Correlation between serum tryptophan metabolism and treatment efficacy of dapoxetine in patients with premature ejaculation: A pilot study.

INTRODUCTION: Primary premature ejaculation (PPE) is a common male neurobiological disorder. Currently, there is consensus that the impairment in central serotonin (5-HT) neurotransmission constitutes a key pathogenic factor in PPE. Selective serotonin reuptake inhibitors (SSRIs) serve as the primary pharmacological intervention; however, a comprehensive elucidation of their mechanism of action remains incomplete. Owing to significant individual variability in efficacy, SSRIs exhibit a high discontinuation rate. Hence, there is an urgent need to address the selection of SSRIs for PPE treatment. OBJECTIVE: This study aims to investigate the characteristics of tryptophan (TRP) metabolism in patients with PPE and to assess its influence on the efficacy of SSRIs. METHODS: The exploratory study included a total of 16 patients with PPE and 16 control subjects who were healthy men without any sexual dysfunction. Upon enrollment in the study, all participants underwent a thorough medical history review and physical examination. Subsequently, their serum levels of TRP, its metabolites, large neutral amino acids (LNAAs), and metabolite ratios were assessed using a liquid chromatography-mass spectrometry (LC-MS) assay. After a period of 4 weeks of dapoxetine treatment, all patients with PPE underwent reassessment using the Premature Ejaculation Diagnostic Tool (PEDT) score and intravaginal ejaculatory latency time (IELT) test. RESULTS: The ratio of serum TRP to other LNAAs (TRP/LNAAs) in patients with PPE was found to be significantly lower compared to the control group (P < 0.05). Conversely, the ratio of kynurenine to TRP (KYN/TRP) was observed to be significantly higher in the PPE patients compared to the control group (P < 0.05). Including the serum TRP/LNAAs ratio and KYN/TRP ratio in the prediction model yielded the highest prediction efficiency for PPE. There was a significant negative correlation between the ratio of TRP/LNAAs before the treatment and the IELT after 4 weeks of the treatment. Additionally, there was a significant positive correlation observed between the ratio of TRP/LNAAs before the treatment and the PEDT score after 4 weeks of the treatment. CONCLUSIONS: This study demonstrates that the reduction in the TRP/LNAAs ratio and the elevation of the KYN/TRP ratio are significant characteristics associated with PPE. These findings suggest that diminished tryptophan availability in the brain and the activation of the kynurenine (KYN) pathway may play a role in the pathogenesis of PPE. The TRP/LNAAs ratio has potential as a reliable indicator of central serotonin (5-HT) levels. Considering the TRP/LNAAs ratio when selecting SSRIs for the treatment of PPE may enhance the response rate of this medication.

Diagnostic Efficacy of Metagenomic Next-Generation Sequencing in Patients with Spinal Infections: A Retrospective Study.

Purpose: Early diagnosis of spinal infections remains challenging, and emerging metagenomic next-generation sequencing (mNGS) technology holds promise in addressing this issue. The aim of this study is to investigate the diagnostic efficacy of mNGS in spinal infections. Patients and Methods: A total of 78 cases with suspected spinal infections were enrolled in this study, all of whom underwent laboratory, histopathological and mNGS examinations upon admission. Lesion samples were obtained by surgical or C-arm-guided puncture. Sensitivity, specificity, positive predictive value and negative predictive value of culture and mNGS were calculated for statistical analysis. Results: With histopathological results as the reference, the included 78 patients were categorized into 50 cases in the spinal infection group and 28 cases in the aseptic group. The sensitivity (84%) and negative predictive value (77.14%) of mNGS were significantly higher than those of culture (32% and 44.26%, respectively), whereas no significant differences were observed in terms of specificity and positive predictive value. In the subgroup analysis for Mycobacterium tuberculosis, the sensitivity of mNGS (90.91%) and T-spot (90.91%) was significantly higher than that of culture (0). Additionally, mNGS demonstrated markedly higher specificity (100%) compared to T-spot (85.07%). Conclusion: This study underscores the substantial advantages of mNGS in terms of diagnostic accuracy and bacterial coverage for spinal infections. The findings provide compelling clinical evidence that supports the enhanced diagnostic efficacy of mNGS.

Is the pelvic incidence a determinant factor for kyphosis curve patterns of ankylosing spondylitis patients?

To investigate the influence of pelvic incidence (PI) on the kyphosis curve patterns and clinical outcomes in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis and to construct a classification of AS according to the PI value for surgical decision-making. 107 AS patients underwent single-level lumbar pedicle subtraction osteotomy (PSO) and finished a minimal of 2-year follow-up. All patients were divided into three groups: low PI (PI ≤ 40°), moderate PI (40° < PI ≤ 60°), and high PI (PI > 60°). Standing lateral radiographs were taken to evaluate the location of kyphotic apex, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (SVA), spino-sacral angle (SSA), global kyphosis (GK), PI, sacral slope (SS), and pelvic tilt (PT). Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) and Bath Ankylosing Spondylitis Functional Index (BASFI) were used to evaluate quality of life. Before surgery, a significant difference was shown in the average LL and the mean GK in high PI group was the largest among the three groups. Correction of SVA, GK and LL in high PI group was the smallest among the three group. No significant difference in clinical outcomes was found among the three groups before surgery and at the final follow-up. Regarding the preoperative sagittal profile, the kyphosis curve pattern of moderate PI group is similar to that of low PI group. For AS patients in these two groups, harmonious sagittal alignment can be restored by a single-level PSO. However, the sagittal imbalance is insufficiently realigned by a single-level PSO in a patient with high PI.

Effects of perfluorododecanoic acid on testicular function in mice.

Perfluorodecanoic acid (PFDoA) is a widely distributed environmental pollutant that can affect the functions of many organs. However, systematic evaluations of the effects of PFDoA on testicular functions are lacking. The aim of this study was to investigate the effects of PFDoA on mouse testicular functions, including spermatogenesis, testosterone synthesis, and stem Leydig cells (SLCs) in the interstitial tissue of the testis. PFDoA (0, 2, 5, 10 mg/kg/d) was administered via gavage to 2-month-old mice for 4 weeks. Serum hormone levels and sperm quality were assayed. Furthermore, to investigate the mechanisms by which PFDoA affects testosterone synthesis and spermatogenesis in vivo, the expression of StAR and P450scc in testicular tissue was measured by immunofluorescence staining and quantitative real-time PCR. In addition, the levels of SLC markers, including nestin and CD51, were studied. PFDoA decreased the luteinizing hormone concentration and sperm quality. Although the difference was not statistically significant, mean testosterone levels showed a downward trend. The expression of StAR, P450scc, CD51, and nestin was also suppressed in the PFDoA-treated groups compared with the control group. Our study suggested that PFDoA exposure can decrease testosterone biosynthesis, and even reduce the number of SLCs. These results indicated that PFDoA suppressed the main functions of testis, and further researches are required to identify strategies for preventing or reducing the effect of PFDoA on testicular function.

Lumbar Spine Infection with Eikenella corrodens Presented as Abdominal Pain: A Case Report and Literature Review.

Background: Eikenella corrodens is a part of the inherent flora on the surface of human mucosa. It usually does not cause disease unless the patient has been bitten, injured or surgically infected. Lumbar spine infection caused by Eikenella corrodens usually presents with conventional symptoms such as low back pain and fever. Herein, we report a case of lumbar intervertebral space infection with Eikenella corrodens presented as abdominal pain. Case Presentation: A 38-year-old man with no medical history of note presented with abdominal pain. Initially, local doctors suspected that the patient had abdominal disease. However, abdominal diseases were ruled out and only lumbar spine infection was confirmed. Then, the patient was misdiagnosed as lumbar tuberculosis. Finally, anaerobic culture and metagenomic next-generation sequencing confirmed the Eikenella corrodens, which was rarely involved in lumbar intervertebral space infection. The patient recovered after operation and antibiotic therapy. Conclusion: This case indicated a rare symptom of lumbar spine infection, abdominal cramping, which is caused by Eikenella corrodens. Blood culture had low sensitivity as a diagnostic method for Eikenella corrodens, but lesion sample culture or metagenomic next-generation sequencing had high sensitivity for early diagnosis.

Distribution of bone voids in the thoracolumbar spine in Chinese adults with and without osteoporosis: A cross-sectional multi-center study based on 464 vertebrae.

Bone void is a novel intuitive morphological indicator to assess bone quality but its use in vertebrae has not been described. This cross-sectional and multi-center study aimed to investigate the distribution of bone voids in the thoracolumbar spine in Chinese adults based on quantitative computed tomography (QCT). A bone void was defined as a trabecular net region with extremely low bone mineral density (BMD) (<40 mg/cm3), detected by an algorithm based on phantom-less technology. A total of 464 vertebrae from 152 patients (51.8 ± 13.4 years old) were included. The vertebral trabecular bone was divided into eight sections based on the middle sagittal, coronal, and horizontal planes. Bone void of the whole vertebra and each section were compared between healthy, osteopenia, and osteoporosis groups and between spine levels. Receiver operator characteristic (ROC) curves were plotted and optimum cutoff points of void volume between the groups were obtained. The total void volumes of the whole vertebra were 124.3 ± 221.5 mm3, 1256.7 ± 928.7 mm3, and 5624.6 ± 3217.7 mm3 in healthy, osteopenia, and osteoporosis groups, respectively. The detection rate of vertebrae with bone voids was higher and the normalized void volume was larger in the lumbar than in thoracic vertebrae. L3 presented the largest void (2165.0 ± 3396.0 mm3), while T12 had the smallest void (448.9 ± 699.4 mm3). The bone void was mainly located in the superior-posterior-right section (40.8 %). Additionally, bone void correlated positively with age and increased rapidly after 55 years. The most significant void volume increase was found in the inferior-anterior-right section whereas the least increase was found in the inferior-posterior-left section with aging. The cutoff points were 345.1 mm3 between healthy and osteopenia groups (sensitivity = 0.923, specificity = 0.932) and 1693.4 mm3 between osteopenia and osteoporosis groups (sensitivity = 1.000, specificity = 0.897). In conclusion, this study demonstrated the bone void distribution in vertebrae using clinical QCT data. The findings provide a new perspective for the description of bone quality and showed that bone void could guide clinical practice such as osteoporosis screening.

Prognostic nomogram in patients with epithelioid sarcoma: A SEER-based study.

OBJECTIVE: The prognostic factors for patients with epithelial sarcoma remain unclear. The study aims to develop a practical clinical nomogram that predicts prognosis in patients with ES using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We extracted clinical data from 2004 to 2015 from the SEER database about patients with ES. All patients were randomly divided into training cohort and validation cohort. Kaplan-Meier analyses were used to compare outcomes between different subgroups. In order to estimate the chance of survival for patients with ES, we developed a nomogram. Nomogram performance was evaluated by discrimination and calibration. Additionally, an analysis of decision curves was conducted to evaluate the clinical usefulness of this newly developed model. RESULTS: In the primary cohort,320 met the inclusion criteria to be entered into this study. The median OS was 66.000 months (range 34.704 to 94.296 months), and the 1-, 3-, and 5-year OS rates were 70.7%, 56.1%, and 50.4%, respectively. For the validation cohort, we studied 136 consecutive patients. Age, primary site, grade, AJCC (American Joint Committee on Cancer) T, AJCC M, and surgery were included in the nomogram. The C-index values for the training set and validation set were 0.817 and 0.832, respectively. The calibration plots showed good agreement between the prediction and the observation. Based on the clinical decision curve, the model has a good clinical net benefit for ES patients. CONCLUSIONS: It is the first study that developed an effective survival prediction model for patients with ES. Using this nomogram can assist in clinical decision-making as it has satisfactory accuracy. Even so, additional external validation is needed.

A Modified Procedure to Diagnose Erectile Dysfunction Using the International Index of Erectile Function (IIEF-6) Combined With the Premature Ejaculation Diagnosis Tool (PEDT) via an Internet Survey.

BACKGROUND: The reliability of the International Index of Erectile Function (IIEF-5) in diagnosing erectile dysfunction (ED) is significantly decreased for the population with premature ejaculation (PE). AIM: We aimed to illustrate a better way of diagnosing ED among the general population through a web survey study. METHODS: We collected online surveys from 2,746 men between the ages of 18 and 65. Two methods were used to determine the prevalence of ED, and these 2 methods were compared. Additionally, we divided our sample into 2 equally sized groups by median age and repeated the analyses for each group. In Method Ⅰ (M Ⅰ), men with an IIEF-5 score ≤ 21 were diagnosed with ED. In Method Ⅱ (M Ⅱ), PE was defined as a PEDT score ≥ 9, and no-PE was defined as a PEDT score ≤ 8. We used an IIEF-6 score cutoff of ≤ 24 among the PE population and a cutoff of ≤ 25 among the no-PE population to diagnose ED. MAIN OUTCOME MEASURES: We examined the results from the IIEF-5, PEDT, and IIEF-6. RESULTS: Of the 2,746 men, 1,540 were in a stable heterosexual relationship, and the prevalence of ED among these men was determined. The prevalence of ED, as measured by Method Ⅰ, was significantly higher than that measured by Method Ⅱ. The kappa coefficients between the 2 methods were 0.595, 0.704, and 0.430 for the overall, no-PE, and PE populations, respectively. The internal consistency of the IIEF-5 for the PE population increased if Question 5 (intercourse satisfaction) was removed. Similar trends were observed for the groups, and there were no substantial differences. CLINICAL IMPLICATIONS: Our research suggests that before using the erectile function assessment scale to evaluate erectile function, ejaculatory function should be assessed with the PEDT. STRENGTHS AND LIMITATIONS: This was the first study to highlight the importance of evaluating ejaculatory function using the PEDT before diagnosing ED via an internet survey. There may have been recruitment bias because our study was an internet survey. CONCLUSION: Establishing the prevalence of ED by using a combination of the IIEF-6 and PEDT was more reliable than using the IIEF-5 alone. Further validation of the modified procedure, especially regarding the effects of age on the results, in future studies is required. Wang C, Zhang H, Liu Z, et al. A Modified Procedure to Diagnose Erectile Dysfunction Using the International Index of Erectile Function (IIEF-6) Combined With the Premature Ejaculation Diagnosis Tool (PEDT) via an Internet Survey. Sex Med 2022;10:100506.

Automatic phantom-less QCT system with high precision of BMD measurement for osteoporosis screening: Technique optimisation and clinical validation.

BACKGROUND: Currently dual-energy X-ray absorptiometry (DXA) and phantom-based quantitative computed tomography (PB-QCT) have been utilized to diagnose osteoporosis widely in clinical practice. While traditional phantom-less QCT (PL-QCT) is limited by the precision of manual calibration using body tissues, such as fat and muscle. OBJECTIVE: The aim of this study is to validate the accuracy and precision of one newly-developed automatic PL-QCT system to measure spinal bone mineral density (BMD) and diagnose osteoporosis. METHODS: A total of 36 patients were enrolled for comparison of BMD measurement between DXA and QCT. CT images of 63 patients were analyzed by both PB-QCT and newly developed automatic PL-QCT system, then the BMD results generated by the automatic PL-QCT were utilized to diagnose osteoporosis. The diagnostic outcomes were compared with that of DXA and PB-QCT to assess the performance of the new system. RESULTS: BMD test results showed that the automatic PL-QCT system had higher precision than previous studies performed with QCT, while maintaining similar capability to diagnose osteoporosis as DXA and PB-QCT. Area under curve (AUC) result of PL-QCT was larger than 0.8 for predicting spine DXA T-score in receiver operating characteristic (ROC) analysis. Pearson correlation analysis (r â€‹= â€‹0.99) showed strong linear correlation and Bland-Altman analysis (bias â€‹= â€‹3.0mg/cc) indicated little difference between the two methods. The precision result (CV â€‹= â€‹0.89%) represented good reproducibility of the new system. CONCLUSION: The traditional PL-QCT system has relatively low reproducibility due to the manual selection of the region of interest (ROI) of body tissues. Automatic selection of ROI in this new system makes the BMD testing more convenient and improves precision significantly. Compared with traditional BMD measurement methods, the automatic PL-QCT system had higher precision in accurate diagnosis of osteoporosis with great potential in translational research and wide clinical application. TRANSLATIONAL POTENTIAL STATEMENT: With high accuracy and precision, the automatic PL-QCT system could serve as an opportunistic screening tool for osteoporosis patients in the future. It could also facilitate related researches by providing more reliable data collection, both retrospectively and longitudinally.

Spatial Multiplex In Situ Tagging (MIST) Technology for Rapid, Highly Multiplexed Detection of Protein Distribution on Brain Tissue.

Highly multiplexed analysis of biospecimens significantly advances the understanding of biological basics of diseases, but these techniques are limited by the number of multiplexity and the speed of processing. Here, we present a rapid multiplex method for quantitative detection of protein markers on brain sections with the cellular resolution. This spatial multiplex in situ tagging (MIST) technology is built upon a MIST microarray that contains millions of small microbeads carrying barcoded oligonucleotides. Using antibodies tagged with UV cleavable oligonucleotides, the distribution of protein markers on a tissue slice could be "printed" on the MIST microarray with high fidelity. The performance of this technology in detection sensitivity, resolution, and signal-to-noise level has been fully characterized by detecting brain cell markers. We showcase the codetection of 31 proteins simultaneously within 2 h, which is about 10 times faster than the other immunofluorescence-based approaches of similar multiplexity. A full set of computational toolkits was developed to segment the small regions and identify the regional differences across the entire mouse brain. This technique enables us to rapidly and conveniently detect dozens of biomarkers on a tissue specimen, and it can find broad applications in clinical pathology and disease mechanistic studies.

Does the Level of Pedicle Subtraction Osteotomy Affect the Surgical Outcomes in Ankylosing Spondylitis-Related Thoracolumbar Kyphosis With the Same Curve Pattern?

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effect of pedicle subtraction osteotomy (PSO) level on the surgical outcomes in ankylosing spondylitis-related thoracolumbar kyphosis with the same curve pattern. METHODS: ankylosing spondylitis (AS) patients with thoracolumbar kyphosis, who underwent 1-level lumbar PSO between March 2006 and June 2017, were retrospectively reviewed. Criteria for curve-matched thoracolumbar kyphosis were: (1) have same level of preoperative apex (pre-apex); (2) have similar global kyphosis (GK, the angle between the superior/inferior endplate of the maximally tilted upper and lower end vertebra) (the difference of GK less than 15˚). The radiographic parameters measured were sagittal vertical axis (SVA, the horizontal distance between the C7 plumb line and the posterosuperior corner of the S1), GK, thoracic kyphosis (TK, the angle between the T5 superior endplate and the T12 inferior endplate), lumbar lordosis (LL, the angle between the L1 and S1 superior endplate), sacral slope (SS, the angle between the sacral endplate and the horizontal line), pelvic tilt (PT, the angle between the vertical and the line joining the midpoint of the sacral plate and hip axis), and pelvic incidence (PI, the angle between the line vertical to the superior margin of S1 and the line connecting the sacral plate midpoint with the hip joint axis). All of these parameters and health-related quality of life (HRQoL, evaluated by preoperative and the last follow-up questionnaires including ODI and VAS) scores were collected before surgery and at the last follow-up. According to their osteotomy level, patients were devided into 2 sub-groups (L1 group and L2 group), and differences of these mentioned parameters between 2 groups were compared. RESULTS: 26 curve-matched patients were recruited with a mean follow-up of 37.2 months. All patients improved significantly after surgery in HRQoL scores (VAS 1.6 vs 5.4, P < 0.001; ODI 11.9 vs 26.4, P < 0.001). Except for TK and PI, those radiographic parameters were also observed to be significantly changed after surgery. Compared to L2 group, PSO at L1 may have larger correction of TK (ΔTK -6.8 vs -0.3°, P = 0.164), PI (ΔPI -7.4 vs -0.7°, P = 0.364) and smaller correction of SVA (ΔSVA -105.3 vs -128.5 mm, P = 0.096), LL (ΔLL -31.1 vs -43.0°, P = 0.307) and SS (ΔSS 6.9 vs 12.2°, P = 0.279) but had no statistical significance. CONCLUSION: The results of this investigation showed that in AS-related thoracolumbar kyphosis patients with the same curve pattern, the different levels of osteotomy had little effect on the improvement of surgical outcomes. However, osteotomy at L2 is more likely to obtain a larger correction of SVA compared to osteotomy at L1.

Insights into the Regulation on Proliferation and Differentiation of Stem Leydig Cells.

Male hypogonadism is a clinical syndrome caused by testosterone deficiency. Hypogonadism can be caused by testicular disease (primary hypogonadism) or hypothalamic-pituitary dysfunction (secondary hypogonadism). The present strategy for treating hypogonadism is the administration of exogenous testosterone. But exogenous testosterone is reported to have negative side effects including adverse cardiovascular events and disruption of physiological spermatogenesis probably due to its inability to mimic the physiological circadian rhythm of testosterone secretion in vivo. In recent years, a growing number of articles demonstrated that stem Leydig cells (SLCs) can not only differentiate into functional Leydig cells (LCs) in vivo to replace chemically disrupted LCs, but also secrete testosterone in a physiological pattern. The proliferation and differentiation of SLCs are regulated by various factors. However, the mechanisms involved in regulating the development of SLCs remain to be summarized. Factors involved in the regulation of SLCs can be divided into environmental pollutants, growth factors, cytokine and hormones. Environmental pollutants such as Perfluorooctanoic acid (PFOA) and Triphenyltin (TPT) could suppress SLCs proliferation or differentiation. Growth factors including FGF1, FGF16, NGF and activin A are essential for the maintenance of SLCs self-renewal and differentiation. Interleukin 6 family could inhibit differentiation of SLCs. Among hormones, dexamethasone suppresses SLCs differentiation, while aldosterone suppresses their proliferation. The present review focuses on new progress about factors regulating SLC's proliferation and differentiation which will undoubtedly deepen our insights into SLCs and help make better clinical use of them. Different factors affect on the proliferation and differentiation of stem Leydig cells. Firstly, each rat was intraperitoneally injected EDS so as to deplete Leydig cells from the adult testis. Secondly, the CD51+ or CD90+ cells from the testis of rats are SLCs, and the p75+ cells from human adult testes are human SLCs. These SLCs in the testis start to proliferate and some of them differentiate into LCs. Thirdly, during the SLCs regeneration period, researchers could explore different function of those factors (pollutants, growth factors, cytokines and hormones) towards SLCs.

Diagnostic performance of discontinuous density gradient centrifugation for estimating human semen quality.

BACKGROUND: Semen analysis plays an important role in the diagnosis of male infertility. However, many studies have demonstrated that the current methods of semen analysis are inefficient for assessing male fertility. OBJECTIVE: To test whether prior discontinuous density gradient centrifugation (DDCG) improves the performance of semen analysis in diagnosing male infertility. MATERIALS AND METHODS: Infertile men and fertile men were recruited from the clinic. Pre- and post-DDGC values for the semen parameters of sperm concentration, total sperm number, percent total motility, percent progressive motility, percent normal sperm morphology, and sperm DNA fragmentation rate were compared. RESULTS: A total of 528 men (252 infertile men and 276 fertile men) were enrolled in the present study. After DDGC, sensitivity was significantly increased for sperm concentration, total sperm number, and sperm morphology (P < .01); specificity was significantly increased for progressive motility and sperm morphology (P < .01); and diagnostic accuracy was significantly improved for all of these parameters (area under the curve (AUC): P < .01). Total motility and sperm DNA fragmentation rate exhibited no obvious change in sensitivity, specificity or accuracy after DDGC (all P > .01). For the combination of all these semen parameters, diagnostic accuracy improved significantly after DDGC (AUC: P < .01). In a multiple regression analysis, only sperm morphology and sperm DNA fragmentation rate had P values less than 0.05 before DDGC, whereas all parameters except total sperm number contributed to the equation after DDGC. DISCUSSION: DDGC is a mature, standardized procedure for clinical commonly used to optimize spermatozoa. The diagnostic accuracy of semen analysis was significantly improved after DDGC, which indicated that assessing "functional spermatozoa" might be a more suitable method for semen analysis than the WHO 2010 criteria. CONCLUSION: Assessing semen parameters after DDGC might improve their diagnostic accuracy for male infertility.

MCP-1 Priming Enhanced the Therapeutic Effects of Human Mesenchymal Stromal Cells on Contact Hypersensitivity Mice by Activating the COX2-PGE2/STAT3 Pathway.

Mesenchymal stromal cells (MSCs) have become a promising treatment for inflammation-related diseases, and their therapeutic efficacy mainly depends on crosstalk between MSCs and inflammation. However, methods to improve the immunosuppressive efficiency of MSCs in different diseases still need to be developed. In this study, we investigated whether preconditioning MSCs with a disease-related inflammatory cytokine could increase their immunosuppressive properties and improve therapeutic efficacy. In a contact hypersensitivity (CHS) mouse model, inflammatory profile screening revealed that among all tested cytokines, monocyte chemotactic protein-1 (MCP-1) exhibited the most significantly increased level in the local microenvironment. As expected, MSCs preconditioned with MCP-1 (P-MSCs) exhibited an enhanced ability to downregulate proinflammatory cytokine secretion, induce regulatory T cells, inhibit T cell proliferation, and polarize M2-type macrophages. In vivo experiments showed that P-MSCs alleviated ear swelling and local proinflammatory cytokine production more effectively than control MSCs. Mechanistically, MCP-1 could significantly activate the signal transducer and activator of transcription 3 (STAT3) signaling pathway and induce the expression of cyclooxygenase-2 (COX2) and prostaglandin E2 (PGE2) in MSCs. STAT3 inhibitor reversed the MCP-1-mediated enhancing of their immunosuppressive ability. Collectively, our findings demonstrate that CHS-related MCP-1 preconditioning enhanced the immunomodulatory effects of MSCs and improved their therapeutic efficacy in CHS. Enhancing the immunosuppressive efficacy of MSCs by preconditioning with certain disease-related inflammatory cytokines may provide a new strategy for MSC-based therapies for inflammatory diseases.

Does relocation of the apex after osteotomy affect surgical and clinical outcomes in patients with ankylosing spondylitis and thoracolumbar kyphosis?

OBJECTIVE: Relocation of the apex is often found in patients with ankylosing spondylitis (AS)-associated thoracolumbar/lumbar kyphosis after corrective surgery. This study evaluates the influence of different postoperative apex locations on surgical and clinical outcomes of osteotomy for patients with AS and thoracolumbar kyphosis. METHODS: Sixty-two patients with a mean age of 34.6 ± 9.7 years (range 17-59 years) and a minimum of 2 years of follow-up, who underwent 1-level lumbar pedicle subtraction osteotomy for AS-related thoracolumbar kyphosis, were enrolled in the study, as well as 62 age-matched healthy individuals. Patients were divided into 2 groups according to the postoperative location of the apex (group 1, T8 or above; group 2, T9 or below). Demographic data, radiographic measurements (including 3 postoperative apex-related parameters), and clinical outcomes were compared between the 2 groups preoperatively, postoperatively, and at the last follow-up. Furthermore, a subgroup analysis was performed among patients with a postoperative apex located at T6-11 and postoperatively the entire AS cohort was compared with normal controls regarding the apex location of the thoracic spine. RESULTS: In the majority of the enrolled patients, the apex location changed from T12-L2 preoperatively to T6-9 postoperatively. The sagittal vertical axis (SVA) differed significantly both postoperatively (25.7 vs 59.0 mm, p = 0.001) and at the last follow-up (34.6 vs 59.9 mm, p = 0.003) between the 2 groups, and the patients in group 1 had significantly smaller horizontal distance between the C7-vertical line and the apex (DCA) than the patients in group 2 (67.5 vs 103.7 mm, p = 0.001). Subgroup analysis demonstrated similar results, showing that the patients with a postoperative apex located at T8 or above had an average SVA < 47 mm. Notably, a significant correlation was found between postoperative SVA and DCA (r = 0.642, p = 0.001). Patients who underwent an osteotomy at L3 had limited apex relocation but larger SVA correction than those at L1 or L2. However, no significant difference was found in health-related quality of life between the 2 groups. CONCLUSIONS: AS patients with an apex located at T8 or above after surgery tended to have better SVA correction (within 47 mm) than those who had a more caudally located apical vertebra. For ideal postoperative apex relocation, a higher (closer to or at the preoperative apex) level of osteotomy is more likely to obtain the surgical goal.

The relationship between global spinal alignment and pelvic orientation from standing to sitting following pedicle subtraction osteotomy in ankylosing spondylitis patients with thoracolumbar kyphosis.

INTRODUCTION: To investigate the relationship between the spinal sagittal alignment and arc of pelvic motion from standing to sitting in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis following pedicle subtraction osteotomy (PSO). MATERIALS AND METHODS: AS patients who underwent PSO for thoracolumbar kyphosis from January 2016 to July 2018 were recruited. EOS standing and sitting images were obtained pre- and postoperatively. Radiographic parameters were measured on the sagittal radiographs, including lumbar lordosis, thoracic kyphosis, pelvic incidence, pelvic tilt, sacral slope, sagittal vertical axis (SVA), spinosacral angle, anterior pelvic plane angle (APPA) and knee flexion angle. RESULTS: Thirty-six patients were enrolled. From standing to sitting, APPA was increased by a mean of 14.7° (P < 0.001) and 3.0° (P = 0.083) before and after surgery, respectively. The increase in APPA from standing to sitting was correlated with the standing SVA (R = 0.592, P < 0.001) preoperatively. After PSO, the change in APPA was correlated with the change in SSA in both the standing and sitting position (R = 0.381, P = 0.022 and R = 0.667, P < 0.001, respectively). The APPA from standing to sitting was decreased in 11 patients with standing C7 plumb line posterior to the femoral head postoperatively. CONCLUSIONS: In AS patients, pelvic orientation was adjusted by the global spinal alignment. When planning total hip arthroplasty for AS patients, global spinal alignment should be considered to improve the joint stability.

Does postoperative PI-LL mismatching affect surgical outcomes in thoracolumbar kyphosis associated with ankylosing spondylitis patients?

OBJECTIVE: To investigate if pelvic incidence (PI) and lumbar lordosis (LL) mismatching affects surgical outcomes for ankylosing spondylitis (AS) related kyphosis following 1-level lumbar pedicle subtraction osteotomy (PSO). PATIENTS AND METHODS: AS patients with thoracolumbar kyphosis, who underwent 1-level lumbar PSO from March 2006 and February 2014 in our institution, were retrospectively reviewed. The radiographic measurements and health-related quality of life (HRQoL) scores, including Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) for pain, were recorded at baseline and the last follow-up. Patients were divided into 2 groups according to PI-LL matching or not postoperatively (Match Group, Mismatch Group), and comparison of the aforementioned parameters between the two groups was performed. RESULTS: Seventy patients were enrolled with a mean age of 34.60 ±â€¯9.45 years (range, 17 yrs.-59 yrs.). Among them, 44 were included in the Match Group and 26 in the Mismatch Group. At baseline, patients in the Match Group had larger LL (p = 0.014) and smaller pelvic tilt (PT, p < 0.001) than patients in the Mismatch Group. At the last follow-up, along with larger LL (p = 0.004) and smaller PT (p = 0.001), Match Group patients also had significantly smaller sagittal vertical axis (SVA, 3.31 cm vs 6.27 cm, p = 0.001) than those in the Mismatch Group. Seventy-five percent (33/44) of the patients in the Match Group had a SVA < 5 cm at the last follow-up, while in the Mismatch Group, only 35% (9/26) of the patients did. However, no significant difference was found between the two groups regarding HRQoL scores. CONCLUSION: Patients with postoperative PI-LL matching were more likely to have a better correction of SVA; they also tended to have a smaller preoperative PT. However, PI-LL mismatching didn't affect HRQoL scores at the last follow-up, which was different from the results of previous studies in the settings of ASD.