BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.

MicroRNA(miRNA),an important type of non-coding RNAs existing widely in viruses and eukaryotes,regulate gene expression at transcriptional and post-transcriptional levels.Recent studies have demonstrated that plant miRNAs could enter microorganisms,animals and human bodies to affect their physiological and pathological processes by cross-kingdom regulation of gene expression.This review summarized the current knowledge of cross-kingdom regulation of gene expression by plant miRNAs,introduced the research progress in intervention of human diseases with plant miRNAs,including anti-virus,anti-tumor,anti-inflammation,immune regulation,anti-fatigue,anti-fibrosis,vascular protection,nerve protection,etc.,and analyzed the reasons why plant miRNAs remain stable in vivo and in vitro and the underlying mechanisms how they regulate human gene expression.Furthermore,the impact of cross-kingdom regulation by plant miRNAs on exploring new active ingredients of traditional Chinese herbs and elucidating their pharmacology were evaluated.Finally,"constructing the complex regulatory network of traditional Chinese medicine miRNAs in human body"and"exploring new mechanisms of gene expression regulation by traditional Chinese medicine miRNAs"were pointed out,which were two scientific problems worthy of further investigation.

BACKGROUND:Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone.In recent years,many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis.Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis.OBJECTIVE:To review the role of stromal derived factor-1 in regulating the proliferation,differentiation,and apoptosis of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis,in order to provide new ideas for the prevention and treatment of osteoarthritis.METHODS:CNKI,WanFang Data,and VIP,were searched with Chinese search terms"stromal cell-derived factor 1,cartilage,chondrocytes,subchondral bone,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,CXC chemokine receptor 4,CXC chemokine receptor 7."PubMed,Medline,and Embase databases were searched with English search terms"stromal cell-derived factor 1,SDF-1,CXCL12,cartilage,chondrocyte,subchondral bone,mesenchymal stem cells,osteoblasts,osteoclasts,CXCR4,CXCR7."Literature retrieval time was from inception to January 2024.A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Stromal cell-derived factor-1 regulates the migration,proliferation,differentiation,and death of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,which plays an important role in maintaining cartilage and subchondral bone homeostasis,promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis.Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4/CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis.(2)Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues,stromal cell-derived factor-1 α is the most widely studied at present.The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1y are mainly focused on exploring the effects on the biological behavior of stem cells,the role in the regulation of cartilage and subchondral bone homeostasis,and the correlation with osteoarthritis.(3)Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites,and induce their proliferation,survival,and cartilage differentiation.The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research.However,previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes,while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis.The whole tissue is vascularized and ossified,which affects the quality of cartilage repair.In addition,when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury,the regenerated tissue is not all ideal hyaline cartilage tissue.Therefore,in the future,in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair.(4)The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100,T140 and TN14003,and most of them are in the basic experimental stage and need to be transformed into clinical practice.The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4/CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support.

MicroRNA(miRNA),an important type of non-coding RNAs existing widely in viruses and eukaryotes,regulate gene expression at transcriptional and post-transcriptional levels.Recent studies have demonstrated that plant miRNAs could enter microorganisms,animals and human bodies to affect their physiological and pathological processes by cross-kingdom regulation of gene expression.This review summarized the current knowledge of cross-kingdom regulation of gene expression by plant miRNAs,introduced the research progress in intervention of human diseases with plant miRNAs,including anti-virus,anti-tumor,anti-inflammation,immune regulation,anti-fatigue,anti-fibrosis,vascular protection,nerve protection,etc.,and analyzed the reasons why plant miRNAs remain stable in vivo and in vitro and the underlying mechanisms how they regulate human gene expression.Furthermore,the impact of cross-kingdom regulation by plant miRNAs on exploring new active ingredients of traditional Chinese herbs and elucidating their pharmacology were evaluated.Finally,"constructing the complex regulatory network of traditional Chinese medicine miRNAs in human body"and"exploring new mechanisms of gene expression regulation by traditional Chinese medicine miRNAs"were pointed out,which were two scientific problems worthy of further investigation.

BACKGROUND:Osteoarthritis is a degenerative disease characterized by cartilage degeneration and abnormal bone remodeling of subchondral bone.In recent years,many studies have shown that stromal cell diffracting factor-1 plays a key role in the pathological progression of osteoarthritis.Targeted regulation of stromal cell-derived factor-1 and its CXC chemokine receptor 4 and CXC chemokine receptor 7 signaling pathways is a new method for prevention and treatment of osteoarthritis.OBJECTIVE:To review the role of stromal derived factor-1 in regulating the proliferation,differentiation,and apoptosis of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,as well as explore the mechanism by which the interaction of these cells leads to cartilage degeneration and abnormal bone remodeling of subchondral bone and accelerates the pathological progression of osteoarthritis,in order to provide new ideas for the prevention and treatment of osteoarthritis.METHODS:CNKI,WanFang Data,and VIP,were searched with Chinese search terms"stromal cell-derived factor 1,cartilage,chondrocytes,subchondral bone,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,CXC chemokine receptor 4,CXC chemokine receptor 7."PubMed,Medline,and Embase databases were searched with English search terms"stromal cell-derived factor 1,SDF-1,CXCL12,cartilage,chondrocyte,subchondral bone,mesenchymal stem cells,osteoblasts,osteoclasts,CXCR4,CXCR7."Literature retrieval time was from inception to January 2024.A total of 77 articles were included and summarized in accordance with the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Stromal cell-derived factor-1 regulates the migration,proliferation,differentiation,and death of chondrocytes,bone marrow mesenchymal stem cells,osteoblasts,and osteoclasts,which plays an important role in maintaining cartilage and subchondral bone homeostasis,promoting or inhibiting cartilage degeneration and abnormal bone remodeling in osteoarthritis.Targeted regulation of stromal cell-derived factor-1/CXC chemokine receptor type 4/CXC chemokine receptor type 7 signaling pathway is expected to become the focus of future research on the prevention and treatment of osteoarthritis.(2)Because of the difference in the expression of stromal cell-derived factor-1 subtypes in tissues,stromal cell-derived factor-1 α is the most widely studied at present.The related studies of stromal cell-derived factor-1β and stromal cell-derived factor-1y are mainly focused on exploring the effects on the biological behavior of stem cells,the role in the regulation of cartilage and subchondral bone homeostasis,and the correlation with osteoarthritis.(3)Stromal cell-derived factor-1 can effectively promote stem cells homing to cartilage injury sites,and induce their proliferation,survival,and cartilage differentiation.The application of stromal cell-derived factor-1-loaded biological scaffolds to improve the quality of cartilage repair has become the focus of cartilage tissue engineering research.However,previous studies have shown that stromal cell-derived factor-1 can promote the differentiation of bone marrow mesenchymal stem cells into hypertrophic chondrocytes,while the hypertrophic phenotype of newborn chondrocytes can lead to endochondral bone formation and chondrocyte apoptosis.The whole tissue is vascularized and ossified,which affects the quality of cartilage repair.In addition,when different scaffolds combined with stromal cell-derived factor-1 can repair partial cartilage injury and full-thickness cartilage injury,the regenerated tissue is not all ideal hyaline cartilage tissue.Therefore,in the future,in-depth exploration of the potential mechanism of stromal cell-derived factor-1 in stem cell biological effects and the best combination of stromal cell-derived factor-1 and scaffold in repairing different cartilage defects will help to improve the quality of cartilage repair.(4)The studies on CXC chemokine receptor 4 antagonists are mainly focused on AMD3100,T140 and TN14003,and most of them are in the basic experimental stage and need to be transformed into clinical practice.The safety and effectiveness of the therapeutic drugs developed for stromal cell-derived factor-1/CXC chemokine receptor 4/CXC chemokine receptor 7 signaling pathway still need a large number of biological and clinical trials to support.

BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.