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Study Objectives: To determine the short-term and long-term impacts of continuous positive airway pressure (CPAP) therapy on health-related quality of life (HRQL) in patients with obstructive sleep apnea (OSA).Design: Prospective longitudinal cohort study.Setting: University sleep disorders center.Patients: Three hundred sixty-five patients with an apnea-hypopnea index (AHI) > or = 20 per hour of sleep and 358 patients with an AHI of < 20.Interventions: All patients with AHIs > or = 20 received CPAP therapy; those with AHIs < 20 did not. The HRQL of all study participants was measured using the 36-item medical outcomes study short form (SF-36) questionnaire at baseline and then at 3 and 12 months of follow-up.Results: Although the SF-36 scores were similar at baseline, after 3 months of therapy, the CPAP group had higher adjusted emotional summary scores than did those who did not receive CPAP therapy (score increase, 1.72; 95% confidence interval [CI], 0.08 to 3.37). These improvements were maintained for 12 months. The gains in the SF-36 scores were most striking in the vitality domain (score increase, 10.52; 95% CI, 7.04 to 14.00 U increment). The severe OSA group (ie, AHIs > or = 40) experienced the largest benefit. Their adjusted vitality scores were 12.3 U higher (95% CI, 8.0 to 16.6) than those persons without OSA (ie, AHIs < 5).Conclusions: CPAP therapy was associated with marked short-term and long-term improvements in the vitality of patients with moderate-to-severe OSA in the community. These findings suggest that CPAP therapy is effective in improving the long-term HRQL of patients with OSA. [ABSTRACT FROM AUTHOR]

Study Objectives: To determine long-term compliance rates to continuous positive airway pressure (CPAP) therapy in patients with obstructive sleep apnea enrolled in a comprehensive CPAP program in the community.Design: Prospective cohort longitudinal study.Setting: University sleep disorders center.Patients: Two hundred ninety-six patients with an apnea-hypopnea index (AHI) > or = 20/h on polysomnography.Interventions: A CPAP device equipped with a monitoring chip was supplied. Within the first week, daily telephone contacts were made. Patients were seen at 2 weeks, 4 weeks, 3 months, and 6 months.Results: Of the 296 subjects enrolled, 81.1% were males. Mean +/- SD AHI was 64.4 +/- 34.2/h of sleep; age, 51 +/- 11.7 years; and body mass index, 35.2 +/- 7.9 kg/m(2). The mean duration of CPAP use was 5.7 h/d at 2 weeks, 5.7 h/d at 4 weeks, 5.9 h/d at 3 months, and 5.8 h/d at 6 months. The percentage of patients using CPAP > or = 3.5 h/d was 89.0% at 2 weeks, 86.6% at 4 weeks, 88.6% at 3 months, and 88.5% at 6 months. There was a decrease in the Epworth Sleepiness Scale (ESS) score of 44% by 2 weeks of therapy. The patients continue to improve over the follow-up period, with the lowest mean ESS score observed at 6 months. With multiple regression analysis, three variables were found to be significantly correlated with increased CPAP use: female gender, increasing age, and reduction in ESS score.Conclusion: A population-based CPAP program consisting of consistent follow-up, "troubleshooting," and regular feedback to both patients and physicians can achieve CPAP compliance rates of > 85% over 6 months. [ABSTRACT FROM AUTHOR]

Background: Total knee replacement is a commonly adopted surgical intervention to reduce physical limitations and pain in advanced-stage knee osteoarthritis. However, these patients may experience physical dysfunction to limit their access during conventional rehabilitation after total knee replacement. The use of telemedicine may be the promising solution. This study aims to compare the effectiveness of telerehabilitation with conventional in-person rehabilitation in patients who underwent a total knee replacement., Methods: For this systematic review on randomized controlled trials, PubMed, Medline, EMBASE, Cochrane Library, ScienceDirect and CINAHL databases were searched for eligible articles published between 1 January 2003 and 28 February 2022. The eligibility criteria were patients who underwent total knee replacement, randomized controlled trials and publications in English. The main outcome measures were focused on pain and physical function. Reference lists of relevant studies were also manually checked to find additional studies. Two independent reviewers conducted study selection separately. PEDro scale was used to assess the methodological quality of the included randomized controlled trials. A meta-analysis was performed on the collected data. Review Manager (RevMan, version 5.3) was used for all analyses., Results: A total of 11 studies met the eligibility criteria and included 1825 participants in the systematic review. Overall, the results revealed that the effectiveness of telerehabilitation is comparable to conventional in-person rehabilitation in improving various pain and functional outcomes in patients who underwent a total knee replacement. In the meta-analysis with the fixed-effects model, no significant difference was found in the improvement of pain and physical function in patients with knee osteoarthritis compared with conventional rehabilitation (Standardized Mean Difference (SMD)  -0.15, 95% CI  -0.47 to 0.16, P  = 0.34 and SMD -0.04, 95% CI -0.19 to 0.12, P  = 0.62, respectively). In addition, the utilization of hospital resources and costs were significantly lower in telerehabilitation when compared with in-person rehabilitation., Conclusion: Telerehabilitation was comparable to conventional in-person rehabilitation in improving clinical outcomes following total knee replacement. However, it might be a more preferable alternative rehabilitation intervention for patients following total knee replacement given the significantly lower cost of telerehabilitation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Endometriosis is a chronic, painful disease whose etiology remains unknown. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to challenges in studying the disease. Recently, a few reports have shown that immunosuppressive cells, such as myeloid-derived suppressor cell (MDSC), may promote the progression of endometriosis. MDSCs are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, in this chapter, we provide a detailed protocol to phenotype MDSC as well as to isolate and assess the functionality from the peritoneal cavity of a mouse model of surgically induced endometriosis. Importantly, the current mouse model has been widely used to study how the immune system, hormones, and environmental factors affect endometriosis as well as the effects of endometriosis on fertility and pain., Competing Interests: Disclosures Y.S., Y.L., Q.X. K.T.L., L.C.K.C., J.P.W.C., K.T.L., C.C.W., X.C., T.Z. and G.C.W.M. have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus. Angiogenesis is a major pathophysiology in endometriosis. Our previous studies have demonstrated that the prodrug of epigallocatechin gallate (ProEGCG) exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate (EGCG). However, their direct binding targets and underlying mechanisms for the differential effects remain unknown. In this study, we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis. Additionally, 1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin (MTDH) and PX domain containing serine/threonine kinase-like (PXK) as novel binding targets of EGCG and ProEGCG, respectively. Computational simulation and BioLayer interferometry were used to confirm their binding affinity. Our results showed that MTDH-EGCG inhibited protein kinase B (Akt)-mediated angiogenesis, while PXK-ProEGCG inhibited epidermal growth factor (EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor (HIF-1a)/vascular endothelial growth factor (VEGF) pathway. In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways. Moreover, our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis., Competing Interests: Chi Chiu Wang is an active member of the World Endometriosis Society and an advisor of Aptorum Group, the licensee of ProEGCG. Chi Chiu Wang and Chi Chiu Wang are the inventor of ProEGCG for endometriosis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 The Authors.)

Over the centuries, influenza and its associated epidemics have been a serious public health problem. Although vaccination and medications (such as neuraminidase inhibitors) are the mainstay of pharmacological approaches to prevent and treat influenza, however, frequent mutations in the influenza genome often result in treatment failure and resistance to standard medications which limit their effectiveness. In recent years, green tea catechins have been evaluated as potential anti-influenza agents. Herein, in this review, we highlighted the effects and mechanisms underlying the inhibitory effects of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea, against different influenza viral infections, and their clinical benefits toward prevention and treatment. In addition, as the severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) causes the outbreak of COVID-19 pandemic, our review also delineates the current perspective on SARS-CoV-2 and future insights as to the potential application of EGCG on suppressing the flu-like symptoms caused by COVID-19., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The dynamics of maternal immunomodulation is essential in early pregnancy. In our previous study, successful implantation is characterized by a transient increase of pro-inflammatory cytokines followed by a switch to an anti-inflammatory state in peripheral blood around 3-6 days after embryo transfer (ET). In this study, we aimed to extend the time points to compare the cytokine and chemokine profiles between women who did or did not subsequently miscarry. We utilized precisely timed serum samples on the day of ET and 3, 6, 9, 16, 23 and 30 days after ET in women undergoing single blastocyst transfer. Our analysis revealed a significant alteration in cytokine profile after day ET+ 9 between the two groups. Regarding pro-inflammatory cytokine profile, there was a significant increase in IL-17 on days ET+ 16, + 23, and + 30 (50.60 ± 9.97 vs 37.09 ± 3.25, 53.20 ± 8.13 vs 36.51 ± 3.34, 57.06 ± 8.83 vs 33.04 ± 3.11 pg/mL), TNF-α on days ET+ 23 and + 30 (73.90 ± 12.42 vs 50.73 ± 3.55, 74.16 ± 12.46 vs 46.59 ± 3.21 pg/mL), IFN-γ on day ET+ 30 (69.52 ± 13.19 vs 42.28 ± 7.76 pg/mL) in women who miscarried compared to women who had a live birth. In contrast, the concentrations of anti-inflammatory cytokines IL-10 on days ET+ 23 and + 30 (26.23 ± 2.11 vs 38.30 ± 4.64, 23.77 ± 2.06 vs 39.16 ± 4.99 pg/mL) and TGF-β1 on day ET+ 30 (20.30 ± 1.25 vs 23.81 ± 0.88 ng/mL) were significantly decreased in women who miscarried compared to women who had a live birth. While for the chemokine profile, there was no significant alteration observed between the two groups across all the time points. These findings suggest that a sustained anti-inflammatory milieu is concomitant with the maintenance of early pregnancy, while the remarkable pro-inflammatory shift as early as day ET+ 16 in women who subsequently miscarried was observed before the diagnosis of miscarriage., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier B.V. All rights reserved.)

(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exact mass method with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01-2.5 μg/mL were within acceptable limits. The sensitivity was improved by 25 folds using pro-EGCG ammonium adduct [M + NH4] + . This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 μg/mL, time-of-maximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr -1 . The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites., Competing Interests: WT was empolyed by Aptorum Group Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chu, Man, Hung, Chan, Lee, Chan, Pang and Wang.)

Background: Loosening is the leading cause of total knee arthroplasty (TKA) revision. This is a heavy burden toward the healthcare system owing to the difficulty in diagnosis and complications occurring from the delay management. Based on automatic analytical model building, machine learning, may potentially help to automatically recognize the risk of loosening based on radiographs alone. The aim of this study was to build an image-based machine-learning model for detecting TKA loosening., Methods: Image-based machine-learning model was developed based on ImageNet, Xception model and a TKA patient X-ray image dataset. Based on a dataset with TKA patient clinical parameters, another system was then created for developing the clinical-information-based machine learning model with random forest classifier. In addition, the Xception Model was pre-trained on the ImageNet database with python and TensorFlow deep learning library for the prediction of loosening. Class activation maps were also used to interpret the prediction decision made by model. Two senior orthopaedic specialists were invited to assess loosening from X-ray images for 3 attempts in setting up comparison benchmark., Result: In the image-based machine learning loosening model, the precision rate and recall rate were 0.92 and 0.96, respectively. While for the accuracy rate, 96.3% for visualization classification was observed. However, the addition of clinical-information-based model, with precision rate of 0.71 and recall rate of 0.20, did not further showed improvement on the accuracy. Moreover, as class activation maps showed corresponding signals over bone-implant interface that is loosened radiographically, this confirms that the current model utilized a similar image recognition pattern as that of inspection by clinical specialists., Conclusion: The image-based machine learning model developed demonstrated high accuracy and predictability of knee arthroplasty loosening. And the class activation heatmap matched well with the radiographic features used clinically to detect loosening, which highlighting its potential role in assisting clinicians in their daily practice. However, addition of clinical-information-based machine-learning model did not offer further improvement in detection. As far as we know, this is the first report of pure image-based machine learning model with high detection accuracy. Importantly, this is also the first model to show relevant class activation heatmap corresponding to loosening location., Translational Potential: The finding in this study indicated image-based machine learning model can detect knee arthroplasty loosening with high accuracy and predictability, which the class activation heatmap can potentially assist surgeons to identify the sites of loosening., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2022 The Chinese University of Hong Kong.)

Background: Our previous studies found disproportionate anteroposterior vertebral size is associated with severity of the scoliotic curves in adolescent idiopathic scoliosis (AIS) patients. Subsequent studies showed wedging of vertebral bodies (VB) had less contribution than intervertebral discs (IVD) to the anterior-posterior vertebral column length discrepancy in severe-AIS. However, the exact morphological changes of IVD were not clearly defined. This study aimed to evaluate the morphological and pathological changes of IVD and VB in AIS girls and healthy female controls., Methods: This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were also evaluated on volumetric images. One-way ANOVA with Bonferroni correction and Pearson correlation tests were used., Results: There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. In addition, Cobb angle was significantly correlated with wedge angle and height ratio, and inversely correlated with the volume of NP., Conclusions: In addition to wedging of VB and IVD, there was significantly reduced volume of IVD and NP in AIS patients with severe curve, insinuating the mechanical effect of scoliosis leads to a compression on both IVD and NP before significant disc desiccation occurs. We postulate that the compression of IVD and NP can contribute to curve progression in severe-AIS, these patients are more prone to disc degeneration in adulthood if no operative treatment is offered. Further longitudinal study on these parameters is still warranted., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

Background: Biplanar X-ray system providing anteroposterior and sagittal plane with an ultra-low radiation dose and in weight-bearing position is increasingly used for spine imaging. The original three-dimensional (3D) reconstruction method from biplanar X-rays has been widely used for clinical parameters, however, the main issue is that manual adjustments of the 3D model was quite time-consuming and limited to thoracolumbar spine. A quasi-automated 3D reconstruction method of the spine from cervical vertebra to pelvis was proposed, which proved fast and accurate in 57 patients with adolescent idiopathic scoliosis. The aim of this study was to compare the newly developed technique of quasi-automatic 3D measurement with classical 2D measurements in a large cohort., Methods: A total of 494 adults with biplanar EOS X-ray scanning were included in this study and divided into health and deformity group according to the presence of spinal deformity. The proposed method of quasi-automatic 3D measurement was applied to all these subjects. The radiographic parameters included: thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sagittal vertical axis (SVA), T1 pelvic angle (TPA) in sagittal plane, and cobb angle in coronal plane. Comparison was made between quasi-automatic and manual measurement., Results: The mean age was 53.7±19.9 years old. In the whole population, the mean differences between the two methods were 3.9° for TK (30.5°±9.9° vs. 26.5°±9.3°, P<0.001), -5.2° for LL (-47.5°±11.2° vs. -42.4°±11.0°, P<0.001), 3.6° for PI (46.9°±10.3° vs. 43.9°±10.3°, P<0.001), -0.2° for PT (11.9°±7.7° vs. 12.0°±8.2°, P=0.328), -2.1 mm for SVA (15.7±26.2 vs. 17.8±26.3 mm, P=0.221) and -1.1° for TPA (9.0°±7.6° vs. 10.1°±7.8°, P=0.051). The deformity group had similar mean differences with the asymptomatic group with the values ranged from -4.1° to 3.8° for sagittal parameters. The mean differences of Cobb angle were 1.9° for patients with Cobb angle <30° and 2.3° for patients with Cobb angle >30°, respectively. Correlation analysis showed r2 for all clinical parameters ranged from 0.667 to 0.923. On average, the new method takes 5 minutes to compute all the parameters for one case., Conclusions: In conclusion, this ergonomic and efficient quasi-automatic method for full spine proved fast and accurate measurement in a large population, which showed great potential in extensive clinical application., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-861). The authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

To establish the age- and sex-related normative values of sagittal alignment in asymptomatic Chinese adults, and to investigate the changes and possible associated compensation mechanisms across age groups. 584 asymptomatic Chinese adults aged 20-89 years were recruited. Subjects were grouped according to age and gender. Whole-body standing radiographs were acquired for evaluating sagittal alignment from spine to lower limb. Sagittal parameters between gender in different age groups were compared via independent t test. Pearson correlation analysis was used to demonstrate relationships between parameters. Thoracic kyphosis (TK) increased steadily while lumbar lordosis decreased gradually in both genders. Pelvic tilt (PT) in male is greater than in female across all age groups with age related gradual increase. There were significant differences between male and female from 20s to 60s in terms of knee flexion angle (KA) and ankle dorsiflexion angle (AA), but the differences were not significant after 60s. T1 pelvic angle (TPA) was significantly correlated with spinal, pelvic and lower-limb alignment. The older group (≥50 years) had a stronger correlation of TPA with PT and KA, whereas the younger (<50 years) had stronger correlation with TK. This study comprehensively presented the normative sagittal alignment based on a large asymptomatic population, which could serve as an age- and gender-specific reference value for spine surgeons when planning for correction surgery. Age can influence the recruitment of compensation mechanism that involve more pelvic and lower limb mechanisms for elderly people.

The purpose of this study was to evaluate the morphological changes of intervertebral discs (IVD) and vertebral bodies (VB) in AIS girls according to the subgroups with different curve severity by magnetic resonance imaging (MRI). This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were evaluated on volumetric images. One-way ANOVA with Bonferroni correction was used. There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. On top of coronal wedging of VB and IVD, there was significantly reduced volume of IVD and NP in severe-AIS patients, despite T2 signal of IVD was preserved. The current findings indicate that early mechanical effects on the discs and vertebrae in adolescent scoliotic spine is evident on quantitative imaging. Importantly, these patients may be vulnerable to disc degeneration if no operative treatment is prescribed.

Background: Vertebral compression fractures (VCFs) are the most common among all osteoporotic fractures. The body may compensate to the kyphosis from vertebral compression fractures with lordosis of the adjacent spinal segments, rotation of the pelvis, knee flexion and ankle dorsiflexion. However, the detailed degree of body compensation, especially the lower limb, remains uncertain. Herein, the aim of this study is to investigate the values of global sagittal alignments (GSA) parameters, including the spine, pelvis and lower limbs, in patients with and without VCFs, as well as to evaluate the effect of VCFs on various quality of life (QoL) parameters., Methods: A cross-sectional study was conducted from May 2015 to June 2018. A total of 142 patients with VCFs aged over 60 years old and 108 age-matched asymptomatic controls were recruited. Whole body sagittal alignment including thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), T1-pelvic angle (TPA), knee-flex angle (KA) and ankle-flex angle (AA) were measured. In addition, lower back pain and quality of life were assessed using self-reported questionnaires., Results: Compared to asymptomatic controls, patients with VCF showed significantly greater TK (33.4 o  ± 16.4 o vs 28.4 o  ± 11.4 o ; p < 0.01), PT (25.4 o  ± 10.5 o vs 16.6 o  ± 8.9 o ; p < 0.001), PI (54.6 o  ± 11.8 o vs 45.8 o  ± 12.0 o ; p < 0.001), SVA (49.1 mm ± 39.6 mm vs 31.5 mm ± 29.3 mm; p < 0.01), and TPA (28.6 o  ± 10.8 o vs 14.8 o  ± 8.6 o ; p < 0.001). Whereas for lower limb alignment, patients with VCF showed significantly higher KA (10.1 o  ± 7.8 o vs 6.0 o  ± 6.4 o ; p < 0.001) and AA (7.0 o  ± 3.9 o vs 4.8 o  ± 3.6 o ; p < 0.001) than controls. The number of VCF significantly correlated with lower limb alignments (KA and AA) and global sagittal balance (TPA). VCF patients showed poorer quality of life assessment scores in terms of SF-12 (30.0 ± 8.3 vs 72.4 ± 16.9; p < 0.001), ODI (37.8 ± 24.0 vs 18.7 ± 16.6; p < 0.001) and VAS (3.8 ± 2.8 vs 1.9 ± 2.2; p < 0.001)., Conclusion: This is the first study to illustrate the abnormal lower limb alignment exhibited in patients with VCF. Patients with VCF showed an overall worse global sagittal alignment and decreased quality of life. Poorer global sagittal alignment of VCF patients also imply worse quality of life and more severe VCF.

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.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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°; R 2  ≥ 0.94; P < 0.01). Similarly, there was significant correlation in apical intervertebral rotation (R 2  = 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.

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., (©2020 American Association for Cancer Research.)

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.

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.

Background: This prospective cohort study was designed to evaluate the survivorship and functional outcomes associated with long-term results of medial open-wedge high tibial osteotomy (MOWHTO) for the treatment of medial compartment knee osteoarthritis in the Chinese population. Although MOWHTO is a well-established procedure in the management of medial osteoarthritis of the knee, the long-term outcome in the Chinese population has not been reported in current literature. We hypothesised that MOWHTO would result in long-term preservation of knee function in Chinese, similar to that reported in the Caucasian population., Methods: A cohort of 22 young adult patients (age < 55 years old) undergoing MOWHTO for the treatment of symptomatic medial compartment knee osteoarthritis between 2002 and 2008 was retrospectively surveyed with a minimum follow-up of 10 years. Kaplan-Meier survival analysis was performed, and the failure modes were investigated. The outcomes on survival (not requiring arthroplasty), clinical outcome (Knee Society Knee Score and Knee Society Function Score) and range of motion (numeric rating scale) at preoperative, 1-year postoperative follow-up and at last follow-up (>10 years) were evaluated. In addition, the mechanical tibiofemoral angle was also measured. The Wilcoxon signed-rank test was used for statistical evaluation of nonparametric data in these related samples., Result: A total of 31 knees in these 22 cases were included. The follow-up rate was 100% at 13.4 ± 1.9 years (11-17). Mean age at time of surgery was 45.8 ± 9.5 years (18-53). At 10-year follow-up, four knees converted to require total knee arthroplasty (survival: 87.1%). Preoperative varus alignment with mechanical tibiofemoral angle of -9.26 ± 2.83 was corrected to 2.58 ± 2.46 after surgery and remained 2.01 ± 3.52 at the latest follow-up. Knee Society Knee Score increased significantly from 53.7 ± 11.1 preoperatively to 93.8 ± 6.8 at 1-year follow-up and 91.8 ± 9.7 at latest follow-up. Similarly, the functional score also increased significantly from 67.4 ± 21.0 preoperatively to 86.3 ± 14.5 at 1-year follow-up and 82.1 ± 16.6 at latest follow-up ( p  < 0.01). Whereas, the range of motion significantly decreased from 122.7 ± 6.6 preoperatively to 116.1 ± 15.5 at the latest follow-up., Conclusion: Even in cases of severe medial osteoarthritis and varus malalignment, MOWHTO would be a good treatment option for management in active Chinese population less than 55 years. Although t he long-term survival and functional outcome after MOWHTO was proven to be satisfactory in our cohort during the 10-year follow-up, a larger cohort to illustrate the long-term functional outcome is still warranted., Translational Potential: The finding in this study indicated MOWHTO is a feasible treatment option for young adult patients with osteoarthritis to achieve long-term satisfactory results., Competing Interests: The authors have no conflicts of interest to disclose in relation to this article., (© 2020 The Author(s).)

Study Design: A cross-sectional radiographic study., Objective: The aim of this study was to establish the age- and sex-related normative values of whole-body sagittal alignment in asymptomatic Chinese adult population, and to investigate the changes and possible associated compensation mechanisms across age groups., Summary of Background Data: Previous studies have reported normative data for sagittal spinal alignment in asymptomatic adults. However, there was a lack of comprehensive investigation on age- and sex-related normative values of whole-body sagittal alignment., Methods: A total of 584 asymptomatic Chinese adults aged 20 to 89 years were recruited. Subjects were grouped according to age and sex. Whole-body standing radiographs were acquired for evaluating sagittal alignment from spine to lower limb. Comparisons of sagittal parameters between sex in different age groups were performed by independent t test. Pearson correlation analysis was used to determine relationships between each parameter., Results: Mean values of each sagittal parameter were presented based on age and sex. Thoracic kyphosis showed steady increasing trend while lumbar lordosis gradual decrease in both sexes. Pelvic tilt (PT) in males is greater than in females across all age groups with age-related gradual increase. There were significant differences between males and females from 20 to 60 years in terms of KneeFlex angle (KA) and AnkleFlex angle, but the differences were not significant after 60s. T1 pelvic angle (TPA) was significantly correlated with spinal, pelvic and lower-limb alignment. The older group (≥50 years) had a stronger correlation of TPA with PT and KA, whereas the younger (<50 years) had stronger correlation with TK., Conclusion: This study presented a comprehensive study of whole-body sagittal alignment based on a large asymptomatic population, which could serve as an age- and sex-specific reference value for spine surgeons when planning for correction surgery. Age can influence the recruitment of compensation mechanism that involves more pelvic and lower limb mechanisms for elderly people., Level of Evidence: 3.

Study Design: A cross-sectional study., Objective: To investigate and compare any morphological differences in paraspinal muscles (PSM) between adolescent idiopathic scoliosis (AIS) patients (with severe or non-severe curves) and healthy controls., Summary of Background Data: Several studies have reported abnormalities in biochemical, electromyographic activity, and histological changes of PSM in AIS. However, these studies only had qualitative data and without comparison with controls. Changes of muscle mass and mean density at the lumbar region have been described for scoliotic spines. All these findings suggested that imbalance of PSM in AIS could be a contributing factor to the development of severe scoliotic curve., Methods: T2-weighted MR images with multi-planar reconstruction were acquired in 41 Chinese AIS girls with a primary right-sided thoracic curve and 23 age-matched controls. In AIS, measurements of PSM were taken on both concavity and convexity of scoliosis starting from two vertebrae above and two below the apex. Morphological assessments of the multifidus (MF) and erector spinae (ES) muscles on both sides were made including signal intensity (SI) and fat deposition using manual tracing and thresholding technique, respectively. Same parameters were measured in controls at matched vertebrae. One-way analysis of variance (ANOVA) and Pearson correlation tests were used for statistical analysis., Results: Abnormalities were found at concavity of muscles between AIS and controls. Significantly higher SI and fatty components was observed in AIS at MF muscles on concavity than controls (P-value <0.001). Additionally, SI at MF muscles was significantly correlated with Cobb angle., Conclusion: Increased SI and fatty components are asymmetrically present in PSM at apex in AIS. Our results showed higher intensity in PSM at concavity in AIS when compared with controls. There was a significant linear correlation between abnormal muscle signal and scoliotic curve. Above features are suggestive of altered muscle composition in concave PSM, possibly due to prolonged compression and reduced muscle activity of PSM caused by the spinal deformity., Level of Evidence: 4.

Endometriosis (EMS), an estrogen-dependent inflammatory disorder affects approximately 5-10% of the general female population of reproductive age and 20-90% of women with pelvic pain and infertility. Many immunological factors are known to contribute significantly to the pathogenesis and pathophysiology of EMS, and both chronic local inflammation and autoantibodies in EMS shares many similarities with autoimmune diseases (AD). However, the autoimmune etiology in EMS remains controversial, and its evidence on autoimmune basis may be limited. Here we aim to review the current understanding between autoimmunity and EMS to provide important knowledge to develop future potential immunomodulatory therapy for the treatment of EMS., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We compared global sagittal alignment and quality of life in osteoporotic patients with and without vertebral compression fracture (VCF) and determined its relationship with VCF severity. The findings revealed osteoporotic patients with VCF showed decreased quality of life and worse global sagittal alignment, which was significantly associated with VCF severity., Introduction: The aim of this study was to compare the global sagittal alignment and quality of life in elderly osteoporotic patients with and without vertebral compression fracture (VCF), and to investigate the relationship between global sagittal alignment and severity of VCF., Methods: A consecutive series of 72 female patients with osteoporosis aged over 60 years and 31 age-matched females without osteoporosis were prospectively enrolled. The patients were divided into VCF and non-VCF group. Patient's clinical demography, nature of VCF, and bone mineral density (BMD) were also recorded. Spinal deformity index was used to evaluate severity of VCF. EOS® biplanar imaging system was then used to evaluate global sagittal parameters: T1 pelvic angle (TPA) and global sagittal angle (GSA). In addition, quality of life was assessed with self-reported questionnaires: the Oswestry Disability Index (ODI) and Short-form 12 (SF-12)., Results: Osteoporotic patients and controls were found to be significantly different in terms of TPA, GSA, and BMD. And in patients with VCF, they were found to have significantly higher TPA and GSA. TPA and GSA were significantly correlated with SF-12 and ODI. The number of VCF and SDI significantly correlated with global sagittal alignment. Using regression analysis, parameters significantly associated with abnormal global alignment were the number of VCF (OR = 1.13) and SDI (OR = 1.84)., Conclusion: Osteoporotic patients with VCF showed worse global sagittal alignment and decreased quality of life. The number and severity of VCF had a negative influence on global sagittal balance, which indicates that poorer sagittal global alignment may imply worse quality of life and more severe VCF.

Endometriosis affects women of reproductive age via unclear immunological mechanism(s). Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, we found MDSCs significantly increased in the peripheral blood of patients with endometriosis and in the peritoneal cavity of a mouse model of surgically induced endometriosis. Majority of MDSCs were granulocytic, produced ROS, and arginase, and suppressed T-cell proliferation. Depletion of MDSCs by antiGr-1 antibody dramatically suppressed development of endometrial lesions in mice. The chemokines CXCL1, 2, and 5 were expressed at sites of lesion while MDSCs expressed CXCR-2. These CXC-chemokines promoted MDSC migration toward endometriotic implants both in vitro and in vivo. Also, CXCR2-deficient mice show significantly decreased MDSC induction, endometrial lesions, and angiogenesis. Importantly, adoptive transfer of MDSCs into CXCR2-KO mice restored endometriotic growth and angiogenesis. Together, this study demonstrates that MDSCs play a role in the pathogenesis of endometriosis and identifies a novel CXC-chemokine and receptor for the recruitment of MDSCs, thereby providing a potential target for endometriosis treatment., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The study aimed to systematically review the association between angiogenesis and clinicopathological characteristics and its prognostic value in patients with endometrial cancer., Methods: Eligible studies were searched in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang database. Studies that assessed blood microvessel density (BMVD) and correlated with clinicopathological features and/or overall survival (OS) were included. Geometric mean values and hazard ratio with 95% confidence interval were pooled to examine the risk or hazard association. Subgroup analyses were conducted based on populations, BMVD criteria, BMVD markers, and type of survival analysis., Results: A total of 29 studies of 2517 patients were included. BMVD was associated with depth of myometrial invasion (MI) [standard mean difference (SMD) 1.24; 95% CI 0.53-1.95; P = 0.0006], lymphovascular space invasion (LVSI) (SMD 0.75; 95% CI 0.3-1.21; P = 0.001), and lymph node metastasis (LNM) (SMD 0.99; 95% CI 0.46-1.52; P = 0.0003). BMVD was also significantly associated with poor OS (HR 2.65; 95% CI 1.86-3.77; P < 0.00001). The association remained significant in the subgroups Asian population, BMVD criteria using Weidner method, BMVD marker CD34 for MI, LVSI, and LNM, CD105 for MI, and factor VIII for MI and LNM, respectively. For OS, either Asian or non-Asian population, BMVD criteria using Weidner or non-Weidner method, BMVD marker CD31, or factor VIII antibody and analysis using univariate or multivariate were all significantly associated., Conclusions: BMVD was associated with deeper MI, positive LVSI, positive LNM, and poor OS in patients with endometrial cancer. Therefore, angiogenesis is a useful measure for poor clinicopathological outcomes and prognosis in patients with endometrial cancer.

Anti-angiogenesis effect of a prodrug of green tea polyphenol (-)-epigallocatechin-3-gallate (Pro-EGCG) in malignant tumors is not well studied. Here, we investigated how the treatment with Pro-EGCG inhibited tumor angiogenesis in endometrial cancer. Tumor xenografts of human endometrial cancer were established and subjected to microarray analysis after Pro-EGCG treatment. First, we showed Pro-EGCG inhibited tumor angiogenesis in xenograft models through down-regulation of vascular endothelial growth factor A (VEGFA) and hypoxia inducible factor 1 alpha (HIF1α) in tumor cells and chemokine (C-X-C motif) ligand 12 (CXCL12) in host stroma by immunohistochemical staining. Next, we investigated how HIF1α/VEGFA was down-regulated and how the reduction of CXCL12 inhibited tumor angiogenesis. We found that VEGFA secretion from endometrial cancer cells was decreased by Pro-EGCG treatment through inhibiting PI3K/AKT/mTOR/HIF1α pathway. Furthermore, the down-regulation of CXCL12 in stromal cells by Pro-EGCG treatment restricted migration and differentiation of macrophages thereby inhibited infiltration of VEGFA-expressing tumor-associated macrophages (TAMs). Taken together, we demonstrated that treatment with Pro-EGCG not only decreases cancer cell-secreted VEGFA but also inhibits TAM-secreted VEGFA in endometrial cancer. These findings demonstrate that Pro-EGCG is a novel angiogenesis inhibitor for endometrial cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Mesenchymal stem cells (MSCs) hold promising translational potential in cartilage regeneration. However, the efficacy of MSC-based tissue engineering is not satisfactory in the treatment of cartilage defect because of the inevitable cellular functional changes during ex vivo cell expansion. How to maintain the chondrogenic capacity of MSCs to improve their therapeutic outcomes remains an outstanding question., Methods: Bone marrow-derived MSCs were firstly primed in chondrogenic induction medium which was then replaced with normal growth medium to attain the manipulated cells (M-MSCs). Methacrylated hyaluronic acid (MeHA) was synthesized as a scaffold to encapsulate the cells. The MSC- or M-MSC-laden constructs were treated with dynamic compressive loading (DL) in a bioreactor or with free loading (FL) for 14 days. Afterwards, the constructs were implanted in nude mice or rat models of osteochondral defects to test their efficiency in cartilage regeneration or repair., Results: Data showed that the resulting M-MSCs exhibited superior chondrogenic differentiation potential and survivability compared with untreated MSCs. More importantly, we found that DL significantly promoted neocartilage formation in the MeHA hydrogel encapsulated with M-MSCs after 30 days of implantation in nude mice. Furthermore, the constructs laden with M-MSCs after DL for 14 days significantly enhanced cartilage healing in a rat model of osteochondral defect., Conclusions: Findings from this study highlight the importance of maintaining chondrogenic potential of MSCs by in-vitro chondrogenic preconditioning and a synergistic effect of mechanical stimulation in cartilage engineering, which may shed light on the stem cell-based tissue engineering for cartilage repair.

Embryo establishes contact with the endometrium during implantation. Proper endometrial vascular development and maintenance at the time of embryo implantation is crucial for successful pregnancy. Vascular development at the maternal-embryo interface can be regulated by various cell types, of which uterine natural killer (uNK) cells play an important role. Abnormal angiogenesis and uNK cell number/function may lead to reproductive failure, particularly in women with recurrent miscarriage (RM) and women with recurrent implantation failure (RIF) after IVF-ET treatment, which are the important clinical hurdles in reproductive medicine to overcome. In this review, we aim to discuss the current knowledge of physiological angiogenic processes and the pathological angiogenesis at the time of implantation, as well as the possible mechanism and potential treatment., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)