Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Surgical accuracy of image-free versus image-based robotic-assisted total knee arthroplasty.

BACKGROUND: This study investigated the accuracy in achieving proper lower limb alignment and component positions after total knee replacement (TKR) with image-free and image-based robotic-assisted TKR. METHODS: A total of 129 patients (166 knees) suffering from end-stage knee arthritis who underwent TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Radiological outcomes were compared between image-free and image-based robotic-assisted surgical systems. RESULTS: There were significant differences between the two robotic systems when comparing the mean planned component alignment and the mean measured alignment on radiographs, in which the image-free robotic-assisted system was more varus, whereas the image-based robotic-assisted system was more valgus for both the mean femoral and tibial component coronal alignment (p < 0.001). For tibial component sagittal alignment, the image-based group had a larger deviation from the planned posterior slope (p < 0.001). CONCLUSION: Image-free and image-based robotic assisted TKR had differing accuracy in femoral and tibial alignment.

Myeloid-derived suppressor cells: A new emerging player in endometriosis.

Endometriosis is a common gynecological disorder defined by the presence of endometrial tissue outside the uterus. This is commonly associated with chronic pelvic pain, infertility, and dysmenorrhea, which occurs in approximately 10% of women of reproductive age. Although the exact mechanism remains uncertain, it has been widely accepted to be an estrogen-dependent and inflammatory disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune cells with immunosuppressive capacity and non-immunological functions. They have been found to be aggressively involved in the pathologies of various disorders. In regards to tumors, the functions of MDSCs have been profoundly shown to inhibit tumor immune response and to promote angiogenesis, tumor metastasis, fibrosis, and epithelial-mesenchymal transition (EMT). In recent years, the elevation of MDSCs in endometriosis was reported by several studies that provoke the assumption that MDSCs might exert similar roles to promote the development of endometriosis. Such that, precision treatments targeting MDSCs might be a promising direction for future study. Herein, we will review the research progress of MDSCs in endometriosis and its potential relevance to the pathogenesis, progression, and therapeutics strategy of endometriosis.

Therapeutic effects of green tea on endometriosis.

Endometriosis is a chronic disorder characterized by the presence of endometrial glands and stroma outside the uterine cavity. It affects 8%-10% of women in their reproductive years, and represents a major clinical problem with deleterious social, sexual and reproductive consequences. Current treatment options include pain relief, hormonal intervention and surgical removal. However, these treatments are deemed unsatisfactory owing to varying success, significant side effects and high recurrence rates. Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly anti-angiogenic, anti-proliferation, anti-metastasis, and apoptosis induction. In recent years, preclinical studies have proposed the use of green tea to inhibit the growth of endometriosis. Herein, the aim of this review is to summarize the potential therapeutic effects of green tea on molecular and cellular mechanism through inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis in endometriosis.

The role of paraspinal muscle degeneration in coronal imbalance in patients with degenerative scoliosis.

Background: Coronal imbalance in degenerative scoliosis is common and is highly correlated with health-related quality of life. Paraspinal muscle is critical to spine stability, but little is known about its contribution to coronal imbalance in degenerative scoliosis. This study aims to investigate the relationship between paraspinal muscle (PSM) degeneration and coronal imbalance in patients with degenerative scoliosis (DS). Methods: This is a retrospective cohort study. A total of 117 patients with DS were retrospectively reviewed. Parameters of PSM (bilateral cross-sectional area, CSA; fat infiltration rate, FI%) at the apical disc and adjacent levels were quantitatively evaluated using MRI. Standing whole-spine radiograph was used to evaluate the coronal (Cobb angle, CA; coronal balance distance, CBD) and sagittal (thoracic kyphosis, TK; lumbar lordosis, LL; sagittal vertical axis, SVA) parameters. Patients were divided into 3 groups: coronal balanced (Type A), coronal imbalanced shifting to concavity (Type B), and coronal imbalanced shifting to convexity (Type C). Results: Based on our criteria, 56 patients were assigned to Type A, 34 patients to Type B, and 27 patients to Type C. There was no significant difference on the sagittal profiles and CSA between the groups. However, Type A showed significantly lower FI% than Type B and Type C on both concavity and convexity (Concave side: Type A vs. Type B vs. Type C, 30.8±8.1 vs. 45.1±7.7 vs. 38.7±12.5, P=0.001; Convex side: Type A vs. Type B vs. Type C, 32.6±10.9 vs. 46.3±7.3 vs. 40.7±11.8, P=0.004). Specifically, Cobb angle was negatively correlated with CSA, mainly at convexity (R=-0.415, P=0.008). Similarly, the increase of CBD significantly correlated with FI% at concavity (R=0.491, P=0.001) and convexity (R=0.354, P=0.025). Conclusions: DS patients with coronal imbalance demonstrated a worse PSM degeneration when compared with those without coronal imbalance. Besides, PSM degeneration strongly correlated with coronal imbalance, which implies that PSM degeneration may contribute to the coronal imbalance in patients with DS.

Effect of pulsed electromagnetic field as an intervention for patients with quadriceps weakness after anterior cruciate ligament reconstruction: a double-blinded, randomized-controlled trial.

BACKGROUND: The ultimate goal of anterior cruciate ligament reconstructions (ACLR) is to fulfil the return-to-play (RTP) criteria. Quadriceps muscle strength is one of the key determinants for a patient's successful return-to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the postoperative period on quadriceps muscle strength in ACL injured patient. Adult patients (aged 18-30) with a unilateral ACL injury, total quadriceps muscle volume is equal or more than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, and both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, and Xtreme CT for bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be drawn before and after intervention. DISCUSSION: This is the first trial evaluating the effects of PEMF on quadriceps muscle recovery after ACLR. The proposed study addresses a huge research gap by evaluating practical use of PEMF as part of rehabilitation. The proposed study will provide much needed scientific support in the use of this noninvasive treatment modality to facilitate recovery of quadriceps strength after PEMF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05184023. Registered on 5 January 2022.

Simultaneous Measurement of Patellofemoral Joint Kinematics and Contact Mechanics in Intact Knees: A Cadaveric Study.

OBJECTIVE: Patellofemoral kinematics and contact mechanics are important measurements for the assessment of patellofemoral joint (PFJ) problems. Simultaneously measuring PFJ contact pressures and kinematics is a challenging task. The purpose of this study was to simultaneously measure the kinematics and mean/peak contact pressures in the PFJs of cadaveric knees. METHODS: This was a comparative study performed on fresh cadaveric knees. The kinematic data was acquired for nine cadaveric knees using an optical tracking system. Data about the contact pressure and contact area in the PFJ was obtained at knee flexion angles of 0°, 30°, 60°, 90°, and 120° using a pressure sensor. Intraclass correlation coefficients (ICCs) and minimal detectable differences (MDDs) of six degrees of freedom (6 DOF) in the PFJs were calculated. ICCs and the MDDs of contact pressure, peak pressure, and contact area in the PFJs were also analyzed. We also compared the kinematics of the cadaveric knees before and after the insertion of the pressure sensor. RESULTS: All ICC values of 6 DOF in the PFJs were found to be greater than or equal to 0.924. Regarding medial-lateral rotation, the patellar showed a simplified movement pattern that demonstrated progressive lateral rotation of 4.8° ± 3.4° at 120° of knee flexion. While for patellar tilting, the patella showed medial tilting that peaked at 7.2 ± 2.5° at 30° of knee flexion. Whereas no significant differences in PFJ kinematics were found between with and without the placement of the pressure sensor at all knee flexions (P > 0.05). Most of the ICC values for contact pressure, peak contact pressure, and contact area ranged from 0.8 to 0.9. The MDDs for rotational displacement were 0.9° and 0.6 mm for translational displacement. No statistical differences in patellar kinematics were found before and after the insertion of the pressure sensor. CONCLUSIONS: The setup in the present study enables researchers to simultaneously and synchronously collect real-time PFJ kinematics and tibiofemoral joint (TFJ) biomechanical kinematic data with high reliability. The low MDDs enabled the researchers to obtain an accurate interpretation of the kinematic and contact mechanics measurement using the experimental setting used in the present study.

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer.

With a rich abundance of natural polyphenols, green tea has become one of the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the predominant catechin found in green tea, which has been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, and anticancer. Clinical studies have also shown the inhibitory effects of EGCG on cancers of the male and female reproductive system, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Autophagy is a natural, self-degradation process that serves important functions in both tumor suppression and tumor cell survival. Naturally derived products have the potential to be an effective and safe alternative in balancing autophagy and maintaining homeostasis during tumor development. Although EGCG has been shown to play a critical role in the suppression of multiple cancers, its role as autophagy modulator in cancers of the male and female reproductive system remains to be fully discussed. Herein, we aim to provide an overview of the current knowledge of EGCG in targeting autophagy and its related signaling mechanism in reproductive cancers. Effects of EGCG on regulating autophagy toward reproductive cancers as a single therapy or cotreatment with other chemotherapies will be reviewed and compared. Additionally, the underlying mechanisms and crosstalk of EGCG between autophagy and other cellular processes, such as reactive oxidative stress, ER stress, angiogenesis, and apoptosis, will be summarized. The present review will help to shed light on the significance of green tea as a potential therapeutic treatment for reproductive cancers through regulating autophagy.

An analysis on the determinants of head to pelvic balance in a Chinese adult population.

Background: Balanced global spinopelvic balance is important in the maintenance of the physiological alignment of all body segments above the pelvis with minimum energy expenditure. The key determinants affecting the 3D index-odontoid-hip axis (OD-HA) angle, and in particular its alterations, have not been clearly defined. The aim of this study is to identify the determinants of the 3D OD-HA angle in maintaining global spinopelvic balance in a large Chinese adult cohort of different gender and age groups. Methods: A total of 516 asymptomatic adults were enrolled in this study. Biplanar radiographies were performed to reconstruct the subject's inter-acetabular axis and C2 odontoid process. The 3D angle formed by the vertical and the line between odontoid and mid-interacetabular axis (OD-HA angle) was computed and projected in the subject's sagittal and coronal planes. Thoracic kyphosis (TK), lumbar lordosis (LL), T1 pelvic angle (TPA) and sagittal vertical axis (SVA) were measured. Results: The mean values of sagittal and coronal OD-HA were -0.2°±2.5° and 0.2°±1.1°, respectively. Both sagittal and coronal OD-HA had significant correlation with age (r=0.265 and r=-0.143, P<0.01, respectively), sagittal OD-HA showed increment from 20s to 80s (-1.3° to 0.8° for female, -0.3° to 1.5° for male) and a significant difference between male and female from 20 to 69 years old. Further analysis showed that sex, weight, TK, PT, SVA, TPA and ODI were determinants of OD-HA. Conclusions: 3D OD-HA angle showed physiological stability with little variability from young to elderly adults, with SD of 2.45° and 1.06° in sagittal and coronal planes, respectively. OD-HA angle confirms the hypothesis that the head tends to remain above the pelvis in a small cone of stability. This study provides an analysis of the determinants of OD-HA and the reference range of the head-pelvis balance in each decade and gender based on a large-scale asymptomatic population.

Large lateral tibial slope and lateral-to-medial slope difference are risk factors for poorer clinical outcomes after posterolateral meniscus root tear repair in anterior cruciate ligament reconstruction.

BACKGROUND: Meniscus root tear is an uncommon but detrimental injury of the knee. Hoop stress is lost during meniscus root tear, which can lead to excessive tibiofemoral contact pressure and early development of osteoarthritis. Posterolateral meniscus root tears (PLRT) are more commonly associated with anterior cruciate ligament (ACL) tears. As the lateral compartment is less congruent than the medial compartment, it is more susceptible to a shearing force, which is increased in the ACL-deficient knee. In accordance with the compressive axial load, the increase in the tibial slope would generate a greater shearing force. The additional lateral compartment mobility caused by ACL tear should be reduced after ACL reconstruction (ACLR). However, there is a lack of evidence to conclude that ACLR can sufficiently limit the effect of large tibial slope (LTS) on the healing after PLRT repair. This study aimed to evaluate whether a steep LTS would be a risk factor for poorer clinical outcomes after PLRT repair concomitant with ACLR. METHODS: In this retrospective study, a chart review was conducted to identify patients with concomitant unilateral primary ACLR and PLRT repair. Patients with a partial tear or healed tear were excluded. Postoperative MRI and clinical assessments were performed at a mean follow up of 35 months. MRI data was used to measure the LTS, medial tibial slope (MTS), coronal tibial slope (CTS), the lateral-to-medial slope difference (LTS-MTS) and meniscus healing and extrusion. Functional outcomes were evaluated by patient-reported outcomes (International Knee Documentation Committee [IKDC], Lysholm and Tegner scores) and KT-1000 arthrometer assessment. Interobserver reproducibility was assessed by two reviewers. RESULTS: Twenty-five patients were identified for the analysis. Patients with larger LTS and larger LTS-MTS differences were shown to be correlated with poorer IKDC scores after surgery (R = -0.472, p = 0.017 and R = -0.429, p = 0.032, respectively). Herein, patients with LTS ≥ 6° or LTS-MTS ≥ 3° demonstrated poorer IKDC scores. CONCLUSION: A large LTS (≥ 6°) and a large difference of LTS-MTS (≥ 3°) were shown to be risk factors for poorer functional and radiological outcomes for PLRT repair in patients after ACLR. Clinically, closer monitoring and a more stringent rehabilitation plan for patients with LTS ≥ 6° or LTS-MTS ≥ 3° would be recommended.

The identification of endometrial immune cell densities and clustering analysis in the mid-luteal phase as predictor for pregnancy outcomes after IVF-ET treatment.

Changes in endometrial immune cell density has been reported to be associated with reproductive failure. The prognostic value of endometrial immune cell density measurement remains uncertain. We aimed to investigate the prognostic value of endometrial immune cells measurement on pregnancy outcome after IVF in women. In this prospective study, one hundred twenty-eight women underwent endometrial sampling in a natural cycle preceding single frozen-thawed embryo transfer (ET). Endometrial biopsy was obtained precisely 7 days after luteinizing hormone surge (LH + 7). Multiplex immunohistochemical method was employed to simultaneously stain the endometrium samples with a panel of human antibodies against CD56 for uterine natural killer (uNK) cells, CD3 and CD8 for T cell, CD3 for pan T cells and CD68 for macrophages. The density of the various immune cells and the clustering levels between them were measured. ET was performed at the blastocyst stage. Women who did not conceive had a significantly higher density of uNK cells and higher clustering level between uNK cells-and-macrophages than women who did conceive. In accordance, the prognostic value of uNK measurement on pregnancy outcome was significantly improved when combined with uNK-to-macrophage clustering analysis simultaneously. Taken together, our results suggested that uNK cells density and clustering level between uNK cells-and macrophages may be a promising predictor for successful implantation after IVF-ET.

Multiplexed Fluorescent Immunohistochemical Staining of Four Endometrial Immune Cell Types in Recurrent Miscarriage.

Immunohistochemistry is the most commonly used method for the identification and visualization of tissue antigens in biological research and clinical diagnostics. It can be used to characterize various biological processes or pathologies, such as wound-healing, immune response, tissue rejection, and tissue-biomaterial interactions. However, the visualization and quantification of multiple antigens (especially for immune cells) in a single tissue section using conventional immunohistochemical (IHC) staining remains unsatisfactory. Hence, multiplexed technologies were introduced in recent years to identify multiple biological markers in a single tissue sample or an ensemble of different tissue samples. These technologies can be especially useful in differentiating the changes in immune cell-to-cell interactions within the endometrium between fertile women and women with recurrent miscarriages during implantation. This paper describes a detailed protocol for multiplexed fluorescence IHC staining to investigate the density and clustering of four major immune cell types simultaneously in precisely timed endometrial specimens during embryo implantation. The method includes sample preparation, multiplex optimization with markers for immune cell subtypes, and the scanning of the slides, followed by data analysis, with specific reference to detecting endometrial immune cells. Using this method, the density and clustering of four major immune cell types in the endometrium can be simultaneously analyzed in a single tissue section. In addition, this paper will discuss the critical factors and troubleshooting to overcome possible fluorophore interference between the fluorescent probes being applied. Importantly, the results from this multiplex staining technique can help provide an in-depth understanding of the immunologic interaction and regulation during embryo implantation.

Global sagittal alignment after surgery of right thoracic idiopathic scoliosis in adolescents and adults with and without thoracic hypokyphosis.

This study aimed to characterize global sagittal alignment in adolescent idiopathic scoliosis (AIS) with normal kyphosis (NTK, kyphosis > 10°) and with thoracic hypokyphosis (THK, kyphosis < 10°), before and after posterior spinal fusion, and compare them with asymptomatic controls. 27 AIS girls and young adults with right thoracic curves were included (seventeen with age ≤ 18 years, then age > 21). Biplanar radiographies were acquired at baseline, immediate post-operatively, 1-year and 2-year follow-up, and 3D reconstruction of the spine and pelvis was performed. NTK and THK showed different global sagittal alignment, as well as differences compared to controls. AIS with THK at baseline had higher SVA/SFD (2.0 ± 2.9 vs - 0.4 ± 1.9; P < 0.05) and OD-HA (0.2 ± 1.4° vs - 1.3 ± 1.6°; P < 0.05) than controls, indicating that THK had compensated balance with unusual forward leaning posture. Immediately post-operation, SVA/SFD remained high (1.3 ± 3.0) while OD-HA reversed (- 1.2 ± 1.7°), indicating that THK patients had found partially compensated balance. After 2-yeas, both SVA/SFD (- 1.3 ± 2.1) and OD-HA (- 1.4 ± 0.9°) were normalized. The changes in global sagittal alignment and mechanism of balance are different in AIS with or without THK. As the head plays a critical role on balance during immediate and delayed post-operation, OD-HA can be complementary parameter for assessing global balance during post-operative follow-up of AIS patients with THK.

Posterior Tibial Loading Results in Significant Increase of Peak Contact Pressure in the Patellofemoral Joint During Anterior Cruciate Ligament Reconstruction: A Cadaveric Study.

BACKGROUND: Inappropriate posterior tibial loading and initial graft tension during anterior cruciate ligament (ACL) reconstruction may cause altered patellofemoral joint (PFJ) contact mechanics, potentially resulting in pain and joint degeneration. HYPOTHESIS: PFJ contact pressure would increase with the increases in posterior tibial loading and graft tension during ACL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Nine fresh-frozen, nonpaired human cadaveric knees were tested in a customized jig from 0° to 120° of knee flexion. First, the knee was tested in the ACL-intact state. Second, reconstruction of the ACLs using different posterior tibial loadings and graft tensions were performed. The posterior tibial loading was evaluated at 2 levels: 33.5 and 67 N. Graft tension was assessed at 3 levels: low tension (20 N), medium tension (60 N), and high tension (80 N). Maximum values of peak contact pressure in the medial and lateral patellar facets were compared between ACL-intact and ACL-reconstructed knees. The PFJ kinematics between ACL-intact knees and ACL-reconstructed knees were compared during knee flexion at 30°, 60°, 90°, and 120°. RESULTS: Reconstruction of ACLs with both low and high posterior tibial loading resulted in significant increases of peak contact pressure in the medial (range of differences, 0.46-0.92 MPa; P < .05) and lateral (range of differences, 0.51-0.83 MPa; P < .05) PFJ compared with the ACL-intact condition. However, no significant differences in PFJ kinematics were identified between ACL-reconstructed knees and ACL-intact knees. In ACL-reconstructed knees, it was found that a high posterior tibial loading resulted in high peak contact pressure on the medial patellar side (range of differences, 0.37-0.46 MPa; P < .05). No significant difference in peak contact pressure was observed among the differing graft tensions. CONCLUSION: In this cadaveric model, ACL reconstruction resulted in significant increases of peak contact pressure in the PFJ facet when compared with the ACL-intact condition. A high posterior tibial loading can lead to high medial PFJ peak contact pressure. Graft tension was found to not significantly affect PFJ contact pressure during ACL reconstruction. CLINICAL RELEVANCE: An excessive posterior tibial loading during ACL reconstruction resulted in increased PFJ contact pressures at time of surgery. These data suggest that a low posterior tibial loading might be preferred during ACL reconstruction surgery to reduce the PFJ contact pressure close to that of the ACL-intact condition.

Patient-specific instrumentation (PSI) Referencing High Tibial Osteotomy Technological Transfer and Education: protocol for a double-blind, randomised controlled trial (PROTECTED HTO Trial).

INTRODUCTION: High tibial osteotomy (HTO) is a treatment of choice for active adult with knee osteoarthritis. With advancement in CT imaging with three-dimensional (3D) model reconstruction, virtual planning and 3D printing, patient-specific instrumentation (PSI) in form of cutting jigs is employed to improve surgical accuracy and outcome of HTO. The aim of this randomised controlled trial (RCT) is to explore the surgical outcomes of HTO for the treatment of medial compartment knee osteoarthritis with or without a 3D printed patient-specific jig. METHODS AND ANALYSIS: A double-blind RCT will be conducted with patients and outcome assessors blinded to treatment allocation. This meant that neither the patients nor the outcome assessors would know the actual treatment allocated during the trial. Thirty-six patients with symptomatic medial compartment knee osteoarthritis fulfilling our inclusion criteria will be invited to participate the study. Participants will be randomly allocated to one of two groups (1:1 ratio): operation with 3D printed patient-specific jig or operation without jig. Measurements will be taken before surgery (baseline) and at postoperatively (6, 12 and 24 months). The primary outcome includes radiological accuracy of osteotomy. Secondary outcomes include a change in knee function from baseline to postoperatively as measured by three questionnaires: Knee Society Scores (Knee Scores and Functional Scores), Oxford Knee Scores and pain visual analogue scale (VAS) score. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (CREC no. 2019.050), in accordance with the Declaration of Helsinki. The results will be presented at international scientific meetings and through publications in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04000672; Pre-results.

Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer.

BACKGROUND: Previous studies have shown a major green tea polyphenol (-)-epigallocatechin-3-gallate ((-)-EGCG) as a powerful anti-cancer agent. However, its poor bioavailability and requirement of a high dosage to manifest activity have restricted its clinical application. Recently, our team synthesized a peracetate-protected derivative of EGCG, which can act as a prodrug of (-)-EGCG (ProEGCG) with enhanced stability and improved bioavailability in vitro and in vivo. Herein, we tested the therapeutic efficacy of this novel ProEGCG, in comparison to EGCG, toward human endometrial cancer (EC). METHODS: In this study, the effects of ProEGCG and EGCG treatments on cell growth, cell survival and modulation of intracellular signaling pathways in RL95-2 and AN3 CA EC cells were compared. The antiproliferative effect was evaluated by cell viability assay. Apoptosis was measured by annexin/propidium iodide staining. Expression of mitogen-activated protein kinases, markers of proliferation and apoptosis were measured by immunoblot analysis. In addition, the effects of ProEGCG and EGCG on tumor growth, vessel formation and gene expression profiles on xenograft models of the EC cells were investigated. RESULTS: We found that treatment with ProEGCG, but not EGCG, inhibited, in a time- and dose-dependent manner, the proliferation and increased apoptosis of EC cells. Treatment with low-dose ProEGCG significantly enhanced phosphorylation of JNK and p38 MAPK and inhibited phosphorylation of Akt and ERK which are critical mediators of apoptosis. ProEGCG, but not EGCG, elicited a significant decrease in the growth of the EC xenografts, promoted apoptotic activity of tumour cells in the EC xenografts, and decreased microvessel formation, by differentially suppressing anti-apoptotic molecules, NOD1 and NAIP. Notably, no obvious adverse effects were detected. CONCLUSIONS: Taken together, ProEGCG at a low dose exhibited anticancer activity in EC cells through its anti-proliferative, pro-apoptotic and anti-tumor actions on endometrial cancer in vitro and in vivo. In contrast, a low dose of EGCG did not bring about similar effects. Importantly, our data demonstrated the efficacy and safety of ProEGCG which manifests the potential of a novel anticancer agent for the management of endometrial cancer.

Accuracy on the preoperative assessment of patients with adolescent idiopathic scoliosis using biplanar low-dose stereoradiography: a comparison with computed tomography.

BACKGROUND: Although computed tomography (CT) is commonly used to diagnose the scoliotic spine in patients with adolescent idiopathic scoliosis (AIS) preoperatively, it is limited by the high radiation and prone scanning position. Recently, a new biplanar stereoradiography (EOS) was used to image the scoliotic spine in an upright posture with significantly less radiation in non-severe AIS subjects. However, its reliability to assess preoperative AIS patients remains unreported. Hence, the purpose of this study is to compare the scoliotic curvature between prone (CT) and upright positions (EOS) in preoperative AIS patients. METHODS: Thirty-three pre-operative AIS patients (mean age:18.4 ± 4.2) were recruited. EOS was used to scan the whole thoracic spine at upright position. Whereas on the same day, a conventional CT scan was used to evaluate the spine in prone position. The three-dimensional reconstruction of EOS and CT of the spine were then generated. Using previous validated techniques, multiple scoliotic parameters in both modalities were determined. The agreement between the two modalities was compared using the Bland-Altman test, whereas the correlation was assessed by the intraclass correlation coefficient (ICC). RESULTS: The mean ICC (prone and upright) of intra-rater/inter-rater reliabilities for the measured parameters were 0.985,0.961/0.969,0.903, respectively. Thoracic Cobb angles, intervertebral wedging and lumbar lordosis correlated significantly between upright EOS imaging radiographs (62.9 ± 9.3°,6.4 ± 2.9° and 48.8 ± 12.4°) and prone CT (47.3 ± 10.0°,5.8 ± 2.7° and 27.9 ± 11.4°; P < 0.001). The apical vertebral wedging and apical intervertebral disc wedging showed a good correlation among the two modalities (upright, 6.5 ± 3.5° and 6.4 ± 2.9°; prone, 6.5 ± 3.6° and 5.8 ± 2.7°; R2 ≥ 0.94; P < 0.01). Similarly, there was significant correlation in apical intervertebral rotation (R2 = 0.834; P < 0.01) between the prone CT (3.4 ± 3.0°) and upright EOS (3.8 ± 3.2°). In addition, the Cobb angle was significantly larger in upright EOS (62.9 ± 9.3°) than in prone CT (47.3 ± 10.0°, P < 0.01) position. There was significant underestimation on scoliotic severity in the prone position when compared with upright position. CONCLUSIONS: Importantly, the image acquisition and reconstruction from EOS can better provide accurate three-dimensional spinal representations of the scoliotic curvature in preoperative AIS patients. Moreover, our findings suggested that scoliotic curvatures in preoperative AIS patients can be largely represented by both imaging modalities despite the difference in body positioning.

Paclitaxel Induces Immunogenic Cell Death in Ovarian Cancer via TLR4/IKK2/SNARE-Dependent Exocytosis.

Emerging evidence shows that the efficacy of chemotherapeutic drugs is reliant on their capability to induce immunogenic cell death (ICD), thus transforming dying tumor cells into antitumor vaccines. We wanted to uncover potential therapeutic strategies that target ovarian cancer by having a better understanding of the standard-of-care chemotherapy treatment. Here, we showed in ovarian cancer that paclitaxel induced ICD-associated damage-associated molecular patterns (DAMP, such as CALR exposure, ATP secretion, and HMGB1 release) in vitro and elicited significant antitumor responses in tumor vaccination assays in vivo Paclitaxel-induced TLR4 signaling was essential to the release of DAMPs, which led to the activation of NF-κB-mediated CCL2 transcription and IkappaB kinase 2-mediated SNARE-dependent vesicle exocytosis, thus exposing CALR on the cell surface. Paclitaxel induced endoplasmic reticulum stress, which triggered protein kinase R-like ER kinase activation and eukaryotic translation initiation factor 2α phosphorylation independent of TLR4. Paclitaxel chemotherapy induced T-cell infiltration in ovarian tumors of the responsive patients; CALR expression in primary ovarian tumors also correlated with patients' survival and patient response to chemotherapy. These findings suggest that the effectiveness of paclitaxel relied upon the activation of antitumor immunity through ICD via TLR4 and highlighted the importance of CALR expression in cancer cells as an indicator of response to paclitaxel chemotherapy in ovarian cancer.

Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials.

This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew's ear (black) fungus or black wood ear fungus Auricularia auricula-judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep's head mushroom Grifola frondosa, lion's mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese "meshimakobu," Chinese "song gen," Korean "sanghwang," American "black hoof mushroom"), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.

New ribosome-inactivating proteins and other proteins with protein synthesis-inhibiting activities.

Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.