Periodontitis is a common chronic inflammatory disease that causes the periodontal bone destruction and may ultimately result in tooth loss.With the progression of periodontitis,the osteoimmunology microenvironment in periodontitis is damaged and leads to the formation of pathological alveolar bone resorption.CD301b+macrophages are specific to the osteoimmunology microenvironment,and are emerging as vital booster for conducting bone regeneration.However,the key upstream targets of CD301b+macrophages and their potential mechanism in periodontitis remain elusive.In this study,we concentrated on the role of Tim4,a latent upstream regulator of CD301b+macrophages.We first demonstrated that the transcription level of Timd4(gene name of Tim4)in CD301b+macrophages was significantly upregulated compared to CD301b-macrophages via high-throughput RNA sequencing.Moreover,several Tim4-related functions such as apoptotic cell clearance,phagocytosis and engulfment were positively regulated by CD301b+macrophages.The single-cell RNA sequencing analysis subsequently discovered that Cd301b and Timd4 were specifically co-expressed in macrophages.The following flow cytometric analysis indicated that Tim4 positive expression rates in total macrophages shared highly synchronized dynamic changes with the proportions of CD301b+macrophages as periodontitis progressed.Furthermore,the deficiency of Tim4 in mice decreased CD301b+macrophages and eventually magnified alveolar bone resorption in periodontitis.Additionally,Tim4 controlled the p38 MAPK signaling pathway to ultimately mediate CD301b+macrophages phenotype.In a word,Tim4 might regulate CD301b+macrophages through p38 MAPK signaling pathway in periodontitis,which provided new insights into periodontitis immunoregulation as well as help to develop innovative therapeutic targets and treatment strategies for periodontitis.

BACKGROUNDThe time until weight-bearing after arthroscopic microfracture when treating osteochondral lesions of the talus (OLT) is very important to the clinical outcomes of the operation. However, there have been no consistent opinions regarding the optimal time to start weight-bearing postoperatively. Many opinions advocate that weight-bearing should begin not earlier than the sixth or eighth week postoperatively, whereas others point out that earlier weight-bearing could also obtain satisfactory outcomes. The purpose of our study was to evaluate the clinical outcomes of early weight-bearing after arthroscopic microfracture during the treatment of OLT.

METHODSFifty-eight ankles in 58 patients with a single OLT <2 cm(2) were retrospectively studied. All lesions were treated with arthroscopic debridement and microfracture under local anesthesia. After the operation, the patients were allowed to bear full weight under the protection of figure-8-shaped splints. The visual analog scale (VAS) for pain and the American Orthopaedic Foot and Ankle Society (AOFAS) ankle--hindfoot scale were evaluated preoperatively and at six postoperative timepoints (1st day, 1st month, 3rd month, 6th month, 12th month, and 24th month). Patients were followed up for 24-52 months (mean (34.97 ± 7.33) months).

RESULTSAll 58 patients achieved excellent recovery with significant relief of their symptoms. The VAS score decreased from 7.31 ± 1.0 preoperatively to 0.95 ± 0.76 at the 24th month follow-up (P = 0.000), whereas the AOFAS score improved from 53.53 ± 8.57 preoperatively to 87.62 ± 5.42 at the 24th month follow-up (P = 0.000).

CONCLUSIONThe successful clinical outcomes of this study demonstrated that early weight-bearing after the treatment of OLT with arthroscopic microfracture can be allowed.

Adolescent ; Adult ; Arthroscopy ; Female ; Fractures, Bone ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Talus ; injuries ; surgery ; Weight-Bearing ; physiology ; Young Adult

BACKGROUNDAnterior cruciate ligament reconstruction (ACLR) has developed dramatically in the last century. Now, ACLR has become a reliable and productive procedure. Patients feel satisfied in >90% cases. The aim of this study was to evaluate the feasibility of allogenetic cortical bone cross-pin (ACBCP) used as a clinical fixation method in anterior cruciate ligament reconstruction on the femoral side based on biomechanical tests in vitro.

METHODSThe specimens were provided by the bone banks of the First Affiliated Hospital of People's Liberation Army of General Hospital from September 2011 to June 2012. Fresh deep frozen human allogenetic cortical bone was machined into cross-pins which is 4.0 mm in diameter and 75.0 mm in length. Biomechanical parameters compared with Rigidfix were collected while cross-pins were tested in double-shear test. The load-to-failure test and cycling test were carried out in a goat model to reconstruct anterior cruciate ligament with Achilles tendon autograft on the femoral side fixed by human 4.0 mm ACBCP and 3.3 mm Rigidfix served as control. Maximum failure load, yield load, and stiffness of fixation in single load-to-failure test were compared between the two groups. Cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 were also compared in between.

RESULTSIn double-shear test both maximum failed load and yield load of 4.0 mm human ACBCP were (1 236.998±201.940) N. Maximum failed load and yield load of Rigidfix were (807.929±110.511) N and (592.483±58.821) N. The differences of maximum failed load and yield load were significant between ACBCP and Rigidfix, P < 0.05. The shear strength of ACBCP and Rigidfix were (49.243±8.039) MPa and (34.637±3.439) MPa, respectively, P < 0.05. In the load-to-failure test ex vivo, yield load and maximum failed load of ACBCP fixation complexity ((867.104±132.856)N, (1 032.243±196.281) N) were higher than those of Rigidfix ((640.935±42.836) N, (800.568±64.890) N, P < 0.05). However, stiffness did not differ significantly between ACBCP group ((247.116±31.897)N/mm) and Rigidfix group ((220.413±51.332) N/mm, P > 0.05). In the cycling test, the cycle-specific stiffness and displacement at cycles 1, 30, 200, 400, and 1 000 did not differ significantly between the ACBCP group and Rigidfix group, P > 0.05.

CONCLUSIONSAllogenetic cortical bone cross-pin possesses satisfactory biomechanical profile which is safe for ACLR and suitable for an aggressive rehabilitation program. Animal and clinical tests should be recommended before clinical use to secure the ACBCP could successfully substituted by host new bone in vivo.

Achilles Tendon ; surgery ; Adult ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Reconstruction ; Female ; Femur ; surgery ; Humans ; Male ; Materials Testing ; Middle Aged ; Orthopedic Fixation Devices

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b⁺ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b⁺ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b⁺ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b⁺ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b⁺ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b⁺ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b⁺ macrophages, and suggests a CD301b⁺ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
Animals ; Mice ; Bone Regeneration ; Cytokines/metabolism* ; Interleukin-4/therapeutic use* ; Macrophages/physiology* ; Mammals ; Osteogenesis ; Periodontitis/drug therapy*

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*