Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the wide-spread use of Esophagogastroduodenoscopy for evaluating a var...Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the wide-spread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age.展开更多
Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative pol...Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene expression.Endochondral ossification is a central process in bone healing,but the impact of APA on gene expression during this process is unknown.Here,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone healing.Importantly,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone formation.Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen 1.APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both transcripts.Taken together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.展开更多
The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent repo...The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the mostcommon outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.展开更多
Computational modeling methods have been increasingly employed to quantify aortic hemodynamic parameters that are challenging to in vivo measurements but important for the diagnosis/treatment of aortic disease.Althoug...Computational modeling methods have been increasingly employed to quantify aortic hemodynamic parameters that are challenging to in vivo measurements but important for the diagnosis/treatment of aortic disease.Although the presence of turbulence-like behaviors of blood flow in normal or diseased aorta has long been confirmed,the majority of existing computational model studies adopted the laminar flow assumption(LFA)in the treatment of sub-grid flow variables.So far,it remains unclear whether LFA would significantly compromise the reliability of hemodynamic simulation.In the present study,we addressed the issue in the context of a specific aortopathy,namely aortic dilation,which is usually accompanied by disturbed flow patterns.Three patient-specific aortas with treated/untreated dilation of the ascending segment were investigated,and their geometrical models were reconstructed from computed tomography angiographic images,with the boundary conditions being prescribed based on flow velocity information measured in vivo with the phase contrast magnetic resonance imaging technique.For the modeling of blood flow,apart from the traditional LFA-based method in which sub-grid flow dynamics is ignored,the large eddy simulation(LES)method capable of incorporating the dissipative energy loss induced by turbulent eddies at the sub-grid level,was adopted and taken as a reference for examining the performance of the LFA-based method.Obtained results showed that the simulated large-scale flow patterns with the two methods had high similarity,both agreeing well with in vivo measurements,although locally large between-method discrepancies in computed hemodynamic quantities existed in regions with high intensity of flow turbulence.Quantitatively,a switch from the LES to the LFAbased modeling method led to mild(<6%)changes in computed space-averaged wall shear stress metrics(i.e.,SA-TAWSS,SA-OSI)in the ascending aortic segment where intensive vortex evolution accompanied by high statistical Reynolds stress was observed.In addition,comparisons among the three aortas revealed that the treatment status of aortic dilation or the concomitant presence of aortic valve disease,despite its remarkable influence on flow patterns in the ascending aortic segment,did not significantly affect the degrees of discrepancies between the two modeling methods in predicting SA-TAWSS and SA-OSI.These findings suggest that aortic dilation per se does not induce strong flow turbulence that substantially negates the validity of LFA-based modeling,especially in simulating macro-scale hemodynamic features.展开更多
Prostate-specific antigen(PSA)is the most widely used biomarker for the early diagnosis of prostate cancer.Existing methods for PSA detection are burdened with some limitations and require improvement.Herein,we develo...Prostate-specific antigen(PSA)is the most widely used biomarker for the early diagnosis of prostate cancer.Existing methods for PSA detection are burdened with some limitations and require improvement.Herein,we developed a novel microfluidic–electrochemical(μFEC)detection system for PSA detection.First,we constructed an electrochemical biosensor based on screen-printed electrodes(SPEs)with modification of gold nanoflowers(Au NFs)and DNA tetrahedron structural probes(TSPs),which showed great detection performance.Second,we fabricated microfluidic chips by DNA TSP-Au NF-modified SPEs and a PDMS layer with designed dense meandering microchannels.Finally,theμFEC detection system was achieved based on microfluidic chips integrated with the liquid automatic conveying unit and electrochemical detection platform.TheμFEC system we developed acquired great detection performance for PSA detection in PBS solution.For PSA assays in spiked serum samples of theμFEC system,we obtained a linear dynamic range of 1–100 ng/mL with a limit of detection of 0.2 ng/mL and a total reaction time<25 min.Real serum samples of prostate cancer patients presented a strong correlation between the“gold-standard”chemiluminescence assays and theμFEC system.In terms of operation procedure,cost,and reaction time,our method was superior to the current methods for PSA detection and shows great potential for practical clinical application in the future.展开更多
Microneedle permits transdermal biosensing and drug delivery with minor pain.However,accurate microneedle transdermal positioning with minimal skin deformation remains a significant technical challenge due to inhomoge...Microneedle permits transdermal biosensing and drug delivery with minor pain.However,accurate microneedle transdermal positioning with minimal skin deformation remains a significant technical challenge due to inhomogeneous skin topology and discontinuous force applied to the microneedle.Here,we introduce bioinspired rotation microneedles for in vivo accurate microneedle positioning as inspired by honeybees’stingers.We demonstrate the benefits of rotation microneedles in alleviating skin resistance through finite element analysis,full-thickness porcine validations,and mathematical derivations of microneedleskin interaction stress fields.The max penetration force was mitigated by up to 45.7%and the force attenuation rate increased to 2.73 times in the holding stage after penetration.A decrease in max skin deflection and a faster deformation recovery introduced by rotation microneedles implied a more precise penetration depth.Furthermore,we applied the rotation microneedles in psoriasis mice,a monogenic disorder animal model,for minimally invasive biological sample extraction and proinflammatory cytokine monitoring.An ultrasensitive detection method is realized by using only one microneedle to achieve cytokine mRNA level determination compared to commonly required biopsies or blood collection.Thus,rotation microneedles permit a simple,rapid,and ultraminimal-invasive method for subcutaneous trace biological sample acquisition and subsequent point-of-care diagnostics with minimal damage to both microneedles and skins.展开更多
Central nervous system diseases commonly occur with the destruction of the blood-brain barrier.As a primary cause of morbidity and mortality,stroke remains unpredictable and lacks cellular biomarkers that accurately q...Central nervous system diseases commonly occur with the destruction of the blood-brain barrier.As a primary cause of morbidity and mortality,stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development.Here,we identify NeuN^(+)/CD45^(−)/DAPI^(+)phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion(MCAO)and stroke patients.Since NeuN is a specific marker of neural cells,we term these newly identified cells as circulating neural cells(CNCs).We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice(p<0:05).Meanwhile,the number of CNCs is significantly higher in stroke patients than in negative subjects(p<0:0001).These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.展开更多
This numerical study proposes a cell sorting technique based on dielectrophoresis(DEP)in a microfluidic chip.Under the joint effect of DEP and fluid drag,white blood cells and circulating tumor cells are separated be...This numerical study proposes a cell sorting technique based on dielectrophoresis(DEP)in a microfluidic chip.Under the joint effect of DEP and fluid drag,white blood cells and circulating tumor cells are separated because of different dielectric properties.First,the mathematical models of device geometry,single cell,DEP force,electric field,and flow field are established to simulate the cell motion.Based on the simulation model,important boundary parameters are discussed to optimize the cell sorting ability of the device.A proper matching relationship between voltage and flow rate is then provided.The inlet and outlet conditions are also investigated to control the particle motion in the flow field.The significance of this study is to verify the cell separating ability of the microfluidic chip,and to provide a logistic design for the separation of rare diseased cells.展开更多
Dozens of human cases infected with H7N9 subtype avian influenza virus (AIV) have been confirmed in China since March, 2013. Distribution data of sexes, ages, professions and regions of the cases were analyzed in this...Dozens of human cases infected with H7N9 subtype avian influenza virus (AIV) have been confirmed in China since March, 2013. Distribution data of sexes, ages, professions and regions of the cases were analyzed in this report. The results showed that the elderly cases, especially the male elderly, were significantly more than expected, which is different from human cases of H5N1 avian influenza and human cases of the pandemic H1N1 influenza. The outbreak was rated as a Grade Ⅲ (severe) outbreak, and it would evolve into a Grade IV (very severe) outbreak soon, using a method reported previously. The H7N9 AIV will probably circulate in humans, birds and pigs for years. Moreover, with the driving force of natural selection, the virus will probably evolve into highly pathogenic AIV in birds, and into a deadly pandemic influenza virus in humans. Therefore, the H7N9 outbreak has been assumed severe, and it is likely to become very or extremely severe in the future, highlighting the emergent need of forceful scientific measures to eliminate any infected animal flocks. We also described two possible mild scenarios of the future evolution of the outbreak.展开更多
The importance of properly treating boundary conditions (BCs) in numerical simulation of hemodynamics in intracranial aneurysm (IA) has been increasingly recognized. In this study, we constructed three types of comput...The importance of properly treating boundary conditions (BCs) in numerical simulation of hemodynamics in intracranial aneurysm (IA) has been increasingly recognized. In this study, we constructed three types of computational model for each IA to investigate how the outcome of numerical simulation is affected by the treatment of BCs. The first type of model (i.e., Type-A model) was obtained by applying 3-D hemodynamic modeling to the entire cerebral arterial network, with its solution being taken as the reference for evaluating the performance of the other two types of model (i.e., Type-B and Type-C models) in which 3-D modeling was confined to the aneurysm region. In addition, patient-specific 1-D models of the cerebral arterial network were developed to provide hemodynamic information for setting the inflow/outflow BCs of the 3-D models. Numerical tests on three IAs revealed that prescribing the outflow BCs of a localized 3-D aneurysm model based on 1-D model-simulated outflow division (i.e., Type-B model) instead of imposing the free outflow BC on all outlets (i.e., Type-C model) helped to improve the fidelity of the simulation of intra-aneurysmal hemodynamics, but could not guarantee a complete reproduction of the reference solution obtained by the Type-A model. Moreover, it was found that the outcome of hemodynamic simulation was more sensitive to the treatment of BCs when an aneurysm was located at arterial bifurcation rather than sidewall. These findings highlight the importance of taking into account systemic cerebroarterial hemodynamics in computational modeling of hemodynamics in IAs, especially those located at bifurcations.展开更多
Effective capture and analysis of a single circulating tumor cell(CTC)is instrumental for early diagnosis and personalized therapy of tumors.However,due to their extremely low abundance and susceptibility to interfere...Effective capture and analysis of a single circulating tumor cell(CTC)is instrumental for early diagnosis and personalized therapy of tumors.However,due to their extremely low abundance and susceptibility to interference from other cells,high-throughput isolation,enrichment,and single-cell-level functional protein analysis of CTCs within one integrated system remains a major challenge.Herein,we present an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation,CTC enrichment,and single-cell immunoblotting(ieSCI).The ieSCI-chip is a multilayer microfluidic system that combines an inertia force-based cell sorter with a membrane filter for label-free CTC separation and enrichment and a thin layer of a photoactive polyacrylamide gel with microwell arrays at the bottom of the chamber for single-cell immunoblotting.The ieSCI-chip successfully identified a subgroup of apoptosis-negative(Bax-negative)cells,which traditional bulk analysis did not detect,from cisplatin-treated cells.Furthermore,we demonstrated the clinical application of the ieSCI-chip with blood samples from breast cancer patients for personalized CTC epithelial-to-mesenchymal transition(EMT)analysis.The expression level of a tumor cell marker(EpCAM)can be directly determined in isolated CTCs at the single-cell level,and the therapeutic response to anticancer drugs can be simultaneously monitored.Therefore,the ieSCI-chip provides a promising clinical translational tool for clinical drug response monitoring and personalized regimen development.展开更多
Inflammatory,proliferative and remodeling phases constitute a cutaneous wound healing program.Therapeutic applications and medication are available;however,they commonly are comprised of fortified preservatives that m...Inflammatory,proliferative and remodeling phases constitute a cutaneous wound healing program.Therapeutic applications and medication are available;however,they commonly are comprised of fortified preservatives that might prolong the healing process.Chick early amniotic fluids(ceAF)contain native therapeutic factors with balanced chemokines,cytokines and growth-related factors;their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development.Instead,they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions.Employing both in vitro and in vivo models,we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence,known to be intimately intermingled with Senescence Associated Secretory Phenotypes(SASP)that function in addition to or in conjunction with ceAF to facilitate wound healing.In our cutaneous wound healing models,a low dose of ceAF exhibited the best efficacies;however,higher doses attenuated the wound healing presumably by inducing p16 expression over a threshold.Our studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing,suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence,expediting cellular proliferation,migration,and describing a homeostatic and balanced dosage strategy in medical intervention.展开更多
While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)...While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.展开更多
文摘Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the wide-spread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age.
基金National Institutes of Health(NIH)R01 DK121327 to R.A.E。
文摘Maturation of the 3′end of almost all eukaryotic messenger RNAs(m RNAs)requires cleavage and polyadenylation.Most mammalian m RNAs are polyadenylated at different sites within the last exon,generating alternative polyadenylation(APA)isoforms that have the same coding region but distinct 3′untranslated regions(UTRs).The 3′UTR contains motifs that regulate m RNA metabolism;thus,changing the 3′UTR length via APA can significantly affect gene expression.Endochondral ossification is a central process in bone healing,but the impact of APA on gene expression during this process is unknown.Here,we report the widespread occurrence of APA,which impacts multiple pathways that are known to participate in bone healing.Importantly,the progression of endochondral ossification involves global 3′UTR shortening,which is coupled with an increased abundance of shortened transcripts relative to other transcripts;these results highlight the role of APA in promoting gene expression during endochondral bone formation.Our mechanistic studies of transcripts that undergo APA in the fracture callus revealed an intricate regulatory network in which APA enhances the expression of the collagen,type I,alpha 1(Col1a1)and Col1a2 genes,which encode the 2 subunits of the abundantly expressed protein collagen 1.APA exerts this effect by shortening the 3′UTRs of the Col1a1 and Col1a2 m RNAs,thus removing the binding sites of mi R-29a-3p,which would otherwise strongly promote the degradation of both transcripts.Taken together,our study is the first to characterize the crucial roles of APA in regulating the 3′UTR landscape and modulating gene expression during fracture healing.
文摘The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the mostcommon outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.
基金The study was supported by the National Natural Science Foundation of China(Grant nos.11972231,11832003,81611530715)the China Postdoctoral Science Foundation(Grant no.2018M640385)the SJTU Medical-Engineering Cross-cutting Research Project(Grant no.YG2017MS45).
文摘Computational modeling methods have been increasingly employed to quantify aortic hemodynamic parameters that are challenging to in vivo measurements but important for the diagnosis/treatment of aortic disease.Although the presence of turbulence-like behaviors of blood flow in normal or diseased aorta has long been confirmed,the majority of existing computational model studies adopted the laminar flow assumption(LFA)in the treatment of sub-grid flow variables.So far,it remains unclear whether LFA would significantly compromise the reliability of hemodynamic simulation.In the present study,we addressed the issue in the context of a specific aortopathy,namely aortic dilation,which is usually accompanied by disturbed flow patterns.Three patient-specific aortas with treated/untreated dilation of the ascending segment were investigated,and their geometrical models were reconstructed from computed tomography angiographic images,with the boundary conditions being prescribed based on flow velocity information measured in vivo with the phase contrast magnetic resonance imaging technique.For the modeling of blood flow,apart from the traditional LFA-based method in which sub-grid flow dynamics is ignored,the large eddy simulation(LES)method capable of incorporating the dissipative energy loss induced by turbulent eddies at the sub-grid level,was adopted and taken as a reference for examining the performance of the LFA-based method.Obtained results showed that the simulated large-scale flow patterns with the two methods had high similarity,both agreeing well with in vivo measurements,although locally large between-method discrepancies in computed hemodynamic quantities existed in regions with high intensity of flow turbulence.Quantitatively,a switch from the LES to the LFAbased modeling method led to mild(<6%)changes in computed space-averaged wall shear stress metrics(i.e.,SA-TAWSS,SA-OSI)in the ascending aortic segment where intensive vortex evolution accompanied by high statistical Reynolds stress was observed.In addition,comparisons among the three aortas revealed that the treatment status of aortic dilation or the concomitant presence of aortic valve disease,despite its remarkable influence on flow patterns in the ascending aortic segment,did not significantly affect the degrees of discrepancies between the two modeling methods in predicting SA-TAWSS and SA-OSI.These findings suggest that aortic dilation per se does not induce strong flow turbulence that substantially negates the validity of LFA-based modeling,especially in simulating macro-scale hemodynamic features.
基金We are thankful for support from the Program of Shanghai Academic/Technology Research Leader(20XD1404600)Shanghai Municipal Science and Technology Commission(Grant nos.20511107600,19511107100,19511107102)+3 种基金Chinese Academy of Sciences(KFJ-STS-QYZD-2021-08-002)National Key Research and Development Program of China(Grant no.2016YFC0100600)Shenzhen Fundamental Research Program(JCYJ20170413164102261)Guangdong Program(2016ZT06D631).
文摘Prostate-specific antigen(PSA)is the most widely used biomarker for the early diagnosis of prostate cancer.Existing methods for PSA detection are burdened with some limitations and require improvement.Herein,we developed a novel microfluidic–electrochemical(μFEC)detection system for PSA detection.First,we constructed an electrochemical biosensor based on screen-printed electrodes(SPEs)with modification of gold nanoflowers(Au NFs)and DNA tetrahedron structural probes(TSPs),which showed great detection performance.Second,we fabricated microfluidic chips by DNA TSP-Au NF-modified SPEs and a PDMS layer with designed dense meandering microchannels.Finally,theμFEC detection system was achieved based on microfluidic chips integrated with the liquid automatic conveying unit and electrochemical detection platform.TheμFEC system we developed acquired great detection performance for PSA detection in PBS solution.For PSA assays in spiked serum samples of theμFEC system,we obtained a linear dynamic range of 1–100 ng/mL with a limit of detection of 0.2 ng/mL and a total reaction time<25 min.Real serum samples of prostate cancer patients presented a strong correlation between the“gold-standard”chemiluminescence assays and theμFEC system.In terms of operation procedure,cost,and reaction time,our method was superior to the current methods for PSA detection and shows great potential for practical clinical application in the future.
基金the State Key Laboratory of Mechanical System and Vibration(Grant No.MSVZD202108)Base for Interdisciplinary Innovative Talent Training.The authors thank all who provided direct technical help and indirect assistance for the study。
文摘Microneedle permits transdermal biosensing and drug delivery with minor pain.However,accurate microneedle transdermal positioning with minimal skin deformation remains a significant technical challenge due to inhomogeneous skin topology and discontinuous force applied to the microneedle.Here,we introduce bioinspired rotation microneedles for in vivo accurate microneedle positioning as inspired by honeybees’stingers.We demonstrate the benefits of rotation microneedles in alleviating skin resistance through finite element analysis,full-thickness porcine validations,and mathematical derivations of microneedleskin interaction stress fields.The max penetration force was mitigated by up to 45.7%and the force attenuation rate increased to 2.73 times in the holding stage after penetration.A decrease in max skin deflection and a faster deformation recovery introduced by rotation microneedles implied a more precise penetration depth.Furthermore,we applied the rotation microneedles in psoriasis mice,a monogenic disorder animal model,for minimally invasive biological sample extraction and proinflammatory cytokine monitoring.An ultrasensitive detection method is realized by using only one microneedle to achieve cytokine mRNA level determination compared to commonly required biopsies or blood collection.Thus,rotation microneedles permit a simple,rapid,and ultraminimal-invasive method for subcutaneous trace biological sample acquisition and subsequent point-of-care diagnostics with minimal damage to both microneedles and skins.
基金supported by the National Natural Science Foundation of China(Nos.81871448,81701353,and 82073380)the Science and Technology commission of Shanghai Municipality(2017SHZDZX01)+1 种基金the MedicalEngineering Cross Foundation of Shanghai Jiao Tong University(Nos.19X190020154,YG2016MS60,ZH2018QNA54,ZH2018QNA49,and YG2021QN129)the Shanghai Sailing Program(19YF1446900).
文摘Central nervous system diseases commonly occur with the destruction of the blood-brain barrier.As a primary cause of morbidity and mortality,stroke remains unpredictable and lacks cellular biomarkers that accurately quantify its occurrence and development.Here,we identify NeuN^(+)/CD45^(−)/DAPI^(+)phenotype nonblood cells in the peripheral blood of mice subjected to middle cerebral artery occlusion(MCAO)and stroke patients.Since NeuN is a specific marker of neural cells,we term these newly identified cells as circulating neural cells(CNCs).We find that the enumeration of CNCs in the blood is significantly associated with the severity of brain damage in MCAO mice(p<0:05).Meanwhile,the number of CNCs is significantly higher in stroke patients than in negative subjects(p<0:0001).These findings suggest that the amount of CNCs in circulation may serve as a clinical indicator for the real-time prognosis and progression monitor of the occurrence and development of ischemic stroke and other nervous system disease.
文摘This numerical study proposes a cell sorting technique based on dielectrophoresis(DEP)in a microfluidic chip.Under the joint effect of DEP and fluid drag,white blood cells and circulating tumor cells are separated because of different dielectric properties.First,the mathematical models of device geometry,single cell,DEP force,electric field,and flow field are established to simulate the cell motion.Based on the simulation model,important boundary parameters are discussed to optimize the cell sorting ability of the device.A proper matching relationship between voltage and flow rate is then provided.The inlet and outlet conditions are also investigated to control the particle motion in the flow field.The significance of this study is to verify the cell separating ability of the microfluidic chip,and to provide a logistic design for the separation of rare diseased cells.
基金supported by the Sci-tech Basic Work Project of the Ministry of Science and Technology (SQ2012FY3260033)
文摘Dozens of human cases infected with H7N9 subtype avian influenza virus (AIV) have been confirmed in China since March, 2013. Distribution data of sexes, ages, professions and regions of the cases were analyzed in this report. The results showed that the elderly cases, especially the male elderly, were significantly more than expected, which is different from human cases of H5N1 avian influenza and human cases of the pandemic H1N1 influenza. The outbreak was rated as a Grade Ⅲ (severe) outbreak, and it would evolve into a Grade IV (very severe) outbreak soon, using a method reported previously. The H7N9 AIV will probably circulate in humans, birds and pigs for years. Moreover, with the driving force of natural selection, the virus will probably evolve into highly pathogenic AIV in birds, and into a deadly pandemic influenza virus in humans. Therefore, the H7N9 outbreak has been assumed severe, and it is likely to become very or extremely severe in the future, highlighting the emergent need of forceful scientific measures to eliminate any infected animal flocks. We also described two possible mild scenarios of the future evolution of the outbreak.
基金This work was supported by the Clinical Research Plan of SHDC(Grant Nos.16CR3031A,16CR2045B)the SJTU Medical-Engineering Cross-cutting Research Foundation(Jrant Nos.YG2015MS53,YG2017MS45).
文摘The importance of properly treating boundary conditions (BCs) in numerical simulation of hemodynamics in intracranial aneurysm (IA) has been increasingly recognized. In this study, we constructed three types of computational model for each IA to investigate how the outcome of numerical simulation is affected by the treatment of BCs. The first type of model (i.e., Type-A model) was obtained by applying 3-D hemodynamic modeling to the entire cerebral arterial network, with its solution being taken as the reference for evaluating the performance of the other two types of model (i.e., Type-B and Type-C models) in which 3-D modeling was confined to the aneurysm region. In addition, patient-specific 1-D models of the cerebral arterial network were developed to provide hemodynamic information for setting the inflow/outflow BCs of the 3-D models. Numerical tests on three IAs revealed that prescribing the outflow BCs of a localized 3-D aneurysm model based on 1-D model-simulated outflow division (i.e., Type-B model) instead of imposing the free outflow BC on all outlets (i.e., Type-C model) helped to improve the fidelity of the simulation of intra-aneurysmal hemodynamics, but could not guarantee a complete reproduction of the reference solution obtained by the Type-A model. Moreover, it was found that the outcome of hemodynamic simulation was more sensitive to the treatment of BCs when an aneurysm was located at arterial bifurcation rather than sidewall. These findings highlight the importance of taking into account systemic cerebroarterial hemodynamics in computational modeling of hemodynamics in IAs, especially those located at bifurcations.
基金We are grateful for financial support from Projects 22077079,31971327,and 81871448 of the National Natural Science Foundation of China(NSFC)a Project of the National Innovation Special Zone+11 种基金Projects 2017SHZDZX01,17DZ2203400,and 18430760500 of Shanghai Municipal Science and TechnologyProject G20180101 of the Shanghai Agriculture Applied Technology Development ProgramProject ZXWF082101 of the Shanghai Municipal Education CommissionProject 2017ZX10203205-006-002 of the National Key Research and Development Program of ChinaProjects 19×190020154,ZH2018ZDA01,YG2016QN24,and YG2016MS60 of the Shanghai Jiao Tong University Biomedical Interdisciplinary ProgramProjects ZH2018QNA54 and ZH2018QNA49 of the Medical-Engineering Cross Foundation of Shanghai Jiao Tong UniversityProject 2019CXJQ03 of the Innovation Group Project of the Shanghai Municipal Health CommissionProject 19MC1910800 of the Shanghai Clinical Medical Research CenterProject SD0820016 of the third batch of industrialization projects of the Innovation Incubation Fund of Nantong and Shanghai Jiao Tong UniversityProject SL2020MS026 of the Oceanic Interdisciplinary Program of Shanghai Jiao Tong UniversityProject Agri-X20200101 of Shanghai Jiao Tong Universityand the SJTU Global Strategic Partnership Fund(2020 SJTU-HUJI).In addition,we thank AEMD SJTU for the support.
文摘Effective capture and analysis of a single circulating tumor cell(CTC)is instrumental for early diagnosis and personalized therapy of tumors.However,due to their extremely low abundance and susceptibility to interference from other cells,high-throughput isolation,enrichment,and single-cell-level functional protein analysis of CTCs within one integrated system remains a major challenge.Herein,we present an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation,CTC enrichment,and single-cell immunoblotting(ieSCI).The ieSCI-chip is a multilayer microfluidic system that combines an inertia force-based cell sorter with a membrane filter for label-free CTC separation and enrichment and a thin layer of a photoactive polyacrylamide gel with microwell arrays at the bottom of the chamber for single-cell immunoblotting.The ieSCI-chip successfully identified a subgroup of apoptosis-negative(Bax-negative)cells,which traditional bulk analysis did not detect,from cisplatin-treated cells.Furthermore,we demonstrated the clinical application of the ieSCI-chip with blood samples from breast cancer patients for personalized CTC epithelial-to-mesenchymal transition(EMT)analysis.The expression level of a tumor cell marker(EpCAM)can be directly determined in isolated CTCs at the single-cell level,and the therapeutic response to anticancer drugs can be simultaneously monitored.Therefore,the ieSCI-chip provides a promising clinical translational tool for clinical drug response monitoring and personalized regimen development.
文摘Inflammatory,proliferative and remodeling phases constitute a cutaneous wound healing program.Therapeutic applications and medication are available;however,they commonly are comprised of fortified preservatives that might prolong the healing process.Chick early amniotic fluids(ceAF)contain native therapeutic factors with balanced chemokines,cytokines and growth-related factors;their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development.Instead,they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions.Employing both in vitro and in vivo models,we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence,known to be intimately intermingled with Senescence Associated Secretory Phenotypes(SASP)that function in addition to or in conjunction with ceAF to facilitate wound healing.In our cutaneous wound healing models,a low dose of ceAF exhibited the best efficacies;however,higher doses attenuated the wound healing presumably by inducing p16 expression over a threshold.Our studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing,suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence,expediting cellular proliferation,migration,and describing a homeostatic and balanced dosage strategy in medical intervention.
基金The work is partially funded by the National Natural Science Foundation of China(No.81871448)the National Key Research and Development Program of China(Nos.2017YFC0107603 and 2017ZX10203205-006-002)the Medical-Engineering Cross Foundation of Shanghai Jiao Tong University(Nos.YG2017QN52,ZH2018QNA54,and ZH2018QNA49).
文摘While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related toxicity.Nanodiamond(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer models.In addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human primates.Before the clinical translation of NDX,it is necessary to verify the safety of ND in large mammals.Studies of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical assessment.Herein,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle dogs.The study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection methods.The dogs are monitored for their health phenotype changes in continuous 5 days.Blood and urine obtained are for clinical pathology research.The results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog model.This study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.
