BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still...BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.展开更多
Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,di...Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.展开更多
BACKGROUND Drug-eluting beads transarterial chemoem-bolization(DEB-TACE)has the advantages of slow and steady release,high local concentration,and low incidence of adverse drug reactions compared to the traditional TA...BACKGROUND Drug-eluting beads transarterial chemoem-bolization(DEB-TACE)has the advantages of slow and steady release,high local concentration,and low incidence of adverse drug reactions compared to the traditional TACE.DEBTACE combined with sequentially ultrasound-guided radiofrequency ablation(RFA)therapy has strong anti-cancer effects and little side effects,but there are fewer related long-term studies until now.AIM To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma(HCC).METHODS Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited.Forty patients with untreated HCC were included in Group A,and 36 patients with recurrent HCC were included in Group B.In addition,40 patients with untreated HCC who were treated with hepatectomy were included in Group C.The serological examination,preoperative magnetic resonance imaging examination,and post-treatment computed tomography enhanced examination were performed for all patients.The efficacy was graded as complete remission(CR),partial remission(PR),stable disease and progressive disease at the 3rd,6th,and 9th.All patients were followed up for 3 years and their overall survival(OS),disease-free survival(DFS)were assessed.RESULTS The efficacy of Group A and Group C was similar(P>0.05),but the alanine aminotransferase,aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C(all P<0.05).The proportions of CR(32.5%),PR(37.5%)were slightly higher than Group A(CR:27.5%,PR:35%),but the difference was not statistically significant(χ2=0.701,P=0.873).No operationalrelated deaths occurred in Group A and Group C.The OS(97.5%,84.7%,and 66.1%)and the DFS(75.0%,51.7%,and 35.4%)of Group A at the 1st,2nd,and 3rd year after treatment were similar with those of Group C(OS:90.0%,79.7%,and 63.8%;DFS:80.0%,59.7%,and 48.6%;P>0.05).The OS rates in Group A and Group B(90%,82.3%,and 66.4%)were similar(P>0.05).The DFS rates in Group B(50%,31.6%,and 17.2%)were lower than that of Group A(P=0.013).CONCLUSION The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy.Patients with recurrent HCC could get a longer survival time through the combined treatment.展开更多
AIM:To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and oridonin on choroidal melanoma cell lines,and to explore its underlying mechanism.METHO...AIM:To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and oridonin on choroidal melanoma cell lines,and to explore its underlying mechanism.METHODS:MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin,and MTT assay used to evaluate the inhibition rate of the two compounds on cells.Then,the cell cycle distribution and apoptosis were detected by flow cytometry,and changes in apoptosis-related proteins such as death receptor 5(DR5),a-caspase-3,and x-linked inhibitor of apoptosis protein(XIAP)were detected by Western blot.MUM-2B cells were transfected with si-DR5,which interfered with the expression of the DR5 gene.MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins.RESULTS:When TRAIL and oridonin were simultaneously administered to the MUM-2B cells,the apoptosis rate was significantly higher than that by the two drugs individually.However,the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone.Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells.The Western blot results showed that the protein expression levels of the DR5,a-caspase-3,and BAX increased,while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells.Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells.CONCLUSION:The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment,which may ascribe to up-regulation of DR5.展开更多
BACKGROUND The incidence rate of breast cancer has exceeded that of lung cancer,and it has become the most malignant type of cancer in the world.BI-RADS 4 breast nodules have a wide range of malignant risks and are as...BACKGROUND The incidence rate of breast cancer has exceeded that of lung cancer,and it has become the most malignant type of cancer in the world.BI-RADS 4 breast nodules have a wide range of malignant risks and are associated with challenging clinical decision-making.AIM To explore the diagnostic value of artificial intelligence(AI)automatic detection systems for BI-RADS 4 breast nodules and to assess whether conventional ultrasound BI-RADS classification with AI automatic detection systems can reduce the probability of BI-RADS 4 biopsy.METHODS A total of 107 BI-RADS breast nodules confirmed by pathology were selected between June 2019 and July 2020 at Hwa Mei Hospital,University of Chinese Academy of Sciences.These nodules were classified by ultrasound doctors and the AI-SONIC breast system.The diagnostic values of conventional ultrasound,the AI automatic detection system,conventional ultrasound combined with the AI automatic detection system and adjusted BI-RADS classification diagnosis were statistically analyzed.RESULTS Among the 107 breast nodules,61 were benign(57.01%),and 46 were malignant(42.99%).The pathology results were considered the gold standard;furthermore,the sensitivity,specificity,accuracy,Youden index,and positive and negative predictive values were 84.78%,67.21%,74.77%,0.5199,66.10%and 85.42%for conventional ultrasound BI-RADS classification diagnosis,86.96%,75.41%,80.37%,0.6237,72.73%,and 88.46%for automatic AI detection,80.43%,90.16%,85.98%,0.7059,86.05%,and 85.94%for conventional ultrasound BI-RADS classification with automatic AI detection and 93.48%,67.21%,78.50%,0.6069,68.25%,and 93.18%for adjusted BI-RADS classification,respectively.The biopsy rate,cancer detection rate and malignancy risk were 100%,42.99%and 0%and 67.29%,61.11%,and 1.87%before and after BI-RADS adjustment,respectively.CONCLUSION Automatic AI detection has high accuracy in determining benign and malignant BI-RADS 4 breast nodules.Conventional ultrasound BI-RADS classification combined with AI automatic detection can reduce the biopsy rate of BI-RADS 4 breast nodules.展开更多
Targeted immune checkpoint-based immunotherapy has achieved remarkable success in the treatment of malignant tumors.Immune checkpoint inhibitor-programmed cell death protein 1(PD-1)antibody opens a new era of immunoth...Targeted immune checkpoint-based immunotherapy has achieved remarkable success in the treatment of malignant tumors.Immune checkpoint inhibitor-programmed cell death protein 1(PD-1)antibody opens a new era of immunotherapy for platinum-refractory recurrent/metastatic oral squamous cell carcinoma(OSCC).The overall survival of patients treated with immunological checkpoint inhibitors was significantly prolonged,and the overall incidence of grade 3-4 drug-related adverse events(AEs)occurred was lower;however,there are still some challenges to the PD-1’s application in OSCC clinic treatment.This article is just to briefly highlight the development of such application to date.展开更多
Tissue injury leads to gradients of chemoattractants,which drive multiple processes for tissue repair,including the inflam-matory response as well as endogenous cell recruitment.However,a limited time window for the g...Tissue injury leads to gradients of chemoattractants,which drive multiple processes for tissue repair,including the inflam-matory response as well as endogenous cell recruitment.However,a limited time window for the gradients of chemoattract-ants as well as their poor stability at the injury site may not translate into healthy tissue repair.Consequently,intelligent multifunctional scaffolds with the capability to stabilize injury-induced cytokines and chemokines hold great promise for tissue repair.Vascular endothelial growth factor(VEGF)plays a significant role in wound healing by promoting angiogen-esis.The overarching objective of this research was to develop intelligent multifunctional scaffolds with the capability to endogenously recruit VEGF and promote wound healing via angiogenic and immunomodulatory dual functions.Prominin-1-derived peptide(PR1P)was encapsulated into electrospun poly(L-lactide-coglycolide)/gelatin(P/G)-based bandages.The sustained release of PR1P recruited VEGF in situ,thereby stabilizing the protein concentration peak in vivo and affording a reparative microenvironment with an adequate angiogenic ability at the wound site.Meanwhile,PR1P-recruited VEGF-induced macrophage reprogramming towards M2-like phenotypes further conferred immunomodulatory functions to the bandages.These dual functions of proangiogenesis and immunomodulation formed a cascade amplification,which regulated matrix metalloproteinases(MMP-9)as well as inflammatory factors(nuclear factor(NF)-κb,tumor necrosis factor(TNF)-α)in the wound microenvironment via the VEGF/macrophages/microenvironment axis.Consequently,the bandages realized multifunctional regeneration in splinted excisional wounds in rats,with or without diabetes,affording a higher skin append-age neogenesis,sensory function,and collagen remodeling.Conclusively,our approach encompassing in situ recruitment of VEGF at the injury site with the capability to promote immunomodulation-mediated tissue repair affords a promising avenue for scarless wound regeneration,which may also have implications for other tissue engineering disciplines.展开更多
Correction to:Advanced Fiber Materials https://doi.org/10.1007/s42765-022-00226-8 In this article the author name Muhammad Shafiq was incorrectly written as Shafiq Muhammad.The original article has been corrected.
Cohort studies are costly and time consuming.They require not only laboratory equipment and assays but also collaboration from participants and health agencies.Due to cost constraints,they are often confined to a spec...Cohort studies are costly and time consuming.They require not only laboratory equipment and assays but also collaboration from participants and health agencies.Due to cost constraints,they are often confined to a specific population.Nevertheless,they play a crucial role in providing fundamental insights for medical advancements,shedding light on the origins of diseases,and acting in socioeconomic influence in policy making.展开更多
Predictive models for assessing the risk of developing lung cancers can help identify high-risk individuals with the aim of recommending further screening and early intervention.To facilitate pre-hospital self-assessm...Predictive models for assessing the risk of developing lung cancers can help identify high-risk individuals with the aim of recommending further screening and early intervention.To facilitate pre-hospital self-assessments,some studies have exploited predictive models trained on non-clinical data(e.g.,smoking status and family history).The performance of these models is limited due to not considering clinical data(e.g.,blood test and medical imaging results).Deep learning has shown the potential in processing complex data that combine both clinical and non-clinical information.However,predicting lung cancers remains difficult due to the severe lack of positive samples among follow-ups.To tackle this problem,this paper presents a generative-discriminative framework for improving the ability of deep learning models to generalize.According to the proposed framework,two nonlinear generative models,one based on the generative adversarial network and another on the variational autoencoder,are used to synthesize auxiliary positive samples for the training set.Then,several discriminative models,including a deep neural network(DNN),are used to assess the lung cancer risk based on a comprehensive list of risk factors.The framework was evaluated on over 55000 subjects questioned between January 2014 and December 2017,with 699 subjects being clinically diagnosed with lung cancer between January 2014 and August 2019.According to the results,the best performing predictive model built using the proposed framework was based on DNN.It achieved an average sensitivity of 76.54%and an area under the curve of 69.24%in distinguishing between the cases of lung cancer and normal cases on test sets.展开更多
Cancer therapeutic nanovaccines are ideal tools to inhibit tumor growth and provide the body with continuous protecting immune surveillance.However,the conventional subcutaneous(SC)vaccination normally induces limited...Cancer therapeutic nanovaccines are ideal tools to inhibit tumor growth and provide the body with continuous protecting immune surveillance.However,the conventional subcutaneous(SC)vaccination normally induces limited anti-tumor immune responses with low therapeutic efficacy.Herein,we devised clay-based nanovaccines and directly delivered them to the spleen via intravenous(IV)injection to induce the stronger anti-tumor immunity with higher efficacy for tumor prevention and treatment.The clay,i.e.,layered double hydroxide(LDH)was prepared as nanoadjuvant with the average size from 77 to 285 nm and co-loaded with the model antigen ovalbumin(OVA)and bioadjuvant CpG to form CpG/OVA-LDH(CO-LDH)nanovaccines.We found that CO-LDH-215(the size of LDH was 215 nm)promoted dendritic cells to present the most antigen,and moreover showed the highest spleen enrichment(~1.67%of CO-LDH-215 enriched in the spleen at 24 h post IV injection).The in vivo immunologic data showed that CO-LDH-215 induced the most potent anti-tumor immune responses and completely prevented the growth of E.G7-OVA tumor in the mouse model.Furthermore,IV injected CO-LDH-215 nanovaccine more effectively delayed tumor growth than that SC injected,largely due to the direct and quick delivery of more nanovaccines to the spleen.This study demonstrates that the therapeutic efficacy of nanovaccines can be greatly enhanced by targeted delivery of nanovaccines to the spleen via the proper vaccination route.展开更多
BACKGROUND Ulcerative colitis(UC)is defined as a chronic inflammatory bowel disease that can occur in any part of the large bowel.In addition,UC affects only the large bowel except for backwash ileitis and pouchitis,w...BACKGROUND Ulcerative colitis(UC)is defined as a chronic inflammatory bowel disease that can occur in any part of the large bowel.In addition,UC affects only the large bowel except for backwash ileitis and pouchitis,whereas Crohn’s disease(CD)affects the entire digestive tract.Inflammatory bowel disease(IBD)patients tend to be diagnosed with CD or indeterminate colitis when combined with gastric lesion.However,in recent years,some UC patients are reported to have various degrees of lesions in gastroduodenum.Here,we report a case of gastroduodenitis associated with UC(GDUC).CASE SUMMARY A 25-year-old man with a history of Klippel-Trenaunay syndrome presented to the hospital with mucopurulent bloody stool and epigastric persistent colic pain for 2 wk.Continuous superficial ulcers and spontaneous bleeding were observed under colonoscopy.Subsequent gastroscopy revealed mucosa with diffuse edema,ulcers,errhysis,and granular and friable changes in the stomach and duodenal bulb,which were similar to the appearance of the rectum.After ruling out other possibilities according to a series of examinations,a diagnosis of GDUC was considered.The patient hesitated about intravenous corticosteroids,so he received a standardized treatment with pentasa of 3.2 g/d.After 0.5 mo of treatment,the patient’s symptoms achieved complete remission.Follow-up endoscopy and imaging findings showed no evidence of recurrence for 26 mo.CONCLUSION The occurrence of gastrointestinal involvement in UC is rare,which may open a new window for studying the etiology and pathogenesis of UC.Physicians should consider broad differential diagnosis by endoscopic biopsy and laboratory examinations.展开更多
Dear editor,The neck is rich in blood vessels.Abnormal origins are rarely seen in clinical practice,but some are found accidentally during relevant imaging examinations,autopsy,and surgery.Abnormal neck vessels are mo...Dear editor,The neck is rich in blood vessels.Abnormal origins are rarely seen in clinical practice,but some are found accidentally during relevant imaging examinations,autopsy,and surgery.Abnormal neck vessels are mostly asymptomatic;however,approximately 10%of patients with abnormal blood vessels may have clinical manifestations due to the compression of adjacent tissues and organs.展开更多
Background:The precise and efficient analysis of single-cell transcriptome data provides powerful support for studying the diversity of cell functions at the single-cell level.The most important and challenging steps ...Background:The precise and efficient analysis of single-cell transcriptome data provides powerful support for studying the diversity of cell functions at the single-cell level.The most important and challenging steps are cell clustering and recognition of cell populations.While the precision of clustering and annotation are considered separately in most current studies,it is worth attempting to develop an extensive and flexible strategy to balance clustering accuracy and biological explanation comprehensively.Methods:The cell marker-based clustering strategy(cmCluster),which is a modified Louvain clustering method,aims to search the optimal clusters through genetic algorithm(GA)and grid search based on the cell type annotation results.Results:By applying cmCluster on a set of single-cell transcriptome data,the results showed that it was beneficial for the recognition of cell populations and explanation of biological function even on the occasion of incomplete cell type information or multiple data resources.In addition,cmCluster also produced clear boundaries and appropriate subtypes with potential marker genes.The relevant code is available in GitHub website(huangyuwei301/cmCluster).Conclusions:We speculate that cmCluster provides researchers effective screening strategies to improve the accuracy of subsequent biological analysis,reduce artificial bias,and facilitate the comparison and analysis of multiple studies.展开更多
基金Supported by the Project of NINGBO Leading Medical Health Discipline,No.2022-B11Ningbo Natural Science Foundation,No.202003N4206Public Welfare Foundation of Ningbo,No.2021S108.
文摘BACKGROUND Colorectal cancer(CRC)is a serious threat worldwide.Although early screening is suggested to be the most effective method to prevent and control CRC,the current situation of early screening for CRC is still not optimistic.In China,the incidence of CRC in the Yangtze River Delta region is increasing dramatically,but few studies have been conducted.Therefore,it is necessary to develop a simple and efficient early screening model for CRC.AIM To develop and validate an early-screening nomogram model to identify individuals at high risk of CRC.METHODS Data of 64448 participants obtained from Ningbo Hospital,China between 2014 and 2017 were retrospectively analyzed.The cohort comprised 64448 individuals,of which,530 were excluded due to missing or incorrect data.Of 63918,7607(11.9%)individuals were considered to be high risk for CRC,and 56311(88.1%)were not.The participants were randomly allocated to a training set(44743)or validation set(19175).The discriminatory ability,predictive accuracy,and clinical utility of the model were evaluated by constructing and analyzing receiver operating characteristic(ROC)curves and calibration curves and by decision curve analysis.Finally,the model was validated internally using a bootstrap resampling technique.RESULTS Seven variables,including demographic,lifestyle,and family history information,were examined.Multifactorial logistic regression analysis revealed that age[odds ratio(OR):1.03,95%confidence interval(CI):1.02-1.03,P<0.001],body mass index(BMI)(OR:1.07,95%CI:1.06-1.08,P<0.001),waist circumference(WC)(OR:1.03,95%CI:1.02-1.03 P<0.001),lifestyle(OR:0.45,95%CI:0.42-0.48,P<0.001),and family history(OR:4.28,95%CI:4.04-4.54,P<0.001)were the most significant predictors of high-risk CRC.Healthy lifestyle was a protective factor,whereas family history was the most significant risk factor.The area under the curve was 0.734(95%CI:0.723-0.745)for the final validation set ROC curve and 0.735(95%CI:0.728-0.742)for the training set ROC curve.The calibration curve demonstrated a high correlation between the CRC high-risk population predicted by the nomogram model and the actual CRC high-risk population.CONCLUSION The early-screening nomogram model for CRC prediction in high-risk populations developed in this study based on age,BMI,WC,lifestyle,and family history exhibited high accuracy.
基金financially supported by National Natural Science Foundation of China(32171035)the major fund project of Ningbo Science and Technology Bureau(2019B10034)+4 种基金Opened-end Fund of Key Laboratory(KFJJ-202101,ZPKLP202202)Public Project of Ningbo(202002N3167)Project of Yinzhou(2022AS025)Ningbo Rehabilitation Hospital(2022KY02)sponsored by a K.C.Wong Magna Fund in Ningbo University。
文摘Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.
基金Supported by Medical and Health Science and Technology Foundation of Zhejiang Province,No.2017KY590 and No.2019KY175and Ningbo Clinical Research Center for Digestive System Tumors,No.2019A21003.
文摘BACKGROUND Drug-eluting beads transarterial chemoem-bolization(DEB-TACE)has the advantages of slow and steady release,high local concentration,and low incidence of adverse drug reactions compared to the traditional TACE.DEBTACE combined with sequentially ultrasound-guided radiofrequency ablation(RFA)therapy has strong anti-cancer effects and little side effects,but there are fewer related long-term studies until now.AIM To explore the outcome of DEB-TACE sequentially combined with RFA for patients with primary hepatocellular carcinoma(HCC).METHODS Seventy-six patients with primary HCC who underwent DEB-TACE sequentially combined with RFA were recruited.Forty patients with untreated HCC were included in Group A,and 36 patients with recurrent HCC were included in Group B.In addition,40 patients with untreated HCC who were treated with hepatectomy were included in Group C.The serological examination,preoperative magnetic resonance imaging examination,and post-treatment computed tomography enhanced examination were performed for all patients.The efficacy was graded as complete remission(CR),partial remission(PR),stable disease and progressive disease at the 3rd,6th,and 9th.All patients were followed up for 3 years and their overall survival(OS),disease-free survival(DFS)were assessed.RESULTS The efficacy of Group A and Group C was similar(P>0.05),but the alanine aminotransferase,aspartate aminotransferase and total bilirubin of Group A were lower than those of Group C(all P<0.05).The proportions of CR(32.5%),PR(37.5%)were slightly higher than Group A(CR:27.5%,PR:35%),but the difference was not statistically significant(χ2=0.701,P=0.873).No operationalrelated deaths occurred in Group A and Group C.The OS(97.5%,84.7%,and 66.1%)and the DFS(75.0%,51.7%,and 35.4%)of Group A at the 1st,2nd,and 3rd year after treatment were similar with those of Group C(OS:90.0%,79.7%,and 63.8%;DFS:80.0%,59.7%,and 48.6%;P>0.05).The OS rates in Group A and Group B(90%,82.3%,and 66.4%)were similar(P>0.05).The DFS rates in Group B(50%,31.6%,and 17.2%)were lower than that of Group A(P=0.013).CONCLUSION The efficacy of DEA-TACE combined with RFA for untreated HCC is similar with hepatectomy.Patients with recurrent HCC could get a longer survival time through the combined treatment.
基金Ningbo Leader and Top Notch Person Training Project(No.20150012).
文摘AIM:To investigate the inhibitory effect of the combined use of tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)and oridonin on choroidal melanoma cell lines,and to explore its underlying mechanism.METHODS:MUM-2B and C918 cells were treated with different concentrations of TRAIL and oridonin,and MTT assay used to evaluate the inhibition rate of the two compounds on cells.Then,the cell cycle distribution and apoptosis were detected by flow cytometry,and changes in apoptosis-related proteins such as death receptor 5(DR5),a-caspase-3,and x-linked inhibitor of apoptosis protein(XIAP)were detected by Western blot.MUM-2B cells were transfected with si-DR5,which interfered with the expression of the DR5 gene.MTT and Western blot assay were used to detect cell activity and apoptosis-related proteins.RESULTS:When TRAIL and oridonin were simultaneously administered to the MUM-2B cells,the apoptosis rate was significantly higher than that by the two drugs individually.However,the effect of combined use of TRAIL and oridonin on C918 cells was not significantly different from that used alone.Cell cycle analysis showed that TRAIL and oridonin could induce G2/M arrest in MUM-2B cells.The Western blot results showed that the protein expression levels of the DR5,a-caspase-3,and BAX increased,while the expression levels of the anti-apoptosis-related proteins XIAP and BCL-2 were suppressed when TRAIL and oridonin simultaneously administered to MUM-2B cells.Interfering the expression of DR5 gene in MUM-2B cells could reverse the inhibitory effect of oridonin and TRAIL on the proliferation and apoptosis induction of MUM-2B cells.CONCLUSION:The inhibitory effects of oridonin and TRAIL on MUM-2B cells are significantly enhanced when they were administered as a combined treatment,which may ascribe to up-regulation of DR5.
文摘BACKGROUND The incidence rate of breast cancer has exceeded that of lung cancer,and it has become the most malignant type of cancer in the world.BI-RADS 4 breast nodules have a wide range of malignant risks and are associated with challenging clinical decision-making.AIM To explore the diagnostic value of artificial intelligence(AI)automatic detection systems for BI-RADS 4 breast nodules and to assess whether conventional ultrasound BI-RADS classification with AI automatic detection systems can reduce the probability of BI-RADS 4 biopsy.METHODS A total of 107 BI-RADS breast nodules confirmed by pathology were selected between June 2019 and July 2020 at Hwa Mei Hospital,University of Chinese Academy of Sciences.These nodules were classified by ultrasound doctors and the AI-SONIC breast system.The diagnostic values of conventional ultrasound,the AI automatic detection system,conventional ultrasound combined with the AI automatic detection system and adjusted BI-RADS classification diagnosis were statistically analyzed.RESULTS Among the 107 breast nodules,61 were benign(57.01%),and 46 were malignant(42.99%).The pathology results were considered the gold standard;furthermore,the sensitivity,specificity,accuracy,Youden index,and positive and negative predictive values were 84.78%,67.21%,74.77%,0.5199,66.10%and 85.42%for conventional ultrasound BI-RADS classification diagnosis,86.96%,75.41%,80.37%,0.6237,72.73%,and 88.46%for automatic AI detection,80.43%,90.16%,85.98%,0.7059,86.05%,and 85.94%for conventional ultrasound BI-RADS classification with automatic AI detection and 93.48%,67.21%,78.50%,0.6069,68.25%,and 93.18%for adjusted BI-RADS classification,respectively.The biopsy rate,cancer detection rate and malignancy risk were 100%,42.99%and 0%and 67.29%,61.11%,and 1.87%before and after BI-RADS adjustment,respectively.CONCLUSION Automatic AI detection has high accuracy in determining benign and malignant BI-RADS 4 breast nodules.Conventional ultrasound BI-RADS classification combined with AI automatic detection can reduce the biopsy rate of BI-RADS 4 breast nodules.
基金Supported by National Natural Science Foundation of China(81602703)the Natural Science Foundation of Ningbo(2018A610382)。
文摘Targeted immune checkpoint-based immunotherapy has achieved remarkable success in the treatment of malignant tumors.Immune checkpoint inhibitor-programmed cell death protein 1(PD-1)antibody opens a new era of immunotherapy for platinum-refractory recurrent/metastatic oral squamous cell carcinoma(OSCC).The overall survival of patients treated with immunological checkpoint inhibitors was significantly prolonged,and the overall incidence of grade 3-4 drug-related adverse events(AEs)occurred was lower;however,there are still some challenges to the PD-1’s application in OSCC clinic treatment.This article is just to briefly highlight the development of such application to date.
基金Funding National Natural Science Foundation of China,81770091,Chang Chen,NSFC32050410286Shafiq Muhammad,Science and Technology Innovation Plan Of Shanghai Science and Technology Commission,No.20DZ2253700+2 种基金Chang Chen,Japan Society for the Promotion of Science,JP21F21353Shafiq Muhammad,Sino German Science Foundation Research Exchange Center,M-0263Xiumei Mo,Science and Technology Commission of Shanghai Municipality,20S31900900,Xiumei Mo,20DZ2254900,Xiumei Mo.
文摘Tissue injury leads to gradients of chemoattractants,which drive multiple processes for tissue repair,including the inflam-matory response as well as endogenous cell recruitment.However,a limited time window for the gradients of chemoattract-ants as well as their poor stability at the injury site may not translate into healthy tissue repair.Consequently,intelligent multifunctional scaffolds with the capability to stabilize injury-induced cytokines and chemokines hold great promise for tissue repair.Vascular endothelial growth factor(VEGF)plays a significant role in wound healing by promoting angiogen-esis.The overarching objective of this research was to develop intelligent multifunctional scaffolds with the capability to endogenously recruit VEGF and promote wound healing via angiogenic and immunomodulatory dual functions.Prominin-1-derived peptide(PR1P)was encapsulated into electrospun poly(L-lactide-coglycolide)/gelatin(P/G)-based bandages.The sustained release of PR1P recruited VEGF in situ,thereby stabilizing the protein concentration peak in vivo and affording a reparative microenvironment with an adequate angiogenic ability at the wound site.Meanwhile,PR1P-recruited VEGF-induced macrophage reprogramming towards M2-like phenotypes further conferred immunomodulatory functions to the bandages.These dual functions of proangiogenesis and immunomodulation formed a cascade amplification,which regulated matrix metalloproteinases(MMP-9)as well as inflammatory factors(nuclear factor(NF)-κb,tumor necrosis factor(TNF)-α)in the wound microenvironment via the VEGF/macrophages/microenvironment axis.Consequently,the bandages realized multifunctional regeneration in splinted excisional wounds in rats,with or without diabetes,affording a higher skin append-age neogenesis,sensory function,and collagen remodeling.Conclusively,our approach encompassing in situ recruitment of VEGF at the injury site with the capability to promote immunomodulation-mediated tissue repair affords a promising avenue for scarless wound regeneration,which may also have implications for other tissue engineering disciplines.
文摘Correction to:Advanced Fiber Materials https://doi.org/10.1007/s42765-022-00226-8 In this article the author name Muhammad Shafiq was incorrectly written as Shafiq Muhammad.The original article has been corrected.
文摘Cohort studies are costly and time consuming.They require not only laboratory equipment and assays but also collaboration from participants and health agencies.Due to cost constraints,they are often confined to a specific population.Nevertheless,they play a crucial role in providing fundamental insights for medical advancements,shedding light on the origins of diseases,and acting in socioeconomic influence in policy making.
基金supported in part by Zhejiang Provincial Natural Science Foundation of China(LQ20F030013)Research Foundation of Hwa Mei Hospital,University of Chinese Academy of Sciences(2020HMZD22)+1 种基金Ningbo Public Service Technology Foundation(202002N3181)Medical Scientific Research Foundation of Zhejiang Province(2021431314)。
文摘Predictive models for assessing the risk of developing lung cancers can help identify high-risk individuals with the aim of recommending further screening and early intervention.To facilitate pre-hospital self-assessments,some studies have exploited predictive models trained on non-clinical data(e.g.,smoking status and family history).The performance of these models is limited due to not considering clinical data(e.g.,blood test and medical imaging results).Deep learning has shown the potential in processing complex data that combine both clinical and non-clinical information.However,predicting lung cancers remains difficult due to the severe lack of positive samples among follow-ups.To tackle this problem,this paper presents a generative-discriminative framework for improving the ability of deep learning models to generalize.According to the proposed framework,two nonlinear generative models,one based on the generative adversarial network and another on the variational autoencoder,are used to synthesize auxiliary positive samples for the training set.Then,several discriminative models,including a deep neural network(DNN),are used to assess the lung cancer risk based on a comprehensive list of risk factors.The framework was evaluated on over 55000 subjects questioned between January 2014 and December 2017,with 699 subjects being clinically diagnosed with lung cancer between January 2014 and August 2019.According to the results,the best performing predictive model built using the proposed framework was based on DNN.It achieved an average sensitivity of 76.54%and an area under the curve of 69.24%in distinguishing between the cases of lung cancer and normal cases on test sets.
基金This work was financially supported by the International Partnership Program of Chinese Academy of Sciences(No.122111KYSB20180005)the Australian Research Council(ARC)Discovery Project(No.DP190103486)+2 种基金Zhejiang Provincial Natural Science Foundation of China(No.LY19H160011)Ningbo Digestive System Clinical Medicine Research Center(No.2019A21003)We also thank the Support from the Dey Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Povince。
文摘Cancer therapeutic nanovaccines are ideal tools to inhibit tumor growth and provide the body with continuous protecting immune surveillance.However,the conventional subcutaneous(SC)vaccination normally induces limited anti-tumor immune responses with low therapeutic efficacy.Herein,we devised clay-based nanovaccines and directly delivered them to the spleen via intravenous(IV)injection to induce the stronger anti-tumor immunity with higher efficacy for tumor prevention and treatment.The clay,i.e.,layered double hydroxide(LDH)was prepared as nanoadjuvant with the average size from 77 to 285 nm and co-loaded with the model antigen ovalbumin(OVA)and bioadjuvant CpG to form CpG/OVA-LDH(CO-LDH)nanovaccines.We found that CO-LDH-215(the size of LDH was 215 nm)promoted dendritic cells to present the most antigen,and moreover showed the highest spleen enrichment(~1.67%of CO-LDH-215 enriched in the spleen at 24 h post IV injection).The in vivo immunologic data showed that CO-LDH-215 induced the most potent anti-tumor immune responses and completely prevented the growth of E.G7-OVA tumor in the mouse model.Furthermore,IV injected CO-LDH-215 nanovaccine more effectively delayed tumor growth than that SC injected,largely due to the direct and quick delivery of more nanovaccines to the spleen.This study demonstrates that the therapeutic efficacy of nanovaccines can be greatly enhanced by targeted delivery of nanovaccines to the spleen via the proper vaccination route.
文摘BACKGROUND Ulcerative colitis(UC)is defined as a chronic inflammatory bowel disease that can occur in any part of the large bowel.In addition,UC affects only the large bowel except for backwash ileitis and pouchitis,whereas Crohn’s disease(CD)affects the entire digestive tract.Inflammatory bowel disease(IBD)patients tend to be diagnosed with CD or indeterminate colitis when combined with gastric lesion.However,in recent years,some UC patients are reported to have various degrees of lesions in gastroduodenum.Here,we report a case of gastroduodenitis associated with UC(GDUC).CASE SUMMARY A 25-year-old man with a history of Klippel-Trenaunay syndrome presented to the hospital with mucopurulent bloody stool and epigastric persistent colic pain for 2 wk.Continuous superficial ulcers and spontaneous bleeding were observed under colonoscopy.Subsequent gastroscopy revealed mucosa with diffuse edema,ulcers,errhysis,and granular and friable changes in the stomach and duodenal bulb,which were similar to the appearance of the rectum.After ruling out other possibilities according to a series of examinations,a diagnosis of GDUC was considered.The patient hesitated about intravenous corticosteroids,so he received a standardized treatment with pentasa of 3.2 g/d.After 0.5 mo of treatment,the patient’s symptoms achieved complete remission.Follow-up endoscopy and imaging findings showed no evidence of recurrence for 26 mo.CONCLUSION The occurrence of gastrointestinal involvement in UC is rare,which may open a new window for studying the etiology and pathogenesis of UC.Physicians should consider broad differential diagnosis by endoscopic biopsy and laboratory examinations.
基金supported by grants from the Research Foundation of Hwa Mei Hospital,University of Chinese Academy of Sciences,China(2020HMKY22)the Zhejiang Medicine and Health Science and Technology Project(2021424731)Ningbo Medical Key Discipline(2022-F16).
文摘Dear editor,The neck is rich in blood vessels.Abnormal origins are rarely seen in clinical practice,but some are found accidentally during relevant imaging examinations,autopsy,and surgery.Abnormal neck vessels are mostly asymptomatic;however,approximately 10%of patients with abnormal blood vessels may have clinical manifestations due to the compression of adjacent tissues and organs.
基金supported by National Major Scientific Instrument and Equipment Development Project of NSFC(81827901)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38030100 and XDB38050200)+1 种基金II Phase External Project of Ningbo Institute of Life and Health Industry,University of Chinese Academy of Sciences(2020YJY0217)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘Background:The precise and efficient analysis of single-cell transcriptome data provides powerful support for studying the diversity of cell functions at the single-cell level.The most important and challenging steps are cell clustering and recognition of cell populations.While the precision of clustering and annotation are considered separately in most current studies,it is worth attempting to develop an extensive and flexible strategy to balance clustering accuracy and biological explanation comprehensively.Methods:The cell marker-based clustering strategy(cmCluster),which is a modified Louvain clustering method,aims to search the optimal clusters through genetic algorithm(GA)and grid search based on the cell type annotation results.Results:By applying cmCluster on a set of single-cell transcriptome data,the results showed that it was beneficial for the recognition of cell populations and explanation of biological function even on the occasion of incomplete cell type information or multiple data resources.In addition,cmCluster also produced clear boundaries and appropriate subtypes with potential marker genes.The relevant code is available in GitHub website(huangyuwei301/cmCluster).Conclusions:We speculate that cmCluster provides researchers effective screening strategies to improve the accuracy of subsequent biological analysis,reduce artificial bias,and facilitate the comparison and analysis of multiple studies.
