Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chine...Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chinese herb patchouli,was developed into biomimetic liposomes for macrophagetargeting delivery for IBD treatment.The developed lactoferrin-modified liposomes(LF-lipo)can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy.LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway.LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1βactivation.LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model,evidenced by the reduced disease activity index,the improved colon functions,and the downregulated inflammatory cytokines in the colon.LF-lipo provided an effective and safe macrophagetargeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.展开更多
Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overpr...Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA hydrogels.Under hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.展开更多
Coronavirus disease-2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The infection is spreading globally and poses a huge threat to human health.Besides common respiratory symptom...Coronavirus disease-2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The infection is spreading globally and poses a huge threat to human health.Besides common respiratory symptoms,some patients with COVID-19 experience gastrointestinal symptoms,such as diarrhea,nausea,vomiting,and loss of appetite.SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2(ACE2)and there is increasing evidence of a possible fecal–oral transmission route.In addition,there exist multiple abnormalities in liver enzymes.COVID-19-related liver injury may be due to drug-induced liver injury,systemic inflammatory reaction,and hypoxia–ischemia reperfusion injury.The direct toxic attack of SARS-CoV-2 on the liver is still questionable.This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.展开更多
Acinetobacter baumannii has been considered the prevailing pathogen responsible for ventilator-associated pneumonia （VAP）,a condition associated with high morbidity and mortality,among patients in Intensive Care Uni...Acinetobacter baumannii has been considered the prevailing pathogen responsible for ventilator-associated pneumonia （VAP）,a condition associated with high morbidity and mortality,among patients in Intensive Care Units （ICUs）. However,data regarding VAP caused by A.baumannii （AbVAP） in China are limited.In this retrospective study,we aimed to assess the clinical features and outcomes of Chinese patients with AbVAP and thus identify risk factors for 30-day ICU mortality.展开更多
Osteoporosis is the most common degenerative orthopedic disease in the elderly.Recently,the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues,which could provid...Osteoporosis is the most common degenerative orthopedic disease in the elderly.Recently,the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues,which could provide a suitable environment for the positive regulation of bone metabolism,promoting osteogenic differentiation and inhibiting osteoclast differentiation.Our previous work demonstrated that iron oxide nanoparticles(IONPs)could positively regulate bone metabolism in vitro.In this study,we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo.Meanwhile,IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice.Besides,alendronate,a clinically used anti-osteoporosis bisphosphate,was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role.Eventually,we verified the bone targeting ability,therapeutic efficiency,and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice.By applying BTNPs,the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of s...Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.展开更多
Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations,while reliable biomarkers to detect or monitor are still under investigation.Recent advances in technologies ...Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations,while reliable biomarkers to detect or monitor are still under investigation.Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers,including proteins,ribonucleic acids(RNAs),and deoxyribonucleic acids(DNAs),for early detection of pathological changes in susceptible patients,rapid diagnosis at the bedside after onset,and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.展开更多
As a type of austenitic stainless steel,316L stainless steel has excellent plasticity,corrosion resistance,and biocompatibility,making it widely used in industries,especially in the marine environments.However,its low...As a type of austenitic stainless steel,316L stainless steel has excellent plasticity,corrosion resistance,and biocompatibility,making it widely used in industries,especially in the marine environments.However,its lower yield strength and wear resistance are the obvious disadvantages that restrict its application in more fields.In this work,an Fe-based amorphous alloy(Fe^(am))was selected as reinforcement to enhance the 316L stainless steel prepared by selective laser melting(SLM),and microstructure evolution,mechanical properties,tribological and corrosion performance of the SLMed samples were investigated in detail.The relative density values of both 316L stainless steel and Fe^(am)-reinforced samples are above 99%,which suggests that Fe^(am)-reinforced samples also have outstanding formability.In the as-etched micrograph,all of the SLMed samples exhibit cellular structure.Fe^(am)-reinforced samples have thicker sub-grain boundaries,and retained amorphous phase can be observed in the samples reinforced with 10 wt%and 15 wt%Fe^(am).As the addition of Fe^(am) increases,the microhardness and compression strength of the Fe^(am)-reinforced samples gradually improve and reach 449.2 HV and 2181.9 MPa,respectively.The wear morphologies show that the 316L stainless steel and Fe^(am)-reinforced samples both experience abrasive wear and corrosion wear in a 3.5 wt%NaCl solution.Meanwhile,as the amount of Fe^(am) added increases,the coefficient of friction and wear rate of SLMed samples gradually decrease.Compared to the unreinforced sample,Fe^(am)-reinforced samples have lower corrosion current density and higher pitting potential according to the potentiodynamic polarization curves and also exhibit superior corrosion resistance in the salt spray environment.This work suggests that the addition of Fe-based amorphous alloy can improve the mechanical properties and wear resistance of 316L stainless steel,as well as its ability to withstand salt spray corrosion.展开更多
Primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical role.Mammalian sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been...Primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical role.Mammalian sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been demonstrated to be a regulator of inflammation.Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive.The expression and function of MST4 in macrophages of ITP patients and THP-1 cells,and of a macrophage-specific Mst4−/−(Mst4ΔM/ΔM)ITP mouse model were determined.Macrophage phagocytic assays,RNA sequencing(RNA-seq)analysis,immunofluorescence analysis,coimmunoprecipitation(co-IP),mass spectrometry(MS),bioinformatics analysis,and phosphoproteomics analysis were performed to reveal the underlying mechanisms.The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients,and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment.The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages.Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines,and impaired phagocytosis,which could be increased by overexpression of MST4.In a passive ITP mouse model,macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid,attenuated the expression of M1 cytokines,and promoted the predominance of FcγRIIb in splenic macrophages,which resulted in amelioration of thrombocytopenia.Downregulation of MST4 directly inhibited STAT1 phosphorylation,which is essential for M1 polarization of macrophages.Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.展开更多
Technological advances in glaucoma have challenged the traditional treatment paradigm. Historically incisional surgery has been used in cases of advanced disease and/or uncontrolled intraocular pressures resistant to ...Technological advances in glaucoma have challenged the traditional treatment paradigm. Historically incisional surgery has been used in cases of advanced disease and/or uncontrolled intraocular pressures resistant to medical or laser interventions. More recently, perhaps due to advancements in imaging, surgery has been suggested to be beneficial earlier in the treatment paradigm. Despite these trends, surgical manipulation of the tissues and unpredictability of wound healing continue to result in surgical failure. Magnesium is an essential element for human body and plays a critically important role in maintaining the functional and structural integrity of several tissues, including the eye. Due to several of its advantageous properties such as non-toxicity, biodegradability, and high biological compatibility, magnesium alloy has attracted great attention as a novel biomaterial. Biodegradable cardiovascular stents made of magnesium alloy have already been introduced into clinical practice. The purpose of this review is to determine if bioabsorbable magnesium alloys can be utilized as a promising candidate for the development of a new generation of glaucoma surgical assistive devices.展开更多
BACKGROUND For patients with acute paraplegia caused by spinal giant cell tumor(GCT)who require emergency decompressive surgery,there is still a lack of relevant reports on surgical options.This study is the first to ...BACKGROUND For patients with acute paraplegia caused by spinal giant cell tumor(GCT)who require emergency decompressive surgery,there is still a lack of relevant reports on surgical options.This study is the first to present the case of an acute paraplegic patient with a thoracic spinal GCT who underwent an emergency total en bloc spondylectomy(TES).Despite tumor recurrence,three-level TES was repeated after denosumab therapy.CASE SUMMARY A 27-year-old female patient who underwent single-level TES in an emergency presented with sudden severe back pain and acute paraplegia due to a thoracic spinal tumor.After emergency TES,the patient's spinal cord function recovered,and permanent paralysis was avoided.The postoperative histopathological examination revealed that the excised neoplasm was a rare GCT.Unfortunately,the tumor recurred 9 months after the first surgery.After 12 months of denosumab therapy,the tumor size was reduced,and tumor calcification.To prevent recurrent tumor progression and provide a possible cure,a three-level TES was performed again.The patient returned to an active lifestyle 1 month after the second surgery,and no recurrence of GCT was found at the last follow-up.CONCLUSION This patient with acute paraplegia underwent TES twice,including once in an emergency,and achieved good therapeutic results.TES in emergency surgery is feasible and safe when conditions permit;however,it may increase the risk of tumor recurrence.展开更多
Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dy...Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.展开更多
BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further stu...BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regressio展开更多
We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of ne...We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.展开更多
SmCo based films with excellent intrinsic magnetic properties have promising applications in micro-electro-mechanical system(MEMS).However,due to the complexity of phase composition and uncontrollable crystallization ...SmCo based films with excellent intrinsic magnetic properties have promising applications in micro-electro-mechanical system(MEMS).However,due to the complexity of phase composition and uncontrollable crystallization degree of SmCo hard magnetic phase in the film,both the coercivity(Hc)and remanence(Mr)of films are difficult to enhance simultaneously.In this paper,SmCo based films were deposited with a Cr underlayer and capping layer on single crystal Si substrates via magnetron sputtering process.The effects of annealing parameters and Sm/Co atomic ratio on the phase structure and coercivity of films are discussed.By adjusting the Sm/Co atomic ratio from 1:5 to 1:4,Co soft magnetic phase disappears and the single phase SmCo5 is obtained,leading to the increase of coercivity of the films from 30 to 34 kOe.The influence of deposition temperature and Cu doping on magnetic properties of SmCo based films was investigated.When the deposition temperature increases from room temperature to 250℃,the coercivity will further increase from 34 to 51 kOe.However,a severe kink is observed in the demagnetization curves due to the poor exchanged coupling.An analysis of transmission electron microscopy(TEM)confirms that the average size of non-hard magnetic amorphous phase exceeds the effective exchanged coupling length of SmCo5,which contributes to the decoupling and low remanence ratio.Therefore,doping Cu and applying a post-annealing process can significantly improve the crystallization degree of the films.Both the coercivity and the remanence ratio of the demagnetization curves are greatly enhanced.We propose a plausible strategy to prepare the SmCo based films with high coercivity and remanence ratio by temperature and chemical optimization,which can be utilized in high performed MEMS devices.展开更多
Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,w...Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.展开更多
AIM:To reveal whether and how Yes-associated protein(YAP)promotes the occurrence of subretinal fibrosis in agerelated macular degeneration(AMD).METHODS:Cobalt chloride(Co Cl2)was used in primary human umbilical vein e...AIM:To reveal whether and how Yes-associated protein(YAP)promotes the occurrence of subretinal fibrosis in agerelated macular degeneration(AMD).METHODS:Cobalt chloride(Co Cl2)was used in primary human umbilical vein endothelial cells(HUVECs)to induce hypoxia in vitro.Eight-week-old male C57 BL/6 J mice weighing 19-25 g were used for a choroidal neovascularization(CNV)model induced by laser photocoagulation in vivo.Expression levels of YAP,phosphorylated YAP,mesenchymal markers[αsmooth muscle actin(α-SMA),vimentin,and Snail],and endothelial cell markers(CD31 and zonula occludens 1)were measured by Western blotting,quantitative real-time PCR,and immunofluorescence microscopy.Small molecules YC-1(Lificiguat,a specific inhibitor of hypoxia-inducible factor 1α),CA3(CIL56,an inhibitor of YAP),and XMU-MP-1(an inhibitor of Hippo kinase MST1/2,which activates YAP)were used to explore the underlying mechanism.RESULTS:Co Cl2 increased expression of mesenchymal markers,decreased expression of endothelial cell markers,and enhanced the ability of primary HUVECs to proliferate and migrate.YC-1 suppressed hypoxia-induced endothelialto-mesenchymal transition(End MT).Moreover,hypoxia promoted total expression,inhibited phosphorylation,and enhanced the transcriptional activity of YAP.XMU-MP-1 enhanced hypoxia-induced End MT,whereas CA3 elicited the opposite effect.Expression of YAP,α-SMA,and vimentin were upregulated in the laser-induced CNV model.However,silencing of YAP by vitreous injection of small interfering RNA targeting YAP could reverse these changes.CONCLUSION:The findings reveal a critical role of the hypoxia-inducible factor-1α(HIF-1α)/YAP signaling axis in End MT and provide a new therapeutic target for treatment of subretinal fibrosis in AMD.展开更多
AIM： To investigate the incidence rate and risk factors for grade Ⅲ flat anterior chamber（FAC） after glaucoma filtration surgery based on 5-year data.METHODS： Patients who underwent glaucoma filtration surgery in...AIM： To investigate the incidence rate and risk factors for grade Ⅲ flat anterior chamber（FAC） after glaucoma filtration surgery based on 5-year data.METHODS： Patients who underwent glaucoma filtration surgery in Daping hospital from January 2009 to December 2013 were enrolled in this retrospective study. The incidence of grade Ⅲ FAC following glaucoma filtration surgery was determined. Regression analysis was performed to investigate the influence of glaucoma type, surgical approach, age, and preoperative intraocular pressure（IOP） on the risk of postoperative FAC.RESULTS： A total of 2179 eyes receiving anti-glaucoma surgery were included. Ninety-one eyes suffered from postoperative FAC, with an overall incidence rate of 4.18%. Of 471 eyes with primary open angle glaucoma（POAG）, grade Ⅲ FAC occurred in only 3 eyes（0.64%）. Primary angleclosure glaucoma（PACG） was diagnosed in 1076 eyes, 39（3.62%） of which developed grade Ⅲ FAC, including 12 eyes（12/300, 4%） with acute PACG（aP ACG） and 27 eyes（27/776, 3.48%） with chronic PACG（c PACG）. Six of 259 eyes（2.32%） with secondary glaucoma, 28 of 186 eyes（15.05%） with neovasular glaucoma, 1 of 66 eyes（1.52%） with congenital glaucoma, and 14 of 115 eyes（12.17%） with remnant glaucoma suffered from grade Ⅲ FAC. Of 6 eyes with mixed glaucoma, none developed grade Ⅲ FAC after surgery. When stratified by surgical approach, 24 of 766 eyes（3.13%） undergoing trabeculectomy, 21 of 924 eyes（2.27%） treated by trabeculectomy plus mitomycin C（MMC）, 18 of 109 eyes（16.51%） undergoing Ahmed glaucoma valve implantation, 23 of 201 eyes（11.44%） managed by Ahmed implantation plus MMC, and 5 of 133 eyes（3.76%） treated by Ahmed implantation plus lens extraction or vitrectomy developed grade Ⅲ FAC. Logistic regression analysis revealed that factors including neovasular glaucoma, remnant glaucoma, glaucoma valve implantation, glaucoma valve implantation＋MMC, glaucoma valve implantation＋vitrectomy,展开更多
Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of ef...Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.展开更多
Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment o...Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging.Here,we present a three-dimensional(3D)printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration.To make the scaffold,cold-water fish skin gelatin was combined with sodium alginate to increase viscosity,printability,and mechanical strength,and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology.Then,the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further.These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere,proliferate,and communicate with each other,transport nutrients,and prevent further damage to the joint.More importantly,we found that cold-water fish gelatin scaffolds were nonimmunogenic,nontoxic,and biodegradable.We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model.Thus,cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.展开更多
基金the financial support of National Natural Science Foundation of China(Nos.81925035,81673382 and 81521005)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA12050307,China)+2 种基金National Special Project for Significant New Drugs Development(2018ZX09711002-010-002,China)Shanghai Sci Tech Innovation Initiative(19431903100 and 18430740800,China)the Fudan-SIMM Joint Research Fund(FU-SIMM20174009,China)for the support
文摘Inflammatory bowel diseases(IBD)are the incurable chronic recurrent gastrointestinal disorders and currently lack in safe and effective drugs.In this study,patchouli alcohol,a main active compound of traditional Chinese herb patchouli,was developed into biomimetic liposomes for macrophagetargeting delivery for IBD treatment.The developed lactoferrin-modified liposomes(LF-lipo)can specifically bind to LRP-1 expressed on the activated colonic macrophages and achieve cell-targeting anti-inflammatory therapy.LF-lipo reduced the levels of inflammatory cytokines and ROS and suppressed the MAPK/NF-κB pathway.LF-lipo also suppressed the formation of NLRP3 inflammasome and the consequent IL-1βactivation.LF-lipo showed improved therapeutic efficacy in a DSS-induced colitis murine model,evidenced by the reduced disease activity index,the improved colon functions,and the downregulated inflammatory cytokines in the colon.LF-lipo provided an effective and safe macrophagetargeting delivery and therapeutic strategy for addressing the unmet medical need in IBD management.
基金supported by National Science Foundation of China(Grant No.32271409,82002370,31800806)National Basic Research Program of China(2021YFA1201404)+5 种基金China Postdoctoral Science Foundation(Grant No.2019M661806)Major Project of NSFC(81991514)Natural Science Foundation of Jiangsu Province(Grant No.BK20200117)Jiangsu postdoctoral research support project(Grant No.2021K059A)Program of Innovation and Entrepreneurship of Jiangsu Province,Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation and Jiangsu Provincial Key Medical Talent Foundation,the Fundamental Research Funds for the Central Universities(14380493,14380494)Changzhou Sci&Tech Program(Grant No.CJ20220103).
文摘Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA hydrogels.Under hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.
基金supported by the State’s Key Project of Research and Development Plan in China(2017YFC1310602,2017YFC1310600)the National Natural Science Foundation of China(81701937).
文摘Coronavirus disease-2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The infection is spreading globally and poses a huge threat to human health.Besides common respiratory symptoms,some patients with COVID-19 experience gastrointestinal symptoms,such as diarrhea,nausea,vomiting,and loss of appetite.SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2(ACE2)and there is increasing evidence of a possible fecal–oral transmission route.In addition,there exist multiple abnormalities in liver enzymes.COVID-19-related liver injury may be due to drug-induced liver injury,systemic inflammatory reaction,and hypoxia–ischemia reperfusion injury.The direct toxic attack of SARS-CoV-2 on the liver is still questionable.This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81770055, No. 81630001,No. 81490533）, and Shanghai Science and Technology Committee Grant （No. 15DZ 1930600, No. 15DZ 1930602）.
文摘Acinetobacter baumannii has been considered the prevailing pathogen responsible for ventilator-associated pneumonia （VAP）,a condition associated with high morbidity and mortality,among patients in Intensive Care Units （ICUs）. However,data regarding VAP caused by A.baumannii （AbVAP） in China are limited.In this retrospective study,we aimed to assess the clinical features and outcomes of Chinese patients with AbVAP and thus identify risk factors for 30-day ICU mortality.
基金supported by Key Program of NSFC(81730067)Major Project of NSFC(81991514)+10 种基金National Science Foundation of China(Grant No 81802135,82002370)Jiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent FoundationJiangsu Provincial Medical Youth Talent FoundationJiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities(14380493,14380494)China Postdoctoral Science Foundation(Grant No 2019M661806,Grant No 2020M671456)Natural Science Foundation of Jiangsu Province(Grant No BK20200117,BK20200121)Program of Innovation and Entrepreneurship of Jiangsu ProvinceJiangsu postdoctoral research support project(Grant No 2021K059A)Nanjing University Innovation Program for PhD candidates(CXYJ21-62).
文摘Osteoporosis is the most common degenerative orthopedic disease in the elderly.Recently,the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues,which could provide a suitable environment for the positive regulation of bone metabolism,promoting osteogenic differentiation and inhibiting osteoclast differentiation.Our previous work demonstrated that iron oxide nanoparticles(IONPs)could positively regulate bone metabolism in vitro.In this study,we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo.Meanwhile,IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice.Besides,alendronate,a clinically used anti-osteoporosis bisphosphate,was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role.Eventually,we verified the bone targeting ability,therapeutic efficiency,and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice.By applying BTNPs,the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.
基金Key Program of NSFC(81730067)Major Project of NSFC(81991514)+5 种基金Fundamental Research Funds for the Central Universities(14380493,14380494)National Science Foundation of China(Grant No 82002370,31800806,82000069)China Postdoctoral Science Foundation(Grant No 2019M661806)Natural science foundation of Jiangsu province(Grant No BK20200117,BK20200314),Jiangsu postdoctoral research support project(Grant No 2021K059A)Nanjing University Innovation Program for PhD candidates(CXYJ21-62)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundation,Program of Innovation and Entrepreneurship of Jiangsu Province.
文摘Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.
基金supported by grants from the National Natural Science Foundation of China(No.81970412)the Science and Technology Innovation Plan of the Shanghai Science and Technology Commission(No.18441902400)
文摘Aortic dissection is a life-threatening condition for which diagnosis mainly relies on imaging examinations,while reliable biomarkers to detect or monitor are still under investigation.Recent advances in technologies provide an unprecedented opportunity to yield the identification of clinically valuable biomarkers,including proteins,ribonucleic acids(RNAs),and deoxyribonucleic acids(DNAs),for early detection of pathological changes in susceptible patients,rapid diagnosis at the bedside after onset,and a superior therapeutic regimen primarily within the concept of personalized and tailored endovascular therapy for aortic dissection.
基金financially supported by the Guangdong Science and Technology Program(Grant No.2023A0505050145)the Zhongshan Municipal Science and Technology Program(Grant No.2021B2017)+2 种基金the Guangdong Provincial Department of Education Program(Grant Nos.2019KZDZX10532022ZDZX3085,2023ZDZX3094,2023ZDZX3099,and 2023KCXTD083)the Guangdong Education Planning Program(Grant No.2020GXJK554).
文摘As a type of austenitic stainless steel,316L stainless steel has excellent plasticity,corrosion resistance,and biocompatibility,making it widely used in industries,especially in the marine environments.However,its lower yield strength and wear resistance are the obvious disadvantages that restrict its application in more fields.In this work,an Fe-based amorphous alloy(Fe^(am))was selected as reinforcement to enhance the 316L stainless steel prepared by selective laser melting(SLM),and microstructure evolution,mechanical properties,tribological and corrosion performance of the SLMed samples were investigated in detail.The relative density values of both 316L stainless steel and Fe^(am)-reinforced samples are above 99%,which suggests that Fe^(am)-reinforced samples also have outstanding formability.In the as-etched micrograph,all of the SLMed samples exhibit cellular structure.Fe^(am)-reinforced samples have thicker sub-grain boundaries,and retained amorphous phase can be observed in the samples reinforced with 10 wt%and 15 wt%Fe^(am).As the addition of Fe^(am) increases,the microhardness and compression strength of the Fe^(am)-reinforced samples gradually improve and reach 449.2 HV and 2181.9 MPa,respectively.The wear morphologies show that the 316L stainless steel and Fe^(am)-reinforced samples both experience abrasive wear and corrosion wear in a 3.5 wt%NaCl solution.Meanwhile,as the amount of Fe^(am) added increases,the coefficient of friction and wear rate of SLMed samples gradually decrease.Compared to the unreinforced sample,Fe^(am)-reinforced samples have lower corrosion current density and higher pitting potential according to the potentiodynamic polarization curves and also exhibit superior corrosion resistance in the salt spray environment.This work suggests that the addition of Fe-based amorphous alloy can improve the mechanical properties and wear resistance of 316L stainless steel,as well as its ability to withstand salt spray corrosion.
基金supported by grants from the National Natural Science Foundation of China(82370130,81870098,82300146)the Program of the Shanghai Academic/Technology Researcher Leader(20XD1401000)+2 种基金the Shanghai Engineering Research Center of Tumor Multi-Target Gene Diagnosis(20DZ2254300)the Key Subject Construction Program of the Shanghai Health Administrative Authority(ZK2019B30)the Science and Technology Commission of the Shanghai Municipality(21ZR1459000).
文摘Primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical role.Mammalian sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been demonstrated to be a regulator of inflammation.Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive.The expression and function of MST4 in macrophages of ITP patients and THP-1 cells,and of a macrophage-specific Mst4−/−(Mst4ΔM/ΔM)ITP mouse model were determined.Macrophage phagocytic assays,RNA sequencing(RNA-seq)analysis,immunofluorescence analysis,coimmunoprecipitation(co-IP),mass spectrometry(MS),bioinformatics analysis,and phosphoproteomics analysis were performed to reveal the underlying mechanisms.The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients,and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment.The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages.Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines,and impaired phagocytosis,which could be increased by overexpression of MST4.In a passive ITP mouse model,macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid,attenuated the expression of M1 cytokines,and promoted the predominance of FcγRIIb in splenic macrophages,which resulted in amelioration of thrombocytopenia.Downregulation of MST4 directly inhibited STAT1 phosphorylation,which is essential for M1 polarization of macrophages.Our study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.
文摘Technological advances in glaucoma have challenged the traditional treatment paradigm. Historically incisional surgery has been used in cases of advanced disease and/or uncontrolled intraocular pressures resistant to medical or laser interventions. More recently, perhaps due to advancements in imaging, surgery has been suggested to be beneficial earlier in the treatment paradigm. Despite these trends, surgical manipulation of the tissues and unpredictability of wound healing continue to result in surgical failure. Magnesium is an essential element for human body and plays a critically important role in maintaining the functional and structural integrity of several tissues, including the eye. Due to several of its advantageous properties such as non-toxicity, biodegradability, and high biological compatibility, magnesium alloy has attracted great attention as a novel biomaterial. Biodegradable cardiovascular stents made of magnesium alloy have already been introduced into clinical practice. The purpose of this review is to determine if bioabsorbable magnesium alloys can be utilized as a promising candidate for the development of a new generation of glaucoma surgical assistive devices.
基金Supported by The Shanghai Municipal Health Commission Clinical Research Project,No.202140140.
文摘BACKGROUND For patients with acute paraplegia caused by spinal giant cell tumor(GCT)who require emergency decompressive surgery,there is still a lack of relevant reports on surgical options.This study is the first to present the case of an acute paraplegic patient with a thoracic spinal GCT who underwent an emergency total en bloc spondylectomy(TES).Despite tumor recurrence,three-level TES was repeated after denosumab therapy.CASE SUMMARY A 27-year-old female patient who underwent single-level TES in an emergency presented with sudden severe back pain and acute paraplegia due to a thoracic spinal tumor.After emergency TES,the patient's spinal cord function recovered,and permanent paralysis was avoided.The postoperative histopathological examination revealed that the excised neoplasm was a rare GCT.Unfortunately,the tumor recurred 9 months after the first surgery.After 12 months of denosumab therapy,the tumor size was reduced,and tumor calcification.To prevent recurrent tumor progression and provide a possible cure,a three-level TES was performed again.The patient returned to an active lifestyle 1 month after the second surgery,and no recurrence of GCT was found at the last follow-up.CONCLUSION This patient with acute paraplegia underwent TES twice,including once in an emergency,and achieved good therapeutic results.TES in emergency surgery is feasible and safe when conditions permit;however,it may increase the risk of tumor recurrence.
基金supported by the National Natural Science Foundation of China,Nos.81771281(to FXS),81471177(to FXS)the Natural Science Foundation of Shanghai of China,No.20ZR1434200(to YF)。
文摘Leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.
基金Our study has been approved by Medical Research Ethics Approval Committee(2023010122HN11C).
文摘BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regressio
文摘We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.
基金Project supported by the National Key R&D Program of China(2022YFB3505700,2022YFB3807900)National Natural Science Foundation of China(51901079)+2 种基金R&D(Research and Development)Plan in Key Areas of Guangdong Province(SDZX2021002,212021032611700001)Natural Science Foundation of Guangdong Province(2020A1515010736,2021A1515010451)the Guangzhou Municipal Science and Technology Program(202007020008)。
文摘SmCo based films with excellent intrinsic magnetic properties have promising applications in micro-electro-mechanical system(MEMS).However,due to the complexity of phase composition and uncontrollable crystallization degree of SmCo hard magnetic phase in the film,both the coercivity(Hc)and remanence(Mr)of films are difficult to enhance simultaneously.In this paper,SmCo based films were deposited with a Cr underlayer and capping layer on single crystal Si substrates via magnetron sputtering process.The effects of annealing parameters and Sm/Co atomic ratio on the phase structure and coercivity of films are discussed.By adjusting the Sm/Co atomic ratio from 1:5 to 1:4,Co soft magnetic phase disappears and the single phase SmCo5 is obtained,leading to the increase of coercivity of the films from 30 to 34 kOe.The influence of deposition temperature and Cu doping on magnetic properties of SmCo based films was investigated.When the deposition temperature increases from room temperature to 250℃,the coercivity will further increase from 34 to 51 kOe.However,a severe kink is observed in the demagnetization curves due to the poor exchanged coupling.An analysis of transmission electron microscopy(TEM)confirms that the average size of non-hard magnetic amorphous phase exceeds the effective exchanged coupling length of SmCo5,which contributes to the decoupling and low remanence ratio.Therefore,doping Cu and applying a post-annealing process can significantly improve the crystallization degree of the films.Both the coercivity and the remanence ratio of the demagnetization curves are greatly enhanced.We propose a plausible strategy to prepare the SmCo based films with high coercivity and remanence ratio by temperature and chemical optimization,which can be utilized in high performed MEMS devices.
基金supported by the National Natural Science Foundation of China(No.52103171,82172738,82272457,22305044)China Postdoctoral Science Foundation(2023M730638)+3 种基金“Technology Innovation Action Plan”of Science and Technology Commission of Shanghai Municipality(21S11902700)Natural Science Foundation of Shanghai(21ZR1412300),Shanghai Science and Technology program(23Y31900202,23010502600)Shanghai“Rising Stars of Medical Talent”Youth Development Program(Youth Medical Talents-Specialist Program,[2020]087)Medical Engineering fund of Fudan University(yg2023-27).
文摘Surgery remains the standard treatment for spinal metastasis.However,uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes.In this study,we develop a thrombin(Thr)-loaded nanorobothydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels.This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma(HCC)with easy bleeding characteristics,before spinal surgery in a mouse model.Under near-infrared irradiation,the self-motile nanorobots penetrate into the deep spinal tumor,releasing Thr in a controlled manner.Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding,inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy.Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth,with potentially reduced surgical complications and enhanced operative outcomes.
基金National Natural Science Foundation of China(No.81970817,No.81873680)。
文摘AIM:To reveal whether and how Yes-associated protein(YAP)promotes the occurrence of subretinal fibrosis in agerelated macular degeneration(AMD).METHODS:Cobalt chloride(Co Cl2)was used in primary human umbilical vein endothelial cells(HUVECs)to induce hypoxia in vitro.Eight-week-old male C57 BL/6 J mice weighing 19-25 g were used for a choroidal neovascularization(CNV)model induced by laser photocoagulation in vivo.Expression levels of YAP,phosphorylated YAP,mesenchymal markers[αsmooth muscle actin(α-SMA),vimentin,and Snail],and endothelial cell markers(CD31 and zonula occludens 1)were measured by Western blotting,quantitative real-time PCR,and immunofluorescence microscopy.Small molecules YC-1(Lificiguat,a specific inhibitor of hypoxia-inducible factor 1α),CA3(CIL56,an inhibitor of YAP),and XMU-MP-1(an inhibitor of Hippo kinase MST1/2,which activates YAP)were used to explore the underlying mechanism.RESULTS:Co Cl2 increased expression of mesenchymal markers,decreased expression of endothelial cell markers,and enhanced the ability of primary HUVECs to proliferate and migrate.YC-1 suppressed hypoxia-induced endothelialto-mesenchymal transition(End MT).Moreover,hypoxia promoted total expression,inhibited phosphorylation,and enhanced the transcriptional activity of YAP.XMU-MP-1 enhanced hypoxia-induced End MT,whereas CA3 elicited the opposite effect.Expression of YAP,α-SMA,and vimentin were upregulated in the laser-induced CNV model.However,silencing of YAP by vitreous injection of small interfering RNA targeting YAP could reverse these changes.CONCLUSION:The findings reveal a critical role of the hypoxia-inducible factor-1α(HIF-1α)/YAP signaling axis in End MT and provide a new therapeutic target for treatment of subretinal fibrosis in AMD.
文摘AIM： To investigate the incidence rate and risk factors for grade Ⅲ flat anterior chamber（FAC） after glaucoma filtration surgery based on 5-year data.METHODS： Patients who underwent glaucoma filtration surgery in Daping hospital from January 2009 to December 2013 were enrolled in this retrospective study. The incidence of grade Ⅲ FAC following glaucoma filtration surgery was determined. Regression analysis was performed to investigate the influence of glaucoma type, surgical approach, age, and preoperative intraocular pressure（IOP） on the risk of postoperative FAC.RESULTS： A total of 2179 eyes receiving anti-glaucoma surgery were included. Ninety-one eyes suffered from postoperative FAC, with an overall incidence rate of 4.18%. Of 471 eyes with primary open angle glaucoma（POAG）, grade Ⅲ FAC occurred in only 3 eyes（0.64%）. Primary angleclosure glaucoma（PACG） was diagnosed in 1076 eyes, 39（3.62%） of which developed grade Ⅲ FAC, including 12 eyes（12/300, 4%） with acute PACG（aP ACG） and 27 eyes（27/776, 3.48%） with chronic PACG（c PACG）. Six of 259 eyes（2.32%） with secondary glaucoma, 28 of 186 eyes（15.05%） with neovasular glaucoma, 1 of 66 eyes（1.52%） with congenital glaucoma, and 14 of 115 eyes（12.17%） with remnant glaucoma suffered from grade Ⅲ FAC. Of 6 eyes with mixed glaucoma, none developed grade Ⅲ FAC after surgery. When stratified by surgical approach, 24 of 766 eyes（3.13%） undergoing trabeculectomy, 21 of 924 eyes（2.27%） treated by trabeculectomy plus mitomycin C（MMC）, 18 of 109 eyes（16.51%） undergoing Ahmed glaucoma valve implantation, 23 of 201 eyes（11.44%） managed by Ahmed implantation plus MMC, and 5 of 133 eyes（3.76%） treated by Ahmed implantation plus lens extraction or vitrectomy developed grade Ⅲ FAC. Logistic regression analysis revealed that factors including neovasular glaucoma, remnant glaucoma, glaucoma valve implantation, glaucoma valve implantation＋MMC, glaucoma valve implantation＋vitrectomy,
基金supported by the National Key Research and Development Project(No.2021YFA1201404)Major Project of the National Natural Science Foundation of China(Nos.81991514,82272530)+2 种基金Jiangsu Province Medical Innovation Center of Orthopedic Surgery(No.CXZX202214)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,Jiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities(Nos.14380493 and 14380494).
文摘Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.
基金supported by the Key Program of NSFC(81730067)Major Project of NSFC(81991514)+3 种基金Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation,and Jiangsu Provincial Key Medical Talent Foundation.The Fundamental Research Funds for the Central Universities(14380493,14380494)the National Natural Science Foundation of China(82102511)the Natural Science Foundation of Jiangsu(BK20210021)Research Project of Jiangsu Province Health Committee(M2021031).
文摘Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging.Here,we present a three-dimensional(3D)printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration.To make the scaffold,cold-water fish skin gelatin was combined with sodium alginate to increase viscosity,printability,and mechanical strength,and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology.Then,the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further.These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere,proliferate,and communicate with each other,transport nutrients,and prevent further damage to the joint.More importantly,we found that cold-water fish gelatin scaffolds were nonimmunogenic,nontoxic,and biodegradable.We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model.Thus,cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.
