Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Melatonin, a potentially effective drug for the treatment of infected bone nonunion.

Osteomyelitis (OM), characterized by heterogeneity and complexity in treatment, has a high risk of infection recurrence which may cause limb disability. Management of chronic inactive osteomyelitis (CIOM) without typical inflammatory symptoms is a great challenge for orthopedic surgeons. On the basis of data analysis of 1091 OM cases, we reported that latent osteogenic decline in CIOM patients was the main cause of secondary surgery. Our research shows that impairment of osteoblasts capacity in CIOM patients is associated with ferroptosis of osteoblasts caused by internalization of Staphylococcus aureus. Further studies show that melatonin could alleviate ferroptosis of osteoblasts in infected states through Nox4/ROS/P38 axis and protect the osteogenic ability of CIOM patients. Knockout of NADPH oxidase 4 (Nox4) in vivo could effectively relieve ferroptosis of osteoblasts in the state of infection and promote osteogenesis. Through a large number of clinical data analyses combined with molecular experiments, this study clarified that occult osteogenic disorders in CIOM patients were related to ferroptosis of osteoblasts. We revealed that melatonin might be a potential therapeutic drug for CIOM patients and provided a new insight for the treatment of OM.

Solute carrier family 11 member 1 genetic polymorphisms rs17235409 and rs3731865 associate with susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population.

Genetic variations in the solute carrier family 11 member 1 (SLC11A1) gene have been implicated in developing inflammatory disorders. However, it is still unclear whether such polymorphisms contribute to the pathogenesis of post-traumatic osteomyelitis (PTOM). Therefore, this study investigated the roles of genetic variations of the SLC11A1 gene (rs17235409 and rs3731865) in PTOM development in a Chinese Han cohort. The SNaPshot method was used for genotyping 704 participants (336 patients and 368 controls) for rs17235409 and rs3731865. Outcomes revealed that rs17235409 increased the risk of PTOM occurrence by dominant (p = .037, odds ratio [OR] = 1.44) and heterozygous models (p = .035, OR = 1.45), implying AG genotype as a risk factor for PTOM development. In addition, patients with AG genotype had relatively higher levels of inflammatory biomarkers than those with AA and GG genotypes, especially for the white blood cell count and C-reactive protein. Despite no statistically significant differences achieved, rs3731865 may reduce the PTOM susceptibility, suggested by the results of dominant (p = .051, OR = 0.67) and heterozygous (p = .068, OR = 0.69) models. In short, rs17235409 confers an elevated chance of developing PTOM, with AG genotype as a risk factor. Whether rs3731865 involves in the pathogenesis of PTOM requires further investigations.

Implant surface culture may be a useful adjunct to standard tissue sampling culture for identification of pathogens accounting for fracture-device-related infection: a within-person randomized agreement study of 42 patients.

BACKGROUND AND PURPOSE: Identification of pathogens causing fracture-device-related infection (FDRI) is always a challenge as the positive rate of standard tissue sampling culture (TSC) remains unsatisfactory. This study evaluates the efficiency of implant surface culture (ISC) as an adjunct to standard TSC for identification of FDRI-associated microorganisms. PATIENTS AND METHODS: Between November 2020 and March 2022, patients diagnosed with FDRI defined by the International Fracture-Related Infection (FRI) Consensus Group, and indicated for implant removal, underwent both methods for bacteria detection. The test order of ISC and TSC was randomly selected for each patient included, as a within-person randomized design. For ISC, the recovered implants were gently covered with tryptic soy agar after rinsing with normal saline twice, and then incubated at 37℃ 5% CO2 for up to 14 days. For TSC, 5 specimens were sampled and sent to the Clinical Laboratory of Southern Medical University Nanfang Hospital, Guangzhou, for culture and identification. RESULTS: 42 consecutive patients were included, with a mean age of 46 years. The most frequent infection site and implant type were the tibia (21 cases) and plates with screws (30 cases), respectively. Altogether 21 patients were found with positive outcomes by both methods, and the identified pathogens were consistent. ISC found an additional 15 patients showing positive results, which were negative by TSC. Furthermore, the mean culture time of ISC was shorter than that of TSC (1.5 days vs. 3.2 days). INTERPRETATION: ISC may be a useful adjunct to TSC for detection of bacteria causing FDRI, with a relatively higher positive rate and a shorter culture time.

Health Care Costs of Post-traumatic Osteomyelitis in China: Current Situation and Influencing Factors.

BACKGROUND: Currently, very limited information is available regarding the economic burdens of patients with extremity post-traumatic osteomyelitis (OM). This study aimed to investigate direct health care costs and utilization for inpatients with extremity post-traumatic OM and analyze its constituent ratios and influencing factors in Southern China. METHODS: We searched in the electronic medical record system for inpatients who had received surgical interventions at our department between 2013 and 2016 for extremity post-traumatic OM. Data of direct health care costs incurred during their hospitalizations were collected in six main categories (service, diagnosis, treatment, materials, pharmaceuticals, and miscellaneous expenses). In addition, data of total medical costs for contemporaneous inpatients with non-post-traumatic OM were also collected as controls. RESULTS: A total of 278 post-traumatic OM and 10,420 controls were included. The median cost for the post-traumatic OM inpatients was $10,504 US dollars, 4.8-fold higher than that for those with non-post-traumatic OM ($2189, P < 0.001). The direct cost in the category of materials accounted for the largest proportion (61%), followed by that in pharmaceuticals (12%) and treatment (11%). The median number of hospital admissions for post-traumatic OM patients was 1 time, with a median length-of-stay of 22 d. The most influencing factors for the health care costs of the post-traumatic OM inpatients were use of an external fixator ($16,016 for those who used versus $4956 for those who did not, P < 0.001), external fixator type ($19,563 for ring fixator versus $14,966 for rail fixator, P < 0.001), infection site ($13,755 for tibia, $14,216 for femur and $5673 for calcaneus, P < 0.001), and infection-associated injury type ($12,890 for infection after open fracture versus $8087 for infection after closed fracture, P = 0.001). CONCLUSIONS: An unexpectedly large proportion of the direct health care costs for inpatients with extremity post-traumatic OM went to cover an external fixator, with expenses for pharmaceuticals and treatment accounting for only a little more than the tenth of the total health care costs. Use of external fixator, external fixator type, infection site, and infection-associated injury type directly influenced the health care costs.

Associations between Interleukin Gene Polymorphisms and Risks of Developing Extremity Posttraumatic Osteomyelitis in Chinese Han Population.

This case-control study aimed to investigate potential associations between interleukin (IL) gene polymorphisms and the risks of developing extremity posttraumatic osteomyelitis (PTOM) in Chinese Han population. Altogether, 189 PTOM patients and 200 healthy controls were genotyped of IL-1α (rs17561, rs1800587), IL-1ß (rs16944, rs1143627, rs1143634, rs2853550), IL-1RN (rs4251961, rs419598, rs315951), IL-4 (rs2243248, rs2243250), IL-6 (rs1800795, rs1800796, rs1800797), IL-8 (rs4073, rs2227306, rs2227307), IL-10 (rs3024491, rs3024496, rs1800871, rs1800872, rs1800896), IL-17A (rs2275913), and IL-17F (rs763780) using the SNaPshot genotyping method. Statistical differences were observed regarding the genotype distributions of rs16944 (P = 0.049) and rs4251961 (P = 0.007) between the patients and healthy controls. In addition, significant associations were found between rs16944 and the risk of PTOM development by dominant (OR = 1.854, P = 0.017), homozygous (OR = 1.831, P = 0.041), and heterozygous (OR = 1.869, P = 0.022) models, and of rs1143627 by dominant (OR = 1.735, P = 0.032) and homozygous (OR = 1.839, P = 0.040) models. Moreover, significant links were also identified between rs4251961 and the susceptibility to PTOM by dominant (OR = 0.446, P = 0.005) and heterozygous (OR = 0.409, P = 0.003) models, and of rs1800796 by dominant (OR = 4.184, P = 0.029), homozygous (OR = 4.378, P = 0.026), and heterozygous (OR = 3.834, P = 0.046) models. The present outcomes demonstrated that rs16944, rs1143627, and rs1800796 associate with increased risks, while rs4251961 links to a decreased risk of PTOM development in Chinese Han population.

Single-stage debridement with implantation of antibiotic-loaded calcium sulphate in 34 cases of localized calcaneal osteomyelitis.

Background and purpose - The successful eradication of calcaneus infection with limb salvage remains a challenge. We describe the outcomes of cortical bone windowing followed by eggshell-like debridement and implantation of antibiotic-loaded calcium sulphate (CS) for localized (Cierny-Mader type III) calcaneal osteomyelitis (CO).Patients and methods - We report a retrospective study of 34 patients. Infection followed trauma or orthopedic surgery in 30 patients and hematogenous spread in 4 patients. 31 patients had a sinus tract, accompanied by a soft tissue defect in 3 patients. All patients received cortical bone windowing, debridement, multiple sampling, local implantation of vancomycin- and gentamicin-loaded CS, skin closure or flap coverage, and culture-specific systematic antibiotic treatment in a single-stage procedure. Patients were followed up for a median of 26 months.Results - Infection was eradicated in 29 patients after the single-stage surgery, and all of the 5 recurrent infections were cleared by repeated surgery without amputation. Other adverse events included 11 patients with aseptic wound leakage and 1 unrelated death. Compared with those before surgery, the median postoperative scores of the American Orthopaedic Foot & Ankle Society (AOFAS) ankle hindfoot scale (65 vs. 86 vs. 89) and the visual analog scale (VAS) for pain (6 vs. 3 vs. 1) improved at the 1-year and 2-year follow-up.Interpretation - This single-stage protocol, cortical bone windowing, and eggshell-like debridement combined with local implantation of antibiotic-loaded CS is effective in treating type III CO. However, the incidence of aseptic wound leakage is high.

Reduced PDGF-AA in subchondral bone leads to articular cartilage degeneration after strenuous running.

To identify the effects of running on articular cartilage and subchondral bone remodeling, C57BL/6 mice were randomly divided into three groups: control, moderate-, and strenuous running. Magnetic resonance imaging showed bone marrow lesions in the knee subchondral bone in the strenuous-running group in contrast with the other two groups. The microcomputed tomography analysis showed promoted bone formation in the subchondral bone in mice subjected to strenuous running. Histological and immunohistochemistry results indicated that terminal differentiation of chondrocytes and degeneration of articular cartilage were enhanced but, synthesis of platelet-derived growth factor-AA (PDGF-AA) in the subchondral bone was suppressed after strenuous running. In vitro, excessive mechanical treatments suppressed the expression of PDGF-AA in osteoblasts, and the condition medium from mechanical-treated osteoblasts stimulated maturation and terminal differentiation of chondrocytes. These results indicate that strenuous running suppresses the synthesis of PDGF-AA in subchondral bone, leading to downregulated PDGF/Akt signal in articular cartilage and thus cartilage degeneration.

Squamous cell carcinoma arising from chronic osteomyelitis of the femur: A case report.

Although chronic osteomyelitis (COM) affecting the extremities is a frequently occurring disease, the incidence of squamous cell carcinoma (SCC) arising from COM is rare. Consequently, understanding the diagnosis, treatment and prognosis of such a disorder remains limited. In the present study, a case of COM-associated SCC was demonstrated. A 65-year-old woman arrived to the Southern Medical University Nanfang Hospital (Guangzhou, China) with multiple sinus tracts and skin ulcers in the distal part of her left thigh, persisting for over 50 years following an open pierce injury by an ox horn. A local biopsy confirmed the diagnosis of COM-related SCC. Although limb amputation was recommended, the female patient declined initially. Instead, the female patient underwent focused debridement and wide resection of the tumor, followed by local implantation of calcium sulfate beads loaded with vancomycin and gentamycin, and application of a rail fixator. A total of 10 months later, the cancer recurred, affecting the osseous tissue. Subsequently, the patient underwent amputation of the thigh. At the one-year follow-up, the patient showed satisfactory recovery without signs of local recurrence. Despite its rarity, the severity of this disorder should not be underestimated. Personalized treatment strategies must be tailored to individual circumstances.

Lipoteichoic acid restrains macrophage senescence via ß-catenin/FOXO1/REDD1 pathway in age-related osteoporosis.

Osteoporosis and its related fractures are common causes of morbidity and mortality in older adults, but its underlying molecular and cellular mechanisms remain largely unknown. In this study, we found that lipoteichoic acid (LTA) treatment could ameliorate age-related bone degeneration and attenuate intramedullary macrophage senescence. FOXO1 signaling, which was downregulated and deactivated in aging macrophages, played a key role in the process. Blocking FOXO1 signaling caused decreased REDD1 expression and increased phosphorylation level of mTOR, a major driver of aging, as well as aggravated bone loss and deteriorated macrophage senescence. Moreover, LTA elevated FOXO1 signaling through ß-catenin pathway while ß-catenin inhibition significantly suppressed FOXO1 signaling, promoted senescence-related protein expression, and accelerated bone degeneration and macrophage senescence. Our findings indicated that ß-catenin/FOXO1/REDD1 signaling plays a physiologically significant role that protecting macrophages from senescence during aging.

The effect of intra-articular injection of different concentrations of ozone on the level of TNF-α, TNF-R1, and TNF-R2 in rats with rheumatoid arthritis.

The objectives of this study were to observe the therapeutic effect of ozone (O3) of different concentrations on rat with rheumatoid arthritis (RA), and to investigate the role of O3 in regulating the level of TNF-α (tumor necrosis factor), TNF-R1 (tumor necrosis factor receptor 1), and TNF-R2. Forty-eight Wistar rats were randomly divided into eight groups. There are five O3 groups which were marked by 10, 20, 30, 40, and 50 µg/mL, respectively, control group, oxygen group, and RA model group. RA was induced in all rats by hypodermic injection of collagen II and complete Freund's adjuvant except that in the control group. At 21 days after modeling, the rats in oxygen group were given an injection of oxygen in the knee joint weekly for 3 weeks, and the rats in O3 groups were injected the concentration of O3 as they marked weekly for 3 weeks. The thickness of hind paw, as well as the serum and synovial levels of TNF-α, TNF-R1, and TNF-R2 was observed. At the end of treatments, the thickness of the hind paws in O3-40 group is much less compared to RA group (P < 0.01). The serum levels of TNF-α, TNF-R1, and TNF-R2 showed no significant difference among all the groups (P > 0.05). However, the synovial levels of TNF-α and TNF-R2 in O3-40 and O3-50 groups are lower than those in RA group (P < 0.01). The synovial level of TNF-R1 in O3-40 group is higher than that in RA group (P < 0.05). In conclusion, intra-articular injection of O3 at 40 µg/mL can effectively suppress the joint swelling caused by RA. This mechanism is probably mediated by down-regulating synovial TNF-α and TNF-R2 and up-regulating TNF-R1 in the joint.

Multiple Reconstructive Osteotomy Treating Malunited Calcaneal Fractures Without Subtalar Joint Fusion.

OBJECTIVE: Various surgical techniques have been reported in treating calcaneal malunions over the decades, while the operations on single plane were accompanied by respective limitations. The purpose of this study is to evaluate the efficacy of a novel multiple reconstructive osteotomy for treating malunited calcaneal fractures without subtalar joint fusion. METHODS: From March 12, 2010, to August 17, 2017, 10 patients (10 feet) with malunited calcaneal fractures were treated with multiple reconstructive osteotomy with subtalar joint-preserving operations. All patients were treated with a corrective osteotomy, joint realignment, soft tissue balancing, and secondary internal fixation at a mean of 5.6 ± 2.41 months since the initial injury. With the utilization of the multiple reconstructive osteotomy, the posterior facet was restored to preserve the subtalar joint. All patients were evaluated clinically and radiographically at a mean follow-up of 3.04 ± 1.21 years. RESULTS: All patients were subjectively satisfied with the treatment. The average time to union was 12.2 ± 1.11 weeks. The American Orthopedic Foot and Ankle (AOFAS) ankle and hind foot score was 86.3 ± 4.45 (t = 27.64, P < 0.0001, paired t-test), which was significantly higher than the preoperative assessment. Postoperative radiographic assessment revealed great improvement in Böhler's angle (from 25.4° to 86.3°), talocalcaneal height (65.15-72.68 mm) and Calcaneus-talus angle (from 34.46° to 39.7°). One patient had mild discomfort after a 1-h brisk walk. One patient was suspected to have early posttraumatic arthritis of the subtalar joint based upon radiographic evidence during the follow-up, but the patients could walk normally for a long time without pain. CONCLUSION: Multiple reconstructive osteotomy is an effective way to restore the calcaneal morphology and preserve the subtalar joint for selected calcaneal malunion.

Nitric oxide synthase 2 genetic variation rs2297514 associates with a decreased susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population.

Background: Previous studies have indicated that nitric oxide synthase 2 (NOS2) genetic variations are involved in delayed fracture healing and fracture non-union. Whether these genetic variants associate with the development of osteomyelitis (OM) remains unclear. Here, we analyzed the potential relationships between NOS2 genetic variations and the risk of developing post-traumatic OM (PTOM) in a Chinese Han population. Methods: Altogether 704 participants, including 336 PTOM patients and 368 healthy controls, were genotyped of rs2297514 and rs2248814 of the NOS2 gene using the SNaPshot genotyping method. Results: Outcomes showed that the frequency of allele C of rs2297514 in the patient group was significantly lower than that in the control group (48.7% vs. 54.5%, P = 0.029, OR = 0.792, 95% CI 0.642 - 0.976). In addition, significant associations were found between rs2297514 and susceptibility to PTOM by the recessive model (P = 0.007, OR = 0.633, 95% CI 0.453 - 0.884), and the homozygous model (P = 0.039, OR = 0.648, 95% CI 0.429 - 0.979). Moreover, patients with the CC genotype of rs2297514 had lower inflammatory biomarkers levels than the TT genotype, especially for the C-reactive protein (CRP) level (median: 4.1 mg/L vs. 8.9 mg/L, P = 0.027). However, no significant relationship was noted between rs2248814 and the risk of developing PTOM. Conclusion: In this Chinese cohort, rs2297514 is correlated with a decreased risk of PTOM development, with genotype CC as a protective factor.

Effects of Dopamine on stem cells and its potential roles in the treatment of inflammatory disorders: a narrative review.

Inflammation is the host's protective response against harmful external stimulation that helps tissue repair and remodeling. However, excessive inflammation seriously threatens the patient's life. Due to anti-inflammatory effects, corticosteroids, immunosuppressants, and monoclonal antibodies are used to treat various inflammatory diseases, but drug resistance, non-responsiveness, and severe side effect limit their development and application. Therefore, developing other alternative therapies has become essential in anti-inflammatory therapy. In recent years, the in-depth study of stem cells has made them a promising alternative drug for the treatment of inflammatory diseases, and the function of stem cells is regulated by a variety of signals, of which dopamine signaling is one of the main influencing factors. In this review, we review the effects of dopamine on various adult stem cells (neural stem cells, mesenchymal stromal cells, hematopoietic stem cells, and cancer stem cells) and their signaling pathways, as well as the application of some critical dopamine receptor agonists/antagonists. Besides, we also review the role of various adult stem cells in inflammatory diseases and discuss the potential anti-inflammation function of dopamine receptors, which provides a new therapeutic target for regenerative medicine in inflammatory diseases.

Surgical versus nonsurgical treatment of displaced intra-articular calcaneal fracture: a meta-analysis of current evidence base.

PURPOSE: Controversy still surrounds the optimal treatment for patients with displaced intra-articular calcaneal fractures (DIACF). An up-to-date meta-analysis was performed to evaluate clinical effectiveness of surgical treatment for DIACF compared with nonsurgical treatment. METHODS: We systematically searched four electronic databases (Medline, BIOSIS, Cochrane library and Google Scholar) to identify randomised controlled trials (RCTs) and clinical controlled trials (CCTs) in which surgical treatment was compared with nonsurgical treatment of DIACF from 1980 to 2011. Trial quality was assessed using the modified Jadad scale and effective data were pooled for meta-analysis. RESULTS: Ten studies (six RCTs and four CCTs) with a total of 891 participants were screened. Results showed that surgical treatment was superior to nonsurgical treatment in better recovery of the Böhler angle (P < 0.0001), more stable calcaneal height (P = 0.0009) and width (P < 0.00001). Moreover, fewer surgically treated patients needed increased shoe size (P = 0.0004) and more were able to resume pre-injury work (P = 0.004) than the nonsurgical patients. No significant difference was identified between the two methods regarding the incidence of residual pain (P = 0.49). However, operative management was associated with a higher risk of complications (P = 0.008). CONCLUSIONS: Although surgical repair may increase the complication probability, it is the price that has to be paid for better reconstruction of the calcaneus and better functional results. Taken as a whole, surgery is probably the optimal choice in DIACF treatment.

Devascularized Bone Surface Culture: A Novel Strategy for Identifying Osteomyelitis-Related Pathogens.

The gold standard for identifying pathogens causing osteomyelitis (OM) is intraoperative tissue sampling culture (TSC). However, its positive rate remains inadequate. Here, we evaluated the efficiency of a novel strategy, known as devitalized bone surface culture (BSC), for detecting OM-related microorganisms and compared it to TSC. Between December 2021 and July 2022, patients diagnosed with OM and received both methods for bacterial identification were screened for analysis. In total, 51 cases were finally recruited for analysis. The mean age was 43.6 years, with the tibia as the top infection site. The positive rate of BSC was relatively higher than that of TSC (74.5% vs. 58.8%, p = 0.093), though no statistical difference was achieved. Both BSC and TSC detected definite pathogens in 29 patients, and their results were in accordance with each other. The most frequent microorganism identified by the BSC method was Staphylococcus aureus. Moreover, BSC took a significantly shorter median culture time than TSC (1.0 days vs. 3.0 days, p < 0.001). In summary, BSC may be superior to TSC for identifying OM-associated pathogens, with a higher detectable rate and a shorter culture time.

Altered Gut Microbiota as an Auxiliary Diagnostic Indicator for Patients With Fracture-Related Infection.

Preoperative diagnosis of fracture-related infection (FRI) is difficult for patients without obvious signs of infection. However, specific profiles of gut microbiota may be used as a potential diagnostic tool for FRI as suggested by a previous study. The fecal microbiome was compared between 20 FRI patients (FRI group), 18 fracture healed patients (FH group), and 12 healthy controls (HC group) included after collection of fecal samples and evaluation. The α and ß diversity indices were used to characterize the fecal microbiome. Dysbiosis indexes were constructed based on the characteristic high-dimensional biomarkers identified in the fecal microbiota from the three groups by linear discriminant analysis and generalized linear model analysis to quantify the dysbiosis of fecal microbiota. The effectiveness of α and ß diversity indices and dysbiosis indexes was assessed in distinguishing the fecal microbiome among the three groups. The influences of serum inflammatory factors on gut microbiota were also addressed. The α diversity indices were significantly different between the three groups, the highest in HC group and the lowest in FRI group (P < 0.05). The ß diversity indices showed significant phylogenetic dissimilarity of gut microbiome composition among the three groups (P < 0.001). The dysbiosis indexes were significantly higher in FRI group than in FH and HC groups (P < 0.001). The area under Receiver operating characteristic curve showed the characteristics of gut microbiota and the gut microbiota was found as effective in distinguishing the three groups. The dysbiosis in the FRI patients was associated with systemic inflammatory factors. In addition, significant differences in the gut microbiota were not observed between the FRI patients versus without sinus tract or pus before operation. Since FRI patients, with or without sinus tract or pus, have a characteristic profile of gut microbiota, their gut microbiota may be used as an auxiliary diagnostic tool for suspected FRI.

Serum Calcium Level Combined with Platelet Count May Be Useful Indicators for Assisted Diagnosis of Extremity Posttraumatic Osteomyelitis: A Comparative Analysis.

BACKGROUND: A previous study had reported that patients with osteomyelitis (OM) appeared to be more likely to develop hypocalcemia before and after surgery. Calcium sulfate (CS) is frequently used as a local antibiotic vehicle in the treatment of OM, which may also affect serum calcium level. However, whether changes of serum calcium level are caused by OM and/or local use of calcium sulfate remains unclear. Also, platelet (PLT) count plays a crucial predictive role in periprosthetic joint infections (PJIs), but its role in assisted diagnosis of OM is largely unknown. The purpose of this study was to determine whether serum calcium level and PLT count may be helpful in assisted diagnosis of PTOM. METHODS: Between January 2013 and December 2018, we analyzed 468 consecutive patients (392 males and 76 females), including 170 patients with posttraumatic OM (PTOM), 130 patients with aseptic bone nonunion (ABN), and 168 patients recovered from fractures with requirement of implant removal set as controls. Preoperative serological levels of calcium, phosphorus, and PLT were detected, and comparisons were conducted among the above three groups. Additionally, correlations and receiver operating characteristic (ROC) curves were displayed to test whether calcium level and PLT can differentiate patients with ABN and PTOM. RESULTS: Outcomes showed that the incidences of asymptomatic hypocalcemia (PTOM vs. ABN vs. controls = 22.94% vs. 6.92% vs. 8.82%, χ 2 = 21.098, P < 0.001) and thrombocytosis (PTOM vs. ABN vs. controls = 35.3% vs. 13.84% vs. 12.35%, χ 2 = 28.512, P < 0.001) were highest in PTOM patients. Besides, the mean serological levels of phosphorus in PTOM and ABN patients were significantly higher than those in the controls (P = 0.007). The Area Under the Curve (AUC) of the ROC curve outcomes revealed that, with the combination of serum calcium level with PLT count, the predictive role was acceptable (AUC 0.730, P < 0.001, 95% CI 0.681-0.780). Also, serological levels of calcium of 2.225 mmol/L and PLT count of 246.5 × 109/L were identified as the optimal cut-off values to distinguish patients with and without PTOM. However, age- and gender-related differences in serum calcium levels (age, P = 0.056; gender, P = 0.978) and PLT count (age, P = 0.363; gender, P = 0.799) were not found to be statistically significant in any groups. In addition, no significant correlations were identified between serum calcium level and PLT count (R = 0.010, P = 0.839). CONCLUSIONS: Asymptomatic hypocalcemia and thrombocytosis appeared to be more frequent in this cohort with PTOM. Serological levels of calcium and PLT count may be useful biomarkers in screening patients suspected of PTOM.

Mangiferin Relieves Lipopolysaccharide-Induced Injury by Up-Regulating miR-181a via Targeting PTEN in ATDC5 Cells.

BACKGROUND: Mangiferin (MF) was reported to possess anti-inflammatory activity. This investigation tried to probe into the underlying mechanism of MF in osteoarthritis. METHODS: ATDC5 cells were pretreated with series concentrations of MF (0.1, 1, 5, 10, 15, 20 µM) for 2 h and then were exposed to lipopolysaccharide (LPS) (5 µg/ml) for 12 h to construct the inflammatory injury model. The cell viability, productions of pro-inflammatory cytokines and enzymes were respectively measured by employing CCK-8 assay, western blot, ELISA, and quantitative reverse-transcription (qRT)-PCR. miR-181a expression was altered by employing cell transfection. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) method was employed for detection of reactive oxygen species (ROS) generation. Dual luciferase activity assay was conducted for analyzing the relationship between miR-181a and PTEN. The underlying mechanism was determined by employing western blot. RESULTS: High doses of MF treatment (15 and 20 µM) noticeably induced inflammatory injury exhibiting as increased the productions of pro-inflammatory cytokines, enzymes and ROS, activated NF-κB pathway and deactivated PTEN/PI3K/AKT pathway in ATDC5 cells. Besides, MF treatment notably remitted LPS-induced inflammatory injury through deactivation of NF-κB pathway and activation of PTEN/PI3K/AKT pathway. PTEN was a target of miR-181a. Inhibition of miR-181a remarkably reversed MF-triggered impacts on ATDC5 cells. CONCLUSION: MF attenuated LPS-induced inflammatory damage through miR-181a/PTEN axis and thereby inhibiting NF-κB pathway and activating PI3K/AKT pathway.

Analysis of the Composition and Functions of the Microbiome in Diabetic Foot Osteomyelitis Based on 16S rRNA and Metagenome Sequencing Technology.

Metagenome sequencing has not been used in infected bone specimens. This prospective observational study explored the microbiome and its function in patients with diabetic foot osteomyelitis (DFO) and posttraumatic foot osteomyelitis (PFO) based on 16S rRNA sequencing and metagenome sequencing technologies. Spearman analysis was used to explore the correlation between dominant species and clinical indicators of patients with DFO. High-throughput sequencing showed that all the specimens were polymicrobial. The microbial diversity was significantly higher in the DFO group than in the PFO group. Firmicutes, Prevotellaceae, and Prevotella were the most abundant microbes in the DFO group. The most abundant microbes in the PFO group were Proteobacteria, Halomonadaceae, and Halomonas Prevotella denticola, Prevotella jejuni, and Prevotella fusca had positive correlation with the duration of diabetic foot infection (DFI_d). Proteus vulgaris was positively correlated with the infection index, while Bacteroides fragilis was negatively correlated. The microbial functional genes were more abundant in the DFO group than in the PFO group. Metagenome sequencing is feasible for the analysis of the microbiome in infected bone specimens. Gram-negative bacteria and anaerobes are dominant in DFO.