搜索结果：Connective tissue research

This is the official English summary of the Japanese 2025 guide. The first edition of the guide for the diagnosis and management of connective tissue disease (CTD) associated with interstitial lung disease (ILD) was published in 2020 as a joint initiative by the Japanese Respiratory Society and the Japanese College of Rheumatology. This updated edition reflects major advances over the past five years, incorporating the latest international guidelines, consensus statements, and considerations unique to the Japanese healthcare reimbursement system. The guide is structured to facilitate timely clinical decision-making by highlighting key diagnostic and therapeutic milestones. The newly added content includes a conceptual framework for understanding ILD in CTD, practical clinical flowcharts, screening strategies, and risk factors, an overview of acute exacerbations, and a comprehensive approach to rehabilitation. Notably, treatment algorithms for ILD associated with polymyositis/dermatomyositis and systemic sclerosis have been revised to align with the most recent evidence and disease-specific recommendations, thereby enhancing their relevance to real-world practice. In addition, a provisional algorithm was proposed for the management of rheumatoid arthritis-associated ILD. The updated guide aims to standardize the multidisciplinary management of CTD-associated ILD and offers future perspectives to guide research and improve patient outcomes.

Background: Pleuroparenchymal fibroelastosis (PPFE) is a rare fibroelastotic lung disease characterized histologically by dense pleural and subpleural fibrosis with upper-lobe predominance. In clinical practice, diagnosis often relies on characteristic radiologic findings, as surgical lung biopsy is rarely feasible. Unlike idiopathic pulmonary fibrosis, robust radiologic criteria validated against biopsy-proven cohorts remain limited, and the diagnostic performance of imaging alone is incompletely defined. Although initially described as idiopathic, PPFE is increasingly recognized in secondary settings, including connective tissue disease-associated interstitial lung disease (CTD-ILD), where it frequently overlaps with more common fibrotic patterns. Methods: We conducted a focused narrative review of the literature on PPFE in CTD-ILD, synthesizing evidence on morphology, epidemiology, clinical course, prognostic implications, and proposed pathobiological mechanisms, with emphasis on distinguishing true PPFE from PPFE-like lesions. Results: CTD-associated PPFE is associated with accelerated lung function decline, increased risk of pneumothorax, and poorer outcomes, particularly in systemic sclerosis and rheumatoid arthritis. However, distinguishing true PPFE from radiologic mimics remains challenging, and diagnostic approaches rely heavily on imaging without robust histopathologic validation. Proposed mechanisms include epithelial injury, immune dysregulation, and vascular or lymphatic abnormalities, although causal links remain unproven. Significant gaps persist regarding natural history and therapeutic responsiveness. Conclusions: Earlier identification of PPFE in CTD-ILD is important, as misclassification may delay risk stratification and management. Longitudinal imaging, multidisciplinary evaluation, and standardized diagnostic criteria are needed to improve clinical care and guide future research.

Given the systemic nature of connective tissue diseases (CTD), open surgical intervention for aortic stenosis is often considered high risk, making transcatheter aortic valve replacement (TAVR) a potentially preferable alternative. However, data on the impact of CTD on TAVR outcomes remain limited. Therefore, we conducted a nationwide analysis using the National Inpatient Sample (NIS) to examine trends and in-hospital outcomes of TAVR in patients with CTD in the United States. A total of 90,298 patients undergoing TAVR between 2016 and 2022 were identified, representing over 451,000 weighted hospitalizations, including 3,821 (4.2%) with CTD. Multivariable regression was used to adjust for demographic, clinical, and hospital-level characteristics. CTD patients were more frequently female and had higher comorbidity indices, although many differences were small in absolute magnitude. In-hospital mortality was comparable between CTD and non-CTD groups (1.0% vs. 1.2%, p = 0.345). Rates of permanent pacemaker implantation and major complications, including vascular events, were similar. CTD patients demonstrated modestly shorter length of stay and lower inflation-adjusted hospitalization costs. Lower rates of cardiogenic shock, cardiac arrest, and mechanical ventilation were observed in the CTD cohort. In-hospital mortality declined significantly over time in the overall cohort, with a similar directional trend in CTD patients that did not reach statistical significance, likely due to smaller sample size. Overall, TAVR appears to be a safe and feasible therapeutic option in patients with CTD, with outcomes comparable to those without CTD.

Background Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a spatially and temporally heterogeneous disease. Determining whether CTD-ILD is in a progressive stage is crucial for guiding clinical management. Purpose To determine whether CTD-ILD is associated with ventilation and perfusion parameters quantified with phase-resolved functional lung (PREFUL) MRI and whether these functional parameters can help predict CTD-ILD progression. Materials and Methods In this prospective study performed from May 2024 to April 2025, healthy participants without pulmonary disease and participants with CTD-ILD underwent baseline PREFUL MRI, chest CT, and pulmonary function tests. Participants with CTD-ILD were followed up for 1 year. Disease progression was defined as meeting at least two of the following criteria: an absolute decline in forced vital capacity of more than 5% predicted or an absolute decline in diffusing capacity of lung for carbon monoxide of more than 10% predicted, CT evidence of disease progression, or worsening respiratory symptoms. Least absolute shrinkage and selection operator regression were applied to identify variables associated with disease progression, and predictive performance was assessed using the area under the receiver operating characteristic curve (AUC). Results A total of 172 participants (mean age, 59 years &#xb1; 11.8 [SD]; 143 women) were included. Compared with controls, participants with CTD-ILD demonstrated reduced dynamic ventilation (mean, 0.97 arbitrary units [au] &#xb1; 0.02 vs 0.95 au &#xb1; 0.05, respectively; P < .001) and lower perfusion (mean, 50.3 mL/min per 100 mL &#xb1; 16.2 vs 22.0 mL/min per 100 mL &#xb1; 9.2; P < .001). At baseline, compared with stable CTD-ILD, progressive CTD-ILD was associated with a higher perfusion defect (mean, 14.7% &#xb1; 6.8 vs 26.5% &#xb1; 9.1; P < .001) and lower healthy ventilation and perfusion matches (mean, 75.6% &#xb1; 8.9 vs 62.1% &#xb1; 10.8; P = .001). The multiparametric PREFUL model achieved the highest predictive performance (AUC, 0.87; 95% CI: 0.78, 0.95) compared with other logistic models (P = .004, P < .001). Conclusion In participants with CTD-ILD, ventilation and perfusion parameters derived from PREFUL MRI characterized distinct pulmonary perfusion phenotypes in CTD-ILD and were associated with disease progression over 1 year. &#xa9; RSNA, 2026 Supplemental material is available for this article. See also the editorial by Rahsepar and Abtin in this issue.

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Background/Objectives: Radiotherapy following mastectomy induces persistent structural alterations in the chest wall, including fibrosis, extracellular matrix disorganization, and vascular changes that compromise reconstructive outcomes. Although autologous fat grafting is widely used to improve tissue quality in irradiated breasts, direct human histological evidence remains limited. The aim of this prospective pilot study was to evaluate intra-patient histological remodeling in irradiated postmastectomy breast tissue before and 4 months after autologous fat grafting using paired core needle biopsies. This study should be considered a hypothesis-generating histological pilot study. Methods: Five female patients with prior mastectomy and adjuvant radiotherapy underwent Tru-Cut core needle biopsy of irradiated chest wall tissue before lipofilling and at approximately four months (range between 3 and 12 months) post-procedure. Specimens were processed using formalin fixation, paraffin embedding, and hematoxylin and eosin staining. Histological assessment focused on collagen density, stromal organization, vascular structures, inflammatory infiltrate, and adipocyte integration. Comparative intra-patient analysis was performed descriptively. Results: Baseline biopsies demonstrated consistent post-radiation alterations, including collagen compaction, stromal disorganization, perivascular fibrosis, and variable inflammatory infiltrate. Post-lipofilling specimens showed heterogeneous remodeling characterized by focal collagen fiber insertion between adipocytes, areas of immature connective tissue formation, and variable preservation of adipose architecture. The extent and pattern of remodeling differed among patients. Inflammatory activity decreased or remained mild in most cases. Conclusions: Autologous fat grafting in irradiated postmastectomy tissue is associated with measurable histological remodeling. Structural adaptation appears heterogeneous and patient-specific, suggesting a dynamic multi-stage process rather than uniform regeneration. Further studies incorporating quantitative and molecular analyses are required to clarify the mechanisms underlying these changes.

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Sarculator is a widely validated prognostic tool that estimates overall survival and crude cumulative incidence (CCI) of distant metastasis in patients with resected soft tissue sarcomas in the extremities. Sarculator relied on external cohorts only for performance testing and could not incorporate new information or adapt to temporal changes. We aimed to develop BayeSarc, a prognostic model based on Bayesian sequential learning (BSL), which enables continuous updating by incorporating new clinical cohorts and provides more accurate estimates. In this retrospective, multicentre cohort study, eligible patients were adults (aged &#x2265;18 years) with primary, localised, surgically treated soft tissue sarcomas in the extremities (excluding desmoid tumours, undifferentiated small round cell sarcoma of soft tissue, alveolar or embryonal rhabdomyosarcoma, dermatofibrosarcoma protuberans, and well differentiated liposarcoma). Data were retrieved from institutional databases at each participating hospital. BayeSarc used the same clinicopathological variables as Sarculator (age, size, grade, and histology) and was developed with a historical cohort of consecutive patients treated surgically at the Istituto Nazionale dei Tumori (Milan, Italy) and sequentially updated with five independent cohorts from Canada, France, the UK, USA, and Italy. Bayesian Cox (overall survival) and Fine-Gray (CCI distant metastasis) models were reformulated within a BSL framework combining Bayesian updating with prior-information adaptive borrowing. The primary objective was to compare the discrimination and calibration of BayeSarc versus Sarculator for predicting overall survival and CCI-distant metastasis. We evaluated the performance of BayeSarc at each update using prequential estimates, reflecting model transport to a new cohort without local recalibration, and post-update estimates, reflecting performance after sequential updating. We included a total of 4916 patients (2204 [44&#xb7;8%] female, 2694 [54&#xb7;8%] male, and 18 [0&#xb7;4%] with sex not recorded) drawn from six cohorts: Istituto Nazionale dei Tumori, Milan, Italy (Jan 1, 1994-Dec 31, 2013; median follow-up 86 months [IQR 81-90]); Mount Sinai Hospital, Toronto, Canada (Jan 1, 1994-Dec 31, 2013; 85 months [81-90]); Institut Gustave Roussy, Villejuif, France (Jan 1, 1996-May 15, 2012; 75 months [68-82]); Royal Marsden Hospital, London, UK (Jan 1, 2006-Dec 31, 2013; 54 months [48-59]); Brigham and Women's Hospital, Boston, USA (Jan 1, 2014-Dec 31, 2021; 72 months [66-84]); and Istituto Nazionale dei Tumori, Milan, Italy (Jan 1, 2014-Dec 31, 2021; 61 months [57-64]). 12 patients from the UK were missing follow-up data and were excluded from survival analyses. At the final step of the BSL update, BayeSarc achieved higher discrimination than Sarculator for both overall survival (prequential mean C index: 0&#xb7;784 [95% credible interval 0&#xb7;759-0&#xb7;794]; after update: 0&#xb7;801 [0&#xb7;790-0&#xb7;809]; Sarculator: 0&#xb7;773) and distant metastasis (prequential mean C index: 0&#xb7;723 [0&#xb7;704-0&#xb7;738]; after update: 0&#xb7;738 [0&#xb7;730-0&#xb7;743]; Sarculator: 0&#xb7;718). Calibration improved consistently across updates, and uncertainty around estimates and predictions decreased. BayeSarc is a continuously updatable, accurate, and precise prognostic tool for soft tissue sarcomas in the extremities. It reduces uncertainty, adapts to temporal changes, and refines variable weights. Its incorporation into the Sarculator app enables immediate clinical use, with potential to improve patient counselling, guide treatment decisions, and refine trial design. More broadly, the BSL framework provides an innovative and generalisable approach to prognostication in rare cancers, moving beyond the traditional two-step development-validation paradigm, enabling more efficient use of patient data. Associazione Italiana per la Ricerca sul Cancro, Cancer Research UK, Fundacion Cient&#xed;fica, and Asociacion Espanola Contra el Cancer.

Fixed contralateral anchored suturing (FICAS) for coronal flap advancement is a novel suturing technique that utilizes ceramic attachments bonded to the buccal or lingual of the teeth as an anchorage point for suspensory sutures. This technique is designed to increase flap stability and improve graft adaptation in periodontal plastic surgery. Two patients with localized gingival recession defects were treated with connective tissue grafting. One case used a tunneling technique, and the other used a coronally advanced flap. A ceramic button is bonded to the tooth surface contralateral to the flap. This is the lingual surface in both cases presented. Subepithelial connective tissue grafts and flaps were coronally advanced using periosteal stretching and then secured with nylon sutures. The sutures are looped over the ceramic button in a specific suspensory configuration. Follow-up at 2 weeks and 6 months revealed uneventful healing. No loss of sutures, ceramic buttons, or any postoperative infection occurred. The bonded buttons successfully protected the sutures and wound from disruption by tongue movements and food. There were visible increases in gingiva thickness, keratinized and attached tissue. Significant root coverage was achieved. The FICAS technique may be a viable alternative for tension-free coronal flap advancement and stable soft tissue adaptation, specifically in complex soft tissue cases such as a dehiscence or Recession type (RT)2 and RT3 defects. Additional research, ideally randomized controlled trials, is necessary to substantiate these observations and determine the long-term success of this technique compared to others previously described. Fixed contralateral anchored suturing used ceramic buttons as a remote anchorage point for suspensory sutures. Maximizing flap stability and minimizing tension on delicate tissues are critical factors for favorable healing in periodontal plastic surgery. Buttons bonded to the contralateral surface of the flap may improve esthetics compared to other suspensory suturing techniques. Fixed contralateral anchored suturing technique is a new suturing technique that involves bonding a button to the tooth surface, which will hold suspensory sutures. Sutures play a critical role in holding the tissues in a stable and favorable position during initial healing. The authors aim to introduce this technique to improve upon the esthetics of previously reported suspensory suturing techniques, and potentially improve outcomes and root coverage in both simple and complex recession cases.

Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening connective tissue disorder that often remains undiagnosed before pregnancy and carries a markedly high risk of maternal mortality. We report the case of a 34-year-old pregnant woman who experienced sudden abdominal pain at 39&#x2009;weeks of gestation and died shortly after delivery. Autopsy revealed an aortic rupture with histopathological findings suggestive of vEDS. Her family history included her father's sudden vascular death, and her personal history was notable for easy bruising and early-onset varicose veins. Next-generation sequencing-based postmortem genetic testing (PMGT) using formalin-fixed, paraffin-embedded liver tissue confirmed a pathogenic variant in COL3A1. This result facilitated genetic counseling for the family, allowing presymptomatic diagnosis and preventive management, including celiprolol therapy for at-risk relatives. This case underscores the value of PMGT in identifying the underlying cause of unexpected maternal death, particularly when conventional samples are unavailable.

A biologically guided, time-efficient analog workflow for anterior implant rehabilitation is presented. Two implants were placed in a horizontally deficient anterior maxilla with simultaneous guided bone regeneration and a de-epithelialized connective tissue graft to restore ridge contour and increase mucosal thickness. After healing, the transmucosal contour was shaped extraorally on a silicone index and transferred intraorally using custom interim restorations with controlled soft-tissue refinement. The emergence profile was captured with a custom impression coping, and multilayer zirconia crowns were cemented extraorally to titanium-base abutments and then screw retained. At 5 years, stable marginal bone levels, healthy peri-implant mucosa, preserved papillae, and harmonious esthetic integration were maintained. This report presents a straightforward, reproducible protocol for achieving a stable peri-implant phenotype.

Odontogenic keratocysts (OKCs) are locally aggressive odontogenic cysts with high recurrence propensity, whereas orthokeratinized odontogenic cysts (OOCs) are indolent. Secreted protein acidic and rich in cysteine (SPARC) and matrix metalloproteinase 9 (MMP-9) have been implicated in tumor invasion. This study aimed to evaluate and compare the immunohistochemical expression of SPARC and MMP-9 in sporadic OKCs and OOCs, and to further explore the potential association between these two proteins in both types of cysts. SPARC and MMP-9 expression were evaluated in 24 sporadic OKCs and 22 OOCs using immunohistochemistry. In the epithelium of OKCs and OOCs, SPARC was absent. In the connective tissue, SPARC was predominantly detected in fibroblast cytoplasm, with significantly higher expression in OKCs than in OOCs (p&#x202f;=&#x202f;0.006). MMP-9 was localized in both epithelium and connective tissue. Compared with OOCs, OKCs showed upregulated MMP-9 expression in the epithelium (p&#x202f;=&#x202f;0.035), whereas no significant difference in MMP-9 expression was observed in the connective tissue between the two types of cysts (p&#x202f;=&#x202f;0.678). A positive correlation was observed between SPARC and MMP-9 in the connective tissue of OKC. Furthermore, both SPARC and MMP-9 demonstrated a significant positive association with inflammatory infiltration in OKCs. Increased SPARC expression in sporadic OKCs compared to OOCs suggests that SPARC may play a role in OKC aggressiveness. Differential expression of SPARC may aid in distinguishing between OKC and OOC. Moreover, the putative association between SPARC and MMP-9 in OKCs may contribute to their local invasiveness.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by defects in collagen I, leading to increased bone fragility and turnover. The zebrafish Chihuahua (Chi/+), carrying a p.(Gly736Asp) substitution in the &#x3b1;1(I) chain, recapitulates key features of human OI, including the presence of misfolded collagen I in extracellular matrix. In this study, we evaluated the specificity of a fluorescently labeled collagen hybridizing peptide (Cy5-CHP) for detecting in vivo misfolded collagen I in adult zebrafish. The CHP or the scrambled control peptides were injected intraperitoneally into WT and Chi/+ zebrafish, and average radiant efficiency was quantified at 24 and 72&#xa0;h post-injection (hpi) in the vertebral column, cranium and heart, representing collagen I-rich organs, as well as the brain, a collagen I-poor tissue. Our results revealed Cy5-CHP specific binding to collagen I-rich tissues in Chi/+ zebrafish at 24 hpi, with minimal signal in the brain, whereas low signal was detectable across all tissues in WT. Cy5-CHP fluorescence was reduced by 72 hpi in all samples, consistent with the low binding affinity of the peptide. Histological analyses confirmed the co-localization of Cy5-CHP with collagen fibers in the endplates of Chi/+ vertebrae at 24 hpi. These findings provide the first in vivo evidence in zebrafish that Cy5-CHP selectively binds misfolded collagen, showing preferential accumulation in collagen I-rich tissues in OI. Overall, the results support the use of Cy5-CHP as a sensitive tool for detecting pathologic collagen and as a potential platform for tissue-targeted drug delivery in OI and other collagen-related disorders.

Implants offer superior physiological and functional outcomes; however, their success depends on the availability of adequate local bone volume. In cases of severe maxillary resorption, this approach is often challenged by anatomical limitations such as expanded maxillary sinuses or other features that compromise the residual bone volume. This study aimed to assess histological outcomes of lateral window sinus augmentation performed with a composite graft comprising a 2:1 mixture of allograft (corticocancellous bone; HC Biologics, USA) and a synthetic bone substitute (30% HA/70% &#x3b2;-TCP) combined with autologous platelet-rich fibrin (PRF). This prospective registered histomorphometric study analyzed 60 biopsy specimens obtained from sinus augmentation sites in a Vietnamese cohort with severely atrophic posterior maxilla (residual bone height&#x2009;&#x2264;&#x2009;4&#xa0;mm). Bone regeneration was evaluated following lateral-window sinus augmentation using a composite graft composed of a 2:1 mixture of allograft (corticocancellous bone; HC Biologics, USA) and a synthetic bone substitute (30% HA/70% &#x3b2;-TCP; Osteon II, Dentium, Korea) combined with autologous platelet-rich fibrin (PRF). Histomorphometric analysis was performed on three non-consecutive sections per specimen using ImageJ. The standardized protocol and relatively large number of biopsies provide clinically relevant histological evidence. The mean proportion of newly formed bone was 31.28% (95% CI: 26.70%-35.85%), while the mean residual graft material accounted for 15.48% (95% CI: 12.29%-18.68%). Histological evaluation revealed no evidence of inflammatory infiltrates or tissue necrosis. The presence of a well-organized lamellar bone architecture, with Haversian canals and osteocytes embedded within lacunae, indicated advanced bone maturation. At the graft periphery, numerous osteoblasts and osteoclasts were identified, reflecting ongoing bone remodeling. Residual bone height averaged 2.31&#x2009;&#xb1;&#x2009;0.93&#xa0;mm. Newly formed bone accounted for 31.28&#x2009;&#xb1;&#x2009;17.71%, while connective tissue represented 53.23&#x2009;&#xb1;&#x2009;18.75%. Primary implant stability (ISQ1) was 58.20&#x2009;&#xb1;&#x2009;6.47 and increased to 74.85&#x2009;&#xb1;&#x2009;7.68 at six months (ISQ2). ISQ1 correlated strongly with residual bone height (r&#x2009;=&#x2009;0.626) and inversely with connective tissue (r&#x2009;=&#x2009;-&#x2009;0.627), and moderately with newly formed bone (r&#x2009;=&#x2009;0.405) (all p&#x2009;&#x2264;&#x2009;0.001). Within the limitations of this prospective single-arm study, sinus augmentation using a composite graft composed of a 2:1 mixture of allograft (corticocancellous bone; HC Biologics, USA) and a synthetic bone substitute (30% HA/70% &#x3b2;-TCP; Osteon II, Dentium, Korea) combined with autologous platelet-rich fibrin (PRF) resulted in favorable histological and histomorphometric outcomes after six months of healing. The regenerated tissue provided a biocompatible osteoconductive environment supporting bone formation within the augmented sinus. Nevertheless, because the study lacked a comparator group, the individual contribution of each graft component cannot be determined, and the findings should be interpreted as descriptive rather than causal evidence. ClinicalTrials.gov NCT07186166, 30 August 2025. Retrospectively registered.

The dorsal root ganglion (DRG) contains the somata of primary sensory neurons. The structure of the DRG is important for understanding the mechanisms of several diseases (e.g., low back pain or sciatica) and the variability in the distribution of regional anesthesia. DRG is also highly sensitive to mechanical compression in radiculopathy. Neuromonitoring and neurostimulation technologies require appropriate electrode placement, which depends on the ganglion's structure. According to certain reports, biganglia occur relatively frequently in the lumbar nerves. This study aimed to investigate the normal morphological features and variations of the human lumbar DRG. Microanatomic dissections of the lumbar nerves were performed in 10 human cadavers fixed in 10% formalin (6 males and 4 females, aged 69-97 years). A total of 100 DRGs were analyzed morphologically. Bilateral dissection of the DRG (L1-L5) revealed three types of structures: single ganglion, biganglion, and triganglion. Monoganglion was found most often at the levels of L1 and L2, while polyganglia, such as biganglion or triganglion, may be found at L2, L3, L4, or L5. Distinct layers of connective tissue separate independent ganglion components. In cases of transitional morphology, the division of ganglion components was partial. The presence of biganglion or triganglion might affect the quality of electrical stimulation of the DRG. The connective tissue between the ganglion components of a polyganglion might influence the spread of impulses. A classification of DRG morphology is proposed. Further research should clarify the distribution of dermatomal innervation of the ganglion components.

Ehlers Danlos Syndromes (EDS) are hereditary connective tissue disorders. The purpose of this participatory action qualitative research study is to describe experiences of dysphagia in people with hypermobile EDS (hEDS). Ten participants (8 F, 1&#xa0;M, and 1 nonbinary-assigned F at birth; ages 19-52&#xa0;years) with hEDS completed the Eating Assessment Tool (EAT-10; Belafsky et al., 2008), Reflux Symptom Index (RSI; Belafsky et al., 2002), and semi-structured interviews. The interviews were audio-recorded, transcribed and verified. Phenomenological qualitative research methods were used to code (Atlas.ti Web) and develop themes. All participants affirmed dysphagia symptoms via the EAT-10 (M&#x2009;=&#x2009;17.65; SD&#x2009;=&#x2009;6.93; Range&#x2009;=&#x2009;4-29) with 6/10 requiring a feeding tube at some point. Most participants also affirmed reflux symptoms on the RSI (M&#x2009;=&#x2009;20.30; SD&#x2009;=&#x2009;8.3; Range 7-36). Four preliminary themes related to dysphagia in people with hEDS were identified: (1) Swallowing discomfort is common, requiring cognitive and physical effort; (2) Gastrointestinal symptoms impact deglutition and often lead to a need for supplemental nutrition / hydration; (3) Dyspnea is common, and may intermittently impact respiratory-swallowing coordination; and (4) Dismissal of physiological symptoms as "anxiety" by at least one provider prior to acknowledgment of an underlying condition occurs frequently. Dysphagia is commonly reported by people with hEDS and appears to be related to underlying symptoms of hEDS and/or dysautonomia. Further research is needed to elucidate the impact and mechanisms of impairments associated with hEDS and dysautonomia across all phases of swallowing.

Exercise can regulate the physiological functions of the body by inducing the secretion of myokines, which are bioactive factors mainly secreted by muscle cells. This review classifies myokines based on their functional characteristics, including metabolic regulation (such as myostatin, interleukin-6), neuroregulation (brain-derived neurotrophic factor), cell proliferation/differentiation regulation (myogenic proteins), immune regulation (tumor necrosis factor- alpha), and factors involved in angiogenesis and extracellular matrix remodeling (such as connective tissue growth factor).Cancer, as a consuming disease, often accompanies muscle atrophy and depletion in its advanced stage, thereby affecting the normal secretion of myokines. Increasing research evidence indicates that myokines play a dual regulatory role in the occurrence and development of cancer. Some myokines (such as interleukin-6, tumor necrosis factor- alpha) have environment-dependent functions and can exhibit pro-cancer or anti-cancer effects depending on the microenvironment; while factors such as myostatin show stable anti-tumor potential by regulating key molecular pathways such as the PI3K/AKT pathway, epithelial-mesenchymal transition, and HIF-1&#x3b1;. It is worth noting that muscle cell factors can indirectly influence the disease outcome of cancer by regulating key cells and structures in the tumor microenvironment (such as tumor-associated macrophages, regulatory T cells, and cancer-associated fibroblasts), as well as by participating in the angiogenesis process. At the clinical application level, muscle cell factors are expected to become potential biomarkers for cancer diagnosis and prognosis assessment (such as elevated irisin levels in patients with renal cancer and elevated interleukin-6 levels in patients with bile duct cancer). They also have great potential as therapeutic targets. For example, MSTN inhibitors can effectively alleviate cancer cachexia symptoms, and the combination of anti-interleukin-6 treatment with immune checkpoint blockade therapy can produce a significant synergistic therapeutic effect. This review systematically summarizes the latest research progress on the molecular interaction mechanisms mediated by myokines in cancer, emphasizing their potential for translational applications in precision oncology. Myokines not only regulate the physiological functions of the musculoskeletal system, but also have a close association with the occurrence and development of cancer. The intrinsic connection between myokines and muscle atrophy as well as cancer-related cachexia still requires further in-depth exploration. As emerging biomarkers, myokines can be combined with various diagnostic and therapeutic techniques, which is expected to further improve the survival rate of cancer patients, protect muscle function, and also provide new research ideas for exploring the interrelationship between muscles and cancer and the pathogenesis of related muscle diseases.