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.

To explore the diagnostic value of detachable string magnetically controlled capsule gastroscope (ds-MCE) for esophageal diseases in plateau area, clinical data of 45 patients who underwent ds-MCE at Qinghai Special Hospital of Cardio-Cerebrovascular Diseases from January 2024 to June 2024 were retrospectively analyzed to explore the application characteristics and advantages of ds-MCE. The results showed that ds-MCE examination was successfully completed in all 45 patients. Diagnosis was confirmed in 30 cases (66.67%, 30/45) including 28 cases (93.33%) of esophagitis, 8 cases (26.67%) of esophageal ulcer, 8 cases (26.67%) of esophageal varices, 5 cases (16.67%) of hiatal herniawere, 3 cases (10.00%) of esophageal polyp, 1 case (3.33%) of achalasia, 1 case (3.33%) of esophageal papilloma, and 1 case (3.33%) of lower esophageal and cardiac carcinoma. Compared with traditional endoscopy and capsule endoscopy, ds-MCE has the advantages of no need for anesthesia and high safety, which provides a new and important diagnostic option for esophageal diseases in plateau area.

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.

To explore the diagnostic value of detachable string magnetically controlled capsule gastroscope (ds-MCE) for esophageal diseases in plateau area, clinical data of 45 patients who underwent ds-MCE at Qinghai Special Hospital of Cardio-Cerebrovascular Diseases from January 2024 to June 2024 were retrospectively analyzed to explore the application characteristics and advantages of ds-MCE. The results showed that ds-MCE examination was successfully completed in all 45 patients. Diagnosis was confirmed in 30 cases (66.67%, 30/45) including 28 cases (93.33%) of esophagitis, 8 cases (26.67%) of esophageal ulcer, 8 cases (26.67%) of esophageal varices, 5 cases (16.67%) of hiatal herniawere, 3 cases (10.00%) of esophageal polyp, 1 case (3.33%) of achalasia, 1 case (3.33%) of esophageal papilloma, and 1 case (3.33%) of lower esophageal and cardiac carcinoma. Compared with traditional endoscopy and capsule endoscopy, ds-MCE has the advantages of no need for anesthesia and high safety, which provides a new and important diagnostic option for esophageal diseases in plateau area.

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 ecological isolation between Oncomelania hupensis snail populations in hilly regions and marshland and lake regions in Yuanjiang valley, Changde City, Hunan Province, and to unravel its underlying mechanisms. Methods Taoyuan County, Shimen County, Linli County and Lixian County in Changde City were selected as snail sampling sites in hilly regions, and Lixian County, Jinshi City, West Lake Administration District, Hanshou County and Dingcheng District were selected as snail sampling sites in marshland and lake areas. Cytochrome C oxidase 1 (cox 1) gene was amplified in snail samples and sequenced. The genetic sequences of O. hupensis snails were aligned using the software MEGA 11, and the haplotypes of O. hupensis snails were determined using the software DNASP 5.10.01. The phylogenetic tree was generated using Bayesian inference with the software MrBayes 3.2, and analysis of molecular variance (AMOVA) was performed to analyze the source of genetic divergence and estimate the genetic divergence index (F_ST) among snail populations with the software Arlequin 3.5.2.2. The genetic barrier among 11 O. hupensis snail populations was estimated using the Monmonier algorithm of adegenet toolkit in R package. The settings with “land in winter and water in summer” in the Yuanjian River section were divided into two categories according to the upstream and downstream, and the areas with “land in winter and water in summer” in the upstream and downstream were transformed into raster data, and then loaded into the software Fragstats 4 for analysis of landscape indicators. The trends in changes of digital elevation were extracted from the Yuanjiang River section based on the digital elevation model, and made three-dimensional visualization using the R package. Results The mitochondrial cox 1 gene were amplified in 165 O. hupensis snais from 11 sampling sites and sequenced, and a total of 152 valid gene sequences were obtained, with 46 haplotypes or 9 populations determined. No haplotype was shared in snails between Taoyuan County and Dingcheng District and Hanshou County along the downstream of the Yuanjiang River. The total area of settings with “land in winter and water in summer” was 617.66 hm² in the upsteram of the Yuanjiang River, which consisted of 473 patches, with each patch measuring 1.31 hm², the largest area index of 0.735 2, the landscape division index of 0.999 9, and the landscape shape index of 45.293 7. The total area of settings with “land in winter and water in summer” was 9 956.92 hm² in the downstream of the Yuanjiang River, which consisted of 771 patches, with each patch measuring 12.91 hm², the largest area index of 97.839 9, the landscape division index of 0.042 7, and the landscape shape index of 7.249 6. The area of settings with “land in winter and water in summer” was much larger in the downstream than that in the upstream of the Yuanjiang River, and the stronger landscape connectivity and non-remarkable alteration of riverbed elevation provided suitable habitats for snail breeding. Conclusion The hydrological and environmental characteristics of the upstream of the Yuanjiang River restrain the breeding and spread of O. hupensis, resulting in ecological isolation between Oncomelania hupensis in Taoyuan County and those in the downstream of Yuanjiang River.

OBJECTIVE To establish the ion mobility mass spectrometry method for simultaneous determination of epiberberine， berberine， coptisine， palmatine， calycosin-7-glucoside， 3，5-O-dicaffeoylquinic acid， 4，5-O-dicaffeoylquinic acid and chlorogenic acid in Jinqi jiangtang tablets. METHODS Ion mobility mass spectrometry method was used. The determination was performed on Waters ACQUITY UPLC HSS T3 （2.1 mm×50 mm， 1.8 μm） with mobile phase consisted of 0.1% formic acid solution-acetonitrile （gradient elution） at the flow rate of 0.3 mL/min. The column temperature was 40 ℃， and the injection volume was 5 μL. The contents of 8 components in Jinqi jiangtang tablets were determined by scanning detection under positive and negative ion modes with an electric spray ion source， and setting ion mobility mass parameters according to the peak response of each component. RESULTS The results showed that the linear relationship of the eight components was good within their respective ranges （r≥0.999）； RSDs of precision， repeatability and stability （24 h） tests were not more than 4.0%； average recoveries were 94.6%-101.2% ， RSDs were 2.6%-3.9% （n＝9）. The contents of the above eight components in three batches of Jinqi jiangtang tablets were 3.060-3.545， 24.50-26.74， 2.795-4.149， 1.437-2.501， 0.204-0.242， 0.950-1.281， 2.272-2.828， 7.314- 7.960 mg/g， respectively. CONCLUSIONS The established method has high sensitivity and good reproducibility， and can provide reference for the quality control of the preparation.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*