The LANCET robotic system can improve surgical efficiency in total hip arthroplasty: A prospective randomized, multicenter, parallel-controlled clinical trial.

Objective: To evaluate the accuracy and safety of the LANCET robotic system, a robot arm assisted operation system for total hip arthroplasty via a multicenter clinical randomized controlled trial. Methods: A total of 116 patients were randomized into two groups: LANCET robotic arm assisted THA group (N = 58) and the conventional THA group (N = 58). General information about the patients was collected preoperatively. Operational time and bleeding were recorded during the surgery. The position of the acetabular prosthesis was evaluated by radiographs one week after surgery and compared with preoperative planning. Harris score, hip mobility, prosthesis position and angle and complications were compared between the two groups at three months postoperatively. Results: None of the 111 patients who ultimately completed the 3-month follow-up experienced adverse events such as hip dislocation and infection during follow-up. In the RAA group, 52 (92.9 %) patients were located in the Lewinnek safe zone and 49 (87.5 %) patients were located in the Callanan safe zone. In the control group were 47 (85.5 %) and 44 (80.0 %) patients, respectively. In the RAA group, 53 (94.6 %) patients had a postoperative acetabular inclination angle and 51 (91.1 %) patients had an acetabular version angle within a deviation of 5° from the preoperative plan. These numbers were significantly higher than those of the control group, which consisted of 42 (76.4 %) and 34 (61.8 %) patients respectively. There were no significant differences between the two groups of subjects in terms of general condition, intraoperative bleeding, hip mobility, and adverse complications. Conclusion: The results of this prospective randomized, multicenter, parallel-controlled clinical study demonstrated that the LANCET robotic system leads conventional THA surgery in accuracy of acetabular cup placement and does not differ from conventional THA surgery in terms of postoperative hip functional recovery and complications. The translational potential of this article: In the past, the success rate of total hip arthroplasty (THA) relied heavily on the surgeon's experience. As a result, junior doctors needed extensive training to become proficient in this technique. However, the introduction of surgical robots has significantly improved this situation. By utilizing robotic assistance, both junior and senior doctors can perform THA quickly and efficiently. This advancement is crucial for the widespread adoption of THA, as patients can now receive surgical treatment in local facilities instead of overwhelming larger hospitals and straining medical resources. Moreover, the development of surgical robots with fully independent intellectual property rights holds immense value in overcoming the limitations of high-end medical equipment. This aligns with the objectives outlined in the 14th Five Year Plan for National Science and Technology Strategy.

Clinicopathological Characteristics and Prognosis in Endometrial Cancer With Bone Metastasis: A SEER-Based Study of 584 Women.

PURPOSE: Bone metastasis from endometrial cancer (EC) is rare and poorly described. The purpose of the present study was to investigate the correlation between the clinically accessible factors and survival time among EC patients with bone metastasis. PATIENTS AND METHODS: We retrospectively identified and reviewed EC patients with bone metastasis from 2010 to 2016, based on the Surveillance, Epidemiology and End Results (SEER) database. Univariable and multivariable Cox regressions were applied to evaluate the effects of clinical variables on survival. Kaplan-Meier plots were used to visually demonstrate the correlation between independent risk factors and survival. RESULTS: Clinical data of 584 EC patients with bone metastasis from the SEER database were analyzed. EC patients with bone metastasis experienced extremely poor survival, with 1-year overall survival (OS) and cancer-specific survival (CSS) rates 33.8 and 35.8%, respectively. Variables associated with OS and CSS in the univariable analysis included race, tumor grade, tumor subtype, tumor size, lung, liver and brain metastases, surgery, radiotherapy, and chemotherapy. In the multivariable analysis, tumor grade, tumor subtype, liver and brain metastases, local surgery, and systemic chemotherapy remained independent risk factors for OS and CSS. However, local radiotherapy was an independent predictor of OS, not CSS. CONCLUSIONS: We identified several factors affect the survival of EC patients with bone metastasis, which is useful for clinicians to assess patients' outcomes. Our study supports surgery and radiotherapy of primary EC, and systemic chemotherapy for prolonging survival among EC patients with bone metastasis, which lays a solid foundation for defining optimal treatment strategy in this specific cohort.

Short- to Midterm Clinical and Radiological Outcomes After Matrix-Associated Autologous Chondrocyte Implantation for Chondral Defects in Knees.

BACKGROUND: Matrix-associated autologous chondrocyte implantation (MACI) has been proven to provide favorable short-term results for chondral defects in knees. However, it remains unclear whether the clinical benefits of MACI persist in the longer term. PURPOSE: The purpose of this prospective study was to evaluate the clinical and radiological outcomes, at short- and midterm follow-up, for patients undergoing MACI for focal chondral defects of the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 30 consecutive patients (31 knees) were treated using MACI between October 2010 and March 2018. There were 24 male patients and 6 female patients with an average age of 26 years (range, 12-48 years). The areas of the cartilage defect were consistently >2 cm2. All patients underwent MACI for a focal chondral defect of the femoral condyles or trochlea in the knee. These patients had been evaluated for up to 5 years, with an average follow-up of 44 months (range, 6-60 months) postoperatively.The International Knee Documentation Committee (IKDC) score, Lysholm score, and magnetic resonance imaging (MRI) with T2 mapping were used to assess the outcomes. RESULTS: No patients were lost to follow-up. Mean IKDC scores improved from 58.6 (range, 40.2-80.5) to 79.1 (range, 39.1-94.3) at 12 months and up to 88.4 (range, 83.9-100) at 5 years; mean Lysholm scores improved from 67.3 (range, 46-95) to 90.6 (range, 71-100) at 12 months and up to 95.9 (range, 85-100) at 5 years. The MRI with T2 mapping value of the transplanted area was evaluated for 21 knees, which revealed no differences compared with the normal area at 12 months postoperatively. CONCLUSION: From the first year onward, the clinical outcome scores and MRI with T2 mapping values showed continuous and marked improvement, suggesting that MACI is a valid option for localized cartilage defects in the knee.

Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities.

Wnt signaling is a highly conserved signaling pathway that plays a critical role in controlling embryonic and organ development, as well as cancer progression. Genome-wide sequencing and gene expression profile analyses have demonstrated that Wnt signaling is involved mainly in the processes of breast cancer proliferation and metastasis. The most recent studies have indicated that Wnt signaling is also crucial in breast cancer immune microenvironment regulation, stemness maintenance, therapeutic resistance, phenotype shaping, etc. Wnt/ß-Catenin, Wnt-planar cell polarity (PCP), and Wnt-Ca2+ signaling are three well-established Wnt signaling pathways that share overlapping components and play different roles in breast cancer progression. In this review, we summarize the main findings concerning the relationship between Wnt signaling and breast cancer and provide an overview of existing mechanisms, challenges, and potential opportunities for advancing the therapy and diagnosis of breast cancer.

Identification of tumorigenicity-associated genes in osteosarcoma cell lines based on bioinformatic analysis and experimental validation.

Osteosarcoma is the most common primary malignant tumor of bone. Tumorigenic investigation of osteosarcoma cell lines may facilitate preclinical studies of targeted therapy. Therefore, the aim of this study was to explore the tumorigenicity-associated genes in osteosarcoma cells. We found that 138 genes were highly expressed and 86 genes were lowly expressed in highly tumorigenic osteosarcoma cell lines (143B, MNNG/HOS, and SJSA-1) compared with poorly tumorigenic osteosarcoma cell lines (MG-63, Saos-2, and U-2 OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that highly expressed genes were associated with amino acids and energy metabolism, while lowly expressed genes were associated with cell cycle and DNA replication. Gene Ontology (GO) analysis showed that highly expressed genes were associated with endoplasmic reticulum stress response and aggrephagy, whereas lowly expressed genes were correlated with extracellular matrix assembly and DNA damage response. Further analysis identified six highly expressed genes and six lowly expressed genes. Three of highly expressed genes (DDX10, FOXA2, and HEY1) were correlated with poor prognosis, while three of lowly expressed genes (CYP26B1, GP1BB, and IFI44) showed the opposite trend in patients with osteosarcoma. Knockdown of HEY1 significantly inhibited the tumorigenicity of 143B cells in BALB/c nude mice.

Postoperative intravenous parecoxib sodium followed by oral celecoxib post total knee arthroplasty in osteoarthritis patients (PIPFORCE): a multicentre, double-blind, randomised, placebo-controlled trial.

OBJECTIVES: To evaluate the morphine-sparing effects of the sequential treatment versus placebo in subjects undergoing total knee arthroplasty (TKA), the effects on pain relief, inflammation control and functional rehabilitation after TKA and safety. DESIGN: Double-blind, pragmatic, randomised, placebo-controlled trial. SETTING: Four tertiary hospitals in China. PARTICIPANTS: 246 consecutive patients who underwent elective unilateral TKA because of osteoarthritis (OA). INTERVENTIONS: Patients were randomised 1:1 to the parecoxib/celecoxib group or the control group. The patients in the parecoxib/celecoxib group were supplied sequential treatment with intravenous parecoxib 40 mg (every 12 hours) for the first 3 days after surgery, followed by oral celecoxib 200 mg (every 12 hours) for up to 6 weeks. The patients in the control group were supplied with the corresponding placebo under the same instructions. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the cumulative opioid consumption at 2 weeks post operation (intention-to-treat analysis). Secondary endpoints included the Knee Society Score, patient-reported outcomes and the cumulative opioid consumption. RESULTS: The cumulative opioid consumption at 2 weeks was significantly smaller in the parecoxib/celecoxib group than in the control group (median difference, 57.31 (95% CI 34.66 to 110.33)). The parecoxib/celecoxib group achieving superior Knee Society Scores and EQ-5D scores and greater Visual Analogue Scale score reduction during 6 weeks. Interleukin 6, erythrocyte sedation rate and C-reactive protein levels were reduced at 72 hours, 2 weeks and 4 weeks and prostaglandin E2 levels were reduced at 48 hours and 72 hours in the parecoxib/celecoxib group compared with the placebo group. The occurrence of adverse events (AEs) was significantly lower in the parecoxib/celecoxib group. CONCLUSIONS: The sequential intravenous parecoxib followed by oral celecoxib regimen reduces morphine consumption, achieves better pain control and functional recovery and leads to less AEs than placebo after TKA for OA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (ID: NCT02198924).

Lesions of the Long Head of the Biceps Tendon Concomitant with Rotator Cuff Tears: Tenotomy or Subpectoral Mini-open Tenodesis? A Comparative Short to Mid-term Follow-up Study.

OBJECTIVE: To compare the clinical and radiological outcomes of patients who underwent rotator cuff repair (RCR) concomitant with long head of the biceps tendon (LHBT) tenotomy or subpectoral mini-open tenodesis. METHODS: Prospectively collected data was reviewed on 154 patients, who underwent a LHBT procedure (tenotomy or tenodesis) concomitant with RCR between January 2010 and January 2017. The exclusion criteria were irreparable massive rotator cuff tear, rotator cuff partial tear, subscapular tendon tear, glenohumeral arthritis, and prior shoulder surgery. The two patient groups are as follows: RCR + Tenotomy (Group A) and RCR + Subpectoral mini-open tenodesis (Group B). The visual analog scale (VAS) for pain, Constant Score scale, American Shoulder and Elbow Surgeons (ASES) scores, and the Disabilities of the Arm, Shoulder and Hand (DASH) scores preoperatively and 1 month, 3 months, 6 months, 1 year postoperatively and the latest out-patient clinic were compared between the two groups. RESULTS: Ninety-two patients in Group A and 62 patients in Group B completed the follow-up, with a median follow-up time of 27 and 42 months respectively. At the final follow-up, the VAS, Constant, ASES, and DASH scores in Group A were 0.1 ± 0.2, 87.0 ± 12.8, 96.4 ± 4.3 and 6.6 ± 4.8 respectively, and the VAS, Constant, ASES, and DASH scores in Group B were 0.1 ± 0.3, 92.5 ± 3.9, 96.3 ± 3.6 and 2.9 ± 1.3 respectively. Clinical evaluation scales showed satisfactory results in both groups, and there were no statistically significant differences between the two groups at the same follow-up time. Popeye sign was detected in one case of Group A (1.1%) and in one case of Group B (1.6%, P > 0.05). CONCLUSION: Both tenotomy and subpectoral mini-open tenodesis are effective for concomitant lesions of the LHBT in patients with reparable rotator cuff tears, and subpectoral mini-open tenodesis of the LHBT does not provide any significant clinical or functional improvement than isolated tenotomy.

WNT5B governs the phenotype of basal-like breast cancer by activating WNT signaling.

BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Metastatic disease remains the primary cause of death in patients with breast cancer. Basal-like breast cancer (BLBC) is associated with aggressive behavior, stem-like phenotype, high histological grade, poor clinical features, and high rates of recurrences and/or metastasis. However, the mechanism of BLBC phenotype shaping remains obscure. METHODS: Seventeen normal breast/breast cancer cell lines were used for evaluating the breast cancer subtype-markers, WNT targets and constitutive components, and epithelial mesenchymal transition (EMT) markers analysis by western blot. One hundred and twenty formalin-fixed breast cancer tissues were used for immunohistochemistry (IHC) staining. Nine online platforms (cBioPortal, CCLE, GEPIA, etc.) were used for related analyses. RESULTS: We identified Wnt5b as a key regulatory factor that governs the phenotype of BLBC by activating canonical and non-canonical WNT signaling. Wnt5b exhibited basal-like specificity in cells and clinical samples both at the mRNA and protein levels and also showed good correlation with basal-like phenotype at the mRNA level. Besides, Wnt5b was also a promising therapeutic target for LGK-974 treatment. In addition, we identified that CK1α was expressed at low levels in BLBC and that the activation of CK1α by pyrvinium was an alternative strategy for BLBC treatment. CONCLUSIONS: Wnt5b is not only a diagnostic biomarker but also a potential therapeutic target of BLBC.

Establishment and Characterization of Two Novel Cholangiocarcinoma Cell Lines.

BACKGROUND: Cholangiocarcinoma (CCA) is a rare, aggressive and highly lethal tumor. The disease is very difficult to diagnose and multi-modality treatments are ineffective. To improve our understanding of the biological characteristics of CCA, and facilitate the identification of valid treatments, an in-depth characterization of two novel Chinese patient-derived primary CCA cell lines was performed. METHODS: Two CCA cell lines were developed and labelled ZJU-0826 and -1125. The two cell lines were characterized with respect to phenotypic, molecular, biomarker, functional and histological properties. RESULTS: Two novel cell lines were cultured for 2 years, and maintained for more than 100 passages. They retained their typical biliary epithelial morphology and ultrastructure. The population doubling times of ZJU-0826, and -1125 were 63.84 h and 44.73 h, respectively. The cells exhibited near-triploid karyotypes with complex structural aberrations. ZJU-1125 cells had mutations in TP53 exons. Short tandem repeats genotyping confirmed the human origin and difference between lines. An immunophenotype analysis showed that ZJU-0826 is positive for CD44, CD29, Pdx1, CD236, FoxA1, FoxA2, and Nanog, and ZJU-1125 positive for CD44, CD29, CD133, Pdx1, FoxA1, FoxA2, and Nanog. ZJU-1125 had greater invasion ability in vitro and tumorigenicity than those of ZJU-0826. CONCLUSIONS: Our results confirm the validity of the ZJU-0826 and -1125 as representative models for the elucidation of the molecular pathogenesis of perihilar CCA, and intrahepatic CCA in both in vitro and in vivo studies, respectively.

Casein kinase 1α: biological mechanisms and theranostic potential.

Casein kinase 1α (CK1α) is a multifunctional protein belonging to the CK1 protein family that is conserved in eukaryotes from yeast to humans. It regulates signaling pathways related to membrane trafficking, cell cycle progression, chromosome segregation, apoptosis, autophagy, cell metabolism, and differentiation in development, circadian rhythm, and the immune response as well as neurodegeneration and cancer. Given its involvement in diverse cellular, physiological, and pathological processes, CK1α is a promising therapeutic target. In this review, we summarize what is known of the biological functions of CK1α, and provide an overview of existing challenges and potential opportunities for advancing theranostics.

How does the inclination of the tibial component matter? A three-dimensional finite element analysis of medial mobile-bearing unicompartmental arthroplasty.

BACKGROUND: Medial unicompartmental knee arthroplasty (UKA) using Oxford mobile-bearing prosthesis is performed in the treatment of medial compartmental arthritis of the knee. However, little is known about the stress distributions for mobile-bearing UKA on the medial tibial plateau. METHODS: In this study, the stresses on the coronal plane were calculated in a three-dimensional model of the proximal tibia. The features of the stress distribution were investigated when the tibial tray was placed in 15°, 10°, six degrees, and three degrees varus, neutral (0°), and in three degrees, six degrees, 10°, and 15° valgus on the coronal plane of the medial plateau. RESULTS: The peak von Mises stress was found on the cortex below the medial plateau while the stresses of cortical bone increased gradually as the inclination of the tibial tray was changed from varus to valgus. The amount of peak stress was almost the same as that in the normal knee model when the tibial tray was placed in six degrees valgus and consistently lower in varus inclination than in the normal knee model. Conversely, the peak stress of soft bone was found at the bottom of the slot. CONCLUSIONS: This study demonstrates that the inclination of the tibial component affects stress distribution in the proximal tibia after UKA. Slight varus inclination of the mobile-bearing tibial component is acceptable as it lowers the peak stress on the medial cortex. Additionally, placing the tibial tray in slight varus avoids a rise in stress between the tip of the keel and the medial tibial cortex.

Efficacy and safety of Postoperative Intravenous Parecoxib sodium Followed by ORal CElecoxib (PIPFORCE) post-total knee arthroplasty in patients with osteoarthritis: a study protocol for a multicentre, double-blind, parallel-group trial.

INTRODUCTION: Total knee arthroplasty (TKA) has been regarded as a most painful orthopaedic surgery. Although many surgeons sequentially use parecoxib and celecoxib as a routine strategy for postoperative pain control after TKA, high quality evidence is still lacking to prove the effect of this sequential regimen, especially at the medium-term follow-up. The purpose of this study, therefore, is to evaluate efficacy and safety of postoperative intravenous parecoxib sodium followed by oral celecoxib in patients with osteoarthritis (OA) undergoing TKA. The hypothesis is that compared to placebo with opioids as rescue treatment, sequential use of parecoxib and celecoxib can achieve less morphine consumption over the postoperative 2 weeks, as well as better pain control, quicker functional recovery in the postoperative 6 weeks and less opioid-related adverse events during the 12-week recovery phase. METHODS AND ANALYSIS: This study is designed as a multicentre, randomised, double-blind, parallel-group and placebo-controlled trial. The target sample size is 246. All participants who meet the study inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either the parecoxib/celecoxib group or placebo group. The randomisation and allocation will be study site based. The study will consist of three phases: an initial screening phase; a 6-week double-blind treatment phase; and a 6-week follow-up phase. The primary end point is cumulative opioid consumption during 2 weeks postoperation. Secondary end points consist of the postoperative visual analogue scale score, knee joint function, quality of life, local skin temperature, erythrocyte sedimentation rate, C reactive protein, cytokines and blood coagulation parameters. Safety end points will be monitored too. ETHICS AND DISSEMINATION: Ethics approval for this study has been obtained from the Ethics Committee, Peking Union Medical College Hospital, China (Protocol number: S-572) Study results will be available as published manuscripts and presentations at national and international meetings. TRIAL REGISTRATION NUMBER: NCT02198924.

Ape1 regulates WNT/ß-catenin signaling through its redox functional domain in pancreatic cancer cells.

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1, Ape1) is a multifunctional protein that is upregulated in human pancreatic cancer. Ape1 redox domain plays an essential role in regulating the effects of reactive oxygen species (ROS) generated during physiological metabolism and pathological stress. In the present study, we explored whether Ape1 and ROS affect WNT/ß-catenin signaling. We used E3330, a small molecule inhibitor of the redox activity of Ape1, and a siRNA approach to knock down Ape1, in two human pancreatic cancer cell lines. Inhibition of Ape1 resulted in growth suppression of pancreatic cancer cells, increased ROS levels, upregulation of ß-catenin and c-myc and downregulation of cyclin D1. Consistent with these data, overexpression of Ape1 in pancreatic cancer cells reduced ROS and c-myc levels and increased cyclin D1 levels. Moreover, treatment of pancreatic cancer cells with H2O2 to induce oxidative stress resulted in upregulated ROS levels, decreased Ape1 at both the mRNA and protein level, and alterations in WNT/ß-catenin pathway components. Finally, treatment of pancreatic cancer cells with the WNT/ß-catenin inhibitor IWR-1 resulted in growth inhibition, which was greatly enhanced when combined with E3330 treatment. In summary, our results demonstrate that ROS is an important intracellular messenger that can modulate WNT/ß­catenin signaling. The present study provides interesting new insight into crosstalk between the redox function of Ape1 and WNT/ß-catenin signaling in cancer cells. Furthermore, our data show that the combination of Ape1 and WNT inhibitors enhanced the inhibition of pancreatic cell proliferation. These results provide a promising novel therapeutic strategy for treating pancreatic cancer in future.

Functional and oncological outcomes after total claviculectomy for primary malignancy.

Primary malignancies of the clavicle are very rare, and scarce data are available regarding the functional and oncologic outcome after total claviculectomy. This is a retrospective review of 9 patients with primary clavicular malignancy, between 2000 and 2010, treated with total claviculectomy. There were 5 females and 4 males with a mean age of 29 years (range, 16 to 56). After a mean follow-up period of 46 months (range, 24-102 months) all patients were alive and without local recurrence or metastases. Patients had almost a full range of motion without pain, without significant functional deficit. The mean Constant-Murley score (best possible score = 100) improved from 26 to 79 (p < 0.001), while the VAS for pain improved from 8.7 to 2.4 (p < 0.001). Therefore, total claviculectomy may be a useful salvage procedure for primary clavicular malignancy.