Inhibition of CILP2 Improves Glucose Metabolism and Mitochondrial Dysfunction in Sarcopenia via the Wnt Signalling Pathway.

BACKGROUND: Skeletal muscle is the primary organ involved in insulin-mediated glucose metabolism. Elevated levels of CILP2 are a significant indicator of impaired glucose tolerance and are predominantly expressed in skeletal muscle. It remains unclear whether CILP2 contributes to age-related muscle atrophy through regulating the glucose homeostasis and insulin sensitivity. METHODS: Initially, the expression levels of CILP2 were assessed in elderly mice and patients with sarcopenia. Lentiviral vectors were used to induce either silencing or overexpression of CILP2 in C2C12 myoblast cells. The effects of CILP2 on proliferation, myogenic differentiation, insulin sensitivity and glucose uptake were evaluated using immunofluorescence, western blotting, real-time quantitative polymerase chain reaction, RNA sequencing, glucose uptake experiments, dual-luciferase reporter assays and co-immunoprecipitation (CO-IP). An adeno-associated virus-9 containing a muscle-specific promoter was injected into SAMP8 senile mice to observe the efficacy of CILP2 knockout. RESULTS: We found that there was more CLIP2 expressed in the skeletal muscle of ageing mice (+1.1-fold, p < 0.01) and in patients with sarcopenia (+2.5-fold, p < 0.01) compared to the control group. Following the overexpression of CILP2, Ki67 (-65%, p < 0.01), PCNA (-32%, p < 0.05), MyoD1 (-89%, p < 0.001), MyoG (-31%, p < 0.05) and MyHC (-85%, p < 0.001), which indicate proliferation and differentiation potential, were significantly reduced. In contrast, MuRF-1 (+59%, p < 0.05), atrogin-1 (+43%, p < 0.05) and myostatin (+31%, p < 0.05), the markers of muscular atrophy, were significantly increased. Overexpression of CILP2 decreased insulin sensitivity, glucose uptake (-18%, p < 0.001), GLUT4 translocation to the membrane and the maximum respiratory capacity of mitochondria. Canonical Wnt signalling was identified through RNA sequencing as a potential pathway for CILP2 regulation in C2C12, and Wnt3a was confirmed as an interacting protein of CILP2 in the CO-IP assay. The addition of recombinant Wnt3a protein reversed the inhibitory effects on myogenesis and glucose metabolism caused by CILP2 overexpression. Conversely, CILP2 knockdown promoted myogenesis and glucose metabolism. CILP2 knockdown improved muscle atrophy in mice, characterized by significant increases in time to exhaustion (+42%, p < 0.001), grip strength (+19%, p < 0.01), muscle mass (+15%, p < 0.001) and mean muscle cross-sectional area (+37%, p < 0.01). CILP2 knockdown enhanced glycogen synthesis (+83%, p < 0.001) and the regeneration of oxidative and glycolytic muscle fibres in SAMP8 ageing mice via the Wnt/ß-catenin signalling pathway. CONCLUSIONS: Our results indicate that CILP2 interacts with Wnt3a to suppress the Wnt/ß-catenin signalling pathway and its downstream cascade, leading to impaired insulin sensitivity and glucose metabolism in skeletal muscle. Targeting CILP2 inhibition could offer potential therapeutic benefits for sarcopenia.

Innovative 3D Navigation Module for Precise Unilateral Pedicle Screw Combined with Contralateral Translaminar Facet Screw Placement in Lumbar Spine Surgery.

OBJECTIVE: The incidence of degenerative diseases of the lumbar spine has increased in recent years. Unilateral pedicle screw combined with contralateral translaminar facet screw fixation offers the advantages of less trauma, better stability, and fewer complications. However, the surgical difficulty and suboptimal pinning accuracy of translaminar facet screw placement in clinical practice limit its use. Therefore, in this study, we designed a novel suspended 3D-printed navigation module to facilitate fast and accurate intraoperative screw placement. The aim of this study is to investigate the digital design, precise implementation, and evaluation methods for placing unilateral pedicle screws in the lumbar spine combined with translaminar facet screw placement using a new suspended 3D navigation module. METHODS: This retrospective study included 46 patients with single-level lumbar lesions who underwent spine surgery at the Affiliated Hospital of Putian University between June 2022 and December 2023. The suspended navigation module was designed digitally. Preoperative screw placement was simulated using 3D printed models, followed by an intraoperative accurate screw placement facilitated by the navigation module and a postoperative evaluation of the accuracy of screw placement. The absolute difference in three-dimensional coordinates of the inlet and outlet points of the preoperative design and the postoperative screw-nail channel served as the precision index. RESULTS: In a study involving 46 patients, surgery was successful with 92 pedicle screws and 46 translaminar facet screws placed without any penetration of the cortex. The difference in coordinates before and after screw insertion was minimal, with entry points varying between 1.21 to 1.36 mm and exit points between 1.97 to 2.46 mm. When screw accuracy met certain thresholds, there was no significant difference between preoperative design and postoperative coordinates, indicating precise replication of the surgical plan. CONCLUSION: The new suspended 3D navigation module enables the precise placement of unilateral pedicle screws in the lumbar spine combined with translaminar pedicle screws for precise surgery.

Comparison of postoperative outcomes between endoscopy assisted minimal invasive direct anterior approach and bikini direct anterior approach in total hip arthroplasty.

BACKGROUND: We have innovatively developed a modified bikini direct anterior approach total hip arthroplasty (THA), endoscopy assisted minimal invasive direct anterior approach (Endo-DAA). The study compared aesthetic appearance of the scar, postoperative radiographic and functional outcomes, and complications of Endo-DAA with Bikini-DAA. METHODS: Patients who underwent primary THA using Endo-DAA or Bikini-DAA were included. The main innovation of Endo-DAA is the use of minimally invasive 5-7 cm proximal transverse incision and distal puncture with an endoscopy assisted split-type tool to complete the acetabular preparation and prosthesis implantation. Outcomes evaluated included evaluation of scar satisfaction, hip reconstruction including inclination, anteversion and leg-length discrepancy (LLD) and patient-reported outcomes including Harris Hip Scores (HHS) and Forgotten Joint Score (FJS). Follow-up time points included preoperative, 6 weeks, 6 months and 12 months. RESULTS: Finally, 195 hips in Endo-DAA and 207 hips in Bikini DAA completed the follow-up. The Endo-DAA group was superior to the Bikini-DAA group in the cosmetic aspects of scars. the cup anteversion angle of Endo-DAA group was significantly better than that in the Bikini-DAA group. The early HHS and FJS of the Endo-DAA group were superior to those of the Bikini-group. Operation time, blood loss, incision length, length of stay and duration to start no-assistive-device walking were also significantly better in the Endo-DAA group. Furthermore, the Bikini-DAA group had a higher incidence of complication. CONCLUSION: Compared with Bikini-incision, Endo-DAA improves patients' subjective satisfaction with scar aesthetics, accelerates rapid recovery of postoperative function, and reduces postoperative complications.

Comparison of the Medium-term Outcomes of Anterior Lumbar Discectomy and Fusion with Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Retrospective Cohort Study.

OBJECTIVE: Lumbar degenerative diseases (LDDs) with huge herniation in the left lateral recess or central canal present challenges for oblique lateral lumbar interbody fusion (OLIF) or endoscope-assisted OLIF procedures. Currently, minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the primary approach for this issue. This study aims to provide a standardized technical description of the anterior lumbar discectomy and fusion (ALDF) and evaluate the medium-term clinical effectiveness of both ALDF and MIS-TLIF techniques. METHODS: A retrospective review was performed on LDDs who underwent ALDF and MIS-TLIF surgery from January 2018 to January 2020. The evaluation encompassed various clinical outcomes, such as the visual analogue scale (VAS) scores for back pain and leg pain (VAS-back, VAS-leg), the Oswestry disability index (ODI), the 36-item short-form health survey mental component summary (SF-36 MCS), and the physical component summary (SF-36 PCS). Additionally, radiological parameters, including disc height (DH), segmental disk angle (SDA), lumbar lordosis (LL), and cross-sectional area (CSA), were assessed. Data including radiculopathy, estimated blood loss, operation time, time of getting out of bed, fusion rate, and complications were recorded. Student's independent samples t test and Pearson's chi-square test were used to compare the differences between groups. RESULTS: In total, 47 patients were treated by ALDF and 48 patients were treated by MIS-TLIF. The ALDF group exhibited statistically significant lower estimated blood loss and earlier time of getting out of bed compared to the MIS-TLIF group (p < 0.05). The ALDF group demonstrated lower VAS-back scores and a higher remission rate of low back pain 3 years after the surgery (p < 0.05). During the entire follow-up period, the ALDF group exhibited higher increases in DH and SDA compared to the MIS-TLIF group (p < 0.05). At 6 months, the fusion rate in the ALDF group was significantly higher than in the MIS-TLIF group (p < 0.05). The comparison revealed no statistically significant differences in complication rates between the two groups (p > 0.05). CONCLUSION: The ALDF could be considered as a viable surgical alternative for the treatment of LDDs that necessitate ventral neural direct decompression. ALDF exhibited favorable medium-term outcomes in patients with LDDs, displaying advantages in facilitating expedited recovery, enhancing radiographic outcomes, and elevating the remission rate of low back pain. Although ALDF presents slightly higher complication rates compared to MIS-TLIF, it does not adversely affect clinical outcomes.

Endoscopic Arthroplasty via Mini-open Direct Anterior Approach Improves Postoperative Complications and Acetabular Components of Total Hip Arthroplasty in Obese Patients.

To overcome the high-risk complications and poor alignment of acetabular components in obese patients associated with direct anterior approach (DAA) for total hip arthroplasty (THA), we innovated an endoscopic arthroplasty via mini-open direct anterior approach technique (Endo-DAA). The purpose of this study was to compare the clinical and radiographic outcomes in obese patients subjected to THA between Endo-DAA, Bikini DAA, and conventional DAA. In this retrospective controlled study, a total of 360 consecutive primary THA on obese patients (body mass index greater than 28 kg/m2) via Endo-DAA, Bikini DAA, and conventional DAA performed from October 2017 to October 2022 by different surgeons and in a single center were included. Assessments including perioperative parameters, clinical outcomes, complications, and radiologic measurements were retrieved from patients before the surgery, perioperative period and the latest follow-up. A total of 360 consecutive THA (Endo-DAA = 108, Bikini DAA = 116, Conventional DAA = 136) with complete follow-up data were analyzed. Compared to Bikini DAA or conventional DAA, Endo-DAA significantly shortened the length of incision (5.46 ± 0.53), the duration of operation (64.47 ± 12.38), and postoperative hospital stay (2.15 ± 0.89). Endo-DAA significantly reduces wound related complications compared with conventional DAA. Besides, Endo-DAA achieved a significantly better alignment of acetabular components compared to Bikini DAA or conventional DAA. Furthermore, Endo-DAA improved postoperative pain at the activity at 24 h postoperatively and early functional scores. The Endo-DAA THA technique provides better short-term clinical and radiographic results in obese patients with a low rate of postoperative complications compared to Bikini DAA or conventional DAA.

Comparison Between Multisite Injection and Single Rotator Interval Injection of Corticosteroid in Primary Frozen Shoulder (Adhesive Capsulitis): A Randomized Controlled Trial.

BACKGROUND: Steroid injection is a commonly used conservative treatment for primary frozen shoulder (PFS), but the optimal injection site remains undetermined. OBJECTIVES: We conducted a prospective randomized controlled trial of multisite combined injection (MCI) vs single rotator interval injection (SRI). STUDY DESIGN: A randomized double-blinded controlled trial. SETTING: Center for Joint Surgery, Department of Orthopaedic Surgery, the Second Affiliated Hospital of Chongqing Medical University. METHODS: Sixty-four patients with PFS were randomly assigned to 2 groups. The experimental group received MCI in the rotator interval, intraarticular, and subacromial bursa; the control group received an SRI. Both groups were injected with one mL of 40 mg triamcinolone acetonide and 4 mL of 2% lidocaine. The injection process was completed under ultrasound guidance. Follow-up points were 4, 8, and 12 weeks postinjection. The outcome measures included the Visual Analog Scale (VAS) score, the American Shoulder and Elbow Surgeons (ASES) score, the Constant-Murley Shoulder (CMS) score, passive range of motion of the shoulder, and patient satisfaction rating. RESULTS: Thirty patients in the MCI group and 29 patients in the SRI group were included in the data analysis. All the outcomes in the 2 groups were significantly better postinjection than preinjection. The MCI group had a lower VAS score than the SRI group at 4 weeks (3.1 ± 1.2 vs 4.3 ± 1.6) and 8 weeks (2.2 ± 1.2 vs. 3.4 ± 1.2) (P < 0.05). Compared with the SRI group, the MCI group had a significant improvement in flexion and abduction (P < 0.01). Additionally, the ASES and CMS scores in the MCI group were better than those in the SRI group at 4, 8 and 12 weeks (P < 0.01). LIMITATIONS: Limitations include the sample size of this study is small and a that it was conducted at a single-center. CONCLUSIONS: Both MCI and SRI effectively alleviated pain and restored range of motion in patients with PFS. However, the MCI group had obviously lower early pain scores, better flexion and abduction, and better function scores than the SRI group; no additional adverse events were observed.

Dynamic Tensile Stress Promotes Regeneration of Achilles Tendon in a Panda Rope Bridge Technique Mice Model.

Regeneration of ruptured Achilles tendon remains a clinical challenge owing to its limited regenerative capacity. Dynamic tensile stress plays a positive role in the regeneration of tendon, although the specific underlying mechanisms remain unclear. In this study, the Achilles tendon defect-regeneration model was created in male C57BL/6 mice aged 8 weeks. The animals were randomly assigned to four groups-repair, non-repair, repair with fixation, and non-repair with fixation. The repair group and repair with fixation group adopted the panda rope bridge technique (PRBT) repair method. Our results demonstrated the presence of more densely aligned and mature collagen fibers, as well as more tendon-related makers, in the repair group at both 2- and 4-week post-surgery. Furthermore, the biomechanical strength of the regenerated tendon in the repair group was highly improved. Most importantly, the expressions of integrin αv and its downstream and the phosphorylation levels of FAK and ERK were remarkably higher in the repair group than in the other groups. Furthermore, blocking FAK or ERK with selective inhibitors PF573228 and U0126 resulted in obvious adverse effects on the histological structure of the regenerated Achilles tendon. In summary, this study demonstrated that dynamic tensile stress based on the PRBT could effectively promote the regeneration of the Achilles tendon, suggesting that dynamic tensile stress enhances the cell proliferation and tenogenic differentiation via the activation of the integrin/FAK/ERK signaling pathway.

Development of a risk model based on autophagy-related genes to predict survival and immunotherapy response in ovarian cancer.

BACKGROUND: Autophagy is a highly conserved cellular proteolytic process that can interact with innate immune signaling pathways to affect the growth of tumor cells. However, the regulatory mechanism of autophagy in the tumor microenvironment, drug sensitivity, and immunotherapy is still unclear. METHODS: Based on the prognostic autophagy-related genes, we used the unsupervised clustering method to divide 866 ovarian cancer samples into two regulatory patterns. According to the phenotypic regulation pattern formed by the differential gene between the two regulation patterns, a risk model was constructed to quantify patients with ovarian cancer. Then, we systematically analyzed the relationship between the risk model and immune cell infiltration, immunotherapeutic response, and drug sensitivity. RESULTS: Based on autophagy-related genes, we found two autophagy regulation patterns, and confirmed that there were differences in prognosis and immune cell infiltration between them. Subsequently, we constructed a risk model, which was divided into a high-risk group and a low-risk group. We found that the high-risk group had a worse prognosis, and the main infiltrating immune cells were adaptive immune cells, such as Th2 cells, Tgd cells, eosinophils cells, and lymph vessels cells. The low-risk group had a better prognosis, and the most infiltrated immune cells were innate immune cells, such as aDC cells, NK CD56dim cells, and NK CD56bright cells. Furthermore, we found that the risk model could predict chemosensitivity and immunotherapy response, suggesting that the risk model may help to formulate personalized treatment plans for patients. CONCLUSIONS: Our study comprehensively analyzed the prognostic potential of autophagy-related risk models in ovarian cancer and determined their clinical guiding role in targeted therapy and immunotherapy.

Outcomes of early versus late functional weight-bearing after the acute Achilles tendon rupture repair with minimally invasive surgery: a randomized controlled trial.

INTRODUCTION: Optimal postoperative rehabilitation regimen for acute Achilles tendon rupture (AATR) remains unclear. It is important to evaluate whether early functional weight-bearing rehabilitation program after minimally invasive repair results in an earlier return to pre-injury activity but increases the risk of re-rupture. MATERIALS AND METHODS: This was a prospective randomized controlled trial involving 68 AATR patients undergoing minimally invasive surgery. 34 patients were enrolled in early weight­bearing mobilization accelerated rehabilitation group (AR group); 34 patients were enrolled in the traditional rehabilitation (TR) group. Outcomes measures included American Orthopaedic Foot and Ankle Society Score (AOFAS) score and Achilles Tendon Total Rupture Score (ATRS) score before surgery and 3, 6, and 12 months after surgery, incidence rate of Achilles tendon re-rupture and total complications, length of hospital stay, time return to work and sports. RESULTS: There was no significant difference in preoperative basic data between the two groups. However, AOFAS score and ATRS score were better in AR group than TR group at 3 months postoperatively (92.4 ± 3.5 vs 88.3 ± 4.5, P < 0.01; 91.1 ± 4.4 vs 88.9 ± 3.4, P = 0.03, respectively), the mean length of hospital stay (4.7 ± 1.5 vs 7.6 ± 2.0 days, P < 0.01) and time return to work (4.5 ± 1.0 vs 7.5 ± 1.6 weeks, P < 0.01) were shorter in AR group than in TR group. No statistical significance was calculated in patient-reported outcomes during the rest of the follow-up time and complications. CONCLUSION: Early accelerated rehabilitation with weight-bearing in patients with AATR after minimally invasive surgery results in better early functional outcomes and shows similar security and feasibility. REGISTRATION NO: ChiCTR2100043398.

The short-term outcomes of cementless stem for hip arthroplasty in the elderly patients: comparison with patients < 65 years.

OBJECTIVE: The use of cement or cementless femoral stem prosthesis for hip arthroplasty in elderly patients has been controversial. This study investigated the efficacy and safety of cementless femoral stem in elderly patients (age ≥ 65 years). METHODS: The short-term efficacy of primary hip arthroplasty with cementless femoral stem in our hospital from January 2014 to June 2021 was retrospectively analyzed. Patients were divided into two groups according to age: young group (< 65 years) and the elder group (≥ 65 years). The evaluation index was the Harris Hip score (Harris), postoperative femoral stem prosthesis sinking distance and femoral plant-related complications (periprosthetic fracture, prosthesis loosening, infection, dislocation, etc.). RESULTS: There were 72 cases of 86 hips in the young group and 83 cases of 92 hips in the elder group. The recovery trend of functional score in the elder group was similar to that in the young group, and the Harris score increased from (38.35 ± 18.21) before surgery to (86.91 ± 12.55) at last follow-up (p < 0.01). Compared with the two groups at the same time of 3 months, 6 months and 12 months after operation, the sinking distance of the elder group was significantly greater (P < 0.05). Even in the elder group, there was a significant difference in sinking distance between 6 and 3 months after surgery (2.44 ± 0.49 mm vs 2.10 ± 0.65 mm, P = 0.004). However, there was no significant difference between 12 and 6 months (2.53 ± 0.53 mm vs 2.44 ± 0.49 mm, P = 0.40). A total of 10 patients in the elder group and 6 patients in the young group had a complication event (P = 0.36). CONCLUSIONS: Elderly patients with cementless femoral stems can achieve metal-bone integration slightly longer than young patients, but short-term clinical outcomes can be restored to a satisfactory level with adequate safety. However, the long-term efficacy still needs to be verified by multicenter, large sample size and prospective clinical follow-up results.

Panda rope bridge technique versus open repair of acute Achilles tendon rupture: A comparative clinical study.

PURPOSE: The treatment options of acute Achilles tendon rupture (AATR) remain controversial. This article aims to compare the efficacy of a new surgical procedure, the panda rope bridge technique (PRBT) with open surgery of AATR. METHODS: Ninety-eight patients with AATR were recruited, 53 underwent the PBRT, and 45 underwent open surgery. The operation time, postoperative American Orthopaedic Foot and Ankle Score, Achilles Tendon Rupture Score, complications and time to return to work and restore exercise were documented. RESULTS: The average operation time, intraoperative blood loss and complication rate were 35.1 min, 18.2 ml and 3.8%, respectively, in the PRBT group, which were significantly lower than those of the open surgery group (P<0.001). The post-operative American Orthopaedic Foot and Ankle Score of 99.6 and the Achilles Tendon Rupture Score of 97.5 in the PRBT group were significantly higher than that of the open surgery group (P<0.001). The time to return to work and return to exercise were shorter in the PRBT group (P<0.001). CONCLUSION: Compared to open surgery, PRBT is a better approach to the management of AATR. PRBT offers accelerated recovery, lower occurrence of post-operative complications and improved recovery of ankle joint function.

In adults, early mobilization may be beneficial for distal radius fractures treated with open reduction and internal fixation: a systematic review and meta-analysis.

OBJECTIVES: It remains debatable if early mobilization (EM) yields a better clinical outcome than the late mobilization (LM) in adults with an acute and displaced distal radial fracture (DRF) of open reduction internal fixation (ORIF). Therefore, we aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs), comparing clinical results with the safety of EM with LM following ORIF. METHODS: Databases such as Medline, Cochrane Central Register, and Embase were searched from Jan 1, 2000, to July 31, 2021, and RCTs comparing EM with LM for DRF with ORIF were included in the analysis. The primary outcome of study included disabilities of the Arm, Shoulder, and Hand (DASH) score at different follow-up times. Wherever the secondary outcomes included patient-rated wrist evaluation (PRWE), grip strength (GS), visual analog scale (VAS), wrist range of motion (WROM), and associated complications, the two independent reviewers did data extraction for the analysis. Effect sizes of outcome for each group were pooled using random-effects models; thereafter, the results were represented in the forest plots. RESULTS: Nine RCTs with 293 EM and 303 LM participants were identified and included in the study. Our analysis showed that the DASH score of the EM group was significantly better than LM group at the six weeks postoperatively (- 10.15; 95% CI - 15.74 to - 4.57, P < 0.01). Besides, the EM group also had better outcomes in PRWE, GS and WROM at 6 weeks. However, EM showed potential higher rate for implant loosening and/or fracture re-displacement complication (3.00; 95% CI 1.02-8.83, P = 0.05). CONCLUSION: Functionally, at earlier stages, EM for patients with DRF of ORIF may have a beneficial effect than LM. The mean differences in the DASH score at 6 weeks surpassed the minimal clinically important difference; however, the potentially higher risk of implant loosening and/or fracture re-displacement cannot be ignored. Due to the lack of definitive evidence, multicenter and large sample RCTs are required for determining the optimal rehabilitation protocol for DRF with ORIF. PROSPERO registration number: CRD42021240214 2021/2/28.