OBJECTIVE: To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema. METHODS: The literature on stem cell-based treatments for lymphedema in recent years at home and abroad was extensively reviewed, and the animal studies and clinical trials on different types of stem cells for lymphedema were summarized. RESULTS: Various types of stem cells have shown certain effects in animal studies and clinical trials on the treatment of lymphedema, mainly through local differentiation into lymphoid endothelial cells and paracrine cytokines with different functions. Current research focuses on two cell types, adipose derived stem cells and bone marrow mesenchymal stem cells, both of which have their own advantages and disadvantages, mainly reflected in the therapeutic effect of stem cells, the difficulty of obtaining stem cells and the content in vivo. In addition, stem cells can also play a synergistic role in combination with other treatments, such as conservative treatment, surgical intervention, cytokines, biological scaffolds, and so on. However, it is still limited to the basic research stage, and only a small number of studies have completed clinical trials. CONCLUSION Stem cells have great transformation potential in the treatment of lymphedema, but there is no unified standard in the selection of cell types, the amount of transplanted cells, and the timing of transplantation.
Animals ; Endothelial Cells ; Lymphedema/therapy* ; Stem Cell Transplantation ; Cytokines

Posterior reversible encephalopathy syndrome is a clinical and radiological entity,caused by a variety of reasons.We report a case of rhabdomyolysis complicated by posterior reversible encephalopathy and suggest that giving fluids early,use of diuretics and alkalization of urine may be reasonable for patients with rhabdomyolysis.Monitoring blood pressure is noteworthy to prevent target organ damage,and if patient condition steadily deteriorates,hemodialysis should be initiated.

Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40％of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated he-patic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and ther-apeutic targets for liver protection.

Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Objective:To study the morphologic features of the fusion site of proximal tibial epiphysis in normal adults and analyze its potential clinical value based on Mimics three-dimensional (3D) reconstruction.Methods:CT images of knee joint of 68 patients without obvious abnormalities of lower limbs were retrospectively analyzed in electronic database of our hospital from June 2020 to June 2021, including 41 males and 27 females. The mean age of the patients was 38.7±8.4 years (range, 25-55 years), and the mean body mass index (BMI) was 25.3±4.0 kg/m 2 (range, 18.75-41.8 kg/m 2). Mimics 3D reconstruction technique was used to reconstruct the 3D model of the proximal tibia and epiphyseal fusion site. The relationship between the surface area of epiphyseal fusion site and age and BMI was studied, and the changes of cortical thickness and density at epiphyseal fusion site were also explored. Results:The fusion site of adult epiphyseal reconstructed by Mimics 3D reconstruction is a complex wavy surface structure in 3D space. The surface area of the epiphyseal fusion site was 2,994.7±645.3 mm 2 (range, 1,704.0-4,650.0 mm 2) obtained by 3-Matic Research 12.0. The fusing area of male epiphysis was 3 269.3±533.9 mm 2 than that of female 2,577.6±578.7 mm 2, the difference was statistically significant ( t=5.06, P<0.001). However, there was no significant correlation between the epiphyseal fusion site surface area and age ( R2=0.02, P=0.268) and BMI ( R2=0.04, P=0.125). Mimics software was used to obtain the CT values of bone cortex at the epiphysis line and the distal end of the epiphysis line at 10 mm and 20 mm levels as 451.059±74.953 Hu, 1,018.412±125.732 Hu and 1,414.162±107.848 Hu, respectively. The thickness of bone cortex was 1.814±0.090 mm, 2.511±0.089 mm and 3.189±0.185 mm at 10 mm and 20 mm layers of epiphysis line and distal epiphysis line, respectively. Conclusion:In this study, Mimics 3D reconstruction technique was used to visualize the fusion site of the proximal tibial epiphysis in normal adults. The epiphyseal fusion site of adult is a undulating plate-like structure, and the cortical bone density of epiphyseal fusion site is low and thin, theoretically, it is easy to fracture under indirect violence.

The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.

Objective:To evaluate the biomechanical stability of our slot-designed compression bolt (SCB) combined with bilateral locking compression plates (LCPs) in the treatment of intra-articular distal femur fracture.Methods:In 24 adult male knee specimens treated with formalin, the femoral bony part was preserved to establish standard models of intra-articular distal femur fracture (AO type 33-C1). According to the random number table, the fracture models were divided into 2 equal groups: an experimental group ( n=12) subjected to fixation with one SCB combined with bilateral LCPs with 10 locking screws and a control group ( n=12) subjected to fixation with bilateral LCPs with 12 locking screws. In each model, a vertical ballast test was conducted to record the maximum axial displacement of the system and a horizontal torsion test to calculate the torsional stiffness of the system. When the loading pressure was 0-1,000 N in the biomechanical machine, structural abnormalities were observed in the 2 groups of models and the system maximum axial displacement and system torsional stiffness were compared between the 2 groups. Results:When the vertical ballast pressure was 400 N, 600 N, 800 N and 1,000 N, the maximum axial displacement of the system was, respectively, (0.14±0.01) mm, (0.25±0.01) mm, (0.41±0.02) mm and (0.63 ± 0.02) mm in the experimental group, and (0.15 ± 0.01) mm, (0.26 ± 0.01) mm, (0.46 ± 0.03) mm, and (0.67 ± 0.04) mm in the control group. Compared with the control group, the average maximum axial displacement in the experimental group decreased significantly under the axial pressure of 600-1,000 N ( P<0.05). When the horizontal torsion reached 5°, the torsional stiffness was, respectively, (2.00±0.12) Nm/° and (2.02±0.07) Nm/° in the experimental group and the control group, showing no significant difference between the 2 groups ( P>0.05). Conclusions:In the treatment of intra-articular distal femur fracture, compared with simple bilateral LCPs, our SCB combined with bilateral LCPs demonstrate similar torsional stability but better axial biomechanical stability. As our SCB has advantages of bilateral compression and minimal invasion in operation, it may be a new option for the reduction and compression treatment of intra-articular fractures.

OBJECTIVE： To study the effects of Tiaopi huxin prescription （TPHXP） on the atherosclerosis （AS） of ApoE－/－ mice， and to investigate its mechanism. METHODS： Forty male ApoE－/－ mice were divided into blank group， model group， simvastatin group （positive control， 5 mg/kg） and TPHXP low-dose and high-dose groups （50， 150 mg/kg）， with 8 mice in each group. Except that blank group was given common diet， other groups were given high-lipid diet to induce AS model. After modeling， administration groups were given relevant medicine intragastrically， and blank group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 12 weeks. After last medication， the serum levels of TC， TG， LDL-C and HDL-C were determined by spectrophotometry. The serum level of NO was detected by nitrate reduction method. The serum levels of IL-6 and VCAM-1 were determined by ELISA. After separating thoracic aorta， HE staining was used to observe the formation of plaque in the thoracic aorta of mice in each group， and the corrected plaque area was calculated. Western blotting was conducted to determine the expression of NF-κB p65， Cav-1 and eNOS. RESULTS： Compared with blank group， the serum levels of TC， TG， LDL-C， IL-6 and VCAM-1 were increased significantly in model group， while the levels of HDL-C and NO were decreased significantly （P＜0.01）. The plaque of thoracic aorta was obvious and the corrected plaque area were increased significantly （P＜0.01）. The relative expression of NF-κB p65 and Cav-1 were increased significantly， while the relative expression of eNOS was decreased significantly （P＜0.01）. Compared with model group， the serum levels of TC， TG and LDL-C in administration groups， the serum levels of IL-6 and VCAM-1 in simvastatin group and TPHXP high-dose group were decreased significantly， while the serum levels of HDL-C and NO were increased significantly in administration groups （P＜0.05 or P＜0.01）. In administration groups， the plaques of thoracic aorta were reduced and the corrected plaque area was decreased significantly （P＜0.05 or P＜0.01）； the relative expression of NF-κB p65 and Cav-1 were decreased significantly， while the relative expression of eNOS was increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： TPHXP can regulate the level of blood lipid， decrease the level of inflammatory factors and inhibit the formation of AS plaque， the mechanism of which may be associated with inhibiting Cav-1/NF-κB pathway.

Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.