A novel classification of lateral malleolus morphological characteristics based on three-dimensional computed tomography reconstruction.

BACKGROUND: The study was to establish a novel classification of the morphological characteristics of fibula anterior-inferior margin (FAIM), which was reported in few studies. METHODS: The 501 images with three-dimensional computed tomography (3D CT) reconstruction were reviewed retrospectively. The width, height, thickness, long axis, short axis, and lateral malleolus angle were measured. RESULTS: The FAIM was divided into Angular, Flat, and Arc. The Flat has no distinct fibular obscure tubercles (FOT). The short axis of Angular and Arc were more significant than the Flat (P < 0. 05). The height of left was larger than the right, but short axis was less than it (P < 0.05). The height and short axis of males were larger than the females (P < 0.05). CONCLUSIONS: A novel classification (the Angular, Flat and Arc) of FAIM was identified based on lateral malleolus morphology, and it suggested that not all have obvious FOT. LEVEL OF EVIDENCE: Level Ⅲ, retrospective study.

Anterior Talofibular Ligament Repair in Combination With Anterior Tibiofibular Ligament Distal Fascicle Transfer for The Treatment of Chronic Lateral Ankle Instability: A Finite Element Analysis.

In recent years, anterior tibiofibular ligament-distal fascicle transfers for anterior talofibular ligament augmentation repair have proposed. However, a comprehensive biomechanical study on the anterior tibiofibular ligament-distal fascicle transfer is still lacking. We are established four distinct groups, namely the normal, the anterior talofibular ligament rupture, the anterior talofibular ligament repair, and the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer. We assessed the anterior drawer test and varus stress test of the ankle in each group. Moreover, we employed the model to simulate and compute the total displacement and von-Mises stress of the talus cartilage at varying gait phases, including foot strike, tibia vertical, and toe-off phases. The results of the anterior drawer test and varus stress test revealed that the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group exhibited greater closeness to the normal group. Regarding von-Mises stress in cartilage, the three gait instants had higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Nevertheless, regarding total displacement, the toe-off phases exhibited higher values in the anterior talofibular ligament repair + anterior tibiofibular ligament-distal fascicle transfer group than the other groups. Using ATiFL-DF transfer to augment ATFL repair is a potential feasible procedure. However, this procedure could potentially compromise the anterior tibiofibular ligament's contribution to the dynamic stability of the ankle. Therefore, we recommend conducting further in-depth research to ensure the suitability and success of this technique in a clinical environment.

Three-dimensional Mapping Analysis of Talus Fractures and Demonstration of Different Surgical Approaches for Talus Fractures.

OBJECTIVE: The talus is an important component in the ankle, and its treatment after injury is crucial. However, complications and adverse events due to incomplete traditional classifications may still occur, and these classifications fail to analyze the patterns and distribution of fractures from a three-dimensional perspective. Therefore, in this study, we aimed to analyze the location and distribution of fracture lines in different types of talus fractures using three-dimensional (3D) and heat mapping techniques. Additionally, we aimed to determine the surface area of the talus that can be utilized for different approaches of internal fixation, aiding in the planning of surgical procedures. METHODS: We retrospectively analyzed data from CT scans from 126 patients diagnosed with talus fractures at our two hospitals. We extracted the CT data of a healthy adult and created a standard talus model. We performed 3D reconstruction using patients' CT images and superimposed the fracture model onto the standard model for drawing fracture lines. Subsequently, we converted the fracture lines into a heat map for visualization. Additionally, we measured 20 specimens to determine the boundary for various ligaments attached to the talus. We determined the surface area of the talus available for different surgical approaches by integrating the boundary data with previously reported data on area of exposure. RESULTS: Without considering the displacement distance of the fracture, fracture types were classified as follows, by combining Hawkins and Sneppen classifications: talar neck, 41.3%; posterior talar tubercle, 22.2%; body for the talus and comminuted, 17.5%; lateral talar tubercle, 11.9%; and talar head, 7.1%. We established fracture line and heat maps using this classification. Additionally, we demonstrated the available area for anteromedial, anterolateral, posteromedial, posterolateral, and medial malleolus osteotomy and Chaput osteotomy approaches. CONCLUSION: Fracture line and heat map analyses can aid surgeons in planning a single or combined surgical approach for the reduction and internal fixation of talus fractures. Demonstrating the different surgical approaches can help surgeons choose the most effective technique for individual cases.

Chronic lateral ankle instability using anterior tibiofibular ligament distal fascicle transfer augmentation repair: an anatomical, biomechanical, and histological study.

Background: The transfer of the anterior tibiofibular ligament distal fascicle (ATiFL-DF) for the augmentation repair of the anterior talofibular ligament (ATFL) shows potential as a surgical technique. However, evidences on the benefits and disadvantages of this method in relation to ankle joint function are lacking. Purpose: This study aimed to provide comprehensive experimental data to validate the feasibility of ATiFL-DF transfer augmentation repair of the ATFL. Methods: This study included 50 embalmed ankle specimens to measure various morphological features, such as length, width, thickness, and angle, for evaluating similarities between the ATiFL-DF and ATFL. Furthermore, 24 fresh-frozen ankle specimens were examined for biomechanical testing of the ATiFL-DF transfer augmented repair of the ATFL. Finally, 12 pairs of ATiFL-DF and ATFL tissues from fresh-frozen ankle specimens were treated with gold chloride staining to analyze mechanoreceptor densities. Results: Anatomical studies found that the lengths and thicknesses of the ATFL and ATiFL-DF are similar. Biomechanical outcomes showed that performing ATiFL-DF transfer for ATFL repair can improve the stability of the talus and ankle joints. This is evident from the results of the anterior drawer, axial load, and ultimate failure load tests. However, performing ATiFL-DF transfer may compromise the stability of the distal tibiofibular joint, based on the Cotton and axial load tests at an external rotation of 5°. Analysis of the histological findings revealed that mechanoreceptor densities for four types of mechanoreceptors were comparable between the ATiFL-DF and ATFL groups. Conclusion: ATiFL-DF transfer is a viable method for augmenting ATFL repair. This technique helps to improve the stability of the talus and ankle joints while compensating for proprioception loss. Although ATiFL-DF transfer augmented repair of the ATFL may negatively affect the stability of the distal tibiofibular joint, this procedure can enhance the stability of the talus and ankle joints.

The morphology of osseous structure in subtalar joint with chronic ankle instability.

BACKGROUND: Osseous structures have been demonstrated as risk factors for chronic ankle instability (CAI). Previously, the researchers only focused on the osseous structures of ankle, but ignored the osseous structures of subtalar joint(STJ). Accordingly, the aim of our study was to investigate the morphological characteristics of STJ osseous structures in CAI. METHODS: 52 patients with CAI and 52 sex- and age- matched control subjects were enrolled from The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University. The lateral radiographs of ankle in weight-bearing were used to compare the diversity of the two groups. Specifically, The Length of calcaneus, Calcaneal facet height and Absolute foot height, Böhler's angle, Gissane's angle, Calcaneal inclination angle, Talocalcaneal angle, Tibiotalar angle, Tibiocalcaneal angle, Talar-horizontal angle, talar declination angle, facet inclination angle were gauged in the two groups. RESULTS: The Böhler's angle, Calcaneal inclination, Talocalcaneal angle, Tibiotalar angle, Talar-horizontal angle, Talar declination angle, Facet inclination angle and Absolute foot height of CAI group were significantly higher than normal control group (P < 0.05). There were no significant differences in Gissane's angle, Tibiocalcaneal angle, Length of calcaneus and Calcaneal facet height between patients with CAI and normal controls (P > 0.05). CONCLUSIONS: The osseous structures of STJ in CAI patients are different from normal people in morphology. Therefore, we should pay more attention to the changes of STJ anatomical parameters in the diagnosis and prevention of CAI. LEVEL OF EVIDENCE: Ⅲ.

The role of AMPK in macrophage metabolism, function and polarisation.

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.

Xanthohumol alleviates palmitate-induced inflammation and prevents osteoarthritis progression by attenuating mitochondria dysfunction/NLRP3 inflammasome axis.

Osteoarthritis (OA) is a prevalent chronic degenerative joint disease worldwide. Obesity has been linked to OA, and increased free fatty acid levels (e.g., palmitate) contribute to inflammatory responses and cartilage degradation. Xanthohumol (Xn), a bioactive prenylated chalcone, was shown to exhibit antioxidative, anti-inflammatory, and anti-obesity capacities in multiple diseases. However, a clear description of the preventive effects of Xn on obesity-associated OA is unavailable. This study aimed to assess the chondroprotective function of Xn on obesity-related OA. The in vitro levels of inflammatory and ECM matrix markers in human chondrocytes were assessed after the chondrocytes were treated with PA and Xn. Additionally, in vivo cartilage degeneration was assessed following oral administration of HFD and Xn. This study found that Xn treatment completely reduces the inflammation and extracellular matrix degradation caused by PA. The proposed mechanism involves AMPK signaling pathway activation by Xn, which increases mitochondrial biogenesis, attenuates mitochondrial dysfunction, and inhibits NLRP3 inflammasome and the NF-κB signaling pathway induced by PA. In summary, this study highlights that Xn could decrease inflammation reactions and the degradation of the cartilage matrix induced by PA by inhibiting the NLRP3 inflammasome and attenuating mitochondria dysfunction in human chondrocytes.

The safe zone of distal fibula was determined based on the classification of lateral malleolus fossa.

BACKGROUND: Lateral malleolus fractures are very common, and the distal fibular geometry is complex. This study aimed to classify the lateral malleolus fossa (MF) into different types by characterizing the lateral MF imaging morphology and exploring the relationship between the lateral MF and internal fixation position after distal fibula fractures. METHODS: Anteroposterior CT reconstruction was performed on 248 subjects. After reconstruction, the deepest point of the lateral MF was located, and then, the cross-sectional shape of the lateral MF was observed and classified. RESULTS: According to the morphology of the CT cross section, the lateral MF was divided into three types: type C (43.1%), type V (32.2%), and type Flat (24.7%). Type V (3.98 ± 0.82) was significantly longer than type C(2.83 ± 0.54) and type Flat (1.84 ± 0.42) in cd. Similarly, in ∠α, Type Flat(136.31 ± 9.63) was the largest, followed by type C (116.51 ± 8.79), and type V (89.31 ± 9.07) was the smallest. Other measurements were not found any significant differences between the above. CONCLUSION: According to the morphology of the CT cross section, the lateral MF was divided into three types: type C, type V and type Flat. Type V is most likely to be invaded when fixing the distal fibula. Screws less than 9 mm should be selected when fixing, and screws no more than 10 mm should be selected when there are type C and type Flat of MF.

The Functions and Mechanisms of Tendon Stem/Progenitor Cells in Tendon Healing.

Tendon injury is one of the prevalent disorders of the musculoskeletal system in orthopedics and is characterized by pain and limitation of joint function. Due to the difficulty of spontaneous tendon healing, and the scar tissue and low mechanical properties that usually develops after healing. Therefore, the healing of tendon injury remains a clinical challenge. Although there are a multitude of approaches to treating tendon injury, the therapeutic effects have not been satisfactory to date. Recent studies have shown that stem cell therapy has a facilitative effect on tendon healing. In particular, tendon stem/progenitor cells (TSPCs), a type of stem cell from tendon tissue, play an important role not only in tendon development and tendon homeostasis, but also in tendon healing. Compared to other stem cells, TSPCs have the potential to spontaneously differentiate into tenocytes and express higher levels of tendon-related genes. TSPCs promote tendon healing by three mechanisms: modulating the inflammatory response, promoting tenocyte proliferation, and accelerating collagen production and balancing extracellular matrix remodeling. However, current investigations have shown that TSPCs also have a negative effect on tendon healing. For example, misdifferentiation of TSPCs leads to a "failed healing response," which in turn leads to the development of chronic tendon injury (tendinopathy). The focus of this paper is to describe the characteristics of TSPCs and tenocytes, to demonstrate the roles of TSPCs in tendon healing, while discussing the approaches used to culture and differentiate TSPCs. In addition, the limitations of TSPCs in clinical application and their potential therapeutic strategies are elucidated.

The mechanisms and functions of TGF-ß1 in tendon healing.

Tendon injury accounts for 30% of musculoskeletal diseases and often leads to disability, pain, healthcare cost, and lost productivity. Following injury to tendon, tendon healing proceeds via three overlapping healing processes. However, due to the structural defects of the tendon itself, the tendon healing process is characterized by the formation of excessive fibrotic scar tissue, and injured tendons rarely return to native tendons, which can easily contribute to tendon reinjury. Moreover, the resulting fibrous scar is considered to be a precipitating factor for subsequent degenerative tendinopathy. Despite this, therapies are almost limited because underlying molecular mechanisms during tendon healing are still unknown. Transforming Growth Factor-ß1 (TGF-ß1) is known as one of most potent profibrogenic factors during tendon healing process. However, blockage TGF-ß1 fails to effectively enhance tendon healing. A detailed understanding of real abilities of TGF-ß1 involved in tendon healing can bring promising perspectives for therapeutic value that improve the tendon healing process. Thus, in this review, we describe recent efforts to identify and characterize the roles and mechanisms of TGF-ß1 involved at each stage of the tendon healing and highlight potential roles of TGF-ß1 leading to the fibrotic response to tendon injury.

Association between the distal tibiofibular syndesmosis morphology classification and ankle osteoarthritis: a retrospective study.

BACKGROUND: Syndesmosis injury is proposed to contribute to ankle stability and osteoarthritis (OA). However, whether distal tibiofibular syndesmosis structure is closely related to ankle OA is unclear. We hypothesized that different DTS morphology classifications would affect the biomechanics properties in ankle OA. The study aimed to determine the association between the distal tibiofibular syndesmosis (DTS) morphological classification and ankle OA. METHODS: This is a retrospective study examining imaging data of 147 patients (87 males and 60 females) with ankle OA. Magnetic resonance imaging was used to access the DTS morphological classification, according to measuring various parameters. Joint space narrowing and osteophytes were measured using ankle weight-bearing radiography. The classification and parameters were analyzed to determine the relationship between the syndesmosis classification and the abnormality of ankle OA. RESULTS: Five morphological classifications of the DTS, including Chevron (19.6%), Widow's peak (16.2%), Flat (22.3%), Trapezoid (32.0%), and Crescent (19.6%), were shown. There were statistical differences between DTS classification and tibial angle surface angle (TAS) (P = .009) and talar tilt angle (TTA) (P = .014). The TAS (degree) of the Crescent (86.47 ± 3.21) was less than Chevron (88.75 ± 2.72) (P = .006), Widow's peak (89.26 ± 3.15) (P = .001), Flat (88.83 ± 3.62) (P = .003) and Trapezoid (88.11 ± 2.62) (P = .041), respectively. The TTA (degree) of Crescent (86.83 ± 5.30) was less than Chevron (89.28 ± 2.46) and Widow's peak (89.82 ± 3.41). The men were greater than women for TAS (P = .008) and angle (P = .003), which are consistent with osteophyte (P = .019) and the modified Kellgren-Lawrence grades (P = .041) between gender. CONCLUSIONS: DTS morphological classification might affect the biomechanics properties in TAS and TTA in ankle OA. In clinical practice, surgeons should pay attention to the effects of DTS on ankle OA. LEVEL OF EVIDENCE: Level III, retrospective study.

In Different Gender Groups, What Is the Impact of the Fibular Notch on the Severity of High Ankle Sprain: A Retrospective Study of 360 Cases.

OBJECTIVES: The role of the distal tibiofibular ligament in the occurrence of high ankle sprain (HAS) has been widely studied. But previous studies have overlooked the physiological and anatomical differences between males and females and have not further refined gender. Therefore, the impact of the anatomical morphology of fibular notch (FN) on HAS in different genders is still unclear. This study aimed to explore the impact of different types of FN on the severity of HAS and to estimate the prognosis of patients with HAS while excluding anatomical differences caused by gender. METHODS: One hundred and eighty patients with HAS were included in this study as the experimental group (i.e., HAS group). They were further divided into four groups according to gender and FN depth, with deep concave FN ≥ 4 mm and shallow flat FN < 4 mm. Another 180 normal individuals were set as the control group. The FN morphological indicators, tibiofibular distance (TFD), and ankle mortise indexes were measured and compared with those in HAS group. The independent t-test was used to compare continuous variables between groups, the intraclass correlation coefficient (ICC) was used to analyze the reliability of intra-observer measurement, and the Pearson correlation coefficient was used to verify the correlation between FN and the severity of HAS. RESULTS: In males with shallow flat type, the measurements of anterior tibiofibular distance (aTFD), middle tibiofibular distance (mTFD), posterior tibiofibular distance (pTFD), front ankle mortise width (fAMW), middle ankle mortise width (mAMW), posterior ankle mortise width (pAMW), and depth of ankle mortise (DOAM) in HAS group were significantly larger than those in normal group (p < 0.05). In male patients with deep concave type, the measurements of aTFD, mTFD, fAMW, mAMW, and DOAM were significantly larger than those in normal group (p < 0.05). Among female patients with shallow flat type, the measurements of aTFD, mTFD, pTFD, fAMW, mAMW, pAMW, and DOAM were found to be significantly larger than those in normal group (p < 0.05). Among female patients with deep concave type, the measurements of mTFD, pTFD, fAMW, mAMW, and DOAM were found to be significantly larger than those of the normal group (p < 0.05). The depth of FN was negatively correlated with TFD, and the AOFAS score of patients with shallow flat type was significantly lower than that of patients with deep concave type after treatment (p < 0.05). CONCLUSIONS: In different gender groups, compared with the normal controls, the TFD and partial ankle mortise indices were significantly different in HAS patients. Moreover, FN depth was negatively correlated with TFD, and the AOFAS score of shallow flat patients was significantly lower than that of deep concave patients. These suggested that shallow flat FN may be associated with more severe distal tibiofibular ligament injury and ankle mortise widening, leading to poorer prognosis. This should be taken seriously in clinical practice.

Research Progress on the Pathogenesis of Knee Osteoarthritis.

Knee osteoarthritis (KOA) is a chronic joint bone disease characterized by inflammatory destruction and hyperplasia of bone. Its main clinical symptoms are joint mobility difficulties and pain, severe cases can lead to limb paralysis, which poses major pressure to the quality of life and mental health of patients, but also brings serious economic burden to society. The occurrence and development of KOA is influenced by many factors, including systemic factors and local factors. The joint biomechanical changes caused by aging, trauma and obesity, abnormal bone metabolism caused by metabolic syndrome, the effects of cytokines and related enzymes, genetic and biochemical abnormalities caused by plasma adiponectin, etc. all directly or indirectly lead to the occurrence of KOA. However, there is little literature that systematically and comprehensively integrates macro- and microscopic KOA pathogenesis. Therefore, it is necessary to comprehensively and systematically summarize the pathogenesis of KOA in order to provide a better theoretical basis for clinical treatment.

The increased anterior talofibular ligament-posterior talofibular ligament angle on MRI may help evaluate chronic ankle instability.

PURPOSE: This study intended to compare the difference between the anterior talofibular ligament (ATFL) and posterior talofibular ligament (PTFL) angle with chronic ankle instability (CAI) patients and healthy volunteers, and to confirm whether using the ATFL-PTFL angle could be a reliable assessment method for CAI, so as to improve the accuracy and specificity of clinical diagnosis. METHODS: This retrospective study included 240 participants: 120 CAI patients and 120 healthy volunteers between 2015 and 2021. The ATFL-PTFL angle of the ankle region was gaged in the cross-sectional supine position on MRI between two groups. After participants undergoing a comprehensive MRI scanning, ATFL-PTFL angles were regarded as the main indicator of patients with the injured ATFLs and healthy volunteers to compare, and were measured by an experienced musculoskeletal radiologist. Moreover, other qualitative and quantitative indicators referring to anatomical and morphological characteristics of the AFTL were included in this study with MRI, such as the length, width, thickness, shape, continuity, and signal intensity of the ATFL, which can be used as secondary indicators. RESULTS: In the CAI group, the ATFL-PTFL angle was 90.8° ± 5.7°, which was significantly different from the non-CAI group where the ATFL-PTFL angle for 80.0° ± 3.7° (p < 0.001). As for the ATFL-MRI characteristics, the length (p = 0.003), width (p < 0.001), and thickness (p < 0.001) in the CAI group were also significantly different from the non-CAI group. Over 90% of the cases, patients of the CAI group had injured ATFL with an irregular shape, non-continuous, and high or mixed signal intensity. CONCLUSION: Compared with healthy people, the ATFL-PTFL angle of most CAI patients is larger, which can be used as a secondary index to diagnose CAI. However, the MRI characteristic changes of ATFL may not relate to the increased ATFL-PTFL angle.

Recent advances of exosomal circRNAs in cancer and their potential clinical applications.

Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed, uninterrupted loop. The expression of circRNA differs among cell types and tissues, and various circRNAs are aberrantly expressed in a variety of diseases, including cancer. Aberrantly expressed circRNAs contribute to disease progression by acting as microRNA sponges, functional protein sponges, or novel templates for protein translation. Recent studies have shown that circRNAs are enriched in exosomes. Exosomes are spherical bilayer vesicles released by cells into extracellular spaces that mediate intercellular communication by delivering cargoes. These cargoes include metabolites, proteins, lipids, and RNA molecules. Exosome-mediated cell-cell or cell-microenvironment communications influence the progression of carcinogenesis by regulating cell proliferation, angiogenesis, metastasis as well as immune escape. In this review, we summarize the current knowledge about exosomal circRNAs in cancers and discuss their specific functions in tumorigenesis. Additionally, we discuss the potential value of exosomal circRNAs as diagnostic biomarkers and the potential applications of exosomal circRNA-based cancer therapy.

miRNAs contributing to the repair of tendon injury.

Tendon injury is one of the most common disorders of the musculoskeletal system, with a higher likelihood of occurrence in elderly individuals and athletes. In posthealing tendons, two undesirable consequences, tissue fibrosis and a reduction in mechanical properties, usually occur, resulting in an increased probability of rerupture or reinjury; thus, it is necessary to propose an appropriate treatment. Currently, most methods do not sufficiently modulate the tendon healing process and restore the function and structure of the injured tendon to those of a normal tendon, since there is still inadequate information about the effects of multiple cellular and other relevant signaling pathways on tendon healing and how the expression of their components is regulated. microRNAs are vital targets for promoting tendon repair and can modulate the expression of biological components in signaling pathways involved in various physiological and pathological responses. miRNAs are a type of noncoding ribonucleic acid essential for regulating processes such as cell proliferation, differentiation, migration and apoptosis; inflammatory responses; vascularization; fibrosis; and tissue repair. This article focuses on the biogenesis response of miRNAs while presenting their mechanisms in tendon healing with perspectives and suggestions.

Cellular senescence - Molecular mechanisms of intervertebral disc degeneration from an immune perspective.

Intervertebral disc degeneration (IVDD) is a frequent and intractable chronic condition in orthopedics that causes enormous discomfort in patients' lives and thoughts, as well as a significant economic burden on society and the nation. As a result, understanding the pathophysiology of IVDD is critical. The pathophysiology of IVDD has been linked to numerous variables, including oxidative stress, apoptosis, matrix metalloproteinases, and inflammatory factors. Cellular senescence has recently attracted a lot of attention in the study of age-related diseases. It has been discovered that IVDD is intimately linked to human senescence, in which nucleus pulposus cell senescence may play a significant role. Previously, our group did a comprehensive and systematic clarification of the pathogenesis of IVDD from an immune perspective and discovered that the fundamental pathogenesis of IVDD is inflammatory upregulation and nucleus pulposus cell death caused by an imbalance in the immune microenvironment. In this review, we will treat nucleus pulposus cell senescence as a novelty point to clarify the pathophysiology of IVDD and further explore the probable relationship between senescence and immunity along with the dysregulation of the immunological microenvironment to propose new therapeutic approaches for IVDD.

The mechanisms and functions of IL-1ß in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the leading cause of low back pain (LBP) and disability in the elderly, imposing significant public health and economic burden worldwide. Meanwhile, the pathological mechanisms of IDD remain complicated, and treatment strategy to reverse IDD is primarily due to the unclear specific mechanisms of IDD and the lack of particular effective targets. Interleukin-1ß (IL-1ß), one of the most important members of the IL-1 family, can induce solid pro-inflammatory activity by stimulating the secretion of various pro-inflammatory mediators and is considered the key to IDD mediator. However, in recent years, IL-1ß is considered to be able to regulate IVD cell death in many ways, such as apoptosis, pyroptosis, ferroptosis, and so on. At the same time, numerous studies on IL-1ß inhibitors suggest that inhibition of IL-1ß may be a promising biological therapy for IDD. Many IL-1ß inhibitors have been investigated through various pathogenic biological mechanisms, including inhibiting inflammatory processes, regulating ECM degradation, and more. Therefore, anti-IL-1ß therapy may have the effect of alleviating disc degeneration. This article mainly reviews the mechanisms and functions of IL-1ß in IDD and investigates advances in IL-1ß inhibition as a promising biotherapeutic approach for disc degeneration.

A double-layered gastric floating tablet for zero-order controlled release of dihydromyricetin: Design, development, and in vitro/in vivo evaluation.

Dihydromyricetin (DHM) is an important natural flavonoid. However, most of DHM preparations have shown shortcomings such as low drug loading, poor drug stability, and/or large fluctuations in blood concentration. This study aimed to develop a gastric floating tablet with a double-layered structure for zero-order controlled release of DHM (DHM@GF-DLT). The final product DHM@GF-DLT showed a high average cumulative drug release at 24 h that best fit the zero-order model, and had a good floating ability in the stomach of the rabbit with a gastric retention time of over 24 h. The FTIR, DSC, and XRPD analyses indicated the good compatibility among the drug and the excipients in DHM@GF-DLT. The pharmacokinetic study revealed that DHM@GF-DLT could prolong the retention time of DHM, reduce the fluctuation of blood drug concentration, and enhance the bioavailability of DHM. The pharmacodynamic studies demonstrated that DHM@GF-DLT had a potent and long-term therapeutic effect on systemic inflammation in rabbits. Therefore, DHM@GF-DLT had the potential to serve as a promising anti-inflammatory agent and may develop into a once-a-day preparation, which was favorable to maintain a steady blood drug concentration and a long-term drug efficacy. Our research provided a promising development strategy for DHM and other natural products with a similar structure to DHM for improving their bioavailability and therapeutic effect.

The mechanisms and functions of TNF-α in intervertebral disc degeneration.

Low back pain (LBP) is one of the most common health problems in people's lives, which brings a massive burden to clinicians, and the leading cause of LBP is intervertebral disc degeneration (IDD). IDD is mainly caused by factors such as aging, mechanical stress, and lack of nutrition. The pathological mechanism of IDD is very complex, involving inflammatory response, cell metabolism disorder, and so on. Unfortunately, in the current treatment of IDD, only relieving symptoms as the primary means of relieving a patient's pain cannot effectively inhibit or reverse the progression of IDD. Tumor necrosis factor-α (TNF-α) is a multifunctional pro-inflammatory factor involved in many diseases' pathological processes. With the in-depth study of the pathological mechanism of IDD, more and more evidence has shown that TNF-α is an essential activator of IDD, which is related to the metabolic disorder, inflammatory responses, apoptosis, and other pathological processes of extracellular dissociation in the intervertebral disc. Therefore, anti-TNF-α therapy is an effective therapeutic target for alleviating IDD, especially in inhibiting extracellular matrix degradation and reducing inflammatory responses. This article reviews the pathological role of TNF-α in IDD and the latest research progress of TNF-α inhibitors in treating IDD.