Mast Cells Initiate Type 2 Inflammation through Tryptase Released by MRGPRX2/MRGPRB2 Activation in Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by T helper 2 inflammation as the core pathogenic mechanism. MRGPRX2 plays a key role in nonhistamine allergies and neuroimmune mechanisms in chronic inflammatory dermatitis. However, the role of MRGPRX2 in AD and the development of type 2 inflammation is not yet clear. This study aimed to define the role of MRGPRX2 in type 2 inflammation development and cytokine release in AD by determining its levels in patients with AD and healthy controls. Furthermore, MrgprB2-conditional knockout (MrgprB2-/-) and wild-type mice were used to construct an MC903-induced AD mouse model to observe skin inflammation and cytokine release. Tryptase and its antagonist were applied separately to MrgprB2-/- mice with AD and wild-type mice with AD to confirm the role of the MRGPRB2-tryptase axis in the development of type 2 inflammation in AD. We found that AD severity and type 2 cytokine levels were not associated with IgE levels but were associated with MRGPRX2/MRGPRB2 expression. MrgprB2-/- mice with AD showed milder phenotypes and inflammatory infiltration in the skin than wild-type mice with AD. Tryptase released by MRGPRX2/MRGPRB2 activation is involved in the release of type 2 cytokines, which contributes to inflammatory development in AD.

Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy.

Autophagy and M1 macrophage polarization play important roles in the regulation of inflammation in atopic dermatitis (AD). Dictamnine is one of the main ingredients in Cortex Dictamni, a widely used traditional Chinese medicine for the treatment of dermatitis. In the present study, we investigated the anti-inflammatory effects of dictamnine on AD like skin lesions and M1 macrophage polarization. A 2,4-dinitrofluorobenzene (DNFB) triggered AD like skin lesions models in mice was established to identify the ameliorative effects of dictamnine on AD in vivo. In addition, an M1 macrophage polarization model was co-stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) using phorbol myristate acetate (PMA) differentiated THP-1 cells, to investigate the effect of dictamnine on promoting autophagy and inhibiting inflammatory factor release. Dictamnine suppressed DNFB-induced skin inflammation by inhibiting M1 macrophage polarization, up-regulating the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, and promoting macrophage autophagy at inflammatory sites. Dictamnine also could reduce the release of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8), and down-regulate the mRNA expression of these genes in LPS-IFN-γ triggered M1 polarized macrophages. Dictamnine ameliorates AD like skin lesions by inhibiting M1 macrophage polarization and promoting autophagy. Hence, dictamnine is expected to be a potential therapeutic candidate for AD.

Surgical Management of Infection Secondary to Cemento-osseous Dysplasia.

Cemento-osseous dysplasia (COD) of the jaws generally has no clinical manifestations when asymptomatic, thus requiring no treatment. However, secondary infection in COD requires surgical intervention. This study was focused on the evaluation of the surgical treatment of COD patients with secondary infections. The clinical data of COD patients with secondary infections, treated at the Peking University, Hospital of Stomatology between March 2021 and June 2022, were retrospectively reviewed. The data included age, sex, lesion characteristics, number of surgeries, and surgical outcomes. Seven COD patients with secondary infections underwent curettage, and the wounds were repaired using local soft tissue flaps, such as the buccal fat pad. Four of the patients had primary wound healing, while 3 presented with wound dehiscence. Healing occurred in 2 of these 3 patients after ~1 month of dressings. The remaining patient showed no improvement after 9 weeks, and underwent a second surgery, which led to primary wound healing. In conclusion, secondary infection in COD is an indication for surgical intervention, which may arrest the disease progression.

Nd:YAG-photobiomodulation enhanced ADSCs multilineage differentiation and immunomodulation potentials.

To investigate the effects of Nd: YAG (1064 nm) photobiomodulation on multilineage differentiation and immunomodulation potentials of adipose tissue-derived stem cells (ADSCs) in vitro and in vivo. For in vitro experiments, cells were divided into the control group (non-irradiated control ADSCs) and photobiomodulation groups. 0.5 J/cm2, 1 J/cm2, 2 J/cm2, and 4 J/cm2 were used for proliferation assays; for ADSCs adipogenic differentiation assays, 0.5 J/cm2, 1 J/cm2 were applied; 1 J/cm2 was used for migration and immunomodulation assays. The differentiation abilities were assessed by qPCR, Oil Red O staining, and Alizarin Red staining. The immunomodulation potential was assessed by qPCR and human cytokine array. DSS-induced colitis model. was used to test the effect of photobiomodulation on ADSCs immunomodulation potentials in vivo. Nd:YAG-based photobiomodulation dose-dependently promoted ADSCs proliferation and migration; 1 J/cm2 showed the best promotion effect on proliferation. Moreover, Nd:YAG photobiomodulation promoted ADSCs osteogenic differentiation and brown adipose adipogenic differentiation. The potential immunomodulation assays showed Nd:YAG photobiomodulation improved Anti-inflammation capacity of ADSCs and photobiomodulation irradiated ADSCs effectively alleviated DSS-induced colitis severity in vivo. Our study suggests Nd:YAG photobiomodulation might enhance the ADSCs multilineage differentiation and immunomodulation potentials. These results might help to enhance ADSCs therapeutic effects for clinical application. However, further studies are needed to explore the mechanisms of Nd:YAG photobiomodulation promoting multilineage differentiation and immunomodulation potentials of ADSCs.

Increased apoptosis of gingival epithelium is associated with impaired autophagic flux in medication-related osteonecrosis of the jaw.

Macroautophagy/autophagy has both negative and positive aspects in the development of many diseases. Yet, its exact role and specific mechanism in the onset of medication-related osteonecrosis of the jaw (MRONJ) is still not fully understood. Retarded gingiva healing is the primary clinical manifestation in patients with MRONJ. In this study, we aimed to explore the relationship between autophagy and apoptosis in MRONJ gingival epithelium and search for a method to prevent this disease. First, we examined clinical samples from patients diagnosed with MRONJ and healthy controls, finding that autophagy-related markers MAP1LC3/LC3 and SQSTM1/p62 synchronously increased, thus suggesting that autophagic flux was suppressed in MRONJ. Moreover, mRNA sequencing analysis and TUNEL assay showed that the process of apoptosis was upregulated in patients and animals with MRONJ, indicating autophagy and apoptosis participate in the development of MRONJ. Furthermore, the level of autophagy and apoptosis in zoledronic acid (ZA)-treated human keratinocytes cell lines (HaCaT cells) was concentration dependent in vitro. In addition, we also found that RAB7 (RAB7, member RAS oncogene family) activator ML098 could rescue MRONJ gingival lesions in mice by activating the autophagic flux and downregulating apoptosis. To sum up, this study demonstrated that autophagic flux is impaired in the gingival epithelium during MRONJ, and the rescued autophagic flux could prevent the occurrence of MRONJ.Abbreviations: ACTB: actin beta; Baf-A1: bafilomycin A1; CASP3: caspase 3; CASP8: caspase 8; CT: computed tomography; DMSO: dimethyl sulfoxide; GFP: green fluorescent protein; HaCaT cells: human keratinocytes cell lines; H&E: hematoxylin and eosin; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MRONJ: medication-related osteonecrosis of the jaw; PARP: poly(ADP-ribose) polymerase; RAB7: RAB7, member RAS oncogene family; RFP: red fluorescent protein; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; ZA: zoledronic acid.

Exosomes Derived from Adipose Tissue-Derived Mesenchymal Stromal Cells Prevent Medication-Related Osteonecrosis of the Jaw through IL-1RA.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.

Risk Factors for Maxillofacial Space Infection Complications: A Retrospective Analysis of 457 Patients.

This study was performed to determine the risk factors associated with systemic complications of maxillofacial space infection (MSI), and to propose an objective evaluation index - severity score of MSI. 457 MSI patients from Jan 2010 to Dec 2020 were reviewed retrospectively. The predictor variables included demographic, origin of infection, underlying systemic disease, pre-hospital medication history, laboratory examinations and severity scores of space infection. The severity score of space infection was proposed to evaluate the airway compromise of anatomic spaces. The primary outcome variable was the complication. The impact factors of complications were analyzed using univariate analysis and multivariate logistic regression. 457 patients were included (average age 46.3 y, male to female ratio 1.43:1). Among them, 39 patients developed postoperative complications. In the complication group, there were 18 patients (46.2%) with pulmonary infection, and two patients died. We found that the history of diabetes mellitus (OR=4.74, 95% confidence interval (CI)=2.22, 10.12), high temperature (≥39°C) (OR=4.16, 95% CI=1.43, 12.06), advanced age (≥65 y) (OR=2.88, 95% CI=1.37, 6.01), and severity score of space infection (OR=1.14, 95% CI=1.04, 1.25) were independent risk factors for complications of MSI. All the risk factors needed to be closely monitored. Severity score of MSI was an objective evaluation index to predict complications.

Low-level laser therapy prevents medication-related osteonecrosis of the jaw-like lesions via IL-1RA-mediated primary gingival wound healing.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. METHODS: Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. RESULTS: LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. CONCLUSIONS: LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.

GWAS of Chronic Spontaneous Urticaria Reveals Genetic Overlap with Autoimmune Diseases, Not Atopic Diseases.

Although chronic spontaneous urticaria (CSU) is a common disease, GWASs of CSU are lacking. We aimed to identify susceptibility SNPs by performing a GWAS in Chinese Han adults with CSU. The discovery cohort included 430 CSU cases and 482 healthy controls. The GWAS findings were validated in 800 CSU cases and 900 healthy controls. Genetic, functional enrichment, and bioinformatic analyses of genome-wide significant SNPs were performed to assess the association between CSU and autoimmunity or atopy. Five genome-wide significant SNPs were identified: rs434124/LILRA3, rs61986182/IGHG1/2, rs73075571/TDGF1, rs9378141/HLA-G, and rs3789612/PTPN22. The first four SNPs were in linkage disequilibrium with autoimmune-related diseases‒associated SNPs and were cis-expression quantitative trait loci in immune cells. The five SNPs-annotated genes were significantly enriched in immune processes. Higher polygenic risk scores and allele frequencies of rs3789612∗T, rs9378141∗C, and rs73075571∗G were significantly associated with autoimmune-related CSU phenotypes, including positive antithyroglobulin IgG, positive anti-FcεRIα IgG, total IgE <40 IU/ml, and positive antithyroid peroxidase IgG but not with atopic or allergic sensitized CSU phenotypes. This GWAS of CSU identifies five risk loci and reveals that CSU shares genetic overlap with autoimmune diseases and that genetic factors predisposing to CSU mainly manifest through associations with autoimmune traits.

Comparison of Postoperative Enophthalmos Between Fresh and Delayed Unilateral Orbital Fractures After Orbital Reconstruction With Titanium Mesh Using Computer-Assisted Navigation.

This study compares postoperative enophthalmos between fresh and delayed unilateral orbital fractures after orbital reconstruction with titanium mesh using computer-assisted navigation. The sample was composed of 45 patients with post-traumatic unilateral enophthalmos who were divided into the fresh fracture group and the delayed fracture group. They underwent orbital reconstruction with standard preformed orbital implants and computer-assisted navigation system. The following parameters were measured with computed tomography images: the degree of enophthalmos, orbital volume, and fracture defect area. Patients were reviewed preoperatively (T0), 1 week postoperatively (T1), and 6 months postoperatively (T2). Computed tomography measurements showed that in both groups, the degree of enophthalmos decreased after surgery but increased significantly from T1 to T2 ( P <0.05). ΔE (difference in the degree of enophthalmos between T1 and T2) was similar in patients with fresh and delayed fractures. There was a significant difference in the degree of ΔE between patients with single-wall orbital fractures and those with two-wall orbital fractures. The findings indicate that postoperative enophthalmos is common in both the groups and is closely related to the degree of preoperative enophthalmos. Furthermore, the recurrence of enophthalmos is similar between the 2 groups, but it is higher in patients with orbital fractures involving 2 walls.

Comparison of the histopathological characteristics of diffuse sclerosing osteomyelitis of the mandible, chronic suppurative osteomyelitis, and craniofacial fibrous dysplasia.

BACKGROUND: There are relatively few reports on the histopathological characteristics of diffuse sclerosing osteomyelitis of the mandible (DSOM), which is difficult to distinguish from chronic suppurative osteomyelitis (CSO) and craniofacial fibrous dysplasia (CFD). This study aimed to summarize and compare the histopathological characteristics of DSOM, CFD, and CSO. MATERIALS AND METHODS: In this study, hematoxylin and eosin-stained sections of patients with DSOM, CSO, and CFD at the Peking University Hospital of Stomatology from 2015 to 2020 were retrieved. The histopathological characteristics were summarized, including new bone formation, inflammatory cell infiltration, bone trabecular morphology, osteoclasts, sequestrum, bacterial mass, and calcified spherules, similar to cementicles. The histopathological characteristics of DSOM, CSO, and CFD were compared, and the results were statistically analyzed. RESULTS: In total, 50, 13, and 10 patients with DSOM, CSO, and CFD were included in this study, respectively. In terms of new bone formation, both DSOM and CSO showed reactive bone formation (p = 1), whereas CFD mainly showed fiber osteogenesis (p < 0.001). The inflammatory cells of DSOM were mainly lymphocytes and plasma cells, whereas those of CSO were mainly lymphocytes and neutrophils (p < 0.001), and there was usually no inflammatory cell infiltration in the CFD specimens (p < 0.001). DSOM, CSO, and CFD showed irregular bone trabeculae (p = 0.045, p = 0.703) and active osteoclasts (p1 = 0.189, p2 = 0.256). DSOM showed a small amount of bacterial mass but no sequestrum; neither of which was found in CFD (p = 1, p = 1), but it was common in CSO (p = 0.011 and p = 0.025). DSOM and CSO showed smooth and regular basophilic lines (p = 0.308), whereas CFD showed a rough and irregular basophilic line (p < 0.001). CONCLUSIONS: The histopathological characteristics of the three diseases were partly similar, but there were evident differences. The main differences are the type of new bone formation, types and distribution of inflammatory cells, and presence of sequestrum and bacterial masses. These differences will help clinicians diagnose DSOM.

Surgical treatment of severe medication-related osteonecrosis of the jaw.

OBJECTIVES: This study aimed to summarize the clinical outcomes of surgical treatment for severe medication-related osteonecrosis of the jaw (MRONJ, stages 2 and 3). METHODS: A retrospective cohort study was conducted to review the patients with severe MRONJ from July 2013 to May 2021. All patients were treated surgically. The characteristics and clinical variables were recorded and analyzed. RESULTS: A total of 104 patients (123 MRONJ lesions) were included, including 42 males and 62 females, aged 64.6±9.1 years. The primary disease was malignant in 91 cases and benign in 13 cases. Forty-three cases (35.0%) were stage 2 lesions, and 80 (65.0%) were stage 3 lesions. Thirty-nine (31.7%) lesions were located in the maxilla, and 84 (68.3%) lesions were located in the mandible. The most commonly used bisphosphonates were zoledronic acid (n=89; 85.6%), followed by alendronate (n=10; 9.6%), and pamidronate (n=10; 9.6%). Antiangiogenic agents were administered in 62 (59.6%) patients. The mean duration of bisphosphonate therapy was 34.7±25.8 months, and the mean duration of drug holiday was 10.1±10.7 months. All operations were performed under general anesthesia. For stage 2 lesions, debridement and saucerization were performed to completely resect the lesions, and the wounds were closed without tension through local mucoperiosteum flaps. For stage 3 lesions, after the lesions were completely resected, the bone defect was covered by reconstruction plate fixation and ipsilateral submandibular gland translocation, iodoform gauze, and buccal fat pad accordingly. The follow-up period ranged from 3 months to 6 years; 81.3% (100/123) of the lesions reached mucosal healing at the last follow-up, whereas wound infection and dehiscence occurred in 18.7% (23/123) of the lesions postoperatively. CONCLUSIONS: Severe MRONJ lesions could be surgically treated to achieve mucosal healing. Vascularized flap reconstruction could be considered if the patient's general condition could tolerate it.

A comparative study of the clinical characteristics of patients with medication-related osteonecrosis of the jaw and osteoporosis or malignancy.

OBJECTIVE: This study aimed to compare the clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and osteoporosis vs malignancy. STUDY DESIGN: The study included patients hospitalized with MRONJ between July 2013 and April 2021. These patients were assigned to the osteoporosis or malignancy groups according to their primary disease. Characteristics and clinical variables were recorded and compared. RESULTS: Nighty-one patients (107 MRONJ lesions) were included, with 12 (14 lesions) in the osteoporosis group and 79 (93 lesions) in the malignancy group. The osteoporosis and malignancy groups differed in their respective incubation periods (57.0 ± 42.8 vs 29.3 ± 19.8 months, respectively; P = .048), bisphosphonates cumulative dose (16,487.4 ± 14,268.8 mg alendronate vs 104.0 ± 79.9 mg zoledronic; P = .014), and rate of patients receiving antiangiogenic agents (0/12, 0.0% vs 48/79, 60.8%; P = .001). The groups were similar in their treatment outcomes, measured as successful surgeries (11/12, 91.7% vs 59/79, 74.7%; P = .351). CONCLUSIONS: For stage 2 or 3 MRONJ, patients with osteoporosis (exposed to oral bisphosphonates) developed MRONJ over a longer incubation period than patients with malignancy. The groups had similar responses to surgery.

GNAS mutation analysis assists in differentiating chronic diffuse sclerosing osteomyelitis from fibrous dysplasia in the jaw.

Chronic diffuse sclerosing osteomyelitis of the mandible (DSOM) and fibrous dysplasia (FD) are distinct lesions with overlapping clinicopathological features that complicate their diagnosis. This study aimed to evaluate the efficacy of GNAS mutation analysis in differentiating between these two conditions. DNA samples from patients with DSOM (n = 35) and FD (n = 29) were collected to analyze the presence of GNAS mutations in exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. Twenty-four of 29 patients (83%) with FD showed missense mutations in codon 201 in exon 8, whereas no mutation was detected in exon 9. No mutations were found in any of the 35 cases with DSOM. We also identified one case with an uncertain diagnosis due to overlapping clinicopathological features of DSOM and FD. A Q227H mutation was detected in this case, that confirmed the diagnosis of FD. Taken together, the findings indicate that mutational analysis of the GNAS is a reliable approach to differentiate between DSOM and FD of the jaw.

IgE and IgG Anti-Thyroid Autoantibodies in Chinese Patients With Chronic Spontaneous Urticaria and a Literature Review.

Immunoglobulin (Ig) E and IgG anti-thyroid autoantibodies (AAbs) play important roles in the immunopathogenesis of chronic spontaneous urticaria (CSU). To date, association of IgE and IgG AAbs with Chinese CSU patients has not been fully investigated. We aimed to explore prevalence rates of IgE and IgG AAbs in Chinese CSU patients and their association with clinical and laboratory parameters. Serum IgE and IgG AAbs against thyroid peroxidase (TPO) and thyroglobulin (TG), total IgE (tIgE) and specific IgEs were measured using enzyme-linked immunosorbent assay, chemiluminescence microparticle immunoassay and immunoblotting. Meta-analyses and literature review were conducted. The meta-analyses indicated that CSU cases were 4.98, 6.90 and 6.68 times more likely to have positive anti-TPO IgE, anti-TPO IgG and anti-TG IgG (all P < 0.001) compared with controls, respectively, and revealed a positive correlation between the prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.53, P = 0.025). A total of 1,100 Chinese Han adult CSU patients and 1,100 ethnicity-, age- and sex-matched healthy controls were recruited from 15 centers. Prevalence rates of anti-TPO IgE, anti-TPO IgG, anti-TG IgE or anti-TG IgG in the patients were all significantly higher than those in the controls. Significant correlations were observed between prevalence rates of anti-TPO IgE and anti-TPO IgG (r = 0.297, P < 0.001) as well as between those of anti-TG IgE and anti-TG IgG in the patients (r = 0.137, P < 0.001). Patients with anti-TPO IgE or anti-TPO IgG had significantly lower tIgE levels (P < 0.001). Positive anti-TPO IgE, positive anti-TPO IgG and tIgE < 40 IU/mL were independent predictors of antihistamine-refractory cases. In conclusion, the prevalence rates of IgE and IgG AAbs in Chinese CSU patients are significantly elevated and reciprocally correlated. This study verifies the results of previous case-control studies of CSU patients from other populations and ethnicities.

Recurrence-Related Factors of Medication-Related Osteonecrosis of the Jaw: A Five-Year Experience.

PURPOSE: The treatment of medication-related osteonecrosis of the jaw (MRONJ) is greatly challenging for surgeons. In this study, we reviewed patients with MRONJ treated in our hospital in the past 5 years and explored the risk factors of recurrence. METHODS: A retrospective cohort study was conducted to review the patients with MRONJ from January 1, 2016 to December 31, 2020. All patients received a monthly intravenous application of zoledronic acid. The primary outcome variable was the treatment outcome during follow-up. The predictor variables were local and systemic factors related to the treatment outcome. Multivariate logistic regression analysis was performed to identify the risk factors of recurrence after MRONJ treatment. RESULTS: A total of 58 patients (62 sites) were included in this study. In multivariate regression analysis, the risk factor associated with recurrence after MRONJ treatment was the duration of medication of more than 18 months (odds ratio = 7.346; 95% confidence interval: 1.461-36.946; P = .016). CONCLUSIONS: Using zoledronic acid over 18 months may increase the risk of recurrence in MRONJ patients.

Is Operative Management Effective for Non-Bacterial Diffuse Sclerosing Osteomyelitis of the Mandible?

PURPOSE: Operative management has been reported to show varying degrees of therapeutic effects for non-bacterial diffuse sclerosing osteomyelitis of the mandible (DSOM). The purpose of this study was to retrospectively analyze and summarize the operative outcomes for non-bacterial DSOM. METHODS: In this retrospective cohort study, patients with non-bacterial DSOM who received operative treatment were enrolled at the Peking University Hospital of Stomatology between 2012 and 2019. The primary predictor variables were the type of operative treatment and number of operations. The outcome variables were operative outcomes (symptom relief or ineffective) and time to recurrent symptoms after operations. Other study variables were demographics, including sex, age, and non-bacterial DSOM onset time. The χ2 test and Kaplan-Meier model were used to evaluate differences. RESULTS: The sample was composed of 72 patients with a mean age at onset of 26.1 ± 17.8 years and showed a female predilection. Decortication was performed for 68 patients with non-bacterial DSOM, and 4 patients underwent segmental mandibulectomy. Symptom relief was achieved in 37 (54.4%) patients after the first decortication, and the median time to symptom recurrence was 2.0 months. Furthermore, the longest time to symptom recurrence was not more than 6 months in all patients. Among the 4 patients who underwent segmental mandibulectomy, 2 who received fibula repair experienced recurrence of symptoms at 4 and 5 months after the operations, respectively, and their normal mandible and the transplanted fibula also presented with imaging manifestations of osteomyelitis. CONCLUSIONS: Decortication and segmental mandibulectomy were not effective for non-bacterial DSOM. This finding is consistent with the results of other reports, and this condition may be best managed non-operatively by rheumatologists.

Adipose-Derived Stem Cells Promote Bone Coupling in Bisphosphonate-Related Osteonecrosis of the Jaw by TGF-ß1.

This study aimed to investigate molecularly targeted therapy to revive bone remodeling and prevent BRONJ by local adipose-derived stem cells (ADSCs) transplantation. Clinical samples of BRONJ and healthy jawbones were used to examine the bone coupling-related cells and TGF-ß1 expression. Bone coupling-related cells and TGF-ß1 expression were also assessed in BRONJ-like animal model to confirm the results in clinical samples. ADSCs were locally administered in vivo and the therapeutic effects were evaluated by gross observation, radiological imaging, and histological examination. Furthermore, ADSCs-conditioned medium (ADSCs-CM) and neutralizing antibody were applied to assess the effects of ADSCs-derived TGF-ß1 on restoring bone coupling in vivo. Osteoclast formation and resorption assays were performed to evaluate the effects of ADSCs-derived TGF-ß1 on ZA-treated pre-osteoclasts. Cell migration was performed to assess the effects of ADSCs-derived TGF-ß1 on patients' bone marrow stem cells (BMSCs). The number of osteoclasts, Runx2-positive bone-lining cells (BLCs) and TGF-ß1 expression were decreased in BRONJ and animal model jaw bone samples. These reductions were significantly rescued and necrotic jawbone healing was effectively promoted by local ADSCs administration in BRONJ-like animal models. Mechanistically, ADSCs-CM mainly contributed to promoting bone coupling, while TGF-ß1 neutralizing antibody in the conditioned medium inhibited these effects. Besides, osteoclastogenesis and patients' BMSCs migration were also rescued by ADSCs-derived TGF-ß1. Furthermore, bone resorption-released bone matrix TGF-ß1, together with ADSCs-derived TGF-ß1, synergistically contributed to rescuing BMSCs migration. Collectively, ADSCs promoted bone healing of BRONJ by TGF-ß1-activated osteoclastogenesis and BMSCs migration capacities.

Finite Element Analysis of Two- and Three-Dimensional Fixation in Treating Mandibular Symphyseal Fracture Combined With Bilateral Condylar Intracapsular Fractures.

ABSTRACT: The aim of this study was to compare through finite element analysis two- and three-dimensional (2D and 3D) fixation in the treatment of mandibular symphyseal fracture combined with bilateral condylar intracapsular fractures. The authors created 2 fixation models for the above fracture, and analyzed the stress and displacement in the mandible and fixation materials under 3 loading conditions. The von Mises stress of the mandible and plates peaked during lateral occlusion, and was lowest during central occlusion. In all conditions, stresses in the fixation materials did not exceed the yield stress of titanium. The inferior border of the symphyseal fracture segments showed opposing displacements, and the mandible tended to widen in the 2D fixation model. However, the fracture displacement did not exceed 150 µm for either fixation method. The results suggested that after well reduction and fixation of condylar intracapsular fractures, either 2D or 3D fixation for symphyseal fracture can provide adequately strong fixation. Compared with 2D fixation, 3D fixation has more advantages in controlling the mandibular width and preventing the fixation materials from enduring excessive stress.

Factors Influencing Severity of Medication-Related Osteonecrosis of the Jaw: A Retrospective Study.

PURPOSE: The progression of medication-related osteonecrosis of the jaw (MRONJ) is influenced by many factors. This study aimed to identify the clinical risk factors associated with severe MRONJ (stage 3). PATIENTS AND METHODS: The data of patients with MRONJ who were hospitalized between July 2013 and December 2019 were retrospectively analyzed. Demographic and clinical factors were the independent variables, and the clinical stage of MRONJ lesions was the dependent variable. Multivariate logistic regression analysis was performed to identify the risk factors for advanced stage disease (MRONJ stage 3). RESULTS: A total of 79 patients (with 93 MRONJ lesions) were included. In multivariate regression analysis, the risk factors associated with stage 3 MRONJ were age ≤65 years (odds ratio [OR] = 3.968, 95% confidence interval [CI]: 1.280-12.301; P = .017); chemotherapy (OR = 3.687, 95% CI: 1.048-12.972; P = .042); preoperative MRONJ duration ≥12 months (OR = 7.616, 95% CI: 1.865-31.110; P = .005); lesion location in maxilla (OR = 1.150, 95% CI: 1.006-1.315; P = .041); lesion location in posterior jaw, that is, in molar area (OR = 1.384, 95% CI; 1.118-1.715; P = .003); and serum albumin <40 g/L (OR = 6.257, 95% CI: 1.313-29.815; P = .021). CONCLUSIONS: Age ≤65 years, chemotherapy, preoperative MRONJ duration ≥12 months, lesion location in maxilla, lesion location in the molar area, and serum albumin <40 g/L may increase the risk for severe MRONJ.