Hoffmann's sign in cervical spondylotic myelopathy patients: pathological insights from neuroimaging.

OBJECTIVE: Hoffmann's sign testing is a commonly used physical examination in clinical practice for patients with cervical spondylotic myelopathy (CSM). However, the pathophysiological mechanisms underlying its occurrence and development have not been thoroughly investigated. Therefore, the present study aimed to explore whether a positive Hoffmann's sign (PHS) in CSM patients is associated with spinal cord and brain remodeling and to identify potential neuroimaging biomarkers with diagnostic value. METHODS: Seventy-six patients with CSM and 40 sex- and age-matched healthy controls (HCs) underwent multimodal MRI. Based on the results of the Hoffmann's sign examination, patients were divided into two groups: those with a PHS (n = 38) and those with a negative Hoffmann's sign (NHS; n = 38). Quantification of spinal cord and brain structural and functional parameters of the participants was performed using various methods, including functional connectivity analysis, voxel-based morphometry, and atlas-based analysis based on functional MRI and structural MRI data. Furthermore, this study conducted a correlation analysis between neuroimaging metrics and neurological function and utilized a support vector machine (SVM) algorithm for the classification of PHS and NHS. RESULTS: In comparison with the NHS and HC groups, PHS patients exhibited significant reductions in the cross-sectional area and fractional anisotropy (FA) of the lateral corticospinal tract (CST), reticulospinal tract (RST), and fasciculus cuneatus, concomitant with bilateral reductions in the volume of the lateral pallidum. The functional connectivity analysis indicated a reduction in functional connectivity between the left lateral pallidum and the right angular gyrus in the PHS group. The correlation analysis indicated a significant positive association between the CST and RST FA and the volume of the left lateral pallidum in PHS patients. Furthermore, all three variables exhibited a positive correlation with the patients' motor function. Finally, using multimodal neuroimaging metrics in conjunction with the SVM algorithm, PHS and NHS were classified with an accuracy rate of 85.53%. CONCLUSIONS: This research revealed a correlation between structural damage to the pallidum and RST and the presence of Hoffmann's sign as well as the motor function in patients with CSM. Features based on neuroimaging indicators have the potential to serve as biomarkers for assessing the extent of neuronal damage in CSM patients.

Contribution of changes in the spinal cord and brain to the onset and progression of hand clumsiness symptoms in cervical spondylotic myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) stands as the most prevalent form of spinal cord injury, frequently prompting various changes in both the brain and spinal cord. However, the precise nature of these changes within the brains and spinal cords of CSM patients experiencing hand clumsiness (HCL) symptoms has remained elusive. The authors aimed to scrutinize these alterations and explore potential links between these changes and the onset of HCL symptoms. METHODS: Using the modified Japanese Orthopaedic Association (mJOA) scale, the authors classified CSM patients into two groups: those without HCL and those with HCL. The authors performed voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (FC) evaluations in the brain. Additionally, they used the Spinal Cord Toolbox to calculate the fractional anisotropy (FA) of spinal cord tracts. The analysis also encompassed an examination of the correlation of these measures with improvements in mJOA scores. RESULTS: Significant disparities in zALFF values surfaced in the right calcarine, right cuneus, right precuneus, right middle occipital gyrus (MOG), right superior occipital gyrus (SOG), and right superior parietal gyrus (SPG) between healthy controls (HC), patients without HCL, and patients with HCL, primarily within the visual cortex. In the patient group, patients with HCL displayed reduced FC between the right calcarine, right MOG, right SOG, right SPG, right SFG, bilateral MFG, and left median cingulate and paracingulate gyri when compared with patients without HCL. Moreover, significant differences in FA values of the corticospinal tract (CST) and reticulospinal tract (REST) at the C2 level emerged among HC, patients without HCL, and patients with HCL. Notably, zALFF, FC, and FA values in specific brain regions and spinal cord tracts exhibited correlations with mJOA upper-extremity scores. Additionally, FA values of the CST and REST correlated with zALFF values in the right calcarine, right MOG, right SOG, and right SPG. CONCLUSIONS: Alterations within brain regions associated with the visual cortex, the fronto-parietal-occipital attention network, and spinal cord pathways appear to play a substantial role in the emergence and progression of HCL symptoms. Furthermore, the existence of a potential connection between the spinal cord and the brain suggests that this link might be related to the clinical symptoms of CSM.

Surgical Procedures of the Correction of Severe Static Glabellar Lines by Utilizing Resection with Free Dermal Fat Grafting (FDFG).

BACKGROUND: Botulinum toxin alone is unable to sufficiently reduce the muscle in cases of severe static glabellar lines due to the folded skin and dermal breakdown that frequently accompany these conditions. Augmentation of the soft tissue and removal of folded skin at the same time is the final solution. To simultaneously resolve interbrow skin laxity and replenish tissue volume, we present for the first time the method of glabellar lines excision combined with FDFG. METHODS: This retrospective study involved 23 patients with moderate-to-severe static glabellar lines underwent resection and/or free dermal fat grafting (FDFG) from June 2022 to June 2023. Fifteen of them underwent glabellar lines excision combined with FDFG, and seven were filled only. These patients were followed up at least 6 months to evaluate the effect. We utilized FACE-Q and WSRS for assessment in order to investigate the clinical results. RESULTS: There is no complication such as discoloration, hematoma, infection and palpability in all cases. After 6-15 months of follow-up, all the patients' dynamic and static lines were improved to a certain degree, and the patients were satisfied with the results with the WSRS score decreased from 3.5 ± 0.47 to 1.8 ± 0.62, and FACE-Q assessments in "Line between the eyebrows" decreased from 87 ± 7.39 to 43 ± 10.3. CONCLUSIONS: Resection in conjunction with FDFG is a brief, innovative and effective technique to correct static and dynamic severe glabellar wrinkles and maintain an acceptable outcome over an extended period of time which worthy clinical promotion. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The enhanced connectivity between the frontoparietal, somatomotor network and thalamus as the most significant network changes of chronic low back pain.

The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Butterfly Vertebra: A Retrospective Study of 30 Patients.

BACKGROUND: Butterfly vertebra (BV) is a rare congenital spinal anomaly for which there is a paucity of large-scale retrospective studies and established guidelines for treatment. The objective of this study was to elucidate the clinical characteristics, imaging findings, and therapeutic approaches for BV. METHODS: We conducted a retrospective analysis of 30 patients diagnosed with BV at our hospital from 2009 to 2023, examining clinical data, imaging findings, and clinical interventions. RESULTS: The analysis comprised a cohort of 30 patients, consisting of 15 males and 15 females, with a mean age of 27.63 ± 19.84 years. Imaging studies indicated that the majority of vertebral bodies affected by BV were single-segmented (63.3%, 19/30) and less commonly multi-segmented (36.7%, 11/30). These findings frequently coexisted with other medical conditions, most notably spinal scoliosis (76.7%, 23/30). Furthermore, the study identified a range of spinal abnormalities among patients, including hemivertebral deformity (30.0%, 9/30), spinal cleft (10.0%, 3/30), lumbar disc protrusion or herniation (10.0%, 3/30), vertebral slippage (10.0%, 3/30), thoracic kyphosis deformity (6.67%, 2/30), vertebral fusion deformity (6.67%, 2/30), compressive fractures (3.3%, 1/30), and vertebral developmental anomalies (3.3%, 1/30). Clinical intervention resulted in symptom relief for 23 nonsurgical patients through lifestyle modifications, analgesic use, and physical therapy. Seven surgical patients underwent appropriate surgical procedures, leading to satisfaction and adherence to regular postoperative follow-up appointments. CONCLUSIONS: BV is a rare vertebral anomaly that can be easily misdiagnosed due to its similarity to other diseases. Consequently, it is imperative to enhance vigilance in the differential diagnosis process in order to promptly recognize BV. Furthermore, in cases where patients present with additional associated radiographic findings, a thorough evaluation is typically warranted and timely measures should be taken for treatment.

Design and Evaluation of a Spoke-Based Double-Lumen Pediatric Gastrostomy Tube.

Gastrostomy tubes (G-tubes) are the gold standard for feeding assistance for children with feeding dysfunction. Current G-tubes pose complications that interrupt the delivery of feed, including tube displacement and difficulty of at-home use. This study details an alternative, spoke-based, double-lumen G-tube design and preliminary validation of its function and usability. Pull force testing was performed on spoke G-tube models across three sizes and two classifications (hard/soft). Preliminary models were evaluated against market standards. Though the pull force of the spoke model was found to be lower than that of both market standards, hard modifications to the spoke model improved retentive force. Ease of use was tested amongst users unfamiliar with G-tube placement. The spoke design required 12.3 ± 4.7 s to deploy, less than half the time required for market standards. However, balloon G-tubes were still perceived to be easiest to use by 70% of participants, with indications that a spoke design may be easier to use if sized similarly to current G-tubes, with auxiliary improvements to factors such as grip. While there is a need for improvements in the material properties and manufacturing of the proposed design, this study provides early validation of the potential to address complications of existing G-tubes.

Dysregulated neural activity between the thalamus and cerebral cortex mediates cortical reorganization in cervical spondylotic myelopathy.

Neuroimaging research has revealed significant changes in brain structure and function in patients with cervical spondylotic myelopathy(CSM). The thalamus plays a crucial role in this process, although its mechanisms of action remain incompletely understood. This study aimed to investigate whether spinal cord compression leads to alterations in the functional connectivity between the thalamus and the cerebral cortex, and to determine if such changes are associated with structural and functional remodeling of the brain in patients with CSM, and to identify potential neuroimaging biomarkers for classification. The study included 40 patients with CSM and 34 healthy controls(HCs) who underwent resting-state functional magnetic resonance imaging(fMRI) and structural MRI scans. Brain structural and functional metrics were quantified using functional connectivity(FC), fractional amplitude of low-frequency fluctuations(fALFF), surface-based morphometry(SBM), and independent component analysis(ICA) based on functional and structural MRI. Patients with CSM exhibited significantly reduced fALFF in the bilateral lateral lingual gyrus, bilateral calcarine fissure, left precentral gyrus and postcentral gyrus, left middle and superior occipital gyrus, left superior marginal gyrus, left inferior parietal gyrus, and right Rolandic operculum. ICA results revealed weakened functional connectivity between the sensorimotor network (SMN) and the left and right frontoparietal network(FPN), and lateral visual network (lVN), along with decreased connectivity between lVN and rFPN, and increased connectivity between lFPN and rFPN. Patients with CSM also had decreased sulcus depth in the bilateral insula, left precentral and postcentral gyrus, and right lingual gyrus and calcarine fissure. Furthermore, cervical spondylotic myelopathy patients showed decreased functional connectivity between the left ventral posterolateral nucleus (VPL) of the thalamus and the right middle occipital gyrus (MOG). Finally,multimodal neuroimaging with support vector machine(SVM) classified patients with CSM and healthy controls with 86.00% accuracy. Our study revealed that the decrease in functional connectivity between the thalamus and cortex mediated by spinal cord compression leads to structural and functional reorganization of the cortex. Features based on neuroimaging markers have the potential to become neuroimaging biomarkers for CSM.

Influence of environmental risk factors on the development of wounds associated with squamous cell carcinoma.

The incidence of squamous cell carcinoma (SCC) is on the rise, making it a significant global health concern. Environmental risk factors are crucial to the development of SCC. This study sought to examine comprehensively the impact of these factors on the onset of SCC. We conducted a cross-sectional study involving 480 participants at Beijing tertiary care hospital. Utilizing structured questionnaires, data on demographics, environmental exposures, medical history and clinical characteristics were collected. The cohort was composed of 272 men (56.67%) and 208 women (43.33%). The majority (44.38%) were between ages of 41 and 60, and Type III skin predominated (34.79%). Most of the participants belonged to the middle socioeconomic class (60.83%). 'Vegetarian' dietary habits (46.67%) were prevalent, as was the 'Sedentary' lifestyle (49.79%). Regarding environmental exposures, moderate sun exposure of 3 to 5 h per day (54.58%) and UV protective eyewear (30.83%) were prevalent. The majority (69.58%) of respondents indicated 'Never' exposure to carcinogens. A variety of wound characteristics were observed, with 'non-smokers' (64.17%) dominating. Most SCC lesions were located on the extremities (40.21%), lasted less than 6 months (44.38%) and measured 1-3 cm (39.79%). The majority (54.58%) did not have a history of cutaneous injuries. Our research uncovered substantial relationships between SCC and numerous environmental variables, gender, Fitzpatrick skin type, occupation, duration of sun exposure, exposure to carcinogens, dietary practices, history of skin wounds, wound location, duration, size and depth were significantly associated with the onset of SCC. These results highlighted the complexity of SCC aetiology and need for individualized prevention and treatment strategies.

The Efficiency and Safety of Platelet-Rich Plasma Dressing in the Treatment of Chronic Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Recently, many clinical trials have applied platelet-rich plasma (PRP) dressings to treat wounds that have stopped healing, which are also called chronic wounds. However, the clinical efficiency of PRP dressings in treating chronic wounds is still controversial. Therefore, we conducted this study to compare PRP dressings with normal saline dressings in treating chronic wounds. Relevant randomized controlled trials focusing on utilizing PRP dressings in treating chronic wounds were extracted from bibliographic databases. Finally, 330 patients with chronic wounds, reported in eight randomized controlled trials, were included in this study. In total, 169 out of 330 (51.21%) were treated with PRP dressings, and 161 out of 330 (48.79%) were treated with normal saline dressings. The pooled results showed that the complete healing rate of the PRP group was significantly higher than that of saline group at 8 weeks and 12 weeks, respectively. In addition, there were no significant differences in wound infection and adverse events. Compared with normal saline dressing, the PRP dressing could effectively enhance the prognosis of chronic wounds. Furthermore, the PRP did not increase wound infection rate or occurrence of adverse events as an available treatment for chronic wounds.

Multiple Injections of Platelet-Rich Plasma Versus Hyaluronic Acid for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Current Evidence in Randomized Controlled Trials.

In recent years, various clinical trials have focused on treating knee osteoarthritis (KOA) with multiple injections of platelet-rich plasma (PRP). However, compared with the multiple hyaluronic acid (m-HA) injections, the clinical efficacy of multiple PRP (m-PRP) injections for KOA still remains controversial among these studies. Therefore, we aimed to compare the clinical effectiveness of m-PRP injections with m-HA injections in the treatment of KOA in this systematic review. Relevant clinical trials were searched via bibliographic databases, including Medline, PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials, to compare the m-PRP and m-HA injections in the treatment of KOA. Finally, fourteen randomized controlled trials, including 1512 patients, showed the postoperative VAS, WOMAC, IKDC, or EQ-VAS scores and were enrolled in this systematic review. Compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections was lower in the VAS scores at 3-month (WMD = -0.25; 95%CI, -0.40 to -0.10, p = 0.0009) and 12-month (WMD = -0.64; 95%CI, -0.79 to -0.49, p < 0.00001) follow-ups. In addition, the group of intra-articular m-PRP injections was also lower in the WOMAC scores at 1-month (WMD = -1.23; 95%CI, -2.17 to -0.29, p = 0.01), 3-month (WMD = -5.34; 95%CI, -10.41 to -0.27, p = 0.04), 6-month (WMD = -11.02; 95%CI, -18.09 to -3.95, p = 0.002), and 12-month (WMD = -7.69; 95%CI, -12.86 to -2.52, p = 0.004) follow-ups. Furthermore, compared with the group of intra-articular m-HA injections, the group of intra-articular m-PRP injections was higher in the IKDC scores at 3-month (WMD = 7.45; 95%CI, 2.50 to 12.40, p = 0.003) and 6-month (WMD = 5.06; 95%CI, 1.94 to 8.18, p = 0.001) follow-ups. However, the long-term adverse side of m-PRP injections for KOA still needs more large-scale trials and long-term follow-ups.

Remodeling of the brain correlates with gait instability in cervical spondylotic myelopathy.

Introduction: Cervical spondylotic myelopathy (CSM) is a common form of non-traumatic spinal cord injury (SCI) and usually leads to remodeling of the brain and spinal cord. In CSM with gait instability, the remodeling of the brain and cervical spinal cord is unclear. We attempted to explore the remodeling of these patients' brains and spinal cords, as well as the relationship between the remodeling of the brain and spinal cord and gait instability. Methods: According to the CSM patients' gait, we divided patients into two groups: normal gait patients (nPT) and abnormal gait patients (aPT). Voxel-wise z-score transformation amplitude of low-frequency fluctuations (zALFF) and resting-state functional connectivity (rs-FC) were performed for estimating brain changes. Cross-sectional area (CSA) and fractional anisotropy (FA) of the spinal cord were computed by Spinal cord toolbox. Correlations of these measures and the modified Japanese Orthopedic Association (mJOA) score were analyzed. Results: We found that the zALFF of caudate nucleus in aPT was higher than that in healthy controls (HC) and lower than that in nPT. The zALFF of the right postcentral gyrus and paracentral lobule in HC was higher than those of aPT and nPT. Compared with the nPT, the aPT showed increased functional connectivity between the caudate nucleus and left angular gyrus, bilateral precuneus and bilateral posterior cingulate cortex (PCC), which constitute a vital section of the default mode network (DMN). No significantly different FA values or CSA of spinal tracts at the C2 level were observed between the HC, nPT and aPT groups. In CSM, the right paracentral lobule's zALFF was negatively correlated with the FA value of fasciculus gracilis (FCG), and the right caudate zALFF was positively correlated with the FA value of the fasciculus cuneatus (FCC). The results showed that the functional connectivity between the right caudate nucleus and DMN was negatively correlated with the CSA of the lateral corticospinal tract (CST). Discussion: The activation of the caudate nucleus and the strengthening functional connectivity between the caudate nucleus and DMN were associated with gait instability in CSM patients. Correlations between spinal cord and brain function might be related to the clinical symptoms in CSM.

A Study of Postoperative Complications Occurring at Home With Pediatric Gastrostomy Feeding Tubes.

OBJECTIVE: Gastrostomy tubes (G-tubes) provide long-term feeding assistance to children with severe feeding dysfunction. Although there are a host of complications that occur at home with current pediatric G-tube feeding, their prevalences and outcomes remain relatively unstudied. This study aims to identify and describe such complications. METHODS: A dual-round survey was administered to 98 participants through the Feeding Tube Awareness Foundation, a 501(c)(3) organization that supports parents and caretakers of G-tube-fed children. Information was collected broadly regarding G-tube complications, causes, and attitudes toward such complications. RESULTS: Infection (56%), itching/irritation/redness (52%), and leakage (51%) were the leading G-tube related complications. The average time that G-tubes were replaced was 3.4 ± 1.2 months as compared to the typical recommended period of up to 6 months. Of the caretakers who had not experienced G-tube displacement, 7.9% wanted to see a change in current G-tubes to address the issue, compared with 75% of those who had experienced displacement. This 67.1% differential in caretakers' attitudes toward G-tubes based on their prior experience with a particular complication was the largest gap among all other listed complications. CONCLUSIONS: G-tube complications are prevalent and varied. A sizable portion of G-tube users experience complications severe enough to require intervention. Of these, G-tube displacement is particularly critical and frequently precedes other prevalent complications, namely gastric leakage, infection, and tissue granulation.

Serum Sp17 Autoantibody Serves as a Potential Specific Biomarker in Patients with SAPHO Syndrome.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome shows a wide variability in musculoskeletal and cutaneous manifestations, and it is therefore underrecognized and misdiagnosed in the clinic due to a lack of specific markers. In this study, we aimed to identify specific biomarkers by screening serum autoantibodies in SAPHO patients with a 17K human whole-proteome microarray. The serum anti-Sp17 autoantibody was identified and verified to be a specific biomarker in patients with SAPHO syndrome. Indeed, the level of the anti-Sp17 autoantibody was significantly increased in patients with active SAPHO compared to patients with an inactive disease and healthy controls (P < 0.05). Additionally, serum anti-Sp17 autoantibody levels correlated with those of serum hypersensitive C-reactive protein (hsCRP), the erythrocyte sedimentation rate (ESR), and ß-crosslaps (ß-CTx) in patients with active SAPHO disease. Moreover, anti-Sp17 autoantibody levels were markedly decreased after anti-inflammatory treatment with pamidronate disodium, which downregulated levels of hsCRP and ESR in patients with active SAPHO. Thus, serum levels of the anti-Sp17 autoantibody might serve as a specific biomarker for the diagnosis of SAPHO syndrome or for monitoring the disease status.

Beneficial Effect of Antibiotics and Microbial Metabolites on Expanded Vδ2Vγ9 T Cells in Hepatocellular Carcinoma Immunotherapy.

Animal experiments and clinical trials have shown that the gut microbiota modulates host immunity and immune checkpoint-mediated responses to tumor cells. However, it remains unclear whether microbiota can also play a role in the tumor immune response of γδT cells, a kind of cell that targets cancer directly. Here, we report that microbiota dysbiosis induced by antibiotics enhanced γδT cell efficacy during tumor therapy in a mouse model. Further microbiota and metabolite analysis revealed that the alteration of γδT cell cytotoxicity might be closely associated with specific metabolites, which are produced by intestinal bacteria and stimulate γδT cells to release more cytotoxic cytokines, such as granzyme B and perforin. Among the metabolites that we analyzed, 3-indopropionic acid (IPA) showed the highest concentration in antibiotic-treated mice and can improve the cytotoxic ability of γδT cells both in vitro and in vivo. Our research determined how the gut microbiota can influence the antitumor ability of γδT cells and identified potential intermediate molecules that connect the gut microbiota and γδT cells.

Lipid Acyl Chain cis Double Bond Position Modulates Membrane Domain Registration/Anti-Registration.

Inter-leaflet coupling is critical to control the dynamics of membrane domain registration/anti-registration, which is important in maintaining proper biological functions. Factors such as lipid acyl chain inter-digitation and membrane remodeling have been found to be able to regulate the inter-leaflet coupling. However, detailed molecular mechanisms that dominate the inter-leaflet coupling are still far from clear. Here, we revealed that lipid acyl chain cis double bond position can regulate the inter-leaflet coupling according to our coarse-grained and all-atom molecular dynamics simulations. The farther the double bond is away from the lipid tail terminal, the weaker the inter-leaflet attractive interactions between unsaturated lipids. Therefore, the relative motions of membrane domains in two membrane leaflets become more obvious (membrane domain anti-registration). Generally, our simulations validated a direct indicator for the inter-leaflet coupling strength, which provides physical insights into the molecular mechanisms of membrane domain registration/anti-registration.

Efficacy of bisphosphonates in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: a prospective open study.

OBJECTIVES: To evaluate the clinical efficacy of bisphosphonates treatment for spinal bone marrow oedema (BME) in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: SAPHO syndrome patients presenting to Peking Union Medical College Hospital from 2015 to 2016 were recruited. Patients were administered pamidronate disodium 1 mg/kg/d intravenously, for 3 days, at baseline and 3 months later. The symptoms were evaluated using the Visual Analog Score (VAS) for pain, and other clinical measures including, spinal BME scores, ß-crosslaps, osteocalcin, and inflammatory factors, were collected. RESULTS: A total of 30 patients (20 women and 10 men) with a median age of 47.2 (interquartile range 8.8) years were recruited. In a short time, the patients showed a significant decrease in VAS (before vs. after; first treatment: 5.70±1.62 vs. 2.30±1.29 cm, second treatment: 4.03±1.88 vs. 2.17±1.23 cm) and ß-crosslaps (first treatment: 0.4441±0.1923 vs. 0.0859±0.0374 pg/ml, second treatment: 0.2891±0.1983 vs. 0.0962±0.0324 pg/ml) (all p<0.05). At 12-month follow-up, compared with the baseline, we noticed a significant drop in the VAS (5.70±1.62 vs. 2.43±1.25 cm), erythrocyte sedimentation rate (28.87±25.26 vs. 18.00±18.65 mm/h), high-sensitivity C-reactive protein level (11.76±10.19 vs. 5.84±5.88 mg/L), osteocalcin (2.30±1.27 vs. 1.65±0.80 ng/ml), and BME (30.50±24.09 vs. 22.13±27.79) (all p<0.05). No one had serious adverse events. CONCLUSIONS: Bisphosphonates can significantly and rapidly relieve symptoms in patients with SAPHO syndrome and have a long-term effect on inflammation and spinal BME. We suggest that bisphosphonates could be used as the first-line therapeutic drug for SAPHO syndrome, especially in patients with spinal BME.

miR-125b-5p and miR-99a-5p downregulate human γδ T-cell activation and cytotoxicity.

As an important component of innate immunity, human circulating γδ T cells function in rapid responses to infections and tumorigenesis. MicroRNAs (miRNAs) play a critical regulatory role in multiple biological processes and diseases. Therefore, how the functions of circulating human γδ T cells are regulated by miRNAs merits investigation. In this study, we profiled the miRNA expression patterns in human peripheral γδ T cells from 21 healthy donors and identified 14 miRNAs that were differentially expressed between peripheral αß T cells and γδ T cells. Of the 14 identified genes, 7 miRNAs were downregulated, including miR-150-5p, miR-450a-5p, miR-193b-3p, miR-365a-3p, miR-31-5p, miR-125b-5p and miR-99a-5p, whereas the other 7 miRNAs were upregulated, including miR-34a-5p, miR-16-5p, miR-15b-5p, miR-24-3p, miR-22-3p, miR-22-5p and miR-9-5p, in γδ T cells compared with αß T cells. In subsequent functional studies, we found that both miR-125b-5p and miR-99a-5p downregulated γδ T cell activation and cytotoxicity to tumor cells. Overexpression of miR-125b-5p or miR-99a-5p in γδ T cells inhibited γδ T cell activation and promoted γδ T cell apoptosis. Additionally, miR-125b-5p knockdown facilitated the cytotoxicity of γδ T cells toward tumor cells in vitro by increasing degranulation and secretion of IFN-γ and TNF-α. Our findings improve the understanding of the regulatory functions of miRNAs in γδ T cell activation and cytotoxicity, which has implications for interventional approaches to γδ T cell-mediated cancer therapy.

Lymphatic endothelial cells regulate B-cell homing to lymph nodes via a NIK-dependent mechanism.

B cells home to the lymph nodes (LNs) via high endothelial venules (HEVs) under the guidance of chemokines, particularly CXCL13. However, as CXCL13 is not directly made in HEVs, the molecular mechanism mediating B-cell homing to LNs has remained unclear. We show here that nuclear factor (NF)-κB-inducing kinase (NIK), a kinase mediating activation of the noncanonical NF-κB pathway, functions in lymphatic endothelial cells (LECs) to regulate B-cell homing to LNs. LEC-conditional deletion of NIK in mice did not affect the integrity or global function of lymphatic vessels but caused a severe reduction in the frequency of B cells in LNs. The LEC-specific NIK deficiency did not affect the survival of B cells or the frequency of B cells in the spleen. B-cell adoptive transfer studies revealed that the LEC-specific NIK deletion impairs the ability of LNs to recruit B cells. We further show that NIK mediates expression of the chemokines CXCL13 and CCL19 in LECs. Although CCL19 is also expressed in blood endothelial cells (BECs), CXCL13 is not produced in BECs. These results suggest that NIK regulates naive B-cell homing to LNs via mediating production of the B-cell homing chemokine CXCL13 in LECs.

Serum levels of proinflammatory, anti-inflammatory cytokines, and RANKL/OPG in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

OBJECTIVE: To measure the expression of proinflammatory, anti-inflammatory cytokines, and receptor activator NK-κB ligand (RANKL)/osteoprotegerin (OPG) in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, and to assess the relationship between those factors and disease activity. METHODS: We studied 30 cases of SAPHO syndrome and 15 healthy controls. According to the Visual Analogue Scale (VAS) pain scores and Bath Ankylosing Spondylitis Activity Index (BASDAI), patients were divided into active group and stable group. The serum levels of IFN-γ, TNF-α, TGF-ß1, IL-1ß, IL-4, IL-6, IL-8, IL-17A, IL-22, RANKL, and OPG were determined by ELISA. RESULTS: The active group IL-6 (2.34 ± 1.31 pg/ml), IL-8 (36.41 ± 12.93 pg/ml), and IL-17A (29.17 ± 4.01 pg/ml) levels were significantly higher than those in the stable group (p < .01) and healthy controls (p < .01). RANKL in active group (73.43 ± 57.07 pg/ml) was significantly higher than the ones in other groups (p < .0001), with increased RANKL/OPG ratio in the active group compared with other groups (p < .05). While the level of TGF-ß1 in the active group was significantly lower than that in the stable and control groups (p < .0001). There was no significant difference with clinical significance were found in IFN-γ, TNF-α, IL-1ß, IL-4, IL-22, and OPG. CONCLUSION: In active SAPHO patients, there was an anomaly of proinflammatory and anti-inflammatory cytokines balance in SAPHO syndrome.