Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability an...Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.展开更多
Background:Interleukin 13 receptor subunit alpha 2(IL13RA2)plays an essential role in the progression of many cancers.However,the role of IL13RA2 in infantile haemangioma(IH)is still unknown.Materials and Methods:IL13...Background:Interleukin 13 receptor subunit alpha 2(IL13RA2)plays an essential role in the progression of many cancers.However,the role of IL13RA2 in infantile haemangioma(IH)is still unknown.Materials and Methods:IL13RA2 expression in IH tissues was analyzed using western blot,qRT-PCR,and immunofluorescence.The role of IL13RA2 in haemangioma-derived endothelial cells(HemECs)was determined following knockdown or overexpression of IL13RA2 using CCK-8,colony formation,apoptosis,wound healing,tubule formation,Transwell,and western blot.Results:IL13RA2 expression was upregulated in IH tissues.IL13RA2 overexpression promoted proliferation,migration,and invasion of HemECs and induced glycolysis,which was confirmed with a glycolysis inhibitor.Specifically,IL13RA2 interacted withβ-catenin and activated the Wnt/β-catenin pathway in HemECs,which were involved in the above-mentioned effects of IL13RA2.Conclusions:These findings revealed that targeting IL13RA2 is a potential therapeutic approach for IH.展开更多
Acute liver failure(ALF)is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis...Acute liver failure(ALF)is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver.The causes of ALF encompass a wide variety of toxic,viral,metabolic,vascular and autoimmune insults to the liver,and identifying the correct cause can be difficult or even impossible.Many patients with ALF develop a cascade of serious complications involving almost every organ system,and death is mostly due to multi-organ failure,hemorrhage,infection,and intracranial hypertension.Fortunately,the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology,and the advanced intensive care management.For most severely affected patients who fail to recover after treatment,rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop.This review focuses on the recent advances in the understanding of various contributing etiologies,the administration of etiology-specific treatment to alleviate the liver injury,and the management of complications(e.g.,encephalopathy,coagulopathy,cardiovascular instability,respiratory failure,renal failure,sepsis and metabolic disturbance)in patients with ALF.Assessment of the need for liver transplantation is also presented.展开更多
AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(...AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay(ELISA).Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type(WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium(RPE) were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS:The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients(F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous).After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity(P〈0.01).In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay(1.486±0.042 vs 1.000±0.104,P〈0.05) and proliferating cell nuclear antigen(PCNA) expression(0.55±0.01 vs 0.29±0.03,P〈0.05).The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1(4.973±0.205 vs 2.720±0.197,P〈0.05),cyclin F(5.690±0.219 vs 4.297±0.292,P〈0.05) and E2 F2(2.297±0.102 vs 1.750±0.146,P〈0.05),and reducing the expression of proliferation-inhibiting factors cdkn1(2.370±0.074 vs 3.317±0.135,P〈0.05) and cdkn2(4.793±0.065 vs 5.387±0.149,P〈0.05).CONCLUSION:The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.展开更多
BACKGROUND: Numerous studies use fluorescent microscopy to obtain two-dimensional optical images of the morphology of nerve fibers in hypertrophic scars. In addition, current confocal microscopy studies have focused ...BACKGROUND: Numerous studies use fluorescent microscopy to obtain two-dimensional optical images of the morphology of nerve fibers in hypertrophic scars. In addition, current confocal microscopy studies have focused on normal, not pathological, cutaneous nerves. However, laser scanning confocal microscopy results in a three-dimensional structure of the nerve fibers. OBJECTIVE: To observe quantitative and morphological differences in nerve fibers from the proliferative and mature stage in hypertrophic scars using fluorescent and confocal microscopy. DESIGN, TIME AND SETTING: Neuropathological, comparison study was conducted at the Provincial Hospital Affiliated to Shandong University, China from June 2006 to July 2007. PARTICIPANTS: Specimens were selected from 30 patients undergoing scar restoration at the Provincial Hospital Affiliated to Shandong University of China at 1 month to 23 years following wound healing. The study comprised 20 males and 10 females. The scars were fibrous lesions, erythematous, tough, confined to skin lesions, did not exhibit ulceration or infection, exhibited telangiectasia, with or without itching and pain, and were not locally treated. Samples were equally assigned to two groups according to course of disease: proliferative group (〈 6 months) and mature group (6-24 months). Control samples were collected from full-thickness skin from donor sites (n = 10). METHODS: Nerve fiber morphology was observed using fluorescent and confocal microscopy following immunofluorescence of the skin specimens. The microscopic images were semi-quantitatively analyzed to acquire a positive area ratio of neurofilament protein-positive nerve fibers. MAIN OUTCOME MEASURES: Morphology and positive area ratio of neurofilament protein/positive nerve fibers was measured. RESULTS: The positive area ratio of neurofilament protein-positive nerve fibers was significantly greater in the proliferative group compared to the normal control group (P 〈 0.05). Nerve fibers were irregularly distributed and exhibited local swelling, twisting, and disconnection. However, the positive area ratio of neurofilament protein-positive nerve fibers was significantly less in the mature group compared with the normal control group (P 〈 0.05). The nerve fibers were arranged in an orderly manner, with intact inner and stereoscopic structures similar to normal skin. CONCLUSION: Compared with mature scars, hypertrophic scars exhibited a greater number of nerve fibers, with more serious pathologies.展开更多
Burn wound healing involves a complex sequence of processes. Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair. Few studies have addressed the process of reinnervati...Burn wound healing involves a complex sequence of processes. Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair. Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers. The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody, and three-dimensional morphology was observed under a laser scanning confocal microscope. Morphology and the volume fraction of collagen and nerve fibers were measured. Skin reinnervation increased during wound healing, peaked during the proliferative scar stage, and then decreased to lower levels during the maturation period. The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis. Disintegration and fragmentation were observed frequently in samples from the proliferative stage, and seldom occurred during the maturation stage. There was a remodeling process of regenerated nerve fibers during wound healing, which comprised changed innervation density and topical morphology. The mechanism of remodeling for nerve fibers requires further investigation.展开更多
Although the surgical treatment is a relatively effective and predictable method for correcting residual or recurrent strabismus, such as posterior fixation sutures,medial rectus marginal myotomy, unilateral or bilate...Although the surgical treatment is a relatively effective and predictable method for correcting residual or recurrent strabismus, such as posterior fixation sutures,medial rectus marginal myotomy, unilateral or bilateral rectus re-recession and resection, unilateral lateral rectus recession and adjustable suture, no standard protocol is established for the surgical style. Different surgical approaches have been recommended for correcting residual or recurrent strabismus. The choice of the surgical procedure depends on the former operation pattern and the surgical dosages applied on the patients, residual or recurrent angle of deviation and the operator’s preference and experience. This review attempts to outline recent publications and current opinion in the management of residual or recurrent esotropia and exotropia.展开更多
In percutaneous coronary intervention (PCI), chronic total occlusion (CTO) coronary artery disease still remains difficult to treat. One of the reasons for the failure is the hard of the CTO lesions that balloon is di...In percutaneous coronary intervention (PCI), chronic total occlusion (CTO) coronary artery disease still remains difficult to treat. One of the reasons for the failure is the hard of the CTO lesions that balloon is difficult to pass through or expand. Previous methods to deal with CTO lesions that cannot be passed by balloon, include selecting reinforced catheter (such as 5 in 6 guiding catheter, Guidzilla catheter, or Tornus microcatheter), guidewire extrusion or rotary grinding technology. In recent years, excimer laser coronary angioplasty (ELCA) has been gradually applied to CTO lesions. Using inert halide as the laser medium, ELCA emits a 308 nm high-intensity unidirectional light wave with absorption depth of only 50 μmL, resulting in less thermal effect and less damage to non-target lesions. In this paper, we will describe a successful PCI case of an in-stent CTO lesion using ELCA with long term coronary angiography follow-up.展开更多
BACKGROUND Coronavirus disease 2019(COVID-19)is a public health emergency of international concern.The global population lacks immunity to COVID-19 and is generally susceptible.Underlying conditions,especially chronic...BACKGROUND Coronavirus disease 2019(COVID-19)is a public health emergency of international concern.The global population lacks immunity to COVID-19 and is generally susceptible.Underlying conditions,especially chronic respiratory diseases,may affect progression,treatment and prognosis of COVID-19.CASE SUMMARY We report a patient with confirmed COVID-19 combined with asthma.It took 41 d from disease onset to discharge to obtain two negative tests for this coronavirus.CONCLUSION This case indicates the dynamic clinical characteristics,laboratory and computed tomography findings and adjustment of treatment,and the possible relationship between glucocorticoid therapy and coronavirus clearance.展开更多
Vibrio vulnificus is an estuarine bacterial pathogen for human.The rapid,specific and sensitive detection of V.vulnificus is urgently needed for early disease diagnosis and timely treatment of V.vulnificus infection.I...Vibrio vulnificus is an estuarine bacterial pathogen for human.The rapid,specific and sensitive detection of V.vulnificus is urgently needed for early disease diagnosis and timely treatment of V.vulnificus infection.In the study,a loop-mediated isothermal amplification(LAMP) technique was developed for V.vulnificus detection with a set of primers,composed of two out primers and two inner primers targeted to vvh A gene.The optimal amplification temperature was 63°C and the reaction only took 35 min.The amplification products could not only be detected by agarose gel electrophoresis with ladder-like pattern bands,but also could be visualized using calcein with naked eye directly.Forty-five strains were tested for the specificity of LAMP assay,and all the V.vulnificus strains were identified correctly while other strains were negative results.The sensitive of the new LAMP assay was 100-fold more sensitive than the conventional PCR.Meanwhile,all the V.vulnificus strains were detected correctly in spiked,clinical and environmental samples by the new LAMP assay.Compared with other well-known techniques,the new LAMP assay targeted to vvh A gene was extremely rapid,simple,sensitive and specific for V.vulnificus identification.展开更多
Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing a...Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis.Methods:Sonographic EHR data were obtained from the EHR database.Pathological reports were used as the gold standard for diagnosing thyroid cancer.We developed thyroid cancer diagnosis based on natural language processing(THCaDxNLP)to interpret unstructured sonographic text reports for thyroid cancer diagnosis.We used the area under the receiver operating characteristic curve(AUROC)as the primary metric to measure the performance of the THCaDxNLP.We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs.those without THCaDxNLP using 5 independent test sets.Results:We obtained a total number of 788,129 sonographic radiological reports.The number of thyroid sonographic data points was 132,277,18,400 of which were thyroid cancer patients.Among the 5 test sets,the numbers of patients per set were 439,186,82,343,and 171.THCaDxNLP achieved high performance in identifying thyroid cancer patients(the AUROC ranged from 0.857–0.932).Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy(93.8%vs.87.2%;one-sided t-test,adjusted P=0.003),precision(92.5%vs.86.0%;P=0.018),and F1 metric(94.2%vs.86.4%;P=0.007).Conclusions:THCaDxNLP achieved a high AUROC for the identification of thyroid cancer,and improved the accuracy,sensitivity,and precision of thyroid ultrasound radiologists.This warrants further investigation of THCaDxNLP in prospective clinical trials.展开更多
Objective: To investigate the changes and clinical significance of serum tumor markers in patients with rheumatoid arthritis (RA) combined with interstitial lung disease. Methods:A total of 50 healthy volunteers were ...Objective: To investigate the changes and clinical significance of serum tumor markers in patients with rheumatoid arthritis (RA) combined with interstitial lung disease. Methods:A total of 50 healthy volunteers were chosen as the normal control group, 47 patients with rheumatoid arthritis alone were chosen as the RA group, and 28 patients with rheumatoid arthritis combined with interstitial lung disease were chosen as combined disease group. The differences in the levels of serum tumor markers, RA markers and inflammatory mediators were compared among the three groups, and Pearson test was used to evaluate the correlation of serum tumor marker levels with RA markers and inflammatory mediators in patients with RA combined with interstitial lung disease. Results: Serum tumor markers CA199, CA153 and CEA levels of combined disease group were higher than those of RA group;RA markers RF and GPI levels were higher than those of RA group whereas CCP and AKA levels were not significantly different from those of RA group;inflammatory mediators HMGB1, GM-CSF, IL-6, IL-17 and IL-27 levels were higher than those of RA group. Correlation analysis showed that serum tumor markers CA199, CA153 and CEA levels in patients with RA combined with interstitial lung disease were positively correlated with RF, GPI, HMGB1, GM-CSF, IL-6, IL-17 and IL-27 levels. Conclusion: Serum tumor markers CA199, CA153 and CEA levels abnormally increase in patients with RA combined with interstitial lung disease, and the specific levels were directly correlated with the disease severity.展开更多
Objectives To study the relationship between alcohol and atherosclerosis (AS). Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imba...Objectives To study the relationship between alcohol and atherosclerosis (AS). Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imbalance of oxidationantioxidation system, oxygen free radical (OFR) and endothelium cell (EC) apoptosis, apoptosis and AS. Results Excessive alcohol could lead to imbalance of oxidation-antioxidation system, and increase OFR, in the meanwhile, OFR could lead to EC apoptosis, which could lead to AS.展开更多
High blood pressure is a significant contributor to premature mortality,resulting in nearly 10 million deaths and over 200 million disabilities worldwide.1 In recent years,hypertension treatment has shifted focus not ...High blood pressure is a significant contributor to premature mortality,resulting in nearly 10 million deaths and over 200 million disabilities worldwide.1 In recent years,hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability(BPV),categorized into very short-term,short-term,and long-term BPV based on the time period of occurrence.2,3 Long-term BPV has emerged as clinically significant,with studies demonstrating its superiority in predicting long-term cardiovascular events,stroke,and mortality compared to short-term variability.Given its association with pre-renal function decline,reducing blood pressure fluctuations is imperative.展开更多
Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively exp...Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy.Methods:Data were collected from seven prospective hospital databases in China from July 2002 to May 2018.Binary logistic regression models were used to predict lymph node metastasis.The cut-off value for LNe was determined using X-tile 3.6.1.Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model.Results:A total of 482 patients were included,of whom 459 had complete overall survival(OS)information.Using the percentile method,the total number of lymph nodes examined(TLNe)was 14-16(40th-60th percentile),and the proportion of patients with lymph node metastasis reached a maximum of 48.1%.Cox multivariate analysis showed that the odds ratio(OR)remained the highest when TLNe was 14-16(OR=3.379,P=0.003).The 3-year and 5-year OS were 85.4% and 77.8%,respectively.Negative lymph nodes examined(NLNe)of≤6 was an independent risk factor for 3-year and 5-year OS(3-year OS 71.1%vs.85.9%,P=0.004;5-year OS 66.3%vs.74.3%,P=0.035).Subgroup analysis for patients with ypN+showed that higher 3-year and 5-year OS were achieved when the TLNe was>10,78.8%vs.54.0%(P=0.005),and 60.8%vs.36.0%(P=0.012),respectively.Patients with ypN0M0 had a higher 5-year OS when the TLNe was>19(P=0.055).Conclusion:The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.展开更多
Background:Lung cancer is the most commonly diagnosed cancer worldwide.Its survival rate can be significantly improved by early screening.Biomarkers based on radiomics features have been found to provide important phy...Background:Lung cancer is the most commonly diagnosed cancer worldwide.Its survival rate can be significantly improved by early screening.Biomarkers based on radiomics features have been found to provide important physiological information on tumors and considered as having the potential to be used in the early screening of lung cancer.In this study,we aim to establish a radiomics model and develop a tool to improve the discrimination between benign and malignant pulmonary nodules.Methods:A retrospective study was conducted on 875 patients with benign or malignant pulmonary nodules who underwent computed tomography(CT)examinations between June 2013 and June 2018.We assigned 612 patients to a training cohort and 263 patients to a validation cohort.Radiomics features were extracted from the CT images of each patient.Least absolute shrinkage and selection operator(LASSO)was used for radiomics feature selection and radiomics score calculation.Multivariate logistic regression analysis was used to develop a classification model and radiomics nomogram.Radiomics score and clinical variables were used to distinguish benign and malignant pulmonary nodules in logistic model.The performance of the radiomics nomogram was evaluated by the area under the curve(AUC),calibration curve and Hosmer-Lemeshow test in both the training and validation cohorts.Results:A radiomics score was built and consisted of 20 features selected by LASSO from 1288 radiomics features in the training cohort.The multivariate logistic model and radiomics nomogram were constructed using the radiomics score and patients’age.Good discrimination of benign and malignant pulmonary nodules was obtained from the training cohort(AUC,0.836;95%confidence interval[CI]:0.793-0.879)and validation cohort(AUC,0.809;95%CI:0.745-0.872).The Hosmer-Lemeshow test also showed good performance for the logistic regression model in the training cohort(P=0.765)and validation cohort(P=0.064).Good alignment with the calibration curve indicated the good performance of the nomogram.Conclusions:The established radiomics nomogram is a noninvasive preoperative prediction tool for malignant pulmonary nodule diagnosis.Validation revealed that this nomogram exhibited excellent discrimination and calibration capacities,suggesting its clinical utility in the early screening of lung cancer.展开更多
Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (...Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS), and subsequent activa-tion of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs), hepatocytes and liver sinusoidal endothelial cells (LSECs). In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for se-vere sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.展开更多
Background: Percutaneous brachytherapy is a valuable method for the treatment of lung cancer and mediastinal lymph nodes metastasis. However, in some of the metastatic lymph nodes in the middle mediastinum, the percu...Background: Percutaneous brachytherapy is a valuable method for the treatment of lung cancer and mediastinal lymph nodes metastasis. However, in some of the metastatic lymph nodes in the middle mediastinum, the percutaneous approach cannot be used safely due to possible damage to surrounding anatomical structures. We established an animal model (group of 12 pigs) to assess the safety and feasibility of computed tomography (CT)-guided vena cava puncture. Methods: Under CT guidance, an 18G needle was used to puncture the anterior wall of the anterior vena cava (AVC) in 12 pigs. The 18G needle was chosen as it is similar in size to the needles employed for clinical application in brachytherapy. The incidence of complications and vital signs was monitored during the procedure. Thoracotomy was performed to remove AVC specimens, which were analyzed for histological evidence of vessel wall damage and repair. Results: Following postoperative enhanced CT, two animals were found to have a small pneumothorax (one being hemopneumothorax). The intraoperative oxygen saturation of both animals was not significantly decreased and was maintained at 93-100%. No animals developed mediastinal hematoma. Preoperative, intraoperative, and postoperative changes in blood pressure, heart rate, hemoglobin, and blood oxygen saturation were not significant. Histological evaluation of AVC specimens showed that by 7 days following the procedure, the endothelial layer was smooth with notable scar repair in the muscularis layer. Conclusions: CT performed after the procedure and histological preparations confirmed the safety of the procedure. This indicates that percutaneous brachytherapy for metastatic middle mediastinal lymph nodes can be carried out via the superior vena cava.展开更多
基金supported by the National Natural Science Foundation of China(No.82272847,82202318,82304417,82303529)The Henan Province Fund for Cultivating Advantageous Disciplines(No.222301420012)+2 种基金Central Plains science and technology innovation leading talent project(No.234200510005)The project tackling of key scientific and technical problems of Henan Provine(No.232102311163)China Postdoctoral Science Foundation(2022TQ0310,2023TQ0307,2023M730971)。
文摘Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.
文摘Background:Interleukin 13 receptor subunit alpha 2(IL13RA2)plays an essential role in the progression of many cancers.However,the role of IL13RA2 in infantile haemangioma(IH)is still unknown.Materials and Methods:IL13RA2 expression in IH tissues was analyzed using western blot,qRT-PCR,and immunofluorescence.The role of IL13RA2 in haemangioma-derived endothelial cells(HemECs)was determined following knockdown or overexpression of IL13RA2 using CCK-8,colony formation,apoptosis,wound healing,tubule formation,Transwell,and western blot.Results:IL13RA2 expression was upregulated in IH tissues.IL13RA2 overexpression promoted proliferation,migration,and invasion of HemECs and induced glycolysis,which was confirmed with a glycolysis inhibitor.Specifically,IL13RA2 interacted withβ-catenin and activated the Wnt/β-catenin pathway in HemECs,which were involved in the above-mentioned effects of IL13RA2.Conclusions:These findings revealed that targeting IL13RA2 is a potential therapeutic approach for IH.
基金Supported by National Natural Science Foundation of China,No.81130035the National Basic Research Program of China,No.2012CB518102
文摘Acute liver failure(ALF)is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver.The causes of ALF encompass a wide variety of toxic,viral,metabolic,vascular and autoimmune insults to the liver,and identifying the correct cause can be difficult or even impossible.Many patients with ALF develop a cascade of serious complications involving almost every organ system,and death is mostly due to multi-organ failure,hemorrhage,infection,and intracranial hypertension.Fortunately,the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology,and the advanced intensive care management.For most severely affected patients who fail to recover after treatment,rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop.This review focuses on the recent advances in the understanding of various contributing etiologies,the administration of etiology-specific treatment to alleviate the liver injury,and the management of complications(e.g.,encephalopathy,coagulopathy,cardiovascular instability,respiratory failure,renal failure,sepsis and metabolic disturbance)in patients with ALF.Assessment of the need for liver transplantation is also presented.
文摘AIM:To confirm the role of angiopoietin-like protein 8(Angptl 8) in proliferative diabetic retinopathy(PDR).METHODS:The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy(NDR) patients(idiopathic macular hole patients) were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay(ELISA).Experimental diabetes mice model was induced with streptozotocin.The expression of glycosylated hemoglobin and Angptl 8 in sera was detected.Recombinant Angptl 8 was re-infused into wild type(WT) diabetic mice and spatial frequency threshold and contrast sensitivity were measured.In vitro retinal pigment epithelium(RPE) were stimulated by recombinant Angptl 8 for 24 h.MMT assay were used to detect cell proliferation.At the same time,q RT-PCR and Western blot was used to measure the expression of proliferation-related factors in PRE cells.RESULTS:The expression of Angptl 8 was markedly increased in the sera and aqueous humor of PDR patients(F=99.02,P〈0.0001 in sera;t=10.42,P〈0.0001 in aqueous).After successfully establishing the diabetic mice model,we found that glycosylated hemoglobin and Angptl 8 expression levels were increased.Re-infusion of recombinant Angptl 8 into WT diabetic mice could further decrease spatial frequency threshold and contrast sensitivity(P〈0.01).In vitro,RPE cells stimulated by recombinant Angptl 8could increase the relative absorbance of MMT assay(1.486±0.042 vs 1.000±0.104,P〈0.05) and proliferating cell nuclear antigen(PCNA) expression(0.55±0.01 vs 0.29±0.03,P〈0.05).The proliferative effect of Angptl 8 is mainly mediated by increasing the expression of proliferation-activating factors cyclin A1(4.973±0.205 vs 2.720±0.197,P〈0.05),cyclin F(5.690±0.219 vs 4.297±0.292,P〈0.05) and E2 F2(2.297±0.102 vs 1.750±0.146,P〈0.05),and reducing the expression of proliferation-inhibiting factors cdkn1(2.370±0.074 vs 3.317±0.135,P〈0.05) and cdkn2(4.793±0.065 vs 5.387±0.149,P〈0.05).CONCLUSION:The expression of Angptl 8 is increased in PDR,and the increased Angptl 8 can promote proliferation and increase proliferation-related factors.
文摘BACKGROUND: Numerous studies use fluorescent microscopy to obtain two-dimensional optical images of the morphology of nerve fibers in hypertrophic scars. In addition, current confocal microscopy studies have focused on normal, not pathological, cutaneous nerves. However, laser scanning confocal microscopy results in a three-dimensional structure of the nerve fibers. OBJECTIVE: To observe quantitative and morphological differences in nerve fibers from the proliferative and mature stage in hypertrophic scars using fluorescent and confocal microscopy. DESIGN, TIME AND SETTING: Neuropathological, comparison study was conducted at the Provincial Hospital Affiliated to Shandong University, China from June 2006 to July 2007. PARTICIPANTS: Specimens were selected from 30 patients undergoing scar restoration at the Provincial Hospital Affiliated to Shandong University of China at 1 month to 23 years following wound healing. The study comprised 20 males and 10 females. The scars were fibrous lesions, erythematous, tough, confined to skin lesions, did not exhibit ulceration or infection, exhibited telangiectasia, with or without itching and pain, and were not locally treated. Samples were equally assigned to two groups according to course of disease: proliferative group (〈 6 months) and mature group (6-24 months). Control samples were collected from full-thickness skin from donor sites (n = 10). METHODS: Nerve fiber morphology was observed using fluorescent and confocal microscopy following immunofluorescence of the skin specimens. The microscopic images were semi-quantitatively analyzed to acquire a positive area ratio of neurofilament protein-positive nerve fibers. MAIN OUTCOME MEASURES: Morphology and positive area ratio of neurofilament protein/positive nerve fibers was measured. RESULTS: The positive area ratio of neurofilament protein-positive nerve fibers was significantly greater in the proliferative group compared to the normal control group (P 〈 0.05). Nerve fibers were irregularly distributed and exhibited local swelling, twisting, and disconnection. However, the positive area ratio of neurofilament protein-positive nerve fibers was significantly less in the mature group compared with the normal control group (P 〈 0.05). The nerve fibers were arranged in an orderly manner, with intact inner and stereoscopic structures similar to normal skin. CONCLUSION: Compared with mature scars, hypertrophic scars exhibited a greater number of nerve fibers, with more serious pathologies.
基金the Natural Science Foundation of Shandong Province, No.Y2002C29
文摘Burn wound healing involves a complex sequence of processes. Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair. Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers. The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody, and three-dimensional morphology was observed under a laser scanning confocal microscope. Morphology and the volume fraction of collagen and nerve fibers were measured. Skin reinnervation increased during wound healing, peaked during the proliferative scar stage, and then decreased to lower levels during the maturation period. The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis. Disintegration and fragmentation were observed frequently in samples from the proliferative stage, and seldom occurred during the maturation stage. There was a remodeling process of regenerated nerve fibers during wound healing, which comprised changed innervation density and topical morphology. The mechanism of remodeling for nerve fibers requires further investigation.
文摘Although the surgical treatment is a relatively effective and predictable method for correcting residual or recurrent strabismus, such as posterior fixation sutures,medial rectus marginal myotomy, unilateral or bilateral rectus re-recession and resection, unilateral lateral rectus recession and adjustable suture, no standard protocol is established for the surgical style. Different surgical approaches have been recommended for correcting residual or recurrent strabismus. The choice of the surgical procedure depends on the former operation pattern and the surgical dosages applied on the patients, residual or recurrent angle of deviation and the operator’s preference and experience. This review attempts to outline recent publications and current opinion in the management of residual or recurrent esotropia and exotropia.
文摘In percutaneous coronary intervention (PCI), chronic total occlusion (CTO) coronary artery disease still remains difficult to treat. One of the reasons for the failure is the hard of the CTO lesions that balloon is difficult to pass through or expand. Previous methods to deal with CTO lesions that cannot be passed by balloon, include selecting reinforced catheter (such as 5 in 6 guiding catheter, Guidzilla catheter, or Tornus microcatheter), guidewire extrusion or rotary grinding technology. In recent years, excimer laser coronary angioplasty (ELCA) has been gradually applied to CTO lesions. Using inert halide as the laser medium, ELCA emits a 308 nm high-intensity unidirectional light wave with absorption depth of only 50 μmL, resulting in less thermal effect and less damage to non-target lesions. In this paper, we will describe a successful PCI case of an in-stent CTO lesion using ELCA with long term coronary angiography follow-up.
文摘BACKGROUND Coronavirus disease 2019(COVID-19)is a public health emergency of international concern.The global population lacks immunity to COVID-19 and is generally susceptible.Underlying conditions,especially chronic respiratory diseases,may affect progression,treatment and prognosis of COVID-19.CASE SUMMARY We report a patient with confirmed COVID-19 combined with asthma.It took 41 d from disease onset to discharge to obtain two negative tests for this coronavirus.CONCLUSION This case indicates the dynamic clinical characteristics,laboratory and computed tomography findings and adjustment of treatment,and the possible relationship between glucocorticoid therapy and coronavirus clearance.
基金The Major PLA Research Project of "The 12th Five-Year Plan" for Medical Science Development under contract No.BWS12J014the Primary Research & Development Plan of Shandong Province under contract No.2016GSF121036
文摘Vibrio vulnificus is an estuarine bacterial pathogen for human.The rapid,specific and sensitive detection of V.vulnificus is urgently needed for early disease diagnosis and timely treatment of V.vulnificus infection.In the study,a loop-mediated isothermal amplification(LAMP) technique was developed for V.vulnificus detection with a set of primers,composed of two out primers and two inner primers targeted to vvh A gene.The optimal amplification temperature was 63°C and the reaction only took 35 min.The amplification products could not only be detected by agarose gel electrophoresis with ladder-like pattern bands,but also could be visualized using calcein with naked eye directly.Forty-five strains were tested for the specificity of LAMP assay,and all the V.vulnificus strains were identified correctly while other strains were negative results.The sensitive of the new LAMP assay was 100-fold more sensitive than the conventional PCR.Meanwhile,all the V.vulnificus strains were detected correctly in spiked,clinical and environmental samples by the new LAMP assay.Compared with other well-known techniques,the new LAMP assay targeted to vvh A gene was extremely rapid,simple,sensitive and specific for V.vulnificus identification.
基金This work was supported by the National Natural Science Foundation of China(Grant No.31801117 to Dr.X.Li and 82073287 to Dr.Zhang)the Program for Changjiang Scholars and Innovative Research Team in University in China(Grant No.IRT_14R40 to Dr.K.Chen)the Chinese National Key Research and Development Project(Grant No.2018YFC1315601).
文摘Objective:Large volume radiological text data have been accumulated since the incorporation of electronic health record(EHR)systems in clinical practice.We aimed to determine whether deep natural language processing algorithms could aid radiologists in improving thyroid cancer diagnosis.Methods:Sonographic EHR data were obtained from the EHR database.Pathological reports were used as the gold standard for diagnosing thyroid cancer.We developed thyroid cancer diagnosis based on natural language processing(THCaDxNLP)to interpret unstructured sonographic text reports for thyroid cancer diagnosis.We used the area under the receiver operating characteristic curve(AUROC)as the primary metric to measure the performance of the THCaDxNLP.We compared the performance of thyroid ultrasound radiologists aided with THCaDxNLP vs.those without THCaDxNLP using 5 independent test sets.Results:We obtained a total number of 788,129 sonographic radiological reports.The number of thyroid sonographic data points was 132,277,18,400 of which were thyroid cancer patients.Among the 5 test sets,the numbers of patients per set were 439,186,82,343,and 171.THCaDxNLP achieved high performance in identifying thyroid cancer patients(the AUROC ranged from 0.857–0.932).Thyroid ultrasound radiologists aided with THCaDxNLP achieved significantly higher performances than those without THCaDxNLP in terms of accuracy(93.8%vs.87.2%;one-sided t-test,adjusted P=0.003),precision(92.5%vs.86.0%;P=0.018),and F1 metric(94.2%vs.86.4%;P=0.007).Conclusions:THCaDxNLP achieved a high AUROC for the identification of thyroid cancer,and improved the accuracy,sensitivity,and precision of thyroid ultrasound radiologists.This warrants further investigation of THCaDxNLP in prospective clinical trials.
文摘Objective: To investigate the changes and clinical significance of serum tumor markers in patients with rheumatoid arthritis (RA) combined with interstitial lung disease. Methods:A total of 50 healthy volunteers were chosen as the normal control group, 47 patients with rheumatoid arthritis alone were chosen as the RA group, and 28 patients with rheumatoid arthritis combined with interstitial lung disease were chosen as combined disease group. The differences in the levels of serum tumor markers, RA markers and inflammatory mediators were compared among the three groups, and Pearson test was used to evaluate the correlation of serum tumor marker levels with RA markers and inflammatory mediators in patients with RA combined with interstitial lung disease. Results: Serum tumor markers CA199, CA153 and CEA levels of combined disease group were higher than those of RA group;RA markers RF and GPI levels were higher than those of RA group whereas CCP and AKA levels were not significantly different from those of RA group;inflammatory mediators HMGB1, GM-CSF, IL-6, IL-17 and IL-27 levels were higher than those of RA group. Correlation analysis showed that serum tumor markers CA199, CA153 and CEA levels in patients with RA combined with interstitial lung disease were positively correlated with RF, GPI, HMGB1, GM-CSF, IL-6, IL-17 and IL-27 levels. Conclusion: Serum tumor markers CA199, CA153 and CEA levels abnormally increase in patients with RA combined with interstitial lung disease, and the specific levels were directly correlated with the disease severity.
文摘Objectives To study the relationship between alcohol and atherosclerosis (AS). Methods The paper reviewed the mechanism of the alcohol leading to AS from four aspects such as the introduction of alcohol and AS, imbalance of oxidationantioxidation system, oxygen free radical (OFR) and endothelium cell (EC) apoptosis, apoptosis and AS. Results Excessive alcohol could lead to imbalance of oxidation-antioxidation system, and increase OFR, in the meanwhile, OFR could lead to EC apoptosis, which could lead to AS.
基金Leading Talents Plan,Beijing Municipal Health Commission(Beijing,China),Grant/Award Number:LJRC20240306。
文摘High blood pressure is a significant contributor to premature mortality,resulting in nearly 10 million deaths and over 200 million disabilities worldwide.1 In recent years,hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability(BPV),categorized into very short-term,short-term,and long-term BPV based on the time period of occurrence.2,3 Long-term BPV has emerged as clinically significant,with studies demonstrating its superiority in predicting long-term cardiovascular events,stroke,and mortality compared to short-term variability.Given its association with pre-renal function decline,reducing blood pressure fluctuations is imperative.
文摘Background:The number of lymph nodes examined(LNe)is often insufficient in patients with rectal cancer(RC)treated with neoadjuvant therapy;however,its prognostic value remains controversial.Thus,we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy.Methods:Data were collected from seven prospective hospital databases in China from July 2002 to May 2018.Binary logistic regression models were used to predict lymph node metastasis.The cut-off value for LNe was determined using X-tile 3.6.1.Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model.Results:A total of 482 patients were included,of whom 459 had complete overall survival(OS)information.Using the percentile method,the total number of lymph nodes examined(TLNe)was 14-16(40th-60th percentile),and the proportion of patients with lymph node metastasis reached a maximum of 48.1%.Cox multivariate analysis showed that the odds ratio(OR)remained the highest when TLNe was 14-16(OR=3.379,P=0.003).The 3-year and 5-year OS were 85.4% and 77.8%,respectively.Negative lymph nodes examined(NLNe)of≤6 was an independent risk factor for 3-year and 5-year OS(3-year OS 71.1%vs.85.9%,P=0.004;5-year OS 66.3%vs.74.3%,P=0.035).Subgroup analysis for patients with ypN+showed that higher 3-year and 5-year OS were achieved when the TLNe was>10,78.8%vs.54.0%(P=0.005),and 60.8%vs.36.0%(P=0.012),respectively.Patients with ypN0M0 had a higher 5-year OS when the TLNe was>19(P=0.055).Conclusion:The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.
基金Key R&D project of Shandong Province,Grant/Award Number:2018GSF118152
文摘Background:Lung cancer is the most commonly diagnosed cancer worldwide.Its survival rate can be significantly improved by early screening.Biomarkers based on radiomics features have been found to provide important physiological information on tumors and considered as having the potential to be used in the early screening of lung cancer.In this study,we aim to establish a radiomics model and develop a tool to improve the discrimination between benign and malignant pulmonary nodules.Methods:A retrospective study was conducted on 875 patients with benign or malignant pulmonary nodules who underwent computed tomography(CT)examinations between June 2013 and June 2018.We assigned 612 patients to a training cohort and 263 patients to a validation cohort.Radiomics features were extracted from the CT images of each patient.Least absolute shrinkage and selection operator(LASSO)was used for radiomics feature selection and radiomics score calculation.Multivariate logistic regression analysis was used to develop a classification model and radiomics nomogram.Radiomics score and clinical variables were used to distinguish benign and malignant pulmonary nodules in logistic model.The performance of the radiomics nomogram was evaluated by the area under the curve(AUC),calibration curve and Hosmer-Lemeshow test in both the training and validation cohorts.Results:A radiomics score was built and consisted of 20 features selected by LASSO from 1288 radiomics features in the training cohort.The multivariate logistic model and radiomics nomogram were constructed using the radiomics score and patients’age.Good discrimination of benign and malignant pulmonary nodules was obtained from the training cohort(AUC,0.836;95%confidence interval[CI]:0.793-0.879)and validation cohort(AUC,0.809;95%CI:0.745-0.872).The Hosmer-Lemeshow test also showed good performance for the logistic regression model in the training cohort(P=0.765)and validation cohort(P=0.064).Good alignment with the calibration curve indicated the good performance of the nomogram.Conclusions:The established radiomics nomogram is a noninvasive preoperative prediction tool for malignant pulmonary nodule diagnosis.Validation revealed that this nomogram exhibited excellent discrimination and calibration capacities,suggesting its clinical utility in the early screening of lung cancer.
基金the National Natural Science Foundation(81130035, 81372054, 81272090, 81121004)the National Basic Research Program of China(2012CB518102)the Medical Research Foundation of Chinese PLA(AWS11J008, BWS12J050)
文摘Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS), and subsequent activa-tion of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs), hepatocytes and liver sinusoidal endothelial cells (LSECs). In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for se-vere sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.
文摘Background: Percutaneous brachytherapy is a valuable method for the treatment of lung cancer and mediastinal lymph nodes metastasis. However, in some of the metastatic lymph nodes in the middle mediastinum, the percutaneous approach cannot be used safely due to possible damage to surrounding anatomical structures. We established an animal model (group of 12 pigs) to assess the safety and feasibility of computed tomography (CT)-guided vena cava puncture. Methods: Under CT guidance, an 18G needle was used to puncture the anterior wall of the anterior vena cava (AVC) in 12 pigs. The 18G needle was chosen as it is similar in size to the needles employed for clinical application in brachytherapy. The incidence of complications and vital signs was monitored during the procedure. Thoracotomy was performed to remove AVC specimens, which were analyzed for histological evidence of vessel wall damage and repair. Results: Following postoperative enhanced CT, two animals were found to have a small pneumothorax (one being hemopneumothorax). The intraoperative oxygen saturation of both animals was not significantly decreased and was maintained at 93-100%. No animals developed mediastinal hematoma. Preoperative, intraoperative, and postoperative changes in blood pressure, heart rate, hemoglobin, and blood oxygen saturation were not significant. Histological evaluation of AVC specimens showed that by 7 days following the procedure, the endothelial layer was smooth with notable scar repair in the muscularis layer. Conclusions: CT performed after the procedure and histological preparations confirmed the safety of the procedure. This indicates that percutaneous brachytherapy for metastatic middle mediastinal lymph nodes can be carried out via the superior vena cava.