Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 ...Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual.展开更多
Selective laser melting(SLM)is an emerging layer-wise additive manufacturing technique that can generate complex components with high performance.Particulate-reinforced aluminum matrix composites(PAMCs)are important m...Selective laser melting(SLM)is an emerging layer-wise additive manufacturing technique that can generate complex components with high performance.Particulate-reinforced aluminum matrix composites(PAMCs)are important materials for various applications due to the combined properties of Al matrix and reinforcements.Considering the advantages of SLM technology and PAMCs,the novel SLM PAMCs have been developed and researched in recent years.Therefore,the current research progress about the SLM PAMCs is reviewed.Firstly,special attention is paid to the solidification behavior of SLM PAMCs.Secondly,the important issues about the design and fabrication of high-performance SLM PAMCs,including the selection of reinforcement,the influence of parameters on the processing and microstructure,the defect evolution and phase control,are highlighted and discussed comprehensively.Thirdly,the performance and strengthening mechanism of SLM PAMCs are systematically figured out.Finally,future directions are pointed out on the advancement of high-performance SLM PAMCs.展开更多
Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires ...Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.展开更多
Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can l...Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.展开更多
Magnesium(Mg) alloys possess comparable physical and mechanical properties to bone, making them an outstanding candidate of implant materials for bone fracture treatment. In addition to the excellent biocompatibility,...Magnesium(Mg) alloys possess comparable physical and mechanical properties to bone, making them an outstanding candidate of implant materials for bone fracture treatment. In addition to the excellent biocompatibility, and bioactivity, the engagement of Mg alloys is key for a number of biological functionalities in the human body. The unique biodegradation nature of Mg alloy implants implies that it may not require a secondary removal procedure when the expected supporting tasks accomplish, as they may simply and safely "disappear" over time. Nonetheless, the demonstrated drawback of potentially rapid degradation, is an issue that must be addressed appropriately for Mg implants and is consequently given unique attention in this review article. Herein, the critical criteria and the state-of-the-art strategies for controlling the degradation process of Mg alloys are reported. Furthermore, future developments of biodegradable Mg and its alloys systems with satisfactory specifications for clinical trials and deployment,are discussed. This review aims to provide information to materials scientists and clinical practitioners in the context of developing practical biodegradable Mg alloys.展开更多
Adult patients with developmental dysplasia of the hip develop secondary osteoarthritis and eventually end up with total hip arthroplasty(THA) at younger age. Because of altered anatomy of dysplastic hips, THA in thes...Adult patients with developmental dysplasia of the hip develop secondary osteoarthritis and eventually end up with total hip arthroplasty(THA) at younger age. Because of altered anatomy of dysplastic hips, THA in these patients represents technically demanding procedure. Distorted anatomy of the acetabulum and proximal femur together with conjoined leg length discrepancy present major challenges during performing THA in patients with developmental dysplasia of the hip. In addition, most patients are at younger age, therefore, soft tissue balance is of great importance(especially the need to preserve the continuity of abductors) to maximise postoperative functional result. In this paper we present a variety of surgical techniques availablefor THA in dysplastic hips, their advantages and disadvantages. For acetabular reconstruction following techniques are described: Standard metal augments(prefabricated), Custom made acetabular augments(3D printing), Roof reconstruction with vascularized fibula, Roof reconstruction with pedicled iliac graft, Roof reconstruction with autologous bone graft, Roof reconstruction with homologous bone graft, Roof reconstruction with auto/homologous spongious bone, Reinforcement ring with the hook in combination with autologous graft augmentation, Cranial positioning of the acetabulum, Medial protrusion technique(cotyloplasty) with chisel, Medial protrusion technique(cotyloplasty) with reaming, Cotyloplasty without spongioplasty. For femoral reconstruction following techniques were described: Distraction with external fixator, Femoral shortening through a modified lateral approach, Transtrochanteric osteotomies, Paavilainen osteotomy, Lesser trochanter osteotomy, Double-chevron osteotomy, Subtrochanteric osteotomies, Diaphyseal osteotomies, Distal femoral osteotomies. At the end we present author's treatment method of choice: for acetabulum we perform cotyloplasty leaving only paper-thin medial wall, which we break during acetabular cup impacting. For femoral side first we peel of all ro展开更多
Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an import...Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an important diagnostic and therapeutic tool leading to avoidance of aggressive and unnecessary surgery in many clinical scenarios. This paper focuses on the newly developed SpyGlass DS technology, its advantages, and the technique of single-operator cholangioscopy(SOC), biliary indications and possible adverse events. We also review the available literature; discuss the limitations and future expectations.Digital SOC(D-SOC) is a useful technique, which provides endoscopic imaging of the biliary tree, optical diagnosis, biopsy under direct vision and therapeutic interventions. The implementations are diagnostic and therapeutic. Diagnostic indications are indeterminate biliary strictures, unclear filling defects, staging of cholangiocarcinoma, staging of ampullary tumors(extension into the common bile duct), unclear bile duct dilation, exploring cystic lesions of the biliary tree,unexplained hemobilia, posttransplant biliary complications. Therapeutic indications are lithotripsy of difficult stones, retrieval of migrated stents, foreign body removal, guide wire placement, transpapillary gallbladder drainage and endoscopic tumor ablative therapy. Most studied and established indications are the diagnosis of indeterminate biliary stricture and intraductal lithotripsy of difficult stones. The adverse events are not different and more common compared to those of Endoscopic retrograde cholangiopancreatography(ERCP)alone. D-SOC is a safe and effective procedure, adjunct to the standard ERCP and the newly available digital technology overcomes many of the limitations of the previous generations of cholangioscopes.展开更多
AIM: To perform a systematic review and metaanalysis on robotic-assisted vs laparoscopic liver resections.METHODS: A systematic literature search was performed using Pub Med, Scopus and the Cochrane Library Central. P...AIM: To perform a systematic review and metaanalysis on robotic-assisted vs laparoscopic liver resections.METHODS: A systematic literature search was performed using Pub Med, Scopus and the Cochrane Library Central. Participants of any age and sex, who underwent robotic or laparoscopic liver resection were considered following these criteria:(1) studies comparing robotic and laparoscopic liver resection;(2) studies reporting at least one perioperative outcome; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measures were set for estimated blood loss, operative time, conversion rate, R1 resection rate, morbidity and mortality rates, hospital stay and major hepatectomy rates.RESULTS: A total of 7 articles, published between 2010 and 2014, fulfilled the selection criteria. The laparoscopic approach was associated with a significant reduction in blood loss and lower operative time(MD = 83.96, 95%CI: 10.51-157.41, P = 0.03; MD = 68.43, 95%CI: 39.22-97.65, P < 0.00001, respectively). No differences were found with respect to conversion rate, R1 resection rate, morbidity and hospital stay.CONCLUSION: Laparoscopic liver resection resulted in reduced blood loss and shorter surgical times compared to robotic liver resections. There was no difference in conversion rate, R1 resection rate, morbidity and length of postoperative stay.展开更多
Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and op...Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.展开更多
According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when c...According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.展开更多
Background Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chi...Background Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chinese patients with Duchenne or Becker muscular dystrophy （DMD/BMD）, and to study genotype-phenotype correlation.展开更多
Liver transplantation is the current standard of care for end-stage liver disease and an accepted therapeutic option for acute liver failure and primary liver tumors.Despite the remarkable advances in the surgical tec...Liver transplantation is the current standard of care for end-stage liver disease and an accepted therapeutic option for acute liver failure and primary liver tumors.Despite the remarkable advances in the surgical techniques and immunosuppressive therapy,the postoperative morbidity and mortality still remain high and the leading causes are biliary complications,which affect up to one quarter of recipients.The most common biliary complications are anastomotic and non-anastomotic biliary strictures,leaks,bile duct stones,sludge and casts.Despite the absence of a recommended treatment algorithm many options are available,such as surgery,percutaneous techniques and interventional endoscopy.In the last few years,endoscopic techniques have widely replaced the more aggressive percutaneous and surgical approaches.Endoscopic retrograde cholangiography is the preferred technique when duct-to-duct anastomosis has been performed.Recently,new devices and techniques have been developed and this has led to a remarkable increase in the success rate of minimally invasive procedures.Understanding the mechanisms of biliary complications helps in their early recognition which is the prerequisite for successful treatment.Aggressive endoscopic therapy is essential for the reduction of morbidity and mortality in these cases.This article focuses on the common post-transplant biliary complications and the available interventional treatment modalities.展开更多
In plants, the hormone auxin shapes gene expression to regulate growth and development. Despite the detailed characterization of auxin-inducible genes, a comprehensive overview of the temporal and spatial dynamics of ...In plants, the hormone auxin shapes gene expression to regulate growth and development. Despite the detailed characterization of auxin-inducible genes, a comprehensive overview of the temporal and spatial dynamics of auxinregulated gene expression is lacking. Here, we analyze transcriptome data from many publicly available Arabidopsis profiling experiments and assess tissue-specific gene expression both in response to auxin concentration and exposure time and in relation to other plant growth regulators. Our analysis shows that the primary response to auxin over a wide range of auxin application conditions and in specific tissues comprises almost exclusively the up-regulation of genes and iden- tifies the most robust auxin marker genes. Tissue-specific auxin responses correlate with differential expression of Aux/ IAA genes and the subsequent regulation of context- and sequence-specific patterns of gene expression. Changes in transcript levels were consistent with a distinct sequence of conjugation, increased transport capacity and down-regulation of biosynthesis in the temperance of high cellular auxin concentrations. Our data show that auxin regulates genes associated with the biosynthesis, catabolism and signaling pathways of other phytohormones. We present a transcriptional overview of the auxin response. Specific interactions between auxin and other phytohormones are highlighted, particularly the regulation of their metabolism. Our analysis provides a roadmap for auxin-dependent processes that underpins the concept of an ＇auxin code＇-a tissue-specific fingerprint of gene expression that initiates specific developmental processes.展开更多
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has m...Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.展开更多
Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T...Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work to- gether to regulate T lymphocyte development and function.展开更多
Chronic hepatitis B virus (HBV) infection affects about 350 million individuals worldwide. Management of HBV infection in pregnancy is difficult because of several peculiar and somewhat controversial aspects. The aim ...Chronic hepatitis B virus (HBV) infection affects about 350 million individuals worldwide. Management of HBV infection in pregnancy is difficult because of several peculiar and somewhat controversial aspects. The aim of the present review is to provide a tool that may help physicians to correctly manage HBV infection in pregnancy. This review focuses on (1) the effect of pregnancy on HBV infection and of HBV infection on pregnancy; (2) the potential viral transmission from mother to newborn despite at-birth prophylaxis with immunoglobulin and vaccine; (3) possible prevention of mother-to-child transmission through antiviral drugs, the type of antiviral drug to use considering their efficacy and potential teratogenic effect, and the timing of their administration and discontinuation; and (4) the evidence for the use of elective caesarean section vs vaginal delivery and the possibility of breastfeeding.展开更多
AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fl...AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.展开更多
文摘Nonalcoholic fatty liver disease (NAFLD) has, although it is a very common disorder, only relatively recently gained broader interest among physicians and scientists. Fatty liver has been documented in up to 10 to 15 percent of normal individuals and 70 to 80 percent of obese individuals. Although the pathophysiology of NAFLD is still subject to intensive research, several players and mechanisms have been suggested based on the substantial evidence. Excessive hepatocyte triglyceride accumulation resulting from insulin resistance is the first step in the proposed 'two hit' model of the pathogenesis of NAFLD. Oxidative stress resulting from mitochondrial fatty acids oxidation, NF-κB-dependent inflammatory cytokine expression and adipocytokines are all considered to be the potential factors causing second hits which lead to hepatocyte injury, inflammation and fibrosis. Although it was initially believed that NAFLD is a completely benign disorder, histologic follow-up studies have showed that fibrosis progression occurs in about a third of patients. A small number of patients with NAFLD eventually ends up with end-stage liver disease and even hepatocellular carcinoma. Although liver biopsy is currently the only way to confirm the NAFLD diagnosis and distinguish between fatty liver alone and NASH, no guidelines or firm recommendations can still be made as for when and in whom it is necessary. Increased physical activity, gradual weight reduction and in selected cases bariatric surgery remain the mainstay of NAFLD therapy. Studies with pharmacologic agents are showing promising results, but available data are still insufficient to make specific recommendations; their use therefore remains highly individual.
基金Project(GJHZ20190822095418365)supported by Shenzhen International Cooperation Research,ChinaProject(2019011)supported by NTUT-SZU Joint Research Program,China+2 种基金Project(2019040)supported by Natural Science Foundation of Shenzhen University,ChinaProject(JCYJ20190808144009478)supported by Shenzhen Fundamental Research Fund,ChinaProject(ZDYBH201900000008)supported by Shenzhen Bureau of Industry and Information Technology,China。
文摘Selective laser melting(SLM)is an emerging layer-wise additive manufacturing technique that can generate complex components with high performance.Particulate-reinforced aluminum matrix composites(PAMCs)are important materials for various applications due to the combined properties of Al matrix and reinforcements.Considering the advantages of SLM technology and PAMCs,the novel SLM PAMCs have been developed and researched in recent years.Therefore,the current research progress about the SLM PAMCs is reviewed.Firstly,special attention is paid to the solidification behavior of SLM PAMCs.Secondly,the important issues about the design and fabrication of high-performance SLM PAMCs,including the selection of reinforcement,the influence of parameters on the processing and microstructure,the defect evolution and phase control,are highlighted and discussed comprehensively.Thirdly,the performance and strengthening mechanism of SLM PAMCs are systematically figured out.Finally,future directions are pointed out on the advancement of high-performance SLM PAMCs.
文摘Mesenchymal stromal cells(MSCs) are currently being investigated for use in a wide variety of clinical applications. For most of these applications, systemic delivery of the cells is preferred. However, this requires the homing and migration of MSCs to a target tissue. Although MSC hominghas been described, this process does not appear to be highly efficacious because only a few cells reach the target tissue and remain there after systemic administration. This has been ascribed to low expression levels of homing molecules, the loss of expression of such molecules during expansion, and the heterogeneity of MSCs in cultures and MSC culture protocols. To overcome these limitations, different methods to improve the homing capacity of MSCs have been examined. Here, we review the current understanding of MSC homing, with a particular focus on homing to bone marrow. In addition, we summarize the strategies that have been developed to improve this process. A better understanding of MSC biology, MSC migration and homing mechanisms will allow us to prepare MSCs with optimal homing capacities. The efficacy of therapeutic applications is dependent on efficient delivery of the cells and can, therefore, only benefit from better insights into the homing mechanisms.
文摘Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.
基金financial support through VC Fellowships and Enabling Capability Platform for Advanced Manufacturing and FabricationFinancial support from the Australian Research Council through DECRA (DE130100090) and Linkage Schemes (LP150100343) is also gratefully acknowledged+2 种基金 support by the National Natural Science Foundation of China (51571134)Shandong University of Science and Technology Research Fund (2014TDJH104)supported by the Natural Science Foundation of the Higher Education Institute of Jiangsu Province (17KJB430003)
文摘Magnesium(Mg) alloys possess comparable physical and mechanical properties to bone, making them an outstanding candidate of implant materials for bone fracture treatment. In addition to the excellent biocompatibility, and bioactivity, the engagement of Mg alloys is key for a number of biological functionalities in the human body. The unique biodegradation nature of Mg alloy implants implies that it may not require a secondary removal procedure when the expected supporting tasks accomplish, as they may simply and safely "disappear" over time. Nonetheless, the demonstrated drawback of potentially rapid degradation, is an issue that must be addressed appropriately for Mg implants and is consequently given unique attention in this review article. Herein, the critical criteria and the state-of-the-art strategies for controlling the degradation process of Mg alloys are reported. Furthermore, future developments of biodegradable Mg and its alloys systems with satisfactory specifications for clinical trials and deployment,are discussed. This review aims to provide information to materials scientists and clinical practitioners in the context of developing practical biodegradable Mg alloys.
文摘Adult patients with developmental dysplasia of the hip develop secondary osteoarthritis and eventually end up with total hip arthroplasty(THA) at younger age. Because of altered anatomy of dysplastic hips, THA in these patients represents technically demanding procedure. Distorted anatomy of the acetabulum and proximal femur together with conjoined leg length discrepancy present major challenges during performing THA in patients with developmental dysplasia of the hip. In addition, most patients are at younger age, therefore, soft tissue balance is of great importance(especially the need to preserve the continuity of abductors) to maximise postoperative functional result. In this paper we present a variety of surgical techniques availablefor THA in dysplastic hips, their advantages and disadvantages. For acetabular reconstruction following techniques are described: Standard metal augments(prefabricated), Custom made acetabular augments(3D printing), Roof reconstruction with vascularized fibula, Roof reconstruction with pedicled iliac graft, Roof reconstruction with autologous bone graft, Roof reconstruction with homologous bone graft, Roof reconstruction with auto/homologous spongious bone, Reinforcement ring with the hook in combination with autologous graft augmentation, Cranial positioning of the acetabulum, Medial protrusion technique(cotyloplasty) with chisel, Medial protrusion technique(cotyloplasty) with reaming, Cotyloplasty without spongioplasty. For femoral reconstruction following techniques were described: Distraction with external fixator, Femoral shortening through a modified lateral approach, Transtrochanteric osteotomies, Paavilainen osteotomy, Lesser trochanter osteotomy, Double-chevron osteotomy, Subtrochanteric osteotomies, Diaphyseal osteotomies, Distal femoral osteotomies. At the end we present author's treatment method of choice: for acetabulum we perform cotyloplasty leaving only paper-thin medial wall, which we break during acetabular cup impacting. For femoral side first we peel of all ro
文摘Due to the need for improvement in the diagnosis and minimally invasive therapy of the bile duct disorders new technologies for cholangioscopy have been recently developed. Per-oral cholangioscopy has become an important diagnostic and therapeutic tool leading to avoidance of aggressive and unnecessary surgery in many clinical scenarios. This paper focuses on the newly developed SpyGlass DS technology, its advantages, and the technique of single-operator cholangioscopy(SOC), biliary indications and possible adverse events. We also review the available literature; discuss the limitations and future expectations.Digital SOC(D-SOC) is a useful technique, which provides endoscopic imaging of the biliary tree, optical diagnosis, biopsy under direct vision and therapeutic interventions. The implementations are diagnostic and therapeutic. Diagnostic indications are indeterminate biliary strictures, unclear filling defects, staging of cholangiocarcinoma, staging of ampullary tumors(extension into the common bile duct), unclear bile duct dilation, exploring cystic lesions of the biliary tree,unexplained hemobilia, posttransplant biliary complications. Therapeutic indications are lithotripsy of difficult stones, retrieval of migrated stents, foreign body removal, guide wire placement, transpapillary gallbladder drainage and endoscopic tumor ablative therapy. Most studied and established indications are the diagnosis of indeterminate biliary stricture and intraductal lithotripsy of difficult stones. The adverse events are not different and more common compared to those of Endoscopic retrograde cholangiopancreatography(ERCP)alone. D-SOC is a safe and effective procedure, adjunct to the standard ERCP and the newly available digital technology overcomes many of the limitations of the previous generations of cholangioscopes.
文摘AIM: To perform a systematic review and metaanalysis on robotic-assisted vs laparoscopic liver resections.METHODS: A systematic literature search was performed using Pub Med, Scopus and the Cochrane Library Central. Participants of any age and sex, who underwent robotic or laparoscopic liver resection were considered following these criteria:(1) studies comparing robotic and laparoscopic liver resection;(2) studies reporting at least one perioperative outcome; and(3) if more than one study was reported by the same institute, only the most recent was included. The primary outcome measures were set for estimated blood loss, operative time, conversion rate, R1 resection rate, morbidity and mortality rates, hospital stay and major hepatectomy rates.RESULTS: A total of 7 articles, published between 2010 and 2014, fulfilled the selection criteria. The laparoscopic approach was associated with a significant reduction in blood loss and lower operative time(MD = 83.96, 95%CI: 10.51-157.41, P = 0.03; MD = 68.43, 95%CI: 39.22-97.65, P < 0.00001, respectively). No differences were found with respect to conversion rate, R1 resection rate, morbidity and hospital stay.CONCLUSION: Laparoscopic liver resection resulted in reduced blood loss and shorter surgical times compared to robotic liver resections. There was no difference in conversion rate, R1 resection rate, morbidity and length of postoperative stay.
文摘Laparoscopic liver resection(LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant(both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments(1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of lap-aroscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation.
文摘According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.
文摘Background Duchenne muscular dystrophy （DMD） and Becker muscular dystrophy （BMD） are X-linked recessive, allelic disorders. This study was conducted to look into the spectrum of DMD gene mutations in Hong Kong Chinese patients with Duchenne or Becker muscular dystrophy （DMD/BMD）, and to study genotype-phenotype correlation.
文摘Liver transplantation is the current standard of care for end-stage liver disease and an accepted therapeutic option for acute liver failure and primary liver tumors.Despite the remarkable advances in the surgical techniques and immunosuppressive therapy,the postoperative morbidity and mortality still remain high and the leading causes are biliary complications,which affect up to one quarter of recipients.The most common biliary complications are anastomotic and non-anastomotic biliary strictures,leaks,bile duct stones,sludge and casts.Despite the absence of a recommended treatment algorithm many options are available,such as surgery,percutaneous techniques and interventional endoscopy.In the last few years,endoscopic techniques have widely replaced the more aggressive percutaneous and surgical approaches.Endoscopic retrograde cholangiography is the preferred technique when duct-to-duct anastomosis has been performed.Recently,new devices and techniques have been developed and this has led to a remarkable increase in the success rate of minimally invasive procedures.Understanding the mechanisms of biliary complications helps in their early recognition which is the prerequisite for successful treatment.Aggressive endoscopic therapy is essential for the reduction of morbidity and mortality in these cases.This article focuses on the common post-transplant biliary complications and the available interventional treatment modalities.
文摘In plants, the hormone auxin shapes gene expression to regulate growth and development. Despite the detailed characterization of auxin-inducible genes, a comprehensive overview of the temporal and spatial dynamics of auxinregulated gene expression is lacking. Here, we analyze transcriptome data from many publicly available Arabidopsis profiling experiments and assess tissue-specific gene expression both in response to auxin concentration and exposure time and in relation to other plant growth regulators. Our analysis shows that the primary response to auxin over a wide range of auxin application conditions and in specific tissues comprises almost exclusively the up-regulation of genes and iden- tifies the most robust auxin marker genes. Tissue-specific auxin responses correlate with differential expression of Aux/ IAA genes and the subsequent regulation of context- and sequence-specific patterns of gene expression. Changes in transcript levels were consistent with a distinct sequence of conjugation, increased transport capacity and down-regulation of biosynthesis in the temperance of high cellular auxin concentrations. Our data show that auxin regulates genes associated with the biosynthesis, catabolism and signaling pathways of other phytohormones. We present a transcriptional overview of the auxin response. Specific interactions between auxin and other phytohormones are highlighted, particularly the regulation of their metabolism. Our analysis provides a roadmap for auxin-dependent processes that underpins the concept of an ＇auxin code＇-a tissue-specific fingerprint of gene expression that initiates specific developmental processes.
文摘Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.
基金National Institutes of Health grant CA92123 and American Cancer Society grant RSG-0125201(to YW HE).
文摘Apoptosis plays an essential role in T cell biology. Thymocytes expressing nonfunctional or autoreactive TCRs are eliminated by apoptosis during development. Apoptosis also leads to the deletion of expanded effector T cells during immune responses. The dysregulation of apoptosis in the immune system results in autoimmunity, tumorogenesis and immunodeficiency. Two major pathways lead to apoptosis: the intrinsic cell death pathway controlled by Bcl-2 family members and the extrinsic cell death pathway controlled by death receptor signaling. These two pathways work to- gether to regulate T lymphocyte development and function.
文摘Chronic hepatitis B virus (HBV) infection affects about 350 million individuals worldwide. Management of HBV infection in pregnancy is difficult because of several peculiar and somewhat controversial aspects. The aim of the present review is to provide a tool that may help physicians to correctly manage HBV infection in pregnancy. This review focuses on (1) the effect of pregnancy on HBV infection and of HBV infection on pregnancy; (2) the potential viral transmission from mother to newborn despite at-birth prophylaxis with immunoglobulin and vaccine; (3) possible prevention of mother-to-child transmission through antiviral drugs, the type of antiviral drug to use considering their efficacy and potential teratogenic effect, and the timing of their administration and discontinuation; and (4) the evidence for the use of elective caesarean section vs vaginal delivery and the possibility of breastfeeding.
文摘AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC). METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117). RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56%vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated. CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.
