Effect of body mass index on postoperative mechanical alignment and long-term outcomes after total knee arthroplasty: a retrospective cohort study of 671 knees.

Background: A high body mass index (BMI) is associated with increased rates of complications after total knee arthroplasty (TKA). However, no study has examined the effect of BMI on lower limb alignment using the World Health Organization's (WHO) BMI classification. We believe that the WHO's BMI classification allows a uniform standard worldwide. We sought to investigate the potential association between a high BMI and the incidence of postoperative misalignment. We also evaluated whether a higher BMI is associated with worse clinical function. Methods: We retrospectively reviewed the data of 671 patients who underwent primary TKA for varus osteoarthritis between January 2010 and December 2015. The patients were divided into the following 5 groups based on their BMI: normal weight (<25.0 kg/m2), overweight (25.0-29.9 kg/m2), class I obese (30.0-34.9 kg/m2), class II obese (35-39.9 kg/m2), and class III obese (>40 kg/m2). Both weight and height were measured by nurses on admission. Patients' preoperative HKA, gender, age, and side of surgery were collected as baseline. All the patients underwent standing, weight-bearing, full-length radiography before and after surgery to measure the mechanical hip-knee-ankle angle (HKA). We followed up patients by telephone. Among the BMI subgroups, we compared the knee function scores, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society-Knee Score (KS-KS), Knee Society-Function Score (KS-FS), Forgotten Joint Score (FJS), and range of motion (ROM). A multivariate linear regression analysis and a logistic regression was conducted to examine the outcomes. Results: The study had a mean follow-up period of 8.16 years. The multivariate and logistic regression analyses revealed that preoperative alignment (P=0.002) and a higher BMI (P=0.015) were associated with a higher risk of postoperative misalignment. The WOMAC scores were higher in the normal and overweight groups than the other groups (P=0.022). The FJS and KS-KS gradually decreased as BMI increased. Conclusions: A higher BMI is associated with a greater risk of misalignment and worse long-term clinical outcome after TKA. When treating patients with high BMI, we should pay more attention to the adjustment of lower limb alignment intraoperatively.

Femoral and tibial cementless fixation neither increases blood loss nor impedes early functional recovery: A randomized controlled trial.

Background: Whether cementless fixation on femoral and tibial components increases blood loss during total knee arthroplasty (TKA) is unclear. The purpose of this randomized controlled trial was to compare blood loss and early functional recovery between patients who underwent cementless or cemented TKA. Methods: Between November 2021 and April 2022, sixty-one eligible patients at our medical center were randomized to cementless and cemented group. The primary outcome was total blood loss (TBL). Secondary outcomes were drainage, knee swelling, anemia, transfusion, hematological indicators, early functional recovery, and postoperative complications. The early functional recovery included range of motion (ROM), Hospital for Special Surgery (HSS) score, walking distance. Results: A total of 61 patients were analyzed, of whom 30 underwent cementless fixation. On postoperative day 1, the mean TBL was 394.39 ml (SD 182.97 ml) in the cementless group and 382.41 ml (SD 208.67 ml) in the cemented group (P = 0.863). By postoperative day 3, the corresponding mean TBL was higher at 593.48 ml (SD 230.04 ml) and 603.80 ml (SD 213.16 ml) (P = 0.751). The two groups did not differ significantly in drainage, knee swelling, anemia, levels of hemoglobin or hematocrit or platelets, ROM, HSS score, walking distance, or rates of transfusion or postoperative complications. Conclusions: Cementless fixation on femoral and tibial components during TKA does not increase blood loss or impede early functional recovery, which suggests that clinicians need not worry about blood loss and early functional recovery when deciding what type of fixation to perform during TKA. Trial registration: Number: ChiCTR2100052857; Date: November 6, 2021.

Characterization of naturally occurring pentacyclic triterpenes as novel inhibitors of deubiquitinating protease USP7 with anticancer activity in vitro.

Deubiquitinating protease USP7 is a promising therapeutic target for cancer treatment, and interest in developing USP7 inhibitors has greatly increased. In the present study, we reported a series of natural pentacyclic triterpenes with USP7 inhibitory activity in vitro. Among them, both the ursane triterpenes and oleanane triterpenes were more active than the lupine triterpenes, whereas ursolic acid was the most potent with IC50 of 7.0±1.5 µmol/L. Molecular docking studies showed that ursolic acid might occupy the ubiquitin binding pocket of USP7, with the 17-carboxyl group and 3-hydroxyl group playing a vital role in the USP7-ursolic acid interaction. Using the cellular thermal shift assay, we demonstrated that ursolic acid interacted with USP7 in RPMI8226 human myeloma cells. Ursolic acid dose-dependently inhibited the proliferation of the myeloma cells with IC50 of 6.56 µmol/L, accompanied by reductions in USP7 substrates such as MDM2, UHRF1 and DNMT1. Overexpression of USP7 partially, but significantly attenuated ursolic acid-induced cell death as well as downregulation of MDM2, UHRF1 and DNMT1. In conclusion, we demonstrate for the first time that pentacyclic triterpenes represent a novel scaffold for developing USP7 inhibitors and that USP7 inhibition contributes to the anti-cancer effect of ursolic acid.