Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time...Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.展开更多
Objective This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia,and explore the differences in bad ending between twins and singletons.Met...Objective This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia,and explore the differences in bad ending between twins and singletons.Methods The present retrospective cohort study was conducted on patients with severe pre-eclampsia,who delivered in Tongji Hospital,Wuhan,China,between 2017 and 2022.The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated.Then,the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid.Results A total of 709 patients were included for the present study.Among these patients,68 patients had twin pregnancies,and 641 patients had singleton pregnancies.The rate of postpartum hemorrhage(2.81%vs.13.24%,P<0.001),and admission rate to the Neonatal Intensive Care Unit(NICU)after birth(30.73%vs.63.24%,P=0.011)were significantly higher in twin pregnancies.The neonatal weight of twins was statistically lower than singletons(1964.73±510.61 g vs.2142.92±731.25 g,P=0.008).For the groups with the third interstitial fluid,the delivery week(P=0.001)and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group,when compared to singleton pregnancy group(P=0.032),and the length of hospital stay was shorter(P=0.044).Furthermore,there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid.Conclusion The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies,when compared to singleton pregnancies.Thus,when patients develop the third interstitial fluid,twin pregnancies would more likely lead to adverse fetal outcomes,when compared to singleton pregnancies,and there would be no significant difference in maternal adverse outcomes.More attention should be given to patients who merge with the third interstitial fluid.展开更多
Interstitial fluid plays a vital role in drug delivery and tumour treatment.However,few non-invasive measurement methods are available for measuring low-velocity biological fluid flow.Therefore,this study aimed to dev...Interstitial fluid plays a vital role in drug delivery and tumour treatment.However,few non-invasive measurement methods are available for measuring low-velocity biological fluid flow.Therefore,this study aimed to develop a novel technology called interstitial flow velocity-MRI.The interstitial flow velocity-MRI sequence consists of a dual inversion recovery preparation and an improved stimulated echo sequence(ISTE)combined with phase-contrast MRI.A homemade flow phantom was used to assess the feasibility and sensitivity of interstitial flow velocity-MRI.In addition,xenografts of female BALB/c mouse models of 4T1 breast cancer administered losartan(40 mg/kg)or saline(n?6)were subjected to imaging on a 7.0 T scanner to assess the in vivo interstitial fluid flow velocity.The results showed a significant correlation(P<0.001)between the theoretical velocities and velocities measured using the flow phantom.Interstitial flow velocity-MRI could detect a velocity as low as 10.21±2.65 mm/s with a spatial resolution of 0.313 mm.The losartan group had a lower mean interstitial fluid velocity than the control group(85±16 vs 113±24 mm/s).In addition,compared to the saline treatment,losartan treatment reduced the proportion of collagen fibres by 10%and 12%in the Masson and Sirius red staining groups,respectively.Interstitial flow velocity-MRI has the potential to determine interstitial fluid flow velocity non-invasively and exhibits an intuitive velocity map.展开更多
The pH of body fluids is one the most important keyfactors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell fun...The pH of body fluids is one the most important keyfactors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body(interstitial) fluids is lower in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. In this review article, I introduce importance of body(interstitial) fluid pH in regulation of body function, evidence on abnormal regulation of body fluid pH in diabetes mellitus, and relationship between the body fluid pH and insulin resistance. Further, this review proposes perspective therapies on the basis of regulation of body fluid pH including propolis(honeybee product) diet.展开更多
The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. Meantime artificial neural network was applied to the estimation of log ?values of complexes. The results sh...The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. Meantime artificial neural network was applied to the estimation of log ?values of complexes. The results show that the precipitate species, GdPO4 and Gd2(CO3)3, are the predominant species. Among soluble species, the free Gd(III), [Gd(HSA)] , [Gd(Ox)] and then the ternary complexes of Gd(III) with citrate are main species and [Gd3(OH)4] becomes the predominant species at the Gd(III) total concentration of 2.2?0-2mol/L.展开更多
In vitro experiments have shown that subtle fluid flow environment plays a significant role in living biological tissues, while there is no in vivo practical dynamical measurement of the interstitial fluid flow veloci...In vitro experiments have shown that subtle fluid flow environment plays a significant role in living biological tissues, while there is no in vivo practical dynamical measurement of the interstitial fluid flow velocity. On the basis of a new finding that capillaries and collagen fibrils in the interosseous membrane form a parallel array, we set up a porous media model simulating the flow field with FLUENT software, studied the shear stress on interstitial cells' surface due to the interstitial fluid flow, and analyzed the effect of flow on protein space distribution around the ceils. The numerical simulation results show that the parallel nature of capillaries could lead to directional interstitial fluid flow in the direction of capillaries. Interstitial fluid flow would induce shear stress on the membrane of interstitial cells, up to 30 Pa or so, which reaches or exceeds the threshold values of cells' biological response observed in vitro. Interstitial fluid flow would induce nonuniform spacial distribution of secretion protein of mast cells. Shear tress on cells could be affected by capillary parameters such as the distance between the adjacent capillaries, blood pressure and the permeability coefficient of capillary's wall. The interstitial pressure and the interstitial porosity could also affect the shear stress on cells. In conclusion, numerical simulation provides an effective way for in vivo dynamic interstitial velocity research, helps to set up the vivid subtle interstitial flow environment of cells, and is beneficial to understanding the physiological functions of interstitial fluid flow.展开更多
A multi-phase model of Pr(III) speciation in human interstitial fluid was constructed and insoluble Pr(III) speciation was studied. When the total concentration of Pr(III) is below 8.401E-10 mol/L, soluble Pr(III) sp...A multi-phase model of Pr(III) speciation in human interstitial fluid was constructed and insoluble Pr(III) speciation was studied. When the total concentration of Pr(III) is below 8.401E-10 mol/L, soluble Pr(III) species are main species. With rising the total concentration of Pr(III), Pr(III) is firstly bound to phosphate to form precipitate of PrPO4, then bound to carbonate and another precipitate of Pr2(CO3)3 was obtained. When the total concentration is between 1.583E-9 mol/L and 4.000E-3 mol/L, the insoluble species are predominant Pr(III) species.展开更多
BACKGROUND DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanc...BACKGROUND DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS)analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation. AIM To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT. METHODS Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated. RESULTS Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively. CONCLUSION Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.展开更多
Objective: To investigate the role of subeschar tissue fluid (STF) in postburn cell damage. Methods: STF was collected from patients with full-thickness burn injury of 10% - 69% total body surface area (TFBSA) during ...Objective: To investigate the role of subeschar tissue fluid (STF) in postburn cell damage. Methods: STF was collected from patients with full-thickness burn injury of 10% - 69% total body surface area (TFBSA) during operation on postburn day 2 - 4, and that from guinea pigs were obtained in escharectomy 24 h after full-thickness scald injury of 30%’TBSA was induced. Respective incubation of human umbilical vein endothelial cells (HUVEC) and hepatocytes with STF were performed for the observation of the effects of STF on the activity, morphology, physiological function and monolayer cell permeability of HUVEC, and the percentages of apoptotic and necrotic hepatocytes were determined. Results: (l) STF had evident deleterious effect on endothelial cells. (2)are could induce apoptosis and necrosis of hepatocytes. Conclusion: STF plays an important role in causing early postburn damages.展开更多
In the previous studies,the phenomenon that the interstitial fluid(ISF)can flow along tunica adventitia of the arteries and veins in both human and animal bodies was reported.On the basis of these studies,this paper a...In the previous studies,the phenomenon that the interstitial fluid(ISF)can flow along tunica adventitia of the arteries and veins in both human and animal bodies was reported.On the basis of these studies,this paper aims to:(i)summarize the basic properties of the ISF flows in the walls of arteries and veins,(ii)combine the basic properties with axiomaticism and abstract the axiom for ISF flows,and(iii)propose three fundamental laws of the ISF flow,(i.e.,the existence law,the homotropic law and the reverse law).The three laws provide solid theoretical basement for exploring the kinematic patterns of interstitial fluid flow in the cardiovascular system.展开更多
In vitro tissue culture of hard woody, endangered, medicinal plant Coscinium fenestratum is most challenging to plant tissue culturists. In the present study, petiole and leaf explants of Coscinium fenestratum were in...In vitro tissue culture of hard woody, endangered, medicinal plant Coscinium fenestratum is most challenging to plant tissue culturists. In the present study, petiole and leaf explants of Coscinium fenestratum were induced to form callus when cultured on vermicompost extract media along with coelomic fluid. Suspension medium was developed using vermicompost extract and coelomic fluid in 3:1 ratio. Phytochemical analysis of the alkaloid berberine was confirmed from callus, suspension cell culture and suspension medium by Thin Layer Chromatography and High Performance Liquid Chromatography. Vermicompost and its extracts with coelomic fluid have shown maximum (100 per cent) response of callus induction. Callus mass enlarged with increasing concentration of coelomic fluid and callus growth was assessed from the biomass. Incubation of culture tubes in dark supported callus development significantly. The Rf value of 0.36 confirmed the presence of berberine by Thin Layer Chromatography. Qualitative analysis confirmed the presence of alkaloid berberine with the retention time of 2.8 minutes similar to that of standard reference sample from Sigma chemicals, USA. The suspension medium turned deep yellow because of the release of the alkaloid. Vermicompost and its extracts along with coelomic fluid have shown the economical approach for micropropagation of economically and medicinally important plants.展开更多
Background:Use of internal filling ports in tissue expander–based reconstructions are advantageous because of easier self-care,lower infection rates,and fewer instances of capsule formation.The appearance of peripros...Background:Use of internal filling ports in tissue expander–based reconstructions are advantageous because of easier self-care,lower infection rates,and fewer instances of capsule formation.The appearance of periprosthetic fluid accumulation after internal-port tissue expander implantation is a common complication that warrants treatment.In this study,we introduced a noninvasive method using fine-needle aspiration(FNA)to remove fluids accumulated after implantation of a remote internal-port tissue expander.Methods:In this study,245 patients who underwent implantation of remote internal-port tissue expanders in our hospital from July 1,2012,to July 1,2019,were included and divided into two groups.In the control group,patients underwent tissue expander implantation before July 1,2016,and large quantities of fluids were removed with surgical aspiration procedures in most cases.In the FNA group,the patients underwent implantation after July 1,2016,and large quantities of fluids were removed first with the FNA procedure.Patients’demographic data,indications for FNA application,and related complications were collected and analyzed.Results:Overall,395 expanders were placed in 245 patients.Postoperative management was similar in both groups.Fluids were managed with 23 expanders in the control group and with 31 expanders in the FNA group.There was no difference in the fluid aspiration rate between the two groups.The surgical aspiration rate was 11.1%(23/208)in the control group.The success rate of FNA was 90.3%(28/31).In the FNA group,the surgical aspiration rate was 1.6%(3/187),which was significantly lower than that in the control group.There were no significant differences in complications between the two groups.Conclusion:FNA can be used for periprosthetic fluid removal after the implantation of a remote internal-port tissue expander in most cases.This method is more convenient and safer than surgical aspiration for the postoperative management of internal-port tissue expander implantation.展开更多
Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial impla...Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial implantation(EAI),for accelerating interstitial fluid(ISF)drainage,which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS).In this study,the method of EAI was modified(m-EAI)to control its function of accelerating the ISF drainage at different time points following ischemic attack.The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model.The results demonstrated the accumulation of IL-1β,IL-6,and TNF-αwas significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats,accompanied with decreased infarct volume and improved neurological function.This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS.Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.展开更多
Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic p...Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow.However,osmotic pressure- related factors have not been studied until now.In this prospective observational study,to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF),we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions.Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg.Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007,respectively,the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e.,290.5–291.5 mOsm/L).There was strong correlation between CSF osmolality and serum osmolality,but the difference in osmolality between serum and CSF was not correlated with serum osmolality,serum electrolyte levels,protein levels,or quotient of albumin.In conclusion,CSF osmolarity was suggested to be equal to serum osmolarity.Osmolarity is not one of the driving forces of this bulk flow.Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma.This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No.IRB No.2015-1-257) on July 29,2015.展开更多
Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general;it also participates actively in many of these processe...Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general;it also participates actively in many of these processes. In humans, there are different vehicles to contain water and its constituents. Our objective is to find out whether there is an overall water-base circulation system in the human body by analyzing the updated findings of different research groups on the physiological functions of various seemingly isolated fluid systems. By 1963, there were five separate fluid systems discovered in mammalians: (i) The Primo Vasculature Fluid (PVF) with protein precursors and micro cells held in the Primo Vasculature System (PVS). (ii) Blood with its constituents held in the cardio vasculature. (iii) Extracranial interstitial fluid (ISF) whose vehicle had a very irregular structure—the interstitium all over the body. (iv) The cerebrospinal fluid had been considered to be within the brain ventricles and spinal canal. (v) The extra-cranial lymphatic system which drained ISF, and had been known to join the subclavian vein. Fluid (i) was first reported in 1963 and fluids (ii) to (v) have been known for many decades, but the failure to detect a lymphatic system inside the skull has also been a mystery for many decades. The intra-cranial ISF (which we name as BISF) has drawn little attention, apart from discussing the mechanism of the blood-brain-barrier. During the past decade, there has been direct evidence indicating that CSF and BISF are actually mixed. After that, the intracranial lymphatic system was discovered and confirmed in animal models only slightly over one year back, and we called such fluid as glymphatic-fluid. After reviewing the stated “classical” five fluid systems together with the new findings in Sections 2 - 7, we propose, for the first time, that the PVF, the blood, ISF, a mixture of CSF-BISF, and a mixture of glymphatic-fluid and lymph form an integrative circulation system in water base in the human and other mammalian bodies, as schematically represented in the last section. In this paper, we point out the positive correlation of chronic neuro degenerative diseases such as Alzheimer’s disease, Parkinson’s diseases and the insufficient brain wastes clearance by the glymphatic system. We also discuss the role played by the venous vessels as part of such clearance in upright posture. Moreover, simple non-invasive maneuver techniques are introduced here, as one example of enhancement of glymphatic fluid flow out of the skull to join the lymphatic system. A series of questions are raised in Section 8, the answers to which would help us to understand the transition from physio- to pathological states in the development of many diseases. Detailed analysis of this paper leads us to consider that research in understanding this integrative circulation system is only at the infancy stage, and fluid dynamics investigation seems to be the plausible modality of approach in the near future.展开更多
To explore the relationship between the heat-clearing and detoxicating functions and the bacteriostatic actions of berberine hydrochloride (Ber. H), chlorogenic acid (Chlo. A), and baicalin (Bai), their concentr...To explore the relationship between the heat-clearing and detoxicating functions and the bacteriostatic actions of berberine hydrochloride (Ber. H), chlorogenic acid (Chlo. A), and baicalin (Bai), their concentrations in rabbit body fluid were compared with their minimal inhibitory concentrations (MICs). Their concentrations in rabbit blood and tissue fluid were determined by reversed-phase high performance liquid chromatography, and their MICs to Escherichia coli were determined by tube dilution method. The results showed that the peak concentrations of Ber. H, Chlo. A, and Bai in rabbit blood were 3.2, 5.03, and 7.63 μg mL^-1, and in rabbit tissue fluid were 0.12, 0.11, and 0.12 μg mL^-1, respectively. Their MICs to E. coli were, respectively, 1.0×10^3, 3.75 × 10^3, and 6.75 ×10^3μg mL^-1, which were far higher than the concentrations in rabbit body fluids. This study indicates that Ber. H, Chlo. A, and Bai have weak bacteriostatic actions and do not reach their effective inhibitory concentrations in rabbit body fluids, and their heat-clearing and detoxicating functions are independent on the bacteriostatic actions.展开更多
A three-porous-medium model for transvascular exchange and extravascular transport of fluid and macromolecules in a spherical solid tumor is developed. The microvasculature , lymphatics, and tissue space are each trea...A three-porous-medium model for transvascular exchange and extravascular transport of fluid and macromolecules in a spherical solid tumor is developed. The microvasculature , lymphatics, and tissue space are each treated as a porous medium with the flow of blood. lymph, and interstitial fluid obeying Darcy's law and Starling 's assumption. In this part, the role of interstitial pressure and fluid convection are studited. The analytical soiutions are obtained for foe isolated tumor and the normal-tissue-surrounded tumor respectively. The calculated interstitial pressure profue are consistent with the experimental observation that the elevated interstitial pressure is a major barrier in the penetration of macromolecular drug into tumors. The factors which may reduce the interstitial pressure are analyzed in details.展开更多
Literature concerning procoagulant activity of the amniotic fluid and pathomechanism of amniotic fluid embolism (AFE) was surveyed and a new concept of its pathogenesis, called the integrated concept of AFE, was prese...Literature concerning procoagulant activity of the amniotic fluid and pathomechanism of amniotic fluid embolism (AFE) was surveyed and a new concept of its pathogenesis, called the integrated concept of AFE, was presented. According to this concept, two components of the amniotic fluid are involved: (i) apoptosis-affected amniotic cells showing a special role in the initiation of disseminated intravascular coagulation (DIC) and (ii) leukotrienes (formerly called slow-reacting substances), inducing bronchial and pulmonary vascular smooth muscle contraction. Although each of these components initiates a different pathogenic pathway, they both lead to the formation of a mechanical barrier on blood flow through the lungs (amniotic debris + microemboli) and/or functional barrier (pulmonary vasoconstriction). An old dilemma, concerning indications for heparin therapy in AFE was recalled in the light of the new concept.展开更多
To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from ...To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from in vivo tests to clinical trials is expensive and time-consuming.Computational model is seen as a useful analysis tool to make the product development.A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed.The challenging is that models for simulating tissue engineering processes are developed separately.From cell to tissue regeneration,it would go through blood injection after moving out the defect;to cell disperse and attach on the scaffold;to proliferation,migration and differentiation;and to the final part-becoming mature tissues.This paper reviewed models that related to tissue engineering process,aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process.This article focuses on the model analysis methods of cell adhesion,nutrient transport and cell proliferation,differentiation and migration in tissue engineering.In cell adhesion model,one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment.As for nutrient transport model,numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process.For cell proliferation,differentiation and migration,finite element method with random-walk algorithm is one the most advanced way to simulate these processes.Most of the model analysis methods require further experiments to verify the accuracy and effectiveness.Due to the lack of technology to detect the rate of nutrient diffusion,there are especially few researches on model analysis methods in the area of blood coagulation.Therefore,there is still a lot of work to be done in the research of the whole process model method of tissue engineering.In the future,the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.展开更多
基金the National Natural Science Foundation of China(Grant No.:82074031)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant No.:TP2020054)China,and Program for Shanghai High-level Local University Innovation Team(Grant No.:SZY20220315),China.
文摘Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.
基金the Hubei Provincial Natural Science Foundation of China(No.2021cfb375).
文摘Objective This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia,and explore the differences in bad ending between twins and singletons.Methods The present retrospective cohort study was conducted on patients with severe pre-eclampsia,who delivered in Tongji Hospital,Wuhan,China,between 2017 and 2022.The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated.Then,the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid.Results A total of 709 patients were included for the present study.Among these patients,68 patients had twin pregnancies,and 641 patients had singleton pregnancies.The rate of postpartum hemorrhage(2.81%vs.13.24%,P<0.001),and admission rate to the Neonatal Intensive Care Unit(NICU)after birth(30.73%vs.63.24%,P=0.011)were significantly higher in twin pregnancies.The neonatal weight of twins was statistically lower than singletons(1964.73±510.61 g vs.2142.92±731.25 g,P=0.008).For the groups with the third interstitial fluid,the delivery week(P=0.001)and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group,when compared to singleton pregnancy group(P=0.032),and the length of hospital stay was shorter(P=0.044).Furthermore,there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid.Conclusion The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies,when compared to singleton pregnancies.Thus,when patients develop the third interstitial fluid,twin pregnancies would more likely lead to adverse fetal outcomes,when compared to singleton pregnancies,and there would be no significant difference in maternal adverse outcomes.More attention should be given to patients who merge with the third interstitial fluid.
文摘Interstitial fluid plays a vital role in drug delivery and tumour treatment.However,few non-invasive measurement methods are available for measuring low-velocity biological fluid flow.Therefore,this study aimed to develop a novel technology called interstitial flow velocity-MRI.The interstitial flow velocity-MRI sequence consists of a dual inversion recovery preparation and an improved stimulated echo sequence(ISTE)combined with phase-contrast MRI.A homemade flow phantom was used to assess the feasibility and sensitivity of interstitial flow velocity-MRI.In addition,xenografts of female BALB/c mouse models of 4T1 breast cancer administered losartan(40 mg/kg)or saline(n?6)were subjected to imaging on a 7.0 T scanner to assess the in vivo interstitial fluid flow velocity.The results showed a significant correlation(P<0.001)between the theoretical velocities and velocities measured using the flow phantom.Interstitial flow velocity-MRI could detect a velocity as low as 10.21±2.65 mm/s with a spatial resolution of 0.313 mm.The losartan group had a lower mean interstitial fluid velocity than the control group(85±16 vs 113±24 mm/s).In addition,compared to the saline treatment,losartan treatment reduced the proportion of collagen fibres by 10%and 12%in the Masson and Sirius red staining groups,respectively.Interstitial flow velocity-MRI has the potential to determine interstitial fluid flow velocity non-invasively and exhibits an intuitive velocity map.
基金Supported by Grants-in-Aid from Japan Society of the Promotion of Science,No.25670111by Adaptable and Seamless Technology Transfer Program through Target-Driven RD Japan Science and Technology Agency(JST),No.2012-2013+1 种基金by KIT-KPUM-KPU-KPh U Collaborative Research Program,No.2013-2014by Salt Science Foundation(1235)and Cell Research Conference
文摘The pH of body fluids is one the most important keyfactors regulating various cell function such as enzyme activity and protein-protein interaction via modification of its binding affinity. Therefore, to keep cell function normal, the pH of body fluids is maintained constant by various systems. Insulin resistance is one of the most important, serious factors making the body condition worse in diabetes mellitus. I have recently found that the pH of body(interstitial) fluids is lower in diabetes mellitus than that in non-diabetic control, and that the lowered pH is one of the causes producing insulin resistance. In this review article, I introduce importance of body(interstitial) fluid pH in regulation of body function, evidence on abnormal regulation of body fluid pH in diabetes mellitus, and relationship between the body fluid pH and insulin resistance. Further, this review proposes perspective therapies on the basis of regulation of body fluid pH including propolis(honeybee product) diet.
基金financial support of this work (Project Nos. 29890280 29971029).
文摘The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. Meantime artificial neural network was applied to the estimation of log ?values of complexes. The results show that the precipitate species, GdPO4 and Gd2(CO3)3, are the predominant species. Among soluble species, the free Gd(III), [Gd(HSA)] , [Gd(Ox)] and then the ternary complexes of Gd(III) with citrate are main species and [Gd3(OH)4] becomes the predominant species at the Gd(III) total concentration of 2.2?0-2mol/L.
基金supported by Shanghai Leading Academic Disci-pline Project (B112 and T0302)Shanghai Science & Technology Development Foundation (09DZ1976600)Shanghai Rising-Star Program (10QA1406100)
文摘In vitro experiments have shown that subtle fluid flow environment plays a significant role in living biological tissues, while there is no in vivo practical dynamical measurement of the interstitial fluid flow velocity. On the basis of a new finding that capillaries and collagen fibrils in the interosseous membrane form a parallel array, we set up a porous media model simulating the flow field with FLUENT software, studied the shear stress on interstitial cells' surface due to the interstitial fluid flow, and analyzed the effect of flow on protein space distribution around the ceils. The numerical simulation results show that the parallel nature of capillaries could lead to directional interstitial fluid flow in the direction of capillaries. Interstitial fluid flow would induce shear stress on the membrane of interstitial cells, up to 30 Pa or so, which reaches or exceeds the threshold values of cells' biological response observed in vitro. Interstitial fluid flow would induce nonuniform spacial distribution of secretion protein of mast cells. Shear tress on cells could be affected by capillary parameters such as the distance between the adjacent capillaries, blood pressure and the permeability coefficient of capillary's wall. The interstitial pressure and the interstitial porosity could also affect the shear stress on cells. In conclusion, numerical simulation provides an effective way for in vivo dynamic interstitial velocity research, helps to set up the vivid subtle interstitial flow environment of cells, and is beneficial to understanding the physiological functions of interstitial fluid flow.
基金We thank the NNSFC for financial support of this work (Project Nos. 29890280, 29971029).
文摘A multi-phase model of Pr(III) speciation in human interstitial fluid was constructed and insoluble Pr(III) speciation was studied. When the total concentration of Pr(III) is below 8.401E-10 mol/L, soluble Pr(III) species are main species. With rising the total concentration of Pr(III), Pr(III) is firstly bound to phosphate to form precipitate of PrPO4, then bound to carbonate and another precipitate of Pr2(CO3)3 was obtained. When the total concentration is between 1.583E-9 mol/L and 4.000E-3 mol/L, the insoluble species are predominant Pr(III) species.
文摘BACKGROUND DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS)analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation. AIM To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT. METHODS Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated. RESULTS Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively. CONCLUSION Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.
文摘Objective: To investigate the role of subeschar tissue fluid (STF) in postburn cell damage. Methods: STF was collected from patients with full-thickness burn injury of 10% - 69% total body surface area (TFBSA) during operation on postburn day 2 - 4, and that from guinea pigs were obtained in escharectomy 24 h after full-thickness scald injury of 30%’TBSA was induced. Respective incubation of human umbilical vein endothelial cells (HUVEC) and hepatocytes with STF were performed for the observation of the effects of STF on the activity, morphology, physiological function and monolayer cell permeability of HUVEC, and the percentages of apoptotic and necrotic hepatocytes were determined. Results: (l) STF had evident deleterious effect on endothelial cells. (2)are could induce apoptosis and necrosis of hepatocytes. Conclusion: STF plays an important role in causing early postburn damages.
基金This work was financially supported by the National Natural Science Foundation of China(Grants 12050001,82050004,and 11672150).
文摘In the previous studies,the phenomenon that the interstitial fluid(ISF)can flow along tunica adventitia of the arteries and veins in both human and animal bodies was reported.On the basis of these studies,this paper aims to:(i)summarize the basic properties of the ISF flows in the walls of arteries and veins,(ii)combine the basic properties with axiomaticism and abstract the axiom for ISF flows,and(iii)propose three fundamental laws of the ISF flow,(i.e.,the existence law,the homotropic law and the reverse law).The three laws provide solid theoretical basement for exploring the kinematic patterns of interstitial fluid flow in the cardiovascular system.
文摘In vitro tissue culture of hard woody, endangered, medicinal plant Coscinium fenestratum is most challenging to plant tissue culturists. In the present study, petiole and leaf explants of Coscinium fenestratum were induced to form callus when cultured on vermicompost extract media along with coelomic fluid. Suspension medium was developed using vermicompost extract and coelomic fluid in 3:1 ratio. Phytochemical analysis of the alkaloid berberine was confirmed from callus, suspension cell culture and suspension medium by Thin Layer Chromatography and High Performance Liquid Chromatography. Vermicompost and its extracts with coelomic fluid have shown maximum (100 per cent) response of callus induction. Callus mass enlarged with increasing concentration of coelomic fluid and callus growth was assessed from the biomass. Incubation of culture tubes in dark supported callus development significantly. The Rf value of 0.36 confirmed the presence of berberine by Thin Layer Chromatography. Qualitative analysis confirmed the presence of alkaloid berberine with the retention time of 2.8 minutes similar to that of standard reference sample from Sigma chemicals, USA. The suspension medium turned deep yellow because of the release of the alkaloid. Vermicompost and its extracts along with coelomic fluid have shown the economical approach for micropropagation of economically and medicinally important plants.
基金the National Natural Science Foundation of China(81501668)Two-hundred Talent(20161424),Shanghai“Rising Stars of Medical Talent”Youth Development Program(Outstanding Youth Medical Talents),and Shanghai Jiao Tong University“Chenxing”Youth Development Program(Associate Professor Type A).
文摘Background:Use of internal filling ports in tissue expander–based reconstructions are advantageous because of easier self-care,lower infection rates,and fewer instances of capsule formation.The appearance of periprosthetic fluid accumulation after internal-port tissue expander implantation is a common complication that warrants treatment.In this study,we introduced a noninvasive method using fine-needle aspiration(FNA)to remove fluids accumulated after implantation of a remote internal-port tissue expander.Methods:In this study,245 patients who underwent implantation of remote internal-port tissue expanders in our hospital from July 1,2012,to July 1,2019,were included and divided into two groups.In the control group,patients underwent tissue expander implantation before July 1,2016,and large quantities of fluids were removed with surgical aspiration procedures in most cases.In the FNA group,the patients underwent implantation after July 1,2016,and large quantities of fluids were removed first with the FNA procedure.Patients’demographic data,indications for FNA application,and related complications were collected and analyzed.Results:Overall,395 expanders were placed in 245 patients.Postoperative management was similar in both groups.Fluids were managed with 23 expanders in the control group and with 31 expanders in the FNA group.There was no difference in the fluid aspiration rate between the two groups.The surgical aspiration rate was 11.1%(23/208)in the control group.The success rate of FNA was 90.3%(28/31).In the FNA group,the surgical aspiration rate was 1.6%(3/187),which was significantly lower than that in the control group.There were no significant differences in complications between the two groups.Conclusion:FNA can be used for periprosthetic fluid removal after the implantation of a remote internal-port tissue expander in most cases.This method is more convenient and safer than surgical aspiration for the postoperative management of internal-port tissue expander implantation.
基金supported by the Major Program of the National Natural Science Foundation of China(62394310,62394313,62394314)the National Natural Science Foundation of China(12126601)+5 种基金the R&D project of Pazhou Lab(Huangpu)(2023K0608)the China Postdoctoral Science Foundation(2022M720294)Intelligent Basic Theory Innovation Research fund(201CXCY-A01-08-00-29)GuangDong Basic and Applied Basic Research Foundation(2022A1515110674)Medical Scientific Research Foundation of Guangdong Province of China(B2022067)Science Foundation of AMHT(2021YK11)。
文摘Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial implantation(EAI),for accelerating interstitial fluid(ISF)drainage,which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS).In this study,the method of EAI was modified(m-EAI)to control its function of accelerating the ISF drainage at different time points following ischemic attack.The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model.The results demonstrated the accumulation of IL-1β,IL-6,and TNF-αwas significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats,accompanied with decreased infarct volume and improved neurological function.This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS.Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.
文摘Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells.The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow.However,osmotic pressure- related factors have not been studied until now.In this prospective observational study,to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF),we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions.Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg.Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007,respectively,the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e.,290.5–291.5 mOsm/L).There was strong correlation between CSF osmolality and serum osmolality,but the difference in osmolality between serum and CSF was not correlated with serum osmolality,serum electrolyte levels,protein levels,or quotient of albumin.In conclusion,CSF osmolarity was suggested to be equal to serum osmolarity.Osmolarity is not one of the driving forces of this bulk flow.Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma.This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No.IRB No.2015-1-257) on July 29,2015.
文摘Water is the key medium to transport numerous constituents and to provide a platform for physiological processes to take place in the living organisms in general;it also participates actively in many of these processes. In humans, there are different vehicles to contain water and its constituents. Our objective is to find out whether there is an overall water-base circulation system in the human body by analyzing the updated findings of different research groups on the physiological functions of various seemingly isolated fluid systems. By 1963, there were five separate fluid systems discovered in mammalians: (i) The Primo Vasculature Fluid (PVF) with protein precursors and micro cells held in the Primo Vasculature System (PVS). (ii) Blood with its constituents held in the cardio vasculature. (iii) Extracranial interstitial fluid (ISF) whose vehicle had a very irregular structure—the interstitium all over the body. (iv) The cerebrospinal fluid had been considered to be within the brain ventricles and spinal canal. (v) The extra-cranial lymphatic system which drained ISF, and had been known to join the subclavian vein. Fluid (i) was first reported in 1963 and fluids (ii) to (v) have been known for many decades, but the failure to detect a lymphatic system inside the skull has also been a mystery for many decades. The intra-cranial ISF (which we name as BISF) has drawn little attention, apart from discussing the mechanism of the blood-brain-barrier. During the past decade, there has been direct evidence indicating that CSF and BISF are actually mixed. After that, the intracranial lymphatic system was discovered and confirmed in animal models only slightly over one year back, and we called such fluid as glymphatic-fluid. After reviewing the stated “classical” five fluid systems together with the new findings in Sections 2 - 7, we propose, for the first time, that the PVF, the blood, ISF, a mixture of CSF-BISF, and a mixture of glymphatic-fluid and lymph form an integrative circulation system in water base in the human and other mammalian bodies, as schematically represented in the last section. In this paper, we point out the positive correlation of chronic neuro degenerative diseases such as Alzheimer’s disease, Parkinson’s diseases and the insufficient brain wastes clearance by the glymphatic system. We also discuss the role played by the venous vessels as part of such clearance in upright posture. Moreover, simple non-invasive maneuver techniques are introduced here, as one example of enhancement of glymphatic fluid flow out of the skull to join the lymphatic system. A series of questions are raised in Section 8, the answers to which would help us to understand the transition from physio- to pathological states in the development of many diseases. Detailed analysis of this paper leads us to consider that research in understanding this integrative circulation system is only at the infancy stage, and fluid dynamics investigation seems to be the plausible modality of approach in the near future.
基金supported by a grant from Beijing Natural Science Foundation, China (6021001)agrant from Learning Innovative Group Programs of Beijing Education Committee, China (5090245)
文摘To explore the relationship between the heat-clearing and detoxicating functions and the bacteriostatic actions of berberine hydrochloride (Ber. H), chlorogenic acid (Chlo. A), and baicalin (Bai), their concentrations in rabbit body fluid were compared with their minimal inhibitory concentrations (MICs). Their concentrations in rabbit blood and tissue fluid were determined by reversed-phase high performance liquid chromatography, and their MICs to Escherichia coli were determined by tube dilution method. The results showed that the peak concentrations of Ber. H, Chlo. A, and Bai in rabbit blood were 3.2, 5.03, and 7.63 μg mL^-1, and in rabbit tissue fluid were 0.12, 0.11, and 0.12 μg mL^-1, respectively. Their MICs to E. coli were, respectively, 1.0×10^3, 3.75 × 10^3, and 6.75 ×10^3μg mL^-1, which were far higher than the concentrations in rabbit body fluids. This study indicates that Ber. H, Chlo. A, and Bai have weak bacteriostatic actions and do not reach their effective inhibitory concentrations in rabbit body fluids, and their heat-clearing and detoxicating functions are independent on the bacteriostatic actions.
文摘A three-porous-medium model for transvascular exchange and extravascular transport of fluid and macromolecules in a spherical solid tumor is developed. The microvasculature , lymphatics, and tissue space are each treated as a porous medium with the flow of blood. lymph, and interstitial fluid obeying Darcy's law and Starling 's assumption. In this part, the role of interstitial pressure and fluid convection are studited. The analytical soiutions are obtained for foe isolated tumor and the normal-tissue-surrounded tumor respectively. The calculated interstitial pressure profue are consistent with the experimental observation that the elevated interstitial pressure is a major barrier in the penetration of macromolecular drug into tumors. The factors which may reduce the interstitial pressure are analyzed in details.
文摘Literature concerning procoagulant activity of the amniotic fluid and pathomechanism of amniotic fluid embolism (AFE) was surveyed and a new concept of its pathogenesis, called the integrated concept of AFE, was presented. According to this concept, two components of the amniotic fluid are involved: (i) apoptosis-affected amniotic cells showing a special role in the initiation of disseminated intravascular coagulation (DIC) and (ii) leukotrienes (formerly called slow-reacting substances), inducing bronchial and pulmonary vascular smooth muscle contraction. Although each of these components initiates a different pathogenic pathway, they both lead to the formation of a mechanical barrier on blood flow through the lungs (amniotic debris + microemboli) and/or functional barrier (pulmonary vasoconstriction). An old dilemma, concerning indications for heparin therapy in AFE was recalled in the light of the new concept.
基金supported by the Versus Arthritis Research UK(Grant No:21977)European Commission via a H2020-MSCA-RISE programme(BAMOS,Grant No:734156)+1 种基金Innovative UK via Newton Fund(Grant No:102872)Engineering and Physical Science Research Council(EPSRC)via DTP CASE programme(Grant No:EP/T517793/1)。
文摘To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites etc.The whole process from in vivo tests to clinical trials is expensive and time-consuming.Computational model is seen as a useful analysis tool to make the product development.A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are reviewed.The challenging is that models for simulating tissue engineering processes are developed separately.From cell to tissue regeneration,it would go through blood injection after moving out the defect;to cell disperse and attach on the scaffold;to proliferation,migration and differentiation;and to the final part-becoming mature tissues.This paper reviewed models that related to tissue engineering process,aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering process.This article focuses on the model analysis methods of cell adhesion,nutrient transport and cell proliferation,differentiation and migration in tissue engineering.In cell adhesion model,one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell attachment.As for nutrient transport model,numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport process.For cell proliferation,differentiation and migration,finite element method with random-walk algorithm is one the most advanced way to simulate these processes.Most of the model analysis methods require further experiments to verify the accuracy and effectiveness.Due to the lack of technology to detect the rate of nutrient diffusion,there are especially few researches on model analysis methods in the area of blood coagulation.Therefore,there is still a lot of work to be done in the research of the whole process model method of tissue engineering.In the future,the numerical model would be seen as an optimal way to investigate tissue engineering products bioperformance and also enable to optimize the parameters and material types of the tissue engineering products.