Radiological characteristics and injury mechanism of Logsplitter injury: a descriptive and retrospective study.

BACKGROUND: Logsplitter Injury is a type of high-energy ankle fracture dislocation. The mechanism of injury has not been described in detail. A detailed understanding of the radiological features and pathological changes can further guide treatment. METHODS: Between April 2009 and December 2018, a retrospective analysis was conducted on 62 patients with Logsplitter injury. The study analysed the characteristics of fibular injury, tibial injury, syndesmosis injury, medial injury and lateral ligament injury on preoperative X-ray and CT scans. The incidence of the different injury types was summarised. The correlation between Logsplitter injuries and the mechanisms causing them were analysed using the Lauge-Hansen classification of ankle fractures. RESULTS: The study provides data on the types of fractures observed. Of the total fractures, 98.4% were open fractures. The fibula injuries were classified as no fracture (1.6%), transverse or short oblique fractures (61.3%), butterfly fragments (25.8%), and comminuted fractures (11.3%). The tibial injuries included compression of lateral articular surfaces (38.7%) and posterior compressions (6.5%). Medial injuries, including medial malleolar fractures, accounted for 87.1%, and deltoid ligament rupture accounted for 12.9%. The study found that injuries to the syndesmosis consisted of simple ligament ruptures (11.3%), Tillaux fractures (8.1%), Volkmann fractures (43.5%), and Tillaux and Volkmann fractures (37.1%). In 12.9% of cases, there was a complete rupture of the lateral collateral ligament. Based on the Lauge-Hansen classification, 87.1% of injuries were pronation-abduction injuries, while 8.1% were pronation and external rotation injuries, and 1.6% were supination external rotation injuries. Furthermore, 3.2% of cases could not be classified. CONCLUSION: The pathoanatomic characteristics of Logsplitter injury are diverse, with some cases accompanied by collateral ligament injury. It is important to note that these evaluations are objective and based on current results. The most common injury mechanism is vertical violence combined with abduction, although in some cases, it may be a vertical combined external-rotation injury. LEVEL OF EVIDENCE: (4) case series. TRIAL REGISTRATION: This study has been approved by the ethical research committee of the Honghui Hospital of Xi'an Jiaotong University, under the code: 202,003,002.

Modified hindfoot alignment radiological evaluation and application in the assessment of flatfoot.

BACKGROUND: Alignment is indispensable for the foot and ankle function, especially in the hindfoot alignment. In the preoperative planning of patients with varus or valgus deformity, the precise measurement of the hindfoot alignment is important. A new method of photographing and measuring hindfoot alignment based on X-ray was proposed in this study, and it was applied in the assessment of flatfoot. METHODS: This study included 28 patients (40 feet) with flatfeet and 20 volunteers (40 feet) from January to December 2018. The hindfoot alignment shooting stand independently designed by our department was used to take hindfoot alignment X-rays at 10 degree, 15 degree, 20 degree, 25 degree, and 30 degree. We measured the modified tibio-hindfoot angle (THA) at the standard hindfoot aligment position (shooting at 20 degree) and evaluated consistency with the van Dijk method and the modified van Dijk method. In addition, we observed the visibility of the tibiotalar joint space from all imaging data at five projection angles and evaluated the consistency of the modified THA method at different projection angles. The angle of hindfoot valgus of flatfoot patients was measured using the modified THA method. RESULTS: The mean THA in the standard hindfoot aligment view in normal people was significantly different among the three evaluation methods (P < .001). The results from the modified THA method were significantly larger than those from the Van Dijk method (P < .001) and modified Van Dijk method (P < .001). There was no significant difference between the results of the modified THA method and the weightbearing CT (P = .605), and the intra- and intergroup consistency were the highest in the modified THA group. The tibiotalar space in the normal group was visible in all cases at 10 degree, 15 degree, and 20 degree; visible in some cases at 25 degree; and not visible in all cases at 30 degree. In the flatfoot group, the tibiotalar space was visible in all cases at 10 degree, visible in some cases at 15 degree and 20 degree, and not visible in all cases at 25 degree and 30 degree. In the normal group, the modified THA was 4.84 ± 1.81 degree at 10 degree, 4.96 ± 1.77 degree at 15 degree, and 4.94 ± 2.04 degree at 20 degree. No significant differences were found among the three groups (P = .616). In the flatfoot group, the modified THA of 18 feet, which was visible at 10 degree, 15 degree and 20 degree, was 13.58 ± 3.57 degree at 10 degree, 13.62 ± 3.83 degree at 15 degree and 13.38 ± 4.06 degree at 20 degree. There were no significant differences among the three groups (P = .425). CONCLUSIONS: The modified THA evaluation method is simple to use and has high inter- and intragroup consistency. It can be used to evaluate hindfoot alignment. For patients with flatfeet, the 10 degree position view and modified THA measurement can be used to evaluate hindfoot valgus.

Comparative safety of sodium-glucose co-transporter 2 inhibitors in elderly patients with type 2 diabetes mellitus and diabetic kidney disease: a systematic review and meta-analysis.

The safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors in elderly patients with diabetic kidney disease (DKD) is still controversial. This study aimed to analyze the safety of SGLT2 inhibitors in elderly patients with type 2 diabetes mellitus (T2DM) and DKD. We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to March 2023. Randomized controlled trials (RCTs) were included. Data including patient characteristics and interesting outcomes were extracted, and the dichotomous data and continuous variables were evaluated using risk ratio (RR) with 95% confidence intervals (CIs) and mean difference (MD) with 95% CIs, respectively. A total of 14 RCTs with 59874 participants were finally included. There were 38,252 males (63.9%) and 21,622 females (36.1%). The patients' mean age was > 64.6 years. SGLT2 inhibitors could delay the further decline of estimated glomerular filtration rate (eGFR) when eGFR ≥ 60 ml/min/1.73m2 (MD: 2.36; 95%CI [1.15-3.57]). SGLT2 inhibitors in elderly patients with eGFR < 60 ml/min/1.73m2 (RR: 0.86; 95%CI [0.67-1.11]) may have a relatively increased risk of acute kidney injury compared to eGFR ≥ 60 ml/min/1.73m2. SGLT2 inhibitors increased the incidence of genital mycotic infections (RR: 3.47; 95%CI [2.97-4.04]) and diabetic ketoacidosis (RR: 2.25; 95%CI [1.57-3.24]). Except for genital mycotic infections and diabetic ketoacidosis, other adverse reactions were few, indicating that SGLT2 inhibitors are relatively safe for elderly patients with T2DM and DKD. Safety and renoprotection may be diminished when SGLT2 inhibitors are used in elderly patients with eGFR < 60 ml/min/1.73m2.

Triplane osteotomy combined with talar non-weight-bearing area autologous osteochondral transplantation for osteochondral lesions of the talus.

BACKGROUND: Traditional medial malleolar osteotomy combined with autologous osteochondral transplantation (AOT) is mostly used in the treatment of osteochondral lesions of the talus (OLTs), but with high osteotomy and donor site complications. We hypothesis a new triplane medial malleolar osteotomy combined with AOT from non-weight-bearing area of the talus could be a promising choice for OLTs. METHODS: We reviewed all the symptomatic OLTs patients who received AOT with triplane osteotomy of the medial malleolus between September 2015 and December 2017 in our department. According to the inclusion and exclusion criteria, 23 patients (23 ankles), including 14 males and 9 females, were included in the study. The mean age was 35.6 years. The mean size of the lesion area was 141.5 mm2. According Ferkel's classification, including 5 type I, 11 typeIIa and 7 typeIIb. The visual analog scale (VAS) for pain during walking and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were used for the pre- and postoperative evaluations. In addition, the incorporation of the grafts was assessed by computed tomography (CT). RESULTS: All patients had a minimum follow-up of 22 months, with an average of 37.1 months. The mean time from osteotomy to full weight-bearing activity was 8.1 ± 2.3 weeks (range, 5-12 weeks). The mean VAS score improved from 5.6 ± 0.7 preoperatively to 0.7 ± 1.0 postoperatively (P < 0.01). The AOFAS ankle-hindfoot score improved significantly in all domains (P < 0.01). Twenty-one patients returned to sport at their previous level, and 2 returned at a lower level compared with preinjury (mean return to play, 7.4 months). According to CT, the medial malleolus recovered in all patients, and the graft was incorporated well. One patient suffered from flexor hallucis longus tendon discomfort due to internal fixation screw irritation posteromedial to the ankle. The general complication rate was 4.3% (1/23). CONCLUSIONS: These results indicate that AOT combined with medial malleolus triplane osteotomy maybe a viable option for OLTs. Patients could perform weight-bearing exercise and return to sport as early as possible, with a lower rate of complications at the osteotomy site and donor site. However, the large sample well-designed prospective comparative studies are still needed.

Ilizarov Gradual Distraction Correction for Distal Tibial Severe Varus Deformity Resulting from Epiphyseal Fracture: Case Report and Literature Review.

We present a case of a 13-year-old female with severe varus deformity and limb discrepancy resulting from epiphyseal fracture. The preoperative tibial articular surface angle was 64.1°, and the affected tibia was 14 mm shorter than the contralateral tibia. She underwent a medial open osteotomy and fibular osteotomy with gradual distraction correction using Ilizarov fixator. The deformity was corrected at 3 months, and the external fixator was removed when bony union was achieved 6 months postoperatively. At 9 months after surgery, the patient could play basketball without feeling pain. At the last follow-up, namely 36 months after the operation, the American Orthopaedic Foot and Ankle Society hindfoot-ankle score was improved from 58 to 90, the patient was pain free, and the radiological measurements were nearly normal. Ilizarov fixator gradual distraction correction for distal tibial severe varus deformity is a safe and cost-effective method that can yield excellent radiological and clinical outcomes.

China's distinctive engagement in global health.

China has made rapid progress in four key domains of global health. China's health aid deploys medical teams, constructs facilities, donates drugs and equipment, trains personnel, and supports malaria control mainly in Africa and Asia. Prompted by the severe acute respiratory syndrome (SARS) outbreak in 2003, China has prioritised the control of cross-border transmission of infectious diseases and other health-related risks. In governance, China has joined UN and related international bodies and has begun to contribute to pooled multilateral funds. China is both a knowledge producer and sharer, offering lessons based on its health accomplishments, traditional Chinese medicine, and research and development investment in drug discovery. Global health capacity is being developed in medical universities in China, which also train foreign medical students. China's approach to global health is distinctive; different from other countries; and based on its unique history, comparative strength, and policies driven by several governmental ministries. The scope and depth of China's global engagement are likely to grow and reshape the contours of global health.

Children trust people who lie to benefit others.

The current research examined whether children consider who benefits from lies when judging the trustworthiness of liars. Across two studies (total N=214), 6- to 11-year-olds trusted individuals who lied to promote the interests of others, but not those who lied to promote their own interests. In contrast, children trusted individuals who told the truth regardless of who benefited. Trust in individuals who lied to promote the interests of others was evident even in the absence of moral approval for their actions. These results demonstrate that children take into account both the truth value of a speaker's statements and who benefits when assessing trustworthiness and that moral approval is not a prerequisite for trust.

Development assistance for health given to Nepal by China and India: a comparative study.

BACKGROUND: Development assistance for health (DAH) promotes health development in low and middle income countries. China and India, as emerging donors, have scaled-up their DAH programs during the recent years. Nepal, as a neighboring country to China and India, has witnessed the history and development of China's and India's DAH. METHODS: This research uses a literature review and in-depth individual interviewing to compare the history and forms of DAH given from China and India to Nepal. RESULTS: During 60-years of DAH to Nepal, China and India have gradually increased the scale and forms of DAH, and both focus on dispatching medical teams or faculty, building health facilities and gifting medicines and equipment. However, the inclusiveness of Nepalese culture, diplomatic interests, and Nepal's cultural, linguistic and geographical closeness to India make the DAH of India different from that of China. India's DAH also includes support to grass roots NGOs and public health interventions. CONCLUSION: China's and India's insistence on a recipient-driven mechanism keeps the aid programs aligned with Nepal's health development plan and respects Nepal's "ownership". China can learn from India to start the development assistance for health related NGOs and public health intervention.

[Progress in global health response to the Post-2015 development agenda].

This research reviews the recent global health response to the Post-2015 development agenda setting. It discusses three burning issues during the on-going country consultation: how health can be fitted into the post-MDG agenda, the achievements and lessons learnt from Millennium Development Goals (MDG), and health related goals and indicators setting. It suggests that the relationship between health and development is dynamic, thus, health acts on not only the contributor to development but also the beneficiary and indicator of sustainable development. Though great achievements on health have been made since 2000, equity and human right remain challenges to the MDG. Universal Health Coverage and Healthy Life Expectancy are two potential goals for the post-MDG agenda. China has also been involved in this global process, but more actions should be taken to make its voice heard by the world.

Therapeutics of Charcot neuroarthropathy and pharmacological mechanisms: A bone metabolism perspective.

Charcot neuroarthropathy (CN) is a chronic, destructive, and painless damage of the skeletal system that affects the life quality of patients. CN, with an unclear mechanism, is characterized with invasive destruction of bones and a serious abnormality of bone metabolism. Unfortunately, development of an effective prevention and treatment strategy for CN is still a great challenge. Of note, recent studies providing an insight into the molecular mechanisms of bone metabolism and homeostasis have propelled development of novel CN therapeutic strategies. Therefore, this review aims to shed light on the pathogenesis, diagnosis, and treatment of CN. In particular, we highlight the eminent role of the osteoprotegerin (OPG)-receptor activator of nuclear factor-κB (RANK)-RANK ligand (RANKL) system in the development of CN. Furthermore, we summarize and discuss the diagnostic biomarkers of CN as well as the potential pharmacological mechanisms of current treatment regimens from the perspective of bone metabolism. We believe that this review will enhance the current state of knowledge on the diagnosis, prevention, and therapeutic efficacy of CN.

Bioprinting-Enabled Biomaterials: A Cutting-Edge Strategy for Future Osteoarthritis Therapy.

Bioprinting is an advanced technology that allows for the precise placement of cells and biomaterials in a controlled manner, making significant contributions in regenerative medicine. Notably, bioprinting-enabled biomaterials have found extensive application as drug delivery systems (DDS) in the treatment of osteoarthritis (OA). Despite the widespread utilization of these biomaterials, there has been limited comprehensive research summarizing the recent advances in this area. Therefore, this review aims to explore the noteworthy developments and challenges associated with utilizing bioprinting-enabled biomaterials as effective DDS for the treatment of OA. To begin, we provide an overview of the complex pathophysiology of OA, highlighting the shortcomings of current treatment modalities. Following this, we conduct a detailed examination of various bioprinting technologies and discuss the wide range of biomaterials employed in DDS applications for OA therapy. Finally, by placing emphasis on their transformative potential, we discuss the incorporation of crucial cellular components such as chondrocytes and mesenchymal stem cells into bioprinted constructs, which play a pivotal role in promoting tissue regeneration and repair.

[Calcaneal V-shaped osteotomy combined with subtalar arthrodesis for Stephens â ¡ and â ¢ calcaneal fractures malunion].

Objective: To investigate the effectiveness of calcaneal V-shaped osteotomy combined with subtalar arthrodesis in the treatment of Stephens Ⅱand Ⅲ calcaneal fracture malunion. Methods: The clinical data of 24 patients with severe calcaneal fracture malunion treated by calcaneal V-shaped osteotomy combined with subtalar arthrodesis between January 2017 and December 2021 were retrospectively analyzed. There were 20 males and 4 females with an average age of 42.8 years (range, 33-60 years). Conservative treatment of calcaneal fracture failed in 19 cases and operation failed in 5 cases. Stephens classification of calcaneal fracture malunion was type Ⅱ in 14 cases, and type Ⅲ in 10 cases. Preoperative Böhler angle of calcaneus was 4.0°-13.5° (mean, 8.6°), Gissane angle was 100°-152° (mean, 119.3°). The time from injury to operation was 6-14 months (mean, 9.7 months). American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analogue scale (VAS) score were used to evaluate the effectiveness before operation and at last follow-up. Bone healing was observed and the healing time was recorded. The talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were measured. Results: Necrosis of the cuticle edge of the incision occurred in 3 cases, which were cured by dressing change and oral administration of antibiotic therapy. The other incisions healed by first intention. All the 24 patients were followed up 12-23 months, with an average of 17.1 months. The foot shape of the patients recovered well, the shoes were restored to the size before injury, and there was no anterior ankle impingement. Bone union was achieved in all patients, and the healing time ranged from 12 to 18 weeks, with an average of 14.1 weeks. At last follow-up, no adjacent joint degeneration occurred in all patients; 5 patients had mild foot pain during walking, which had no significant impact on daily life and work; no patient needed revision surgery. The AOFAS ankle and hindfoot score was significantly higher than that before operation ( P<0.001), the results were excellent in 16 cases, good in 4 cases, and poor in 4 cases, and the excellent and good rate was 83.3%. The VAS score, talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were significantly improved after operation ( P<0.001). Conclusion: Calcaneal V-shaped osteotomy combined with subtalar arthrodesis can effectively relieve hindfoot pain, correct talocalcaneal height, restore talus inclination angle, and reduce the risk of nonunion after subtalar arthrodesis.

[Effectiveness and risk factors of supramalleolar osteotomy in treatment of varus-type ankle arthritis].

Objective: To assess the effectiveness of supramalleolar osteotomy (SMOT) as a therapeutic intervention for varus-type ankle arthritis, while also examining the associated risk factors that may contribute to treatment failure. Methods: The clinical data of 82 patients (89 feet) diagnosed with varus-type ankle arthritis and treated with SMOT between January 2016 and December 2020 were retrospectively analyzed. The patient cohort consisted of 34 males with 38 feet and 48 females with 51 feet, with the mean age of 54.3 years (range, 43-72 years). The average body mass index was 24.43 kg/m 2 (range, 20.43-30.15 kg/m 2). The preoperative tibial anterior surface angle (TAS) ranged from 77.6° to 88.4°, with a mean of 84.4°. The modified Takakura stage was used to classify the severity of the condition, with 9 feet in stage Ⅱ, 41 feet in stage Ⅲa, and 39 feet in stage Ⅲb. Clinical functional assessment was conducted using the Maryland sore, visual analogue scale (VAS) score, and psychological and physical scores in Health Survey 12-item Short From (SF-12). Radiology evaluations include TAS, talar tilt (TT), tibiocrural angle (TC), tibial medial malleolars (TMM), tibiocrural distance (TCD), tibial lateral surface angle (TLS), and hindfoot alignment angle (HAA). The results of clinical failure, functional failure, and radiology failure were statistically analyzed, and the related risk factors were analyzed. Results: The operation time ranged from 45 to 88 minutes, with an average of 62.2 minutes. No complication such as fractures and neurovascular injuries was found during operation. There were 7 feet of poor healing of the medial incision; 9 pin tract infections occurred in 6 feet using external fixator; there were 20 cases of allograft and 3 cases of autograft with radiographic bone resorption. Except for 1 foot of severe infection treated with bone cement, the remaining 88 feet were primary healing, and the healing area was more than 80%. All patients were followed up 24-82 months, with an average of 50.2 months. Maryland score, VAS score, SF-12 psychological and physiological scores, and TAS, TC, TLS, TCD, TT, TMM, HAA, and Takakura stage were significantly improved at last follow-up ( P<0.05). Postoperative clinical failure occurred in 13 feet, functional failure in 15 feet, and radiology failure in 23 feet. Univariate analysis showed that obesity, TT>10°, and Takakura stage Ⅲb were risk factors for clinical failure, HAA≥15° and Takakura stage Ⅲb were risk factors for functional failure, and TT>10° was risk factor for radiographic failure ( P<0.05). Further logistic regression analysis showed that TT>10°, HAA≥15°, and TT>10° were risk factors for clinical failure, functional failure, and radiographic failure, respectively ( P<0.05). Conclusion: SMOT is effective in the mid- and long-term in the treatment of varus-type ankle arthritis, but it should be used with caution in patients with obesity, severe hindfoot varus, severe talus tilt, and preoperative Takakura stage Ⅲb.

[Progress in clinical diagnosis and treatment of diabetic Charcot neuroarthropathy of foot and ankle].

Objective: To summarize the progress of clinical diagnosis and treatment of diabetic Charcot neuroarthropathy (CNO) of foot and ankle to provide reference for clinical treatment. Methods: The research literature on diabetic CNO of foot and ankle at home and abroad was widely reviewed, and the stages and classification criteria of CNO were summarized, and the treatment methods at different stages of the disease course were summarized. Results: CNO is a rapidly destructive disease of bone and joint caused by peripheral neuropathy, which leads to the formation of local deformities and stress ulcers due to bone and joint destruction and protective sensory loss, which eventually leads to disability and even life-threatening. At present, the modified Eichenholtz stage is a commonly used staging criteria for CNO of foot and ankle, which is divided into 4 stages by clinical and imaging manifestations. The classification mainly adopts the modified Brodsky classification, which is divided into 6 types according to the anatomical structure. The treatment of diabetic CNO of foot and ankle needs to be considered in combination with disease stage, blood glucose, comorbidities, local soft tissue conditions, degree of bone and joint destruction, and whether ulcers and infections are present. Conservative treatment is mainly used in the active phase and surgery in the stable phase. Conclusion: The formulation of individualized and stepped treatment regimens can help improve the effectiveness of diabetic CNO of foot and ankle. However, there is still a lack of definitive clinical evidence to guide the treatment of active and stable phases, and further research is needed.

Biomaterial-based scaffolds in promotion of cartilage regeneration: Recent advances and emerging applications.

Osteoarthritis (OA) poses a significant burden for countless individuals, inflicting relentless pain and impairing their quality of life. Although traditional treatments for OA focus on pain management and surgical interventions, they often fall short of addressing the underlying cause of the disease. Fortunately, emerging biomaterial-based scaffolds offer hope for OA therapy, providing immense promise for cartilage regeneration in OA. These innovative scaffolds are ingeniously designed to provide support and mimic the intricate structure of the natural extracellular matrix, thus stimulating the regeneration of damaged cartilage. In this comprehensive review, we summarize and discuss current landscape of biomaterial-based scaffolds for cartilage regeneration in OA. Furthermore, we delve into the diverse range of biomaterials employed in their construction and explore the cutting-edge techniques utilized in their fabrication. By examining both preclinical and clinical studies, we aim to illuminate the remarkable versatility and untapped potential of biomaterial-based scaffolds in the context of OA. Thetranslational potential of this article: By thoroughly examining the current state of research and clinical studies, this review provides valuable insights that bridge the gap between scientific knowledge and practical application. This knowledge is crucial for clinicians and researchers who strive to develop innovative treatments that go beyond symptom management and directly target the underlying cause of OA. Through the comprehensive analysis and multidisciplinary approach, the review paves the way for the translation of scientific knowledge into practical applications, ultimately improving the lives of individuals suffering from OA and shaping the future of orthopedic medicine.

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy.

Background: Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods: The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results: Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group (28.1 ± 2.3 vs. 11.9 ± 0.7; P < 0.05). The expression of RANKL, TNF-α, IL-1ß, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group (P < 0.05). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions: DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1ß, IL-6, and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

Interaction between N6-methyladenosine and autophagy in the regulation of bone and tissue degeneration.

Bone and tissue degeneration are the most common skeletal disorders that seriously affect people's quality of life. N6-methyladenosine (m6A) is one of the most common RNA modifications in eukaryotic cells, affecting the alternative splicing, translation, stability and degradation of mRNA. Interestingly, increasing number of evidences have indicated that m6A modification could modulate the expression of autophagy-related (ATG) genes and promote autophagy in the cells. Autophagy is an important process regulating intracellular turnover and is evolutionarily conserved in eukaryotes. Abnormal autophagy results in a variety of diseases, including cardiomyopathy, degenerative disorders, and inflammation. Thus, the interaction between m6A modification and autophagy plays a prominent role in the onset and progression of bone and tissue degeneration. In this review, we summarize the current knowledge related to the effect of m6A modification on autophagy, and introduce the role of the crosstalk between m6A modification and autophagy in bone and tissue degeneration. An in-depth knowledge of the above crosstalk may help to improve our understanding of their effects on bone and tissue degeneration and provide novel insights for the future therapeutics.

Serum proteomic analysis of differentially expressed proteins and pathways involved in the mechanism of endemic osteoarthritis.

Kashin-Beck disease (KBD) is a chronic and endemic osteochondral disease and the etiology and pathogenic mechanism of KBD are still unknown. This study aimed to elucidate and screen KBD-associated proteins, which were differentially expressed between KBD patients and healthy controls. We combined protein fractionation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a high-resolution mass spectrometer coupled with tandem mass tags (TMTs) to quantitatively analyze and screen KBD-associated proteins, which were differentially expressed between KBD patients and healthy controls. In addition, we used parallel reaction monitoring (PRM) to quantify proteins in serum from patients with KBD and healthy controls in order to verify the differentially expressed proteins in patients with KBD. We identified 224 differentially expressed proteins, including 11 up-regulated and 213 down-regulated proteins. Catalase (CAT) was observed to be significantly elevated in patients with KBD compared with control patients. Further, the fold difference of CAT is significantly elevated in PRM compared with label-free quantification. The results in this study suggest that CAT may be the reflection of the dynamic nature of KBD and could be considered as a novel pathogenic indicator for patients with KBD.

The RANK/RANKL/OPG system and tumor bone metastasis: Potential mechanisms and therapeutic strategies.

With the markedly increased diagnosis and incidence of cancer in the population, tumor bone metastasis has become a frequent event in tumor patients. Healthy bone integrity is maintained by a delicate balance between bone formation and bone resorption. Unfortunately, many tumors, such as prostate and breast, often metastasize to the bone, and the alterations to the bone homeostasis can particularly favor tumor homing and consequent osteolytic or osteoblastic lesions. Receptor activator of NF-κB ligand (RANKL), its receptor RANK, and osteoprotegerin (OPG) are involved in the regulation of the activation, differentiation, and survival of osteoclasts, which play critical roles in bone metastasis formation. High rates of osteoclastic bone resorption significantly increase fracture risk, cause severe bone pain, and contribute to homing tumor cells in bone and bone marrow. Consequently, suppression of the RANK/RANKL/OPG system and osteoclastic activity can not only ameliorate bone resorption but may also prevent tumor bone metastases. This review summarizes the important role of the RANK/RANKL/OPG system and osteoclasts in bone homeostasis and its effect on tumor bone metastasis and discusses therapeutic strategies based on RANKL inhibition.