Oral squamous cell carcinoma(OSCC)is typified by extensive stromal fibrosis and an immunosuppressive microenvironment,both of which impede effective responses to immune checkpoint blockade.In this study,we identify pr...Oral squamous cell carcinoma(OSCC)is typified by extensive stromal fibrosis and an immunosuppressive microenvironment,both of which impede effective responses to immune checkpoint blockade.In this study,we identify prolyl 3-hydroxylase family member 4(P3H4)as a critical mediator of extracellular matrix(ECM)remodeling,epithelial-mesenchymal transition(EMT),and the exclusion of cytotoxic CD8+T lymphocytes.Elevated P3H4 expression correlates with unfavorable clinical outcomes and resistance to immunotherapy.Genetic ablation of P3H4 significantly attenuates tumor progression and promotes CD8^(+)T cell infiltration.To pharmacologically target P3H4,we engineered a liposomal formulation of 1,4-dihydrophenanthroline-2,5-dicarboxylic acid(1,4-DPCA),a small-molecule prolyl hydroxylase inhibitor.This nanomedicine,designated Lipo-1,4-DPCA,effectively downregulates P3H4 expression,mitigates tumor-associated fibrosis,reprograms the immune microenvironment,and elicits robust anti-tumor responses in vivo.Collectively,our findings establish P3H4 as a promising therapeutic target and highlight Lipo-1,4-DPCA as a dualfunctional nanotherapeutic candidate capable of enhancing the efficacy of immunotherapy in OSCC.展开更多
Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim...Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.展开更多
In this review,we propose a comprehensive overview of additive manufacturing(AM)technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field,of which many are i...In this review,we propose a comprehensive overview of additive manufacturing(AM)technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field,of which many are inspired by nature itself.It describes how new AM technologies(e.g.continuous liquid interface production and multiphoton polymerization,etc)and recent developments in more mature AM technologies(e.g.powder bed fusion,stereolithography,and extrusion-based bioprinting(EBB),etc)lead to more precise,efficient,and personalized biomedical components.EBB is a revolutionary topic creating intricate models with remarkable mechanical compatibility of metamaterials,for instance,stress elimination for tissue engineering and regenerative medicine,negative or zero Poisson’s ratio.By exploiting the designs of porous structures(e.g.truss,triply periodic minimal surface,plant/animal-inspired,and functionally graded lattices,etc),AM-made bioactive bone implants,artificial tissues,and organs are made for tissue replacement.The material palette of the AM metamaterials has high diversity nowadays,ranging from alloys and metals(e.g.cobalt-chromium alloys and titanium,etc)to polymers(e.g.biodegradable polycaprolactone and polymethyl methacrylate,etc),which could be even integrated within bioactive ceramics.These advancements are driving the progress of the biomedical field,improving human health and quality of life.展开更多
AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection wer...AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total T cells was detected by flow cytometry.Levels of total CD8+T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULTS:The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.展开更多
BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, li...BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.展开更多
BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury, secondary to obstructive jaundice, is one of the main causes of postoperative multiple system failure. This investigation evaluated renal funct...BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury, secondary to obstructive jaundice, is one of the main causes of postoperative multiple system failure. This investigation evaluated renal function and renal aquaporin 2 (AQP2) expression changes in obstructive jaundice. METHODS: Forty male Wistar rats were equally randomized into two groups. Twenty in the obstructive jaundice group were subjected to common bile duct ligation, and then were subdivided into 7- and 14-day obstruction groups, and the other 20 sham-operated rats were also subdivided into 7- and 14-day groups. At the end of each experiment, rats were sacrificed, venous blood was collected from the inferior vena cava, and serum creatinine and urine nitrogen concentrations were measured. At the same time, the medulla of the right kidney was separated and AQP2 expression was assessed. The RT-PCR technique was used to detect AQP2 mRNA expression. RESULTS: Ligation of the common bile duct caused significant rises in serum bilirubin, creatinine clearance and urine nitrogen. AQP2 expression in the medulla decreased mere significantly (38.35 +/- 2.08) in the 7-day ligation group than in the sham-operated group (41.06 +/- 1.04), as did that in the 14-day ligation group, even more than (31.89 +/- 1.57). The expression of AQP2 mRNA also decreased more significantly in the 14-day group (0.5429 +/- 0.1107) than in the 7-day group (0.6071 +/- 0.1328). CONCLUSION: AQP2 expression is inhibited in obstructive jaundice, and so is its gene expression.展开更多
BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an ...BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a fine needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib. (Hepatobiliary Pancreat Dis Int 2009; 8: 329-331)展开更多
Objective Jiedu Recipe(JR),a Chinese herbal remedy,has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma(HCC).This work investigated the...Objective Jiedu Recipe(JR),a Chinese herbal remedy,has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma(HCC).This work investigated the mechanism of JR in HCC treatment.Methods The chemical constituents of JR were detected using liquid chromatography-mass spectrometry.The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid(mRNA)microarray chip assay,followed by experimental validation in human HCC cells(SMMC-7721 and Huh7)in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo.HCC cell characteristics of proliferation,migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide,wound healing and Transwell assays,respectively.Image-i^(TM)Hypoxia Reagent was added to reveal hypoxic conditions.Stem cell sphere formation assay was used to detect the stemness.Epithelial-mesenchymal transition(EMT)markers like E-cadherin,vimentin andα-smooth muscle actin,and pluripotent transcription factors including nanog homeobox,octamer-binding transcription factor 4,and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction.Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.Results According to network pharmacology and mRNA microarray chip analysis,JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway.In vitro and in vivo experiments showed that JR significantly decreased hypoxia,and suppressed HCC cell features of proliferation,migration and invasion;furthermore,the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR.Results based on the co-administration of JR and an agonist(LiCl)or inhibitor(IWR-1-endo)verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.Conclusion JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions.展开更多
OBJECTIVE:To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy(IT) in patients after resection of small hepatocellular carcinoma(HCC).METHODS:A retrospective study wa...OBJECTIVE:To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy(IT) in patients after resection of small hepatocellular carcinoma(HCC).METHODS:A retrospective study was conducted in 399 patients after resection of small HCC who were admitted between January 1987 and December 2008 in the Department of Hepatobiliary Surgery and Center of Minimlly Invasive Surgery,First Affiliated Hospital of Guangxi Medical University.Four groups were based on different therapy modes:a TCM-only(TCMO) group,a TCM combined with interventional therapy(TCM-IT) group,an interventional therapy-only(ITO) group,and a simple operation(SO) group.Prognostic factors were correlated with overall survival(OS) and OS rates were calculated with the Kaplan-Meier method,and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model.RESULTS:The median OS was 151.20 months in the TCM-IT group,43.87 months in the ITO group,and 20.77 months in the SO group.All survival rates of the TCMO group were higher than those of the other three groups(>50%).The 5-,10-,and 15-year OS in the TCMO and ITO patients were 83.94%,45.50%,and 71.22% and 33.34%,55.58%,and 9.26%,respectively(risk ratio,0.209;95% confidence interval,0.126-0.347;P=0.000).Multivariate analysis revealed that the independent risk factors were therapy mode(P=0.000),sex(P=0.005),family history(P=0.011),TNM Classification of Malignant Tumor staging(P=0.000),medical care-seeking behavior(P=0.021),and maximum diameter(P=0.030).CONCLUSION:Long-term oral use of compound RJH tablets may improve OS for small HCC after resection compared with IT.展开更多
Alzheimer's disease (AD) is an irreversible neurodegenerative disease with a variety of pathogenic factors and complex pathogenesis, so that the disease has a high prevalence and mortality in the world. Although t...Alzheimer's disease (AD) is an irreversible neurodegenerative disease with a variety of pathogenic factors and complex pathogenesis, so that the disease has a high prevalence and mortality in the world. Although the current diagnosis and treatment equipment and drug research and development keep pace with the times, the current medical technology still can not completely cure the disease, so it is of great significance to explore the pathogenesis and treatment target of AD. The disorder of energy metabolism is one of the characteristic changes in the pathological process of AD. Aerobic glycolysis (AEG) is a special metabolic pathway in the brain, which can rapidly consume glucose to produce energy and substrate for neurons, improve synaptic plasticity, neuroinflammation and oxidative damage, and contribute to the recovery of memory and cognitive function. In recent years, many literatures have reported the mechanism of AEG in AD and the intervention of Tradit Chin Med on this mechanism. The purpose of this paper is to summarize the role of AEG in AD and the related research on the regulation and control of AEG in the treatment of AD by Tradit Chin Med, in order to provide reference and ideas for the prevention and treatment of AD with Tradit Chin Med in the future.展开更多
Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality ...Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.展开更多
Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea offici...Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.展开更多
Objective The aim of this study is to analyze the ultrastructural changes and dopamine 2 receptor (D2R) expression levels of pituitary adenomas to clarify the mechanism of medical management. Methods 9 patients with p...Objective The aim of this study is to analyze the ultrastructural changes and dopamine 2 receptor (D2R) expression levels of pituitary adenomas to clarify the mechanism of medical management. Methods 9 patients with prolactinomas and 4 with nonfunctioning pituitary adenomas(NFPAs) were treated with bromocriptine preoperatively. Ultrastructure changes of tumor cells were observed through electron microscopy.展开更多
Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were random...Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-展开更多
Objective To analyze factors affecting operative prognosis of intramedullary ependymomas in medulla oblongata and cervical cord. Methods Thirty patients harboring intramedullary ependymomas in medulla oblongata and ce...Objective To analyze factors affecting operative prognosis of intramedullary ependymomas in medulla oblongata and cervical cord. Methods Thirty patients harboring intramedullary ependymomas in medulla oblongata and cervical cord were operated. The preoperative and postoperative status was taken by follow-up and展开更多
Objective To explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells ( Dcs) in renal allograft recipients to guide individualized immunosuppressive therapy. Methods From Jan. 2008...Objective To explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells ( Dcs) in renal allograft recipients to guide individualized immunosuppressive therapy. Methods From Jan. 2008 to Jan. 2010,30 recipients received living related kidney transplantation were successively and divided into展开更多
Objective To discuss the application of medial planta island flaps pedicled with anterior tibial artery perforator in front of inner malleolus for repairing small wounds around ankle Methods From Jan. 2005 to Jun. 200...Objective To discuss the application of medial planta island flaps pedicled with anterior tibial artery perforator in front of inner malleolus for repairing small wounds around ankle Methods From Jan. 2005 to Jun. 2009,10 cases with small wounds around ankle展开更多
To investigate the optimal time to perform breast reconstruction after mastectomy for breast cancer.Methods From May,2001 to March,2004,52 patients were performed immediate or delayed breast reconstruction after maste...To investigate the optimal time to perform breast reconstruction after mastectomy for breast cancer.Methods From May,2001 to March,2004,52 patients were performed immediate or delayed breast reconstruction after mastectomy.They were given questionnaires to assess for satisfaction,sexuality,anxiety depression,body image and self-esteem.Results 97% of the IR group patients were very or moderately satisfied while only 75% of the DR group were so (P=0.026).Only 6% of the IR group compared with 30% of the DR group felt an obvious impairment of their sexual attractiveness (P=0.043).Anxiety (P=0.014) and depression (P=0.006) were less in the IR group than the DR group.Body image (P=0.012) and self-esteem (P=0.003) were superior in the IR group.Conclusion If tumor characters and patient health permit,immediate breast reconstruction should be performed after mastectomy for breast cancer.11 refs,5 tabs.展开更多
BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cell...BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.展开更多
基金supported by grants from the National Natural Science Foundation of China(Nos.82501207,81700993,52403312,and 82571151)Postdoctoral Fellowship Program of CPSF(No.GZC20251219)+1 种基金the Beijing Nova Program(No.20250484855)the Beijing Natural Science Foundation(No.L252168).
文摘Oral squamous cell carcinoma(OSCC)is typified by extensive stromal fibrosis and an immunosuppressive microenvironment,both of which impede effective responses to immune checkpoint blockade.In this study,we identify prolyl 3-hydroxylase family member 4(P3H4)as a critical mediator of extracellular matrix(ECM)remodeling,epithelial-mesenchymal transition(EMT),and the exclusion of cytotoxic CD8+T lymphocytes.Elevated P3H4 expression correlates with unfavorable clinical outcomes and resistance to immunotherapy.Genetic ablation of P3H4 significantly attenuates tumor progression and promotes CD8^(+)T cell infiltration.To pharmacologically target P3H4,we engineered a liposomal formulation of 1,4-dihydrophenanthroline-2,5-dicarboxylic acid(1,4-DPCA),a small-molecule prolyl hydroxylase inhibitor.This nanomedicine,designated Lipo-1,4-DPCA,effectively downregulates P3H4 expression,mitigates tumor-associated fibrosis,reprograms the immune microenvironment,and elicits robust anti-tumor responses in vivo.Collectively,our findings establish P3H4 as a promising therapeutic target and highlight Lipo-1,4-DPCA as a dualfunctional nanotherapeutic candidate capable of enhancing the efficacy of immunotherapy in OSCC.
基金supported by the National Natural Science Foundation of China,Nos.82272470 (to GN),82072439 (to GN),81930070 (to SF)the Tianjin Health Key Discipline Special Project,No.TJWJ2022XK011 (to GN)+2 种基金the Outstanding Youth Foundation of Tianjin Medical University General Hospital,No.22ZYYJQ01 (to GN)Tianjin Key Medical Disciplines,No.TJYXZDXK-027A (to SF)National Key Research and Development Program-Stem Cells and Transformation Research,No.2019YFA0112100 (to SF)
文摘Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.
基金sponsored by the Science and Technology Program of Hubei Province,China(2022EHB020,2023BBB096)support provided by Centre of the Excellence in Production Research(XPRES)at KTH。
文摘In this review,we propose a comprehensive overview of additive manufacturing(AM)technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field,of which many are inspired by nature itself.It describes how new AM technologies(e.g.continuous liquid interface production and multiphoton polymerization,etc)and recent developments in more mature AM technologies(e.g.powder bed fusion,stereolithography,and extrusion-based bioprinting(EBB),etc)lead to more precise,efficient,and personalized biomedical components.EBB is a revolutionary topic creating intricate models with remarkable mechanical compatibility of metamaterials,for instance,stress elimination for tissue engineering and regenerative medicine,negative or zero Poisson’s ratio.By exploiting the designs of porous structures(e.g.truss,triply periodic minimal surface,plant/animal-inspired,and functionally graded lattices,etc),AM-made bioactive bone implants,artificial tissues,and organs are made for tissue replacement.The material palette of the AM metamaterials has high diversity nowadays,ranging from alloys and metals(e.g.cobalt-chromium alloys and titanium,etc)to polymers(e.g.biodegradable polycaprolactone and polymethyl methacrylate,etc),which could be even integrated within bioactive ceramics.These advancements are driving the progress of the biomedical field,improving human health and quality of life.
基金Supported by Grants from the"Yucai"Research Program of Changhai Hospital
文摘AIM:To investigate if and how programmed death type-1(PD-1)expression affects the natural course of hepatitis B virus(HBV)infection. METHODS:Sixty-four patients in different natural stages of chronic HBV infection were enrolled in this study.PD-1 expression in total T cells was detected by flow cytometry.Levels of total CD8+T cell responses and proliferation in relation to PD-1 expression levels were analyzed with intracellular staining and PD-1/ PD-L1 blockage. RESULTS:The PD-1 expression in T cells was dynamically changed during the natural course of chronic HBV infection,did not significantly increase in the immune tolerance phase,and returned to normal in the inactive virus carrier stage.Blockage of the PD-1/PD-L1 pathway could not affect the T-cell response in the immune tolerance and inactive virus carrier stages of chronic HBV infection.However,it could significantly restore the T-cell response in the immune clearance stage of chronic HBV infection.Furthermore,the PD-1 expression level in T cells was associated with the alanine aminotransferase level during the immune clearance stage of chronic HBV infection. CONCLUSION:The PD-l/PD-L1 pathway plays a different role in T-cell response during the natural course of chronic HBV infection.
基金supported by grants from the Technological Foundation Project of Traditional Chinese Medical Science of Zhejiang Province(No.2003C130No.2004C142)the Foundation Project for Medical Science and Technology of Zhejiang Province(No.2003B134).
文摘BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.
基金This study was supported by a grant from the Liaoning Province Research Project for Institution of Higher Education (2004D282).
文摘BACKGROUND: Obstructive jaundice is a common disease. Acute renal injury, secondary to obstructive jaundice, is one of the main causes of postoperative multiple system failure. This investigation evaluated renal function and renal aquaporin 2 (AQP2) expression changes in obstructive jaundice. METHODS: Forty male Wistar rats were equally randomized into two groups. Twenty in the obstructive jaundice group were subjected to common bile duct ligation, and then were subdivided into 7- and 14-day obstruction groups, and the other 20 sham-operated rats were also subdivided into 7- and 14-day groups. At the end of each experiment, rats were sacrificed, venous blood was collected from the inferior vena cava, and serum creatinine and urine nitrogen concentrations were measured. At the same time, the medulla of the right kidney was separated and AQP2 expression was assessed. The RT-PCR technique was used to detect AQP2 mRNA expression. RESULTS: Ligation of the common bile duct caused significant rises in serum bilirubin, creatinine clearance and urine nitrogen. AQP2 expression in the medulla decreased mere significantly (38.35 +/- 2.08) in the 7-day ligation group than in the sham-operated group (41.06 +/- 1.04), as did that in the 14-day ligation group, even more than (31.89 +/- 1.57). The expression of AQP2 mRNA also decreased more significantly in the 14-day group (0.5429 +/- 0.1107) than in the 7-day group (0.6071 +/- 0.1328). CONCLUSION: AQP2 expression is inhibited in obstructive jaundice, and so is its gene expression.
文摘BACKGROUND: Extramedullary pancreatic plasmacytoma treated with bortezomib is rarely reported. METHODS: We admitted a 53-year-old woman with an asymptomatic mass above the left clavicle for over three months, then an asymptomatic swelling of the pancreas was found. A biopsy on the mass and a fine needle aspiration of the pancreas were performed. The diagnosis of extramedullary plasmacytoma (EMP) was made. The patient was initially treated with combination chemotherapy consisting of vincristine, doxorubicin and dexamethasone (VAD regimen). She progressed to painless jaundice during the chemotherapy. Then she was treated with bortezomib and hyper-dose dexamethasone. As a result, she had a near complete remission. RESULTS: The data demonstrated that the diagnosis was EMP of the pancreas. The patient responded very well to bortezomib, while failing to respond to the traditional chemotherapy regimen of VAD. CONCLUSION: EMP of the pancreas is rare. This case gives evidence for an excellent response of EMP of the pancreas to bortezomib. (Hepatobiliary Pancreat Dis Int 2009; 8: 329-331)
基金This study was supported by the National Natural Science Foundation of China(No.81803929 and 82074138)the Natural Science Foundation of Shanghai(No.21ZR1479500).
文摘Objective Jiedu Recipe(JR),a Chinese herbal remedy,has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma(HCC).This work investigated the mechanism of JR in HCC treatment.Methods The chemical constituents of JR were detected using liquid chromatography-mass spectrometry.The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid(mRNA)microarray chip assay,followed by experimental validation in human HCC cells(SMMC-7721 and Huh7)in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo.HCC cell characteristics of proliferation,migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide,wound healing and Transwell assays,respectively.Image-i^(TM)Hypoxia Reagent was added to reveal hypoxic conditions.Stem cell sphere formation assay was used to detect the stemness.Epithelial-mesenchymal transition(EMT)markers like E-cadherin,vimentin andα-smooth muscle actin,and pluripotent transcription factors including nanog homeobox,octamer-binding transcription factor 4,and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction.Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.Results According to network pharmacology and mRNA microarray chip analysis,JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway.In vitro and in vivo experiments showed that JR significantly decreased hypoxia,and suppressed HCC cell features of proliferation,migration and invasion;furthermore,the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR.Results based on the co-administration of JR and an agonist(LiCl)or inhibitor(IWR-1-endo)verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.Conclusion JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions.
基金Supported by Grants from the 11th National Key Technology R&D Program(No.2006BAI04A06)E-institutes of Shanghai Municipal Education Commission Support Program(No.E03008)
文摘OBJECTIVE:To compare the long-term effectiveness of compound Ruanjianhugan(RJH)tablets and interventional therapy(IT) in patients after resection of small hepatocellular carcinoma(HCC).METHODS:A retrospective study was conducted in 399 patients after resection of small HCC who were admitted between January 1987 and December 2008 in the Department of Hepatobiliary Surgery and Center of Minimlly Invasive Surgery,First Affiliated Hospital of Guangxi Medical University.Four groups were based on different therapy modes:a TCM-only(TCMO) group,a TCM combined with interventional therapy(TCM-IT) group,an interventional therapy-only(ITO) group,and a simple operation(SO) group.Prognostic factors were correlated with overall survival(OS) and OS rates were calculated with the Kaplan-Meier method,and multivariate analyses for factors affecting survival were evaluated by the Cox proportional hazard model.RESULTS:The median OS was 151.20 months in the TCM-IT group,43.87 months in the ITO group,and 20.77 months in the SO group.All survival rates of the TCMO group were higher than those of the other three groups(>50%).The 5-,10-,and 15-year OS in the TCMO and ITO patients were 83.94%,45.50%,and 71.22% and 33.34%,55.58%,and 9.26%,respectively(risk ratio,0.209;95% confidence interval,0.126-0.347;P=0.000).Multivariate analysis revealed that the independent risk factors were therapy mode(P=0.000),sex(P=0.005),family history(P=0.011),TNM Classification of Malignant Tumor staging(P=0.000),medical care-seeking behavior(P=0.021),and maximum diameter(P=0.030).CONCLUSION:Long-term oral use of compound RJH tablets may improve OS for small HCC after resection compared with IT.
基金National Natural Science Foundation of China Regional Fund(No.82060844)Guangxi Natural Science Foundation General Project(No.2022GXNSFAA035461)+4 种基金Guangxi Clinical Medical Research Center for Tradit Chin Med Encephalopathy(No.Guike AD20238028)Academic Team Construction Project of the First Affiliated Hospital of Guangxi Univ Tradit Chin Med[Hospital Letter(2018)No.146]The 2020 Guangxi Higher Education High level Innovation Team and Outstanding Scholar Program[Guijiao Talent(2020)No.6]Guangxi Univ Tradit Chin Med"Qihuang Project"High level Talent Team Cultivation Project(No.2018003)Guangxi Key Discipline Construction Project of Tradit Chin Med(No.GZXK-Z-20-13)Alzheimer’s disease(AD)is an irreversible neurodegenerative disease.At present,the number of AD cases has exceeded 30 million and continues to rise in the world,especially in developing countries including China.Due to the superposition of factors such as an aging population,social pressure and improper lifestyle,it is speculated that the number of AD cases will double in the next 30 years[1].Although a large amount of money has been invested in the drug development and diagnosis and treatment of AD,the current medical methods can only delay the disease of AD but can not cure it completely.It is undeniable that AD is a recognized health problem and health problem in the current society.Therefore,it is particularly important to further study the molecular mechanism of AD in order to identify the pathogenic factors and therapeutic targets,and to explore effective treatment.Modern medicine believes that its pathological mechanism is complex and interact with each other,includingβ-amyloid(Aβ)toxic damage,abnormal modification of Tau protein,oxidative stress,neuroinflammation,mitochondrial dysfunction and so on[2].In fact,in the process of inevitable aging,the metabolic network is affected by related signal pathways,proteins and genes,which leads to the gradual down-regulation of aerobic glycolysis(AEG),which can directly or indirectly participate in the pathogenesis of the above-mentioned AD and affect its pathological changes.Therefore,taking AEG as the research target can provide a new idea for the prevention and treatment of AD.The name of AD disease is not seen in Tradit Chin Med,and it is Alzheimer's disease(AD)is an irreversible neurodegenerative disease with a variety of pathogenic factors and complex pathogenesis,so that the disease has a high prevalence and mortality in the world.Although the current diagnosis and treatment equipment and drug research and development keep pace with the times,the current medical technology still can not completely cure the disease,so it is of great significance to explore the pathogenesis and treatment target of AD.The disorder of energy metabolism is one of the characteristic changes in the pathological process of AD.Aerobic glycolysis(AEG)is a special metabolic pathway in the brain,which can rapidly consume glucose to produce energy and substrate for neurons,improve synaptic plasticity,neuroinflammation and oxidative damage,and contribute to the recovery of memory and cognitive function.In recent years,many literatures have reported the mechanism of AEG in AD and the intervention of Tradit Chin Med on this mechanism.The purpose of this paper is to summarize the role of AEG in AD and the related research on the regulation and control of AEG in the treatment of AD by Tradit Chin Med,in order to provide reference and ideas for the prevention and treatment of AD with Tradit Chin Med in the future。
文摘Alzheimer's disease (AD) is an irreversible neurodegenerative disease with a variety of pathogenic factors and complex pathogenesis, so that the disease has a high prevalence and mortality in the world. Although the current diagnosis and treatment equipment and drug research and development keep pace with the times, the current medical technology still can not completely cure the disease, so it is of great significance to explore the pathogenesis and treatment target of AD. The disorder of energy metabolism is one of the characteristic changes in the pathological process of AD. Aerobic glycolysis (AEG) is a special metabolic pathway in the brain, which can rapidly consume glucose to produce energy and substrate for neurons, improve synaptic plasticity, neuroinflammation and oxidative damage, and contribute to the recovery of memory and cognitive function. In recent years, many literatures have reported the mechanism of AEG in AD and the intervention of Tradit Chin Med on this mechanism. The purpose of this paper is to summarize the role of AEG in AD and the related research on the regulation and control of AEG in the treatment of AD by Tradit Chin Med, in order to provide reference and ideas for the prevention and treatment of AD with Tradit Chin Med in the future.
基金The National Natural Science Foundation of China (grant number 81773891)the National Great New Drugs Development Project of China (grant number 2017ZX09301-040)+1 种基金the Beijing Municipal Science and Technology Commission (grant number XMLX201704, 2018-2-2242, 7194280)the Open Research Fund of the State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicinal Resources.
文摘Quality evaluation is a bottleneck restricting the modernization and internationalization of Chinese materia medica (CMM). Due to characteristics of multi-component, multi-efficacy, multi-target, the existing quality evaluation system still cannot fully meet quality control needs of CMM. Hence, the author put forward “Bio-characteristic profiling related to clinic, BPRC” academic concept, meanwhile, fully take the advantage of analysis method with clinical monitoring superiority or profiling characteristics, build up “BPRC” new technology platform, in order to realize “real-time, dynamic and full-range monitoring” new technologies of CMM quality evaluation system and promote the further development of CMM industry.
基金Key Science and Technology Project of Hainan Province(No.ZDKJ202003)Hainan Provincial Natural Science Foundation of China(No.821QN262)+1 种基金Hainan Provincial Natural Science Foundation of China(No.2019RC207)Hainan Provincial Natural Science Foundation of China(No.820RC628)。
文摘Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.
文摘Objective The aim of this study is to analyze the ultrastructural changes and dopamine 2 receptor (D2R) expression levels of pituitary adenomas to clarify the mechanism of medical management. Methods 9 patients with prolactinomas and 4 with nonfunctioning pituitary adenomas(NFPAs) were treated with bromocriptine preoperatively. Ultrastructure changes of tumor cells were observed through electron microscopy.
文摘Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-
文摘Objective To analyze factors affecting operative prognosis of intramedullary ependymomas in medulla oblongata and cervical cord. Methods Thirty patients harboring intramedullary ependymomas in medulla oblongata and cervical cord were operated. The preoperative and postoperative status was taken by follow-up and
文摘Objective To explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells ( Dcs) in renal allograft recipients to guide individualized immunosuppressive therapy. Methods From Jan. 2008 to Jan. 2010,30 recipients received living related kidney transplantation were successively and divided into
文摘Objective To discuss the application of medial planta island flaps pedicled with anterior tibial artery perforator in front of inner malleolus for repairing small wounds around ankle Methods From Jan. 2005 to Jun. 2009,10 cases with small wounds around ankle
文摘To investigate the optimal time to perform breast reconstruction after mastectomy for breast cancer.Methods From May,2001 to March,2004,52 patients were performed immediate or delayed breast reconstruction after mastectomy.They were given questionnaires to assess for satisfaction,sexuality,anxiety depression,body image and self-esteem.Results 97% of the IR group patients were very or moderately satisfied while only 75% of the DR group were so (P=0.026).Only 6% of the IR group compared with 30% of the DR group felt an obvious impairment of their sexual attractiveness (P=0.043).Anxiety (P=0.014) and depression (P=0.006) were less in the IR group than the DR group.Body image (P=0.012) and self-esteem (P=0.003) were superior in the IR group.Conclusion If tumor characters and patient health permit,immediate breast reconstruction should be performed after mastectomy for breast cancer.11 refs,5 tabs.
基金Supported by Russian Science Foundation,No.16-15-10432。
文摘BACKGROUND The development of regenerative therapy for human spinal cord injury(SCI)is dramatically restricted by two main challenges:the need for a safe source of functionally active and reproducible neural stem cells and the need of adequate animal models for preclinical testing.Direct reprogramming of somatic cells into neuronal and glial precursors might be a promising solution to the first challenge.The use of non-human primates for preclinical studies exploring new treatment paradigms in SCI results in data with more translational relevance to human SCI.AIM To investigate the safety and efficacy of intraspinal transplantation of directly reprogrammed neural precursor cells(drNPCs).METHODS Seven non-human primates with verified complete thoracic SCI were divided into two groups:drNPC group(n=4)was subjected to intraspinal transplantation of 5 million drNPCs rostral and caudal to the lesion site 2 wk post injury,and lesion control(n=3)was injected identically with the equivalent volume of vehicle.RESULTS Follow-up for 12 wk revealed that animals in the drNPC group demonstrated a significant recovery of the paralyzed hindlimb as well as recovery of somatosensory evoked potential and motor evoked potential of injured pathways.Magnetic resonance diffusion tensor imaging data confirmed the intraspinal transplantation of drNPCs did not adversely affect the morphology of the central nervous system or cerebrospinal fluid circulation.Subsequent immunohistochemical analysis showed that drNPCs maintained SOX2 expression characteristic of multipotency in the transplanted spinal cord for at least 12 wk,migrating to areas of axon growth cones.CONCLUSION Our data demonstrated that drNPC transplantation was safe and contributed to improvement of spinal cord function after acute SCI,based on neurological status assessment and neurophysiological recovery within 12 wk after transplantation.The functional improvement described was not associated with neuronal differentiation of the allogeneic drNPCs.Instead,directed drNPCs migration to the areas of active growth cone formation may provide exosome and paracrine trophic support,thereby further supporting the regeneration processes.
