Functional involvement of endothelial lipase in hepatitis B virus infection.

BACKGROUND: HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence. METHODS: The present study focused on endothelial lipase (LIPG), which binds to heparan sulfate proteoglycans (HSPGs) in the cell membrane. RESULTS: We found HBV infection was impaired in humanized liver chimeric mouse-derived hepatocytes that were transduced with lentivirus expressing short hairpin RNA against LIPG. Long-term suppression of LIPG combined with entecavir further suppressed HBV replication. LIPG was shown to be involved in HBV attachment to the cell surface by using 2 sodium taurocholate cotransporting peptide (NTCP)-expressing cell lines, and the direct interaction of LIPG and HBV large surface protein was revealed. Heparin and heparinase almost completely suppressed the LIPG-induced increase of HBV attachment, indicating that LIPG accelerated HBV attachment to HSPGs followed by HBV entry through NTCP. Surprisingly, the attachment of a fluorescently labeled NTCP-binding preS1 probe to NTCP-expressing cells was not impaired by heparin, suggesting the HSPG-independent attachment of the preS1 probe to NTCP. Interestingly, attachment of the preS1 probe was severely impaired in LIPG knockdown or knockout cells. Inhibitors of the lipase activity of LIPG similarly impaired the attachment of the preS1 probe to NTCP-expressing cells. CONCLUSIONS: LIPG participates in HBV infection by upregulating HBV attachment to the cell membrane by means of 2 possible mechanisms: increasing HBV attachment to HSPGs or facilitating HSPG-dependent or HSPG-independent HBV attachment to NTCP by its lipase activity.

Prediction of delayed union of tibial shaft fracture treated with intramedullary nailing: multicenter-study analysis and literature review -the TRON study.

PURPOSE: We aimed to 1) identify predictors of delayed and nonunion of tibial shaft fractures in patients treated with intramedullary nailing (IMN), including patient demographics and surgical factors, and 2) determine whether the nail/shaft ratio is associated with delayed and nonunion. METHODS: This retrospective, multicenter study included 315 patients with tibial shaft fracture treated with IMN between 2014 and 2019 and excluded patients with insufficient follow-up for 12 months, lost data and inadequate radiographs. Finally, we analyzed 258 patients (184 males; 74 females). Main outcome measurements were delayed union at 6 and nonunion at 12 months after surgery as determined on anteroposterior and lateral radiographs. We extracted the following as risk factors of delayed and nonunion: age, sex, BMI, fracture site, fracture type, injury energy, smoking history, and nail/shaft ratio. We conducted logistic regression analysis to investigate risk factors of delayed and nonunion using these extracted items as explanatory variables. RESULTS: Type C fracture was independently associated with delayed union (odds ratio 2.9, 95% confidential interval: 1.04-8.09, P = 0.04). Nail/shaft ratio was not an independent factor of delayed union. No independent explanatory factors were related to nonunion. CONCLUSIONS: Type C fractures, which were unstable and fragmented, was associated with delayed union in tibia fractures treated with IMN, whereas nail thickness was not associated with delayed or nonunion fractures.

Early versus delayed weight bearing after intramedullary nailing for tibial shaft fracture: A multicenter, propensity score-matched study, the TRON study.

OBJECTIVES: The purpose of this multicenter study was to assess the differences in the rates of implant failure and bone union by X-ray examination, and walking ability between an early weight-bearing group (EWB) and a non-weight-bearing group (NWB) following treatment with intramedullary nailing (IMN) for tibial shaft fractures with a propensity score-matching method. MATERIAL AND METHODS: We collected data from 336 patients with tibia fractures that were treated surgically. We excluded patients lost to follow-up and polytrauma patients. Finally, 263 patients were included who were divided into two groups, the early weight-bearing (EWB) group, in which partial weight-bearing walking within four weeks was encouraged, and a non-weight-bearing (NWB) group, in which no weight bearing was allowed for more than four weeks. To adjust for baseline differences between groups, a propensity score algorithm was used to match the EWB group with the NWB group in a 1:1 ratio of 75 cases each. After matching, we compared the rate of implant failure, the rate of bone union at six months and one year after surgery, and walking ability at the last follow-up between the two groups. RESULT: Implant failure occurred in 0 of 75 patients in the EWB group vs. 1 of 75 in the NWB group (P = 1.0). Delayed bone union at six months occurred in 20 of 75 (26%) vs. 13 of 75 (17%) patients, and that at one year occurred in 5 of 75 (6.7%) vs. 3 of 75 (4%) patients. The median New Mobility Score was 9 (4-9) vs. 9 (0-9) points. CONCLUSIONS: There were no statistically significant differences in the rate of implant failure, the rates of the bone union at six months and one year after surgery, and walking ability between the EWB group and NWB group. We suggest that instruction in early weight-bearing after IMN nailing for tibial shaft fracture may not be harmful.