BACKGROUND:Osteoarthritis is a progressive joint condition identified by ongoing deterioration of the cartilage matrix,and there is currently no effective drug treatment plan.Metformin-modified exosomes isolated from bone marrow-derived mesenchymal stem cells can become a new method for treating osteoarthritis due to their avoidance of oral drug adverse reactions and immunogenicity.OBJECTIVE:To study the controlling impact of exosomes from metformin-altered bone marrow-derived mesenchymal stem cells on chondrocytes.METHODS:Rabbit bone marrow-derived mesenchymal stem cells and chondrocytes were cultured in vitro.Bone marrow-derived mesenchymal stem cells derived exosomes and metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes were collected using a high-speed centrifuge.Chondrocytes were cultured with exosome-containing culture medium for 24 hours and then treated with 100 μmol/L H2O2 for 24 hours.The capability changes of two extracellular vesicles on chondrocyte proliferation and migration were detected using CCK8 assay and scratch healing experiment,respectively.Western blot analysis and RT-qPCR were employed to examine the alterations in the expression of type Ⅱ collagen,P16 protein,and their mRNA in chondrocytes.Western blot analysis was utilized to assess the changes in the expression of MKK7/JNK pathway proteins.ELISA kits were utilized to measure the activity of cell superoxide dismutase and the levels of malondialdehyde in chondrocytes.RESULTS AND CONCLUSION:(1)In an oxidative stress environment,the proliferation and migration abilities of chondrocytes were weakened.The two types of exosomes could restore the proliferation and migration abilities of chondrocytes to a certain extent.Metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes had a significantly better improvement effect(P＜0.05).(2)Compared with normal bone marrow mesenchymal stem cell-derived exosomes,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes could more effectively increase type Ⅱ collagen expression and superoxide dismutase activity(P＜0.05),and were also more effective in reducing P16 expression and malondialdehyde levels(P＜0.05).(3)The two types of exosomes could inhibit the expression of MKK7 and p-JNK proteins to a certain extent,and the inhibitory effect of metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes was more significant(P＜0.05).The results show that in an oxidative stress environment,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes resist chondrocyte aging and promote chondrocyte proliferation by inhibiting the MKK7/JNK pathway.

BACKGROUND:Osteoarthritis is a progressive joint condition identified by ongoing deterioration of the cartilage matrix,and there is currently no effective drug treatment plan.Metformin-modified exosomes isolated from bone marrow-derived mesenchymal stem cells can become a new method for treating osteoarthritis due to their avoidance of oral drug adverse reactions and immunogenicity.OBJECTIVE:To study the controlling impact of exosomes from metformin-altered bone marrow-derived mesenchymal stem cells on chondrocytes.METHODS:Rabbit bone marrow-derived mesenchymal stem cells and chondrocytes were cultured in vitro.Bone marrow-derived mesenchymal stem cells derived exosomes and metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes were collected using a high-speed centrifuge.Chondrocytes were cultured with exosome-containing culture medium for 24 hours and then treated with 100 μmol/L H2O2 for 24 hours.The capability changes of two extracellular vesicles on chondrocyte proliferation and migration were detected using CCK8 assay and scratch healing experiment,respectively.Western blot analysis and RT-qPCR were employed to examine the alterations in the expression of type Ⅱ collagen,P16 protein,and their mRNA in chondrocytes.Western blot analysis was utilized to assess the changes in the expression of MKK7/JNK pathway proteins.ELISA kits were utilized to measure the activity of cell superoxide dismutase and the levels of malondialdehyde in chondrocytes.RESULTS AND CONCLUSION:(1)In an oxidative stress environment,the proliferation and migration abilities of chondrocytes were weakened.The two types of exosomes could restore the proliferation and migration abilities of chondrocytes to a certain extent.Metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes had a significantly better improvement effect(P＜0.05).(2)Compared with normal bone marrow mesenchymal stem cell-derived exosomes,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes could more effectively increase type Ⅱ collagen expression and superoxide dismutase activity(P＜0.05),and were also more effective in reducing P16 expression and malondialdehyde levels(P＜0.05).(3)The two types of exosomes could inhibit the expression of MKK7 and p-JNK proteins to a certain extent,and the inhibitory effect of metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes was more significant(P＜0.05).The results show that in an oxidative stress environment,metformin pretreated bone marrow-derived mesenchymal stem cells derived exosomes resist chondrocyte aging and promote chondrocyte proliferation by inhibiting the MKK7/JNK pathway.

Objective To establish small-for-size (SFS) graft injury models in miniature pigs with high standardization, reproducibility and similarity to clinical situation. Methods Ba-Ma miniature pigs were introduced in this study and orthotopic liver transplantations (OLTs) were performed in 12 pigs with 30% liver volume allogeneil grafts (small portion of right paramedian lobe, right lateral lobe and caudate lobe) without veno-venous bypass. The profiles of intra-operational hemodynamics and metabolism were investigated. Animals were observed for 7 days with daily serum biochemistry and coagulation function exam. The survival rate related to operation itself and the SFS grafts were respectively calculated as well as the graft regenerative ratio at post-operational day (POD) 7. Results Graft weight as a percentage of the recipient's native liver weight (GW/RLW) and the total body weight (GW/BW) were (28. 63±4. 42)% and (0. 73±0.06)%. The mean operation time, anhepatic phase, and the time of blockage of infra-hepatic IVC were (191. 7±14. 2) min, (28. 3±3. 6) min, and (45. 0±5. 8) min. The survival rate related to the operation itself and the SFS graft were 83. 33% (10/12) and 40% (4/10), and the graft regenerative ratio at POD7 was (278. 06±42. 95) %. Contrast to the remarkable increase of heart rate and serum potassium during anhepatic phase, the mean arterial pressure, central venous pressure, rectal temperature, PH value and buffer excess had a significant decrease (P<0.01) with a gradual recovery after reperfusioa Serum ALT, AST, PT, Cr, and TB were significantly increased with a peak level at POD1 for the former 4 and POD2 for TB, and then began to decrease and favorably recovered at POD7, but TB, PT, and AST levels were still high when compared to those of prereperfusion (P<0. 05). Conclusion This model of OLT performed with 30% liver volume graft without veno-venous bypass was an ideal large animal model for series studies related to SFS graft injury.

OBJECTIVETo evaluate therapeutical effect of combined hepatic resection and fenestration on patients with severe adult polycystic liver disease (APLD).

METHODSPreoperative clinical symptoms, postoperative complications and prognoses from 33 patients with severe adult polycystic liver disease (APLD) treated with combined hepatic resection and fenestration were recorded. According to the number and location of cysts before surgery and the remnant liver parenchyma after operation, all patients were classified into two types: class A and B. And patients in each type were further classified into three grades: Grade I, II and III. The frequency of postoperative complications of two types patients was compared.

RESULTSThe mean follow-up time was 57 months. There were three patients with recurrence of symptoms at 81, 68 and 43 mouths after operation. Two patients died of renal failure due to polycystic kidney disease at 137 and 85 mouths after operation. And one patient with postoperative hepatic inadequacy received an orthotopic liver transplantation. The total number of patients with postoperative complications was 26 cases, including one patient with bleeding, two patients with bile leakage, fourteen patients with mild ascites, twelve patients with severe ascites and eighteen patients with pleural effusion, and the overall incidence was 78.8%. There were 22 patients with imaging data, including 6 patients within A type and sixteen patients within B type. The frequencies of postoperative complications were 4 and 31, respectively, and the difference was statistically significant (Chi-square test = 4.99, P less than 0.05).

CONCLUSIONCombined hepatic resection and fenestration is a safe and acceptable procedure for the treatment of severe APLD.

Adult ; Aged ; Ascites ; epidemiology ; etiology ; Cysts ; diagnostic imaging ; pathology ; surgery ; Female ; Follow-Up Studies ; Hepatectomy ; methods ; Humans ; Liver ; diagnostic imaging ; pathology ; surgery ; Liver Diseases ; diagnostic imaging ; pathology ; surgery ; Male ; Middle Aged ; Pleural Effusion ; epidemiology ; etiology ; Postoperative Complications ; epidemiology ; prevention & control ; Prognosis ; Recurrence ; Retrospective Studies ; Severity of Illness Index ; Tomography, X-Ray Computed ; Treatment Outcome