Obstructive jaundice is a common clinical symptom generally caused by bile duct stones,inflammatory hyperplasia,and tumors.It is characterized by hyperbilirubinemia and may trigger a variety of complications such as h...Obstructive jaundice is a common clinical symptom generally caused by bile duct stones,inflammatory hyperplasia,and tumors.It is characterized by hyperbilirubinemia and may trigger a variety of complications such as hypotension,kidney injury,endotoxemia,multiple organ dysfunction syndrome,and even death(Pavlidis and Pavlidis,2018;Liu et al.,2021).Relieving bile duct obstruction and providing adequate drainage have been considered as the most effective therapies for obstructive jaundice.However,it has not yet been established whether it is beneficial to treat affected patients by pre-operative biliary drainage(Blacker et al.,2021).Moreover,the pathophysiological changes or mechanisms associated with the reversal of organ function following the relief of bile-duct obstruction are unclear(Huang et al.,2004).Therefore,it is necessary to establish an experimental model of reversible obstructive jaundice to simulate biliary drainage in clinical practice.展开更多
Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironmen...Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.展开更多
Sepsis is responsible for approximately 5.3 million deaths globally each year.Here,we constructed hierarchical chitin microspheres loaded with MOF-919(Ch/metal–organic frameworks[MOFs])for the rapid and efficient rem...Sepsis is responsible for approximately 5.3 million deaths globally each year.Here,we constructed hierarchical chitin microspheres loaded with MOF-919(Ch/metal–organic frameworks[MOFs])for the rapid and efficient removal of lipopolysaccharide(LPS)in complex blood environments.Furthermore,abun-dant active sites on MOF-919(Sc)also enable a record-high adsorption capacity of 9.56 mg/g in biomass-based adsorbents due to the coordination interactions between endotoxin and MOF-919(Sc).The LPS level of sepsis rabbits was less than 2 EU/mL(clearance rate>95%)after 90-min hemoperfusion,showing no adverse effect on the rabbit organs.Additionally,compared to the commonly used LPS scrubber Toraymyxin(polymethyl methacrylate),the chitin adsorbent is significantly more cost-effective and environmentally friendly.The prepara-tion strategy for hierarchical porous microspheres offers notable advantages in designability,recyclability,and renewability,providing a new approach to sepsis treatment and promising prospects for the biomedical application of sustainable biomass materials.展开更多
Background:Minimally invasive surgeries are increasingly central to modern medicine,particularly in liver transplantation.These techniques,which offer reduced trauma,precise operations,minimal bleeding,and swift recov...Background:Minimally invasive surgeries are increasingly central to modern medicine,particularly in liver transplantation.These techniques,which offer reduced trauma,precise operations,minimal bleeding,and swift recovery,are,however,unevenly adopted across China.Only a limited number of centers routinely perform minimally invasive donor hepatectomies,indicating a significant imbalance in the development and application of these advanced procedures.Additionally,there lacks a set of standardized guidelines that are tailored to meet China’s unique healthcare challenges and conditions.Methods:In August 2023,the Branch of Organ Transplant of Chinese Medical Association and the Branch of Organ Transplant Physicians of Chinese Medical Doctor Association convened a group of national liver transplantation experts to establish a guideline development committee.This committee conducted a thorough review of relevant literature,evaluated existing guidelines and consensus,and assessed factors such as the evidence base,patient preferences,and the cost-effectiveness of interventions within China.After multiple rounds of discussions,both online and offline,the committee finalized the guidelines.Results:This collaborative effort led to the creation of the“Chinese guidelines for minimally invasive donor hepatectomy in living donor liver transplantation(2024 edition)”.These guidelines address crucial aspects such as the safety and advantages of minimally invasive surgery for living donor liver transplantation,donor selection criteria,anesthesia strategies,surgical technical details,and learning curves associated with these procedures,resulting in a comprehensive set of 26 recommendations.Conclusions:The formulation of these guidelines represents a significant advancement towards standardizing minimally invasive liver transplantation surgeries in China.They are designed to enhance outcomes for both donors and recipients by synthesizing expert consensus with contemporary research and clinical practices.Moreover,they serve as a crucial reference for surgeons and medical institutions,promoting the refinement and adoption of minimally invasive surgical techniques in liver transplantation.展开更多
Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα i...Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.展开更多
基金National Natural Science Foundation of China(Nos.51803153 and 81970548)Wuhan Science and Technology Project(No.2019020701011485)+1 种基金Medical Science Advancement Program(Clinical Medicine)of Wuhan University(No.TFLC 2018003)Zhongnan Hospital of Wuhan University Science,Technology,and Innovation Seed Fund(No.CXPY2020049),China.
文摘Obstructive jaundice is a common clinical symptom generally caused by bile duct stones,inflammatory hyperplasia,and tumors.It is characterized by hyperbilirubinemia and may trigger a variety of complications such as hypotension,kidney injury,endotoxemia,multiple organ dysfunction syndrome,and even death(Pavlidis and Pavlidis,2018;Liu et al.,2021).Relieving bile duct obstruction and providing adequate drainage have been considered as the most effective therapies for obstructive jaundice.However,it has not yet been established whether it is beneficial to treat affected patients by pre-operative biliary drainage(Blacker et al.,2021).Moreover,the pathophysiological changes or mechanisms associated with the reversal of organ function following the relief of bile-duct obstruction are unclear(Huang et al.,2004).Therefore,it is necessary to establish an experimental model of reversible obstructive jaundice to simulate biliary drainage in clinical practice.
基金This work was supported by the National Natural Science Foundation of China(Grant No.:NSFC 81871493,81871503)the Medical Science Advancement Program(Clinical Medicine)of Wuhan University(Grant No.:TFLC2018002,2018003)。
文摘Peripheral nerve regeneration requires stepwise and well-organized establishment of microenvironment.Since local delivery of VEGF-A in peripheral nerve repair is expected to promote angiogenesis in the microenvironment and Schwann cells(SCs)play critical role in nerve repair,combination of VEGF and Schwann cells may lead to efficient peripheral nerve regeneration.VEGF-A overexpressing Schwann cells were established and loaded into the inner wall of hydroxyethyl cellulose/soy protein isolate/polyaniline sponge(HSPS)conduits.When HSPS is mechanically distorted,it still has high durability of strain strength,thus,can accommodate unexpected strain of nerve tissues in motion.A 10 mm nerve defect rat model was used to test the repair performance of the HSPS-SC(VEGF)conduits,meanwhile the HSPS,HSPS-SC,HSPS-VEGF conduits and autografts were worked as controls.The immunofluorescent co-staining of GFP/VEGF-A,Ki67 and MBP showed that the VEGF-A overexpressing Schwann cells could promote the proliferation,migration and differentiation of Schwann cells as the VEGF-A was secreted from the VEGF-A overexpressing Schwann cells.The nerve repair performance of the multifunctional and flexible conduits was examined though rat behavioristics,electrophysiology,nerve innervation to gastrocnemius muscle(GM),toluidine blue(TB)staining,transmission electron microscopy(TEM)and NF200/S100 double staining in the regenerated nerve.The results displayed that the effects on the repair of peripheral nerves in HSPS-SC(VEGF)group was the best among the conduits groups and closed to autografts.HSPS-SC(VEGF)group exhibited notably increased CD31+endothelial cells and activation of VEGFR2/ERK signaling pathway in the regenerated nerve tissues,which probably contributed to the improved nerve regeneration.Altogether,the comprehensive strategy including VEGF overexpressing Schwann cells-mediated and HSPS conduit-guided peripheral nerve repair provides a new avenue for nerve tissue engineering.
基金National Natural Science Foundation of China,Grant/Award Number:22075215Key Research and Development Program of Hubei Province,Grant/Award Number:2021BCA122+1 种基金Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University,Grant/Award Number:ZNJC202238Fundamental Research Funds for the Central Universities,Grant/Award Number:691000003。
文摘Sepsis is responsible for approximately 5.3 million deaths globally each year.Here,we constructed hierarchical chitin microspheres loaded with MOF-919(Ch/metal–organic frameworks[MOFs])for the rapid and efficient removal of lipopolysaccharide(LPS)in complex blood environments.Furthermore,abun-dant active sites on MOF-919(Sc)also enable a record-high adsorption capacity of 9.56 mg/g in biomass-based adsorbents due to the coordination interactions between endotoxin and MOF-919(Sc).The LPS level of sepsis rabbits was less than 2 EU/mL(clearance rate>95%)after 90-min hemoperfusion,showing no adverse effect on the rabbit organs.Additionally,compared to the commonly used LPS scrubber Toraymyxin(polymethyl methacrylate),the chitin adsorbent is significantly more cost-effective and environmentally friendly.The prepara-tion strategy for hierarchical porous microspheres offers notable advantages in designability,recyclability,and renewability,providing a new approach to sepsis treatment and promising prospects for the biomedical application of sustainable biomass materials.
基金supported by grants from National Key R&D Program of China(No.2022YFC2304705 to Jiayin Yang)National Natural Science Foundation of China(No.82270691 to Jiayin Yang)+2 种基金Sichuan Province Key Research and Development Project(Nos.2023YFS0026 and 23ZDYF2182 to Jiayin Yang)Chengdu Province Key Research and Development Project(No.2022YF0900009SN to Jiayin Yang)1.3.5 Project for Disciplines of Excellence from West China Hospital of Sichuan University(No.ZYGD24002 to Jiayin Yang).
文摘Background:Minimally invasive surgeries are increasingly central to modern medicine,particularly in liver transplantation.These techniques,which offer reduced trauma,precise operations,minimal bleeding,and swift recovery,are,however,unevenly adopted across China.Only a limited number of centers routinely perform minimally invasive donor hepatectomies,indicating a significant imbalance in the development and application of these advanced procedures.Additionally,there lacks a set of standardized guidelines that are tailored to meet China’s unique healthcare challenges and conditions.Methods:In August 2023,the Branch of Organ Transplant of Chinese Medical Association and the Branch of Organ Transplant Physicians of Chinese Medical Doctor Association convened a group of national liver transplantation experts to establish a guideline development committee.This committee conducted a thorough review of relevant literature,evaluated existing guidelines and consensus,and assessed factors such as the evidence base,patient preferences,and the cost-effectiveness of interventions within China.After multiple rounds of discussions,both online and offline,the committee finalized the guidelines.Results:This collaborative effort led to the creation of the“Chinese guidelines for minimally invasive donor hepatectomy in living donor liver transplantation(2024 edition)”.These guidelines address crucial aspects such as the safety and advantages of minimally invasive surgery for living donor liver transplantation,donor selection criteria,anesthesia strategies,surgical technical details,and learning curves associated with these procedures,resulting in a comprehensive set of 26 recommendations.Conclusions:The formulation of these guidelines represents a significant advancement towards standardizing minimally invasive liver transplantation surgeries in China.They are designed to enhance outcomes for both donors and recipients by synthesizing expert consensus with contemporary research and clinical practices.Moreover,they serve as a crucial reference for surgeons and medical institutions,promoting the refinement and adoption of minimally invasive surgical techniques in liver transplantation.
基金National Natural Science Foundation of China(Nos.81673503 and 82204485)China Postdoctoral Science Foundation(2022M712459)+5 种基金Fundamental Research Funds for the Central Universities(2042022kf0022,China)Joint Incubation Fund for Basic Medical and Clinical Research in Wuhan University(JCZN2022006,China)Joint Foundation for Translational Medicine and Interdisciplinary Research in Zhongnan Hospital(ZNLH201903,ZNLH202319,China)Science and Technology Innovation Cultivation Fund of Zhongnan Hospital(CXPY2022083,China)Program of Excellent Doctoral(Postdoctoral)of Zhongnan Hospital of Wuhan University(ZNYB20240002,China)12th batch of grassland talents innovation and entrepreneurship talent team in Inner Mongolia(China).
文摘Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.
