Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement.

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

Facial profile evaluation and prediction of skeletal class II patients during camouflage extraction treatment: a pilot study.

BACKGROUND: The evaluation of the facial profile of skeletal Class II patients with camouflage treatment is of great importance for patients and orthodontists. The aim of this study is to explore the key factors in evaluating the facial profile esthetics and to predict the posttreatment facial profile esthetics of skeletal Class II extraction patients. METHODS: 124 skeletal Class II extraction patients were included. The pretreatment and posttreatment cephalograms were analyzed by a trained expert orthodontist. The facial profile esthetics of pretreatment and posttreatment lateral photographs were evaluated by 10 expert orthodontists using the visual analog scale (VAS). The correlation between subjective facial profile esthetics and objective cephalometric measurements was assessed. Three machine-learning methods were used to predict posttreatment facial profile esthetics. RESULTS: The distances from lower and upper lip to the E plane and U1-APo showed the stronger correlation with profile esthetics. The changes in lower lip to the E plane and U1-APo during extraction exhibited the stronger correlation with changes in VAS score (r = - 0.551 and r = - 0.469). The random forest prediction model had the lowest mean absolute error and root mean square error, demonstrating a better prediction accuracy and fitting effect. In this model, pretreatment upper lip to E plane, pretreatment Pog-NB and the change of U1-GAll were the most important variables in predicting the posttreatment score of facial profile esthetics. CONCLUSIONS: The maxillary incisor protrusion and lower lip protrusion are key objective indicators for evaluating and predicting facial profile esthetics of skeletal Class II extraction patients. An artificial intelligence prediction model could be a new method for predicting the posttreatment esthetics of facial profiles.

Self-promoted electroactive biomimetic mineralized scaffolds for bacteria-infected bone regeneration.

Infected bone defects are a major challenge in orthopedic treatment. Native bone tissue possesses an endogenous electroactive interface that induces stem cell differentiation and inhibits bacterial adhesion and activity. However, traditional bone substitutes have difficulty in reconstructing the electrical environment of bone. In this study, we develop a self-promoted electroactive mineralized scaffold (sp-EMS) that generates weak currents via spontaneous electrochemical reactions to activate voltage-gated Ca2+ channels, enhance adenosine triphosphate-induced actin remodeling, and ultimately achieve osteogenic differentiation of mesenchymal stem cells by activating the BMP2/Smad5 pathway. Furthermore, we show that the electroactive interface provided by the sp-EMS inhibits bacterial adhesion and activity via electrochemical products and concomitantly generated reactive oxygen species. We find that the osteogenic and antibacterial dual functions of the sp-EMS depend on its self-promoting electrical stimulation. We demonstrate that in vivo, the sp-EMS achieves complete or nearly complete in situ infected bone healing, from a rat calvarial defect model with single bacterial infection, to a rabbit open alveolar bone defect model and a beagle dog vertical bone defect model with the complex oral bacterial microenvironment. This translational study demonstrates that the electroactive bone graft presents a promising therapeutic platform for complex defect repair.

Deep Learning-Predicted Dihydroartemisinin Rescues Osteoporosis by Maintaining Mesenchymal Stem Cell Stemness through Activating Histone 3 Lys 9 Acetylation.

Maintaining the stemness of bone marrow mesenchymal stem cells (BMMSCs) is crucial for bone homeostasis and regeneration. However, in vitro expansion and bone diseases impair BMMSC stemness, limiting its functionality in bone tissue engineering. Using a deep learning-based efficacy prediction system and bone tissue sequencing, we identify a natural small-molecule compound, dihydroartemisinin (DHA), that maintains BMMSC stemness and enhances bone regeneration. During long-term in vitro expansion, DHA preserves BMMSC stemness characteristics, including its self-renewal ability and unbiased differentiation. In an osteoporosis mouse model, oral administration of DHA restores the femur trabecular structure, bone density, and BMMSC stemness in situ. Mechanistically, DHA maintains BMMSC stemness by promoting histone 3 lysine 9 acetylation via GCN5 activation both in vivo and in vitro. Furthermore, the bone-targeted delivery of DHA by mesoporous silica nanoparticles improves its therapeutic efficacy in osteoporosis. Collectively, DHA could be a promising therapeutic agent for treating osteoporosis by maintaining BMMSC stemness.

Prim-O-glucosylcimifugin ameliorates aging-impaired endogenous tendon regeneration by rejuvenating senescent tendon stem/progenitor cells.

Adult tendon stem/progenitor cells (TSPCs) are essential for tendon maintenance, regeneration, and repair, yet they become susceptible to senescence with age, impairing the self-healing capacity of tendons. In this study, we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness. The top-ranked candidate, prim-O-glucosylcimifugin (POG), a saposhnikovia root extract, could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans, as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs. In vivo, the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals. Mechanistically, POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy. Thus, the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.

Immediately or delayed sinus augmentation after pseudocyst removal: A randomized trial.

PURPOSE: To compare clinical and histological outcomes of sinus augmentation performed immediately or 3 months after pseudocyst removal through a prospective randomized controlled study. MATERIALS AND METHODS: In total, 33 sinus augmentation procedures were performed in 31 patients. Augmentation was performed either immediately after pseudocyst removal (one-stage intervention) or after 3 months (two-stage intervention). Six months postoperatively, bone specimens were harvested, and histomorphometric analysis was performed as primary outcome. Data were recorded and evaluated for implant survival rates, marginal bone resorption, complication rate, and patient-centered outcomes (visual analogue scale [VAS]). RESULTS: There were no baseline differences between groups or dropouts. Twelve biopsies obtained for histomorphometric analysis showed that delayed sinus augmentation, when compared to immediated led to a 1.1% increased mineralized bone ratio (95% confidence interval [CI]: -15.9 to 13.7). Graft leakage and acute sinusitis occurred in one patient in the one-stage group, none in the two-stage group. No pseudocyst recurrence was observed until the end of 1-year follow-up. Median VAS scores for overall acceptance were significantly increase of 1.4 (95% CI: 0.3-2.56) in immediate group. The degree of post-operative discomfort was not significantly different, although an increase of VAS (0.52, 95% CI: -0.32 to 1.37) was observed in delay group. CONCLUSIONS: Both procedures of sinus augmentation immediately and 3 months after pseudocyst removal could obtain comparable histological outcomes and had low complication rates. Patients who underwent the one-stage procedure had a short treatment course and high satisfaction rates, but this procedure is technically challenging to perform. This clinical trial was not registered prior to participant recruitment and randomization. The clinical trial registration number is ChiCTR2200063121. The hyperlink is as follows: https://www.chictr.org.cn/showproj.html?proj=172755.

Neural regulation of alveolar bone remodeling and periodontal ligament metabolism during orthodontic tooth movement in response to therapeutic loading.

With increased understanding of orthodontic tooth movement (OTM) in recent years, neural regulation of OTM has become an emerging and expanding area of research. Numerous studies have shown that the nervous system, including the central and peripheral systems, regulates bone remodeling through various neuropeptides, receptor expression, etc. OTM is a unique periodontal tissue remodeling process induced by mechanical force, including changes in the periodontal ligament metabolism and alveolar bone remodeling. Various studies have shown that the nervous system participates in the OTM process and regulates the periodontal ligament metabolism. This review summarizes the current researches on neural regulation of bone remodeling and the biological responses within the periodontal ligamentduring OTM under therapeutic loading. We also discuss the issues that remain to be addressed in this field. The exploration of neural regulation on OTM not only assists us to understand the mechanism of OTM more thoroughly, but also provides a new insight to accelerate tooth movement in the future.

Apolipoprotein E is an effective biomarker for orthodontic tooth movement in patients treated with transmission straight wire appliances.

INTRODUCTION: Orthodontic tooth movement (OTM) is the core component of orthodontic treatment and is increasingly popular for treating malocclusions. In this study, we aimed to investigate the role of apolipoprotein E (ApoE) in OTM. METHODS: Thirty patients treated with transmission straight wire technology were selected and longitudinally tracked at 2 different stages of orthodontic treatment (initial 2 months and 12 months of orthodontic treatment). Total saliva was collected and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Western blotting was used to detect the difference in ApoE expression in the saliva samples of the 2 groups. The expression of ApoE was further verified by immunohistochemical staining in a mouse model of tooth movement. RESULTS: The results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry showed significant differences in the components of the salivary peptides in the 2 groups and peptides with a molecular weight of 2010.7 Da were predicted to be ApoE by database analysis. Western blotting further verified a significant difference in the expression of salivary ApoE in the 2 groups. In addition, an OTM model was successfully constructed in mice. The immunohistochemical staining results showed that ApoE expression significantly increased after force loading in the OTM model. CONCLUSIONS: This study indicated that ApoE participated in and played a role during OTM in patients treated with transmission straight wire technology. This relationship might be related to alveolar bone reconstruction and root resorption. The results provide new ideas for research on the mechanism of tooth movement using precision medicine based on saliva detection.

A hierarchical bilayer architecture for complex tissue regeneration.

Engineering a complete, physiologically functional, periodontal complex structure remains a great clinical challenge due to the highly hierarchical architecture of the periodontium and coordinated regulation of multiple growth factors required to induce stem cell multilineage differentiation. Using biomimetic self-assembly and microstamping techniques, we construct a hierarchical bilayer architecture consisting of intrafibrillarly mineralized collagen resembling bone and cementum, and unmineralized parallel-aligned fibrils mimicking periodontal ligament. The prepared biphasic scaffold possesses unique micro/nano structure, differential mechanical properties, and growth factor-rich microenvironment between the two phases, realizing a perfect simulation of natural periodontal hard/soft tissue interface. The interconnected porous hard compartment with a Young's modulus of 1409.00 ± 160.83 MPa could induce cross-arrangement and osteogenic differentiation of stem cells in vitro, whereas the micropatterned soft compartment with a Young's modulus of 42.62 ± 4.58 MPa containing abundant endogenous growth factors, could guide parallel arrangement and fibrogenic differentiation of stem cells in vitro. After implantation in critical-sized complete periodontal tissue defect, the biomimetic bilayer architecture potently reconstructs native periodontium with the insertion of periodontal ligament fibers into newly formed cementum and alveolar bone by recruiting host mesenchymal stem cells and activating the transforming growth factor beta 1/Smad3 signaling pathway. Taken together, integration of self-assembly and microstamping strategies could successfully fabricate a hierarchical bilayer architecture, which exhibits great potential for recruiting and regulating host stem cells to promote synergistic regeneration of hard/soft tissues.

Force-Induced Autophagy in Periodontal Ligament Stem Cells Modulates M1 Macrophage Polarization via AKT Signaling.

Autophagy, a lysosomal degradation pathway, serves as a protective cellular mechanism in maintaining cell and tissue homeostasis under mechanical stimulation. As the mechanosensitive cells, periodontal ligament stem cells (PDLSCs) play an important role in the force-induced inflammatory bone remodeling and tooth movement process. However, whether and how autophagy in PDLSCs influences the inflammatory bone remodeling process under mechanical force stimuli is still unknown. In this study, we found that mechanical force stimuli increased the expression of the autophagy protein LC3, the number of M1 macrophages and osteoclasts, as well as the ratio of M1/M2 macrophages in the compression side of the periodontal ligament in vivo. These biological changes induced by mechanical force were repressed by the application of an autophagy inhibitor 3-methyladenine. Moreover, autophagy was activated in the force-loaded PDLSCs, and force-stimulated PDLSC autophagy further induced M1 macrophage polarization in vitro. The macrophage polarization could be partially blocked by the administration of autophagy inhibitor 3-methyladenine or enhanced by the administration of autophagy activator rapamycin in PDLSCs. Mechanistically, force-induced PDLSC autophagy promoted M1 macrophage polarization via the inhibition of the AKT signaling pathway. These data suggest a novel mechanism that force-stimulated PDLSC autophagy steers macrophages into the M1 phenotype via the AKT signaling pathway, which contributes to the inflammatory bone remodeling and tooth movement process.

Functional regeneration and repair of tendons using biomimetic scaffolds loaded with recombinant periostin.

Tendon injuries disrupt the balance between stability and mobility, causing compromised functions and disabilities. The regeneration of mature, functional tendons remains a clinical challenge. Here, we perform transcriptional profiling of tendon developmental processes to show that the extracellular matrix-associated protein periostin (Postn) contributes to the maintenance of tendon stem/progenitor cell (TSPC) functions and promotes tendon regeneration. We show that recombinant periostin (rPOSTN) promotes the proliferation and stemness of TSPCs, and maintains the tenogenic potentials of TSPCs in vitro. We also find that rPOSTN protects TSPCs against functional impairment during long-term passage in vitro. For in vivo tendon formation, we construct a biomimetic parallel-aligned collagen scaffold to facilitate TSPC tenogenesis. Using a rat full-cut Achilles tendon defect model, we demonstrate that scaffolds loaded with rPOSTN promote endogenous TSPC recruitment, tendon regeneration and repair with native-like hierarchically organized collagen fibers. Moreover, newly regenerated tendons show recovery of mechanical properties and locomotion functions.

Mesenchymal Stem Cell-Derived Exosome Therapy of Microbial Diseases: From Bench to Bed.

Microbial diseases are a global health threat, leading to tremendous casualties and economic losses. The strategy to treat microbial diseases falls into two broad categories: pathogen-directed therapy (PDT) and host-directed therapy (HDT). As the typical PDT, antibiotics or antiviral drugs directly attack bacteria or viruses through discerning specific molecules. However, drug abuse could result in antimicrobial resistance and increase infectious disease morbidity. Recently, the exosome therapy, as a HDT, has attracted extensive attentions for its potential in limiting infectious complications and targeted drug delivery. Mesenchymal stem cell-derived exosomes (MSC-Exos) are the most broadly investigated. In this review, we mainly focus on the development and recent advances of the application of MSC-Exos on microbial diseases. The review starts with the difficulties and current strategies in antimicrobial treatments, followed by a comprehensive overview of exosomes in aspect of isolation, identification, contents, and applications. Then, the underlying mechanisms of the MSC-Exo therapy in microbial diseases are discussed in depth, mainly including immunomodulation, repression of excessive inflammation, and promotion of tissue regeneration. In addition, we highlight the latest progress in the clinical translation of the MSC-Exo therapy, by summarizing related clinical trials, routes of administration, and exosome modifications. This review will provide fundamental insights and future perspectives on MSC-Exo therapy in microbial diseases from bench to bedside.

Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4.

OBJECTIVES: Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear. MATERIALS AND METHODS: An animal model of force-induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting. RESULTS: Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force-stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force-induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling. CONCLUSIONS: Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement.

Correlations between objective measurements and subjective evaluations of facial profile after orthodontic treatment.

OBJECTIVE: To investigate the correlations between objective measurements and subjective evaluations of post-treatment facial attractiveness. METHODS: Ten orthodontists rated the subjective visual analog scale (VAS) scores of the facial profiles of 95 patients who had undergone orthodontic treatment. Post-treatment cephalograms and photographs were used. Eleven soft tissue measurements and eight maxillary incisor measurements were constructed and analyzed. Correlations between objective measurements and subjective VAS scores were evaluated using Pearson correlation and quadratic regression analysis. RESULTS: The VAS scores of different facial proportions were all correlated with the total VAS score. Among soft tissue measurements, the distances from the upper and lower lips to the E line, H angle, forehead inclination, distance from lower lip to the H line, and pogonion-menton angle were negatively correlated with the VAS scores. The Z angle, with a parabolic distribution, was also correlated with the VAS scores. Among maxillary incisor measurements, the distance from the maxillary incisors to the forehead's anterior limit line and the angulation of the maxillary incisors to the APo line were negatively correlated with the VAS scores. CONCLUSIONS: Several soft tissue and maxillary incisor position measurements were correlated with facial profile evaluation and therefore might be used to evaluate facial attractiveness.

Effects of the multifunctional hormone leptin on orthodontic tooth movement in rats.

This study aims to investigate the effects of leptin, which is a multifunctional hormone, on orthodontic tooth movement (OTM) and the underlying mechanism. Sprague-Dawley rat OTM models were established and divided into two groups with the administration of vehicle or leptin respectively. Stereomicroscope and microcomputed tomography were used to evaluate the amount of OTM. TRAP staining, immunohistochemical and immunofluorescence staining were used to detect osteoclasts and relative protein expressions. After treated with compression force, human periodontal ligament cells (hPDLCs) were co-cultured with human peripheral blood mononuclear cells (hPBMCs) with the presence or absence of leptin. Small interfering RNA (siRNA) was transfected to knock down the leptin receptor (LepR). The mRNA expressions of the targeted genes were evaluated by quantitative real-time polymerase chain reaction. We found that leptin receptors were expressed on both rat periodontal ligament cells and hPDLCs. OTM was significantly attenuated in the leptin-treated group comparing to the control group. The number of osteoclasts was reduced in the periodontal ligament tissues in vivo and in vitro co-cultured system when treated with leptin. The expression of RANKL was inhibited by leptin administration either in vivo and in vitro. Leptin administration also inhibited the force-induced up-regulation of RANKL expression in hPDLCs, which was rescued by LepR siRNA transfection. The osteoclastogenesis was attenuated by leptin administration which was reversed by the LepR siRNA transfection. Taken together, leptin was able to attenuate OTM by inhibiting osteoclastogenesis which can be attributed to the reduced expression of RANKL in the periodontal ligament. Leptin may possess the potential for reinforcing anchorage clinically.

Mechanical load-induced H2S production by periodontal ligament stem cells activates M1 macrophages to promote bone remodeling and tooth movement via STAT1.

BACKGROUND: Tooth movement is a unique bone remodeling process induced by mechanical stimulation. Macrophages are important in mediating inflammatory processes during mechanical load-induced tooth movement. However, how macrophages are regulated under mechanical stimulation remains unclear. Mesenchymal stem cells (MSCs) can modulate macrophage polarization during bone remodeling. Hydrogen sulfide (H2S) can be produced by MSCs and have been linked to bone homeostasis. Therefore, this study aimed to investigate whether H2S contributed to periodontal ligament stem cell (PDLSC)-regulated macrophage polarization and bone remodeling under mechanical stimulation. METHODS: An experimental mechanical load-induced tooth movement animal model was established. Changes in cystathionine-ß-synthase (CBS), markers of M1/M2 macrophages, tooth movement distance, and the number of osteoclasts were examined. The conditioned medium of PDLSCs with or without mechanical loading was utilized to treat THP-1 derived macrophages for 24 h to further investigate the effect of PDLSCs on macrophage polarization. Different treatments with H2S donor, CBS inhibitor, or the inhibitor of STAT1 were used to investigate the related mechanism. Markers of M1/M2 polarization and STAT1 pathway expression were evaluated in macrophages. RESULTS: Mechanical load promoted tooth movement and increased the number of M1-like macrophages, M1-associated pro-inflammatory cytokines, and the expression of CBS on the compression side of the periodontal ligament. The injection of CBS inhibitor or H2S donor could further repress or increase the number of M1-like macrophages, tartrate-resistant acid phosphatase-positive osteoclasts and the distance of tooth movement. Mechanistically, load-induced PDLSCs enhanced H2S production, which increased the expression of M1-associated cytokines in macrophages. These effects could be blocked by the administration of CBS inhibitor. Moreover, load-induced H2S steered M1 macrophage polarization via the STAT1 signaling pathway. CONCLUSIONS: These data suggest a novel mechanism indicating that mechanical load-stimulated PDLSCs produce H2S to polarize macrophages toward the M1 phenotype via the STAT1 signaling pathway, which contributes to bone remodeling and tooth movement process. These results provide new insights into the role of PDLSCs in regulating macrophage polarization and mediating bone remodeling under mechanical stimulation, and indicate that appropriate H2S supplementation may accelerate tooth movement.

CD4+ T cells and TGFß1/MAPK signal pathway involved in the valvular hyperblastosis and fibrosis in patients with rheumatic heart disease.

The aim of this study was to investigate the roles of CD4+ T cells and transforming growth factor beta (TGFß1) in the pathological process of valvular hyperblastosis and fibrosis of patients with rheumatic heart disease (RHD). A total of 151 patients were enrolled, among whom, 78 patients were with RHD, and 73 were age and gender matched RHD negative patients. Blood samples and valve specimens were collected for analysis. Pathological changes and collagen fibers contents of valves were analyzed using HE and Masson staining. Percentage of peripheral blood CD4+ T cells was tested through flow cytometry. TGFß1 level in serum were identified by ELISA. CD4+ T cells infiltration and expression of TGFß1, p-p38, p-JNK, p-ERK in valves were detected by immunohistochemistry. The mRNA and protein levels of p38, JNK, ERK, TGFß1, I-collagen and α-SMA were detected by qRT-PCR and western blotting, respectively. The heart valve tissues of RHD patients showed higher degrees of fibrosis, calcification and lymphocytes infiltration, which were mainly CD4+ T cells. In addition, compared with control group, RHD patients had more total CD4+ T cells in peripheral blood and valve tissues. Expression of TGFß1, phosphorylation of JNK and p38, and synthesis of I-collagen in valve tissues of RHD patients were also significantly increased. Furthermore, we found a strong positive correlation between TGFß1 expression and phosphorylation of JNK and p38. CD4+ T cells, and fibrogenic cytokine TGFß1, which activate the intracellular MAPK signaling pathway may participate in the fibrosis of heart valve in RHD patients.

Diagnosis of liver fibrosis in patients with hepatitis B-related liver disease using ultrasound with wave-number domain attenuation coefficient.

BACKGROUND/AIMS: The importance of identifying the stage of liver fibrosis has motivated the development of non-invasive methods. This study aimed to evaluate the applicability of ultrasound analysis involving the wave-number domain attenuation coefficient (W-Ac) in the non-invasive quantitative differentiation of liver fibrosis. MATERIALS AND METHODS: This was a prospective study of inpatients with hepatitis B-related liver disease treated between October 2016 and January 2018. In ultrasound, the echo from the near-field liver tissue was selected as the reference signal. The W-Ac of liver tissues was based on the fast Fourier transform of the acquired post-beamforming radio frequency signals. These values were compared with fibrosis from biopsy METAVIR score results. A receiver operating characteristic (ROC) curve tested the W-Ac method. RESULTS: A total of 46 patients were enrolled, including 27 males and 19 females. Fibrosis was stage F0 in 12 patients, F1 in 13 patients, F2 in 10 patients, F3 in 7 patients, and F4 in 4 patients. W-Ac increased with the progression of liver fibrosis up to stage F3. There were differences between F0 and F4 stages (p<0.001) and between any 2 stages of fibrosis (p<0.05), except for stages F3 and F4. There was a significant correlation between W-Ac and METAVIR score (r=0.795, p<0.001). W-Ac differed between non-fibrosis (F0) and fibrosis (F1-F4) groups (p<0.001) and in the normal (F0), early fibrosis (F1-2), and late fibrosis groups (F3-4) (p<0.001). ROC area under the curve was 0.890, and at a cut-off of 0.12153, sensitivity was 0.706 and specificity was 0.830. CONCLUSIONS: W-Ac allowed assessment of liver fibrosis in clinical practice.