which could serve as credible biomarkers for lung cancer molecular categorization,early diagnosis,prognosis classification,and treatment efficacy prediction.3 Through integrative clustering of the gene expression profiles regulated by epigenetics,we determined and validated four lung adenocarcinoma epigenetic subtypes(LAESs)with distinct prognoses and biological peculiarities from four independent multi-center lung adenocarcinoma cohorts.
基金supported by the Major Science and Technology projects of Henan Province,China(No.221100310100).
文摘The interaction of lactate metabolism with immunity plays a crucial role in the remodeling of the immune microenvironment and even in the heterogeneous progression of hepatocellular carcinoma(HCC).The intratumor-accumulated lactate served a vital role in the inefficacy of antitumor immune responses,the aggressiveness of tumor cells,and immunotherapy.1 Furthermore,lactate generated from the tumor microenvironment can be used as fuel for the proliferation and infiltration of immunosuppressive cells.2 Previous studies regarding the taxonomies of HCC,solely from the perspective of lactate3 or tumor immune microenvironment4 may introduce the potential for bias in the comprehension of HCC heterogeneity.Thus,deciphering the crosstalk properties between lactate and immune is imperative.
基金supported by the Henan Provincial Science and Technology Research Project(grant number 221100310100 to Z.L.and X.H.).
文摘Human microbiota constitute a complex and dynamic community that interacts with the innate immunity of the host at various anatomical sites,influencing both physiological and pathological states.In individuals with a genetic predisposition,disruptions to the“innate immunity‒microbiota”axis appear to rewire immune responses within the tumor microenvironment(TME),thereby driving cancer pathogenesis.This review summarizes the intricate crosstalk between the microbiota and innate immunity in both healthy and cancerous states,focusing on the modulation of immune recognition and polarization during tumor progression,including immune escape,barrier disruption,chronic inflammatory transformation,and angiogenesis in the initiation phase,as well as the regulation of local invasion,vascular invasion,and pre-metastatic ecological niche formation involved in the metastatic phase.This review also highlights recent advances and challenges in leveraging microbiota for cancer immunotherapy,covering innovations in bacteriophages,genetically engineered probiotics,and bioinformatic applications.Moreover,this review proposes potential approaches to enhance therapeutic efficacy by targeting innate immunity‒microbiota interactions.Further mechanistic insights into these interactions may pave the way for developing innovative microbiota-based cancer immunotherapies.
基金Major Science and Technology projects of Henan Province,Grant/Award Number:221100310100。
文摘Copper,one of the essential nutrients for the human body,acts as an electron relay in multiple pathways due to its redox properties.Both deficiencies and excesses of copper lead to cellular fragility.Therefore,it can manifest pro-and anti-cancer properties in tumors.Therefore,it is crucial to clarify the copper activity within the cell.We have thoughtfully summarized the metabolic activi-ties of copper from a macro and micro perspective.Cuproptosis,as well as other forms of cell death,is directly or indirectly interfered with by Cu2+,causing cancer cell death.Meanwhile,we did pan-cancer analysis of cuproptosis-related genes to further clarify the roles of these genes.In addition,copper has been found to be involved in multiple pathways within the metastasis of cancer cells.Given the complexity of copper’s role,we are compelled to ask:is copper a friend or a foe?Up to now,copper has been used in various clinical applications,including protocols for measurement of copper concentration and bioimaging of radioactive 64Cu.But therapeutically it is still a continuation of the old medicine,and new possibilities need to be explored,such as the use of nanomaterials.Some studies have also shown that copper has considerable interventional power in metabolic cancers,which provides the great applications potential of copper therapy in specific cancer types.This paper reviews the dual roles played by cuproptosis in cancer from the new perspectives of oxidative stress,cell death,and tumor metastasis,and points out the value of its application in specific can-cer types,summarizes the value of its testing and imaging from the perspective of clinical application as well as the current feasible options for the new use of the old drugs,and emphasizes the prospects for the application of nano-copper.
基金supported by the Medical Science and Technology Research Program of Henan Province(Nos.2018020042 and LHGJ20190226).
文摘Gastroesophageal reflux disease(GERD)is caused by esophageal dysfunction resulting in reflux of gastric and duodenal contents into the esophagus,which leads to a series of symptoms.[1]The incidence of GERD in East Asia ranges from 2.5%to 7.8%.[2]Hiatal hernia(HH)refers to the upper part of the stomach protruding into the chest through the esophageal hiatus.HH is closely related to GERD and can play a role in the development and increased incidence of GERD.[3]The surgical treatment of patients with GERD and HH includes HH repair and Nissen,Toupet,or Dor fundoplication(DF).However,post-operative complications have been associated with fundoplication,including dysphagia and abdominal distension,which reduce the benefit of fundoplication.
基金This work was supported by the Young and middle-aged health science and technology innovation talent project of Henan Province(YXKC2020037),the Henan Medical Science and Technology Public Relations Program(SB201902014)and the Horizontal Research Program of Zhengzhou University(Grant No.24110005).
文摘Anti-inflammatory and antihyperplasia activities are essential requirements for the successful use of airway stents.In this work,silver nanoparticles(AgNPs)and cisplatin(DDP)were combined in a synergistic modification strategy to improve the surface function of airway stents.Using polycaprolactone(PCL)as a drug carrier,a dual-functional PCL-AgNPs-DDP fiber film-coated airway stent was fabricated by electrospinning.The physicochemical and biological properties of the obtained fiber films were examined.The ATR-FTIR,XPS,SEM-EDS and TEM results suggested that AgNPs and DDP could be successfully immobilized onto the airway stent surface.The drug release and surface degradation results revealed that AgNPs and DDP can undergo sustained release from films for 30 d,and the weight loss was approximately 50%after 35 d.In addition,the dual-functional fiber film suppressed human embryonic lung fibroblast growth and exhibited excellent antibacterial activity against Staphylococcus aureus,Pseudomonas aeruginosa and Candida albicans.Furthermore,the effectiveness of the dual-functional fiber film-coated airway stent was evaluated by application to the trachea of New Zealand rabbits.The in vivo results indicated that PCL-AgNPs-DDP fiber film-coated airway stent can significantly inhibit granulation tissue formation and collagen deposition,reduced the expression of IL-8,TNF-α,IL-1α,PCNA,α-SMA and CD68,and ultimately achieved anti-inflammatory and antihyperplasia effects.Hence,this study provides a dual-functional surface-coated airway stent to address the clinical complications associated with respiratory tract inflammation and granulation tissue hyperplasia,thus inhibiting tracheal stenosis.
基金supported by the National Natural Science Foundation of China(No.U2004119)Major Science and Technology Projects in Henan Province(No.221100310100)the Henan Province Medical Science and Technology Public Relations Plan Province Department joint construction project(No.SBGJ202102100).
文摘This randomized,prospective,multicenter(12 centers in China)phase III trial(Chinese Clinical Trial Registry#ChiCTR2000041170)compared drug-eluting bead transarterial chemoembolization(DEB-TACE)combined with apatinib and DEB-TACE monotherapy for patients with unresectable hepatocellular carcinoma(uHCC).Progression-free survival(PFS)was the primary endpoint.Overall survival(OS),mRECIST-based objective response rates(ORR)and disease control rates(DCR),and treatment-related adverse events(TRAEs)were secondary endpoints.Totally 243 cases were randomized,with 122 and 121 in the DEB-TACE+apatinib and DEBTACE groups,respectively.Cases administered DEB-TACE+apatinib displayed markedly improved median PFS(7.1 months[95%CI 6.6-8.3]vs.5.2 months[95%CI 5.0-5.9])and OS(23.3 months[95%CI 20.7-29.6]vs.18.9 months[95%CI 17.9-20.1]compared with those treated with DEB-TACE(both p<0.001).Additionally,patients administered DEB-TACE+apatinib had elevated ORR(56.6%vs.38.8%)and DCR(89.3%vs.80.2%)versus the DEB-TACE group(both p<0.001).Majority of TRAEs were mild and manageable.Regarding DEB-TACE-related TRAEs,the rates of hepatic artery thinning and spasms were elevated during the second DEB-TACE in cases administered DEB-TACE+apatinib vs.DEB-TACE.The commonest apatinib-related TRAEs in the DEB-TACE+apatinib group included hypertension,hand-foot syndrome,fatigue,and diarrhea.In conclusion,DEB-TACE plus apatinib demonstrates superior PFS versus DEB-TACE monotherapy in uHCC cases,maintaining a favorable safety profile with similar occurrences of AEs.
基金This work was supported by the Medical Science Advancement Program(Clinical Medicine)of Wuhan University(TFLC2018003)the Horizontal Research Program of Zhengzhou University(24110005)+1 种基金the Science and Technology Department of Hubei Province Key Project(2018ACA159)the Chinese Central Special Fund for Local Science and Technology Development of Hubei Province(2018ZYYD023).
文摘Innovative biomedical applications have high requirements for biomedical materials.Herein,a series of biocompatible,antibacterial and hemostatic sponges were successfully fabricated for the treatment of acute upper gastrointestinal bleeding(AUGB).Quaternized chitosan(QC)and soy protein isolate(SPI)were chemically cross-linked to obtain porous SPI/QC sponges(named SQS-n,with n¼30,40,50 or 60 corresponding to the weight percentage of the QC content).The chemical composition,physical properties and biological activity of SQS-n were investigated.SQS-n could support the adhesion and proliferation of L929 cells while triggering no obvious blood toxicity.Meanwhile,SQS-n exhibited good broad-spectrum antibacterial activity against both grampositive bacteria(Staphylococcus aureus)and gram-negative bacteria(Escherichia coli).The in vivo hemostatic effect of SQS-n was evaluated using three different bleeding models.The results revealed that SQS-50 performed best in reducing blood loss and hemostatic time.The overall hemostatic effect of SQS-50 was comparable to that of a commercial gelatin sponge.The enhanced antibacterial and hemostatic activities of SQS-n were mainly attributed to the QC component.In conclusion,this work developed a QC-functionalized hemostatic sponge that is highly desirable for innovative biomedical applications,such as AUGB.
