Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of～260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.

Graphene family nanomaterials(GFNs)are highly popular in the field of bone tissue engineering because of their excellent mechanical properties,biocompatibility,and ability to promote the osteogenic differentiation of stem cells.GFNs play a multifaceted role in promoting the bone regeneration microenvironment.First,GFNs activate the ad-hesion kinase/extracellularly regulated protein kinase(FAK/ERK)signaling pathway through their own micromorphology and promote the expression of osteogenesis-related genes.Second,GFNs adapt to the mechanical strength of bone tis-sue,which helps to maintain osseointegration;by adjusting the stiffness of the extracellular matrix,they transmit the me-chanical signals of the matrix to the intracellular space with the help of focal adhesions(FAs),thus creating a favorable physiochemical microenvironment.Moreover,they regulate the immune microenvironment at the site of bone defects,thus directing the polarization of macrophages to the M2 type and influencing the secretion of relevant cytokines.GFNs also act as slow-release carriers of bioactive molecules with both angiogenic and antibacterial abilities,thus accelerating the repair process of bone defects.Multiple types of GFNs regulate the bone regeneration microenvironment,including scaffold materials,hydrogels,biofilms,and implantable coatings.Although GFNs have attracted much attention in the field of bone tissue engineering,their application in bone tissue regeneration is still in the basic experimental stage.To promote the clinical application of GFNs,there is a need to provide more sufficient evidence of their biocompatibility,elucidate the mechanism by which they induce the osteogenic differentiation of stem cells,and develop more effective form of applications.

Objective:To investigate the pathogen spectrum and the epidemiological characteristics of hospitalized severe acute respiratory tract infection (SARI) cases in a sentinel hospital in Tongzhou District of Beijing from 2019 to 2022, and provide reference for scientific prevention and control of SARI.Methods:This study enrolled SARI patients in the Beijing Luhe Hospital from January 2019 to December 2022. Nasopharyngeal swabs or respiratory secretions of the patients were collected and analyzed by quantitative real-time PCR to detect the pathogens and their types. The epidemiological and clinical characteristics of the cases were analyzed.Results:In this study, 1 124 SARI cases were enrolled, of which 379 were positive for respiratory pathogens with a detection rate of 33.72%. Most of the SARI cases were positive for bacteria pathogens, and the detection rates of Mycoplasma pneumoniae, Streptococcus pneumoniae, and Stenotrophomonas maltophilia were high. Influenza A virus, parainfluenza virus, and respiratory syncytial virus were the main viral pathogens detected in the cases. There were significant differences in the number of cases and the detection rate of respiratory pathogens among different age groups (χ 2=555, P=0.000 1). The predominant pathogens in different years were different. Mycoplasma pneumoniae [27.27% (51/187)] and influenza A virus [17.65% (33/187), ] were the predominant pathogens in 2019; parainfluenza virus [16.67% (10/60)], Mycoplasma pneumoniae [11.67% (7/60)], and Haemophilus influenzae [11.67% (7/60)] were the predominant pathogens in 2020; Stenotrophomonas maltophilia [24.39% (20/82)] and respiratory syncytial virus [19.51% (16/82)] were the predominant pathogens in 2021; Stenotrophomonas maltophilia [20% (10/50)] and parainfluenza virus [12% (6/50)] were the predominant pathogens in 2022. Conclusions:Most of the SARI cases in Tongzhou district of Beijing from 2019 to 2022 are caused by bacteria. More attention should be paid to the prevalence of Stenotrophomonas maltophilia and Mycoplasma pneumoniae, as well as the prevalence of respiratory syncytial virus, parainfluenza virus, and influenza A virus. The predominant pathogens change every year from 2019 to 2022. Therefore, the prevention and control strategies should be made accordingly. This study provides basis data for the national respiratory multipathogen surveillance program.

The dynamic balance between bone formation and bone resorption is a critical process of bone remodeling.The imbalance of bone formation and bone resorption is closely associated with the occurrence and development of various bone-related diseases.Under both physiological and pathological conditions,non-coding RNAs(ncRNAs)play a crucial regulatory role in protein expression through either inhibiting mRNAs translation or promoting mRNAs degradation.Circular RNAs(circRNAs)are a type of non-linear ncRNAs that can resist the degradation of RNA exonucleases.There is accumulating evidence suggesting that circRNAs and microRNAs(miRNAs)serve as critical regulators of bone remodeling through their direct or indirect regulation of the expression of osteogenesis-related genes.Additionally,recent studies have revealed the involvement of the circRNAs-miRNAs regulatory network in the process by which mesenchymal stem cells(MSCs)differentiate towards the osteoblasts(OB)lineage and the process by which bone marrow-derived macrophages(BMDM)differentiate towards osteoclasts(OC).The circRNA-miRNA network plays an important regulatory role in the osteoblastic-osteoclastic balance of bone remodeling.Therefore,a thorough understanding of the circRNA-miRNA regulatory mechanisms will contribute to a better understanding of the regulatory mechanisms of the balance between osteoblastic and osteoclastic activities in the process of bone remodeling and the diagnosis and treatment of related diseases.Herein,we reviewed the functions of circRNA and microRNA.We also reviewed their roles in and the mechanisms of the circRNA-miRNA regulatory network in the process of bone remodeling.This review provides references and ideas for further research on the regulation of bone remodeling and the prevention and treatment of bone-related diseases.

Craniomaxillofacial development involves a series of highly ordered temporal-spatial cellular differentiation processes in which a variety of cell signaling factors,such as fibroblast growth factors,play important regulatory roles.As a classic fibroblast growth factor,fibroblast growth factor 7(FGF7)serves a wide range of regulatory functions.Previous studies have demonstrated that FGF7 regulates the proliferation and migration of epithelial cells,protects them,and promotes their repair.Furthermore,recent findings indicate that epithelial cells are not the only ones subjected to the broad and powerful regulatory capacity of FGF7.It has potential effects on skeletal system development as well.In addition,FGF7 plays an important role in the development of craniomaxillofacial organs,such as the palate,the eyes,and the teeth.Nonetheless,the role of FGF7 in oral craniomaxillofacial development needs to be further elucidated.In this paper,we summarized the published research on the role of FGF7 in oral craniomaxillofacial development to demonstrate the overall understanding of FGF7 and its potential functions in oral craniomaxillofacial development.

Orthodontically induced tooth root resorption (OIRR) is a serious complication during orthodontic treatment. Stimulating cementum repair is the fundamental approach for the treatment of OIRR. Parathyroid hormone (PTH) might be a potential therapeutic agent for OIRR, but its effects still lack direct evidence, and the underlying mechanisms remain unclear. This study aims to explore the potential involvement of long noncoding RNAs (lncRNAs) in mediating the anabolic effects of intermittent PTH and contributing to cementum repair, as identifying lncRNA-disease associations can provide valuable insights for disease diagnosis and treatment. Here, we showed that intermittent PTH regulates cell proliferation and mineralization in immortalized murine cementoblast OCCM-30 via the regulation of the Wnt pathway. In vivo, daily administration of PTH is sufficient to accelerate root regeneration by locally inhibiting Wnt/β-catenin signaling. Through RNA microarray analysis, lncRNA LITTIP (LGR6 intergenic transcript under intermittent PTH) is identified as a key regulator of cementogenesis under intermittent PTH. Chromatin isolation by RNA purification (ChIRP) and RNA immunoprecipitation (RIP) assays revealed that LITTIP binds to mRNA of leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and heterogeneous nuclear ribonucleoprotein K (HnRNPK) protein. Further co-transfection experiments confirmed that LITTIP plays a structural role in the formation of the LITTIP/Lgr6/HnRNPK complex. Moreover, LITTIP is able to promote the expression of LGR6 via the RNA-binding protein HnRNPK. Collectively, our results indicate that the intermittent PTH administration accelerates root regeneration via inhibiting Wnt pathway. The lncRNA LITTIP is identified to negatively regulate cementogenesis, which activates Wnt/β-catenin signaling via high expression of LGR6 promoted by HnRNPK.
Mice ; Animals ; Cementogenesis ; Wnt Signaling Pathway ; beta Catenin/metabolism* ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism* ; RNA, Long Noncoding/genetics* ; Parathyroid Hormone ; Receptors, G-Protein-Coupled/metabolism*

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To understand the epidemic situation of Redondoviridae in Beijing and analyze its epidemiologic characteristics.Methods:Pharyngeal swab samples of healthy people and patients with acute respiratory infection in Beijing, including influenza like cases and severe acute respiratory infection (SARI) cases in hospitals were collected. Real time PCR was used to detect the nucleic acid of Redondoviridae. The positive samples were amplified and sequenced to analyze their species. The age and sex distribution of patients and species distribution of Redondoviridae were obtained through statistical analysis. Multiplex PCR was used to detect other common respiratory pathogens in the positive samples of Redondoviridae in influenza like cases and SARI cases, and the pathogenicity of Redondoviridae was analyzed.Results:The positive rates of Redondoviridae in healthy people and acute respiratory infection cases were 20.48% (189/923) and 11.23% (43/390), respectively, with a statistically significant difference ( P<0.05). The positive rate of male was higher than that of female in the healthy population, and the positive rate of the elderly group was higher than that of the adult group and the underage group, with a statistically significant difference ( P<0.05). The positive rate of male patients with acute respiratory tract infection was higher than that of female patients, but there was no significant difference. The proportion of Vientovirus in the positive samples of Redondoviridae was higher than that of Brisavirus, and the difference was statistically significant ( P<0.05). Among the throat swabs of respiratory tract infection cases, 43 were positive for Redondoviridae, of whom 24 were not detected for other pathogens. Conclusions:Redondoviridae widely exists in healthy people of all age groups in Beijing, and is also found in acute respiratory infection cases. The positive rate of Redondoviridae is different in different ages and genders. Both Vientovirus and Brisavirus were detected, and the proportion of Vientovirus was significantly higher than Brisavirus.

Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3'-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.
Adipose Tissue/metabolism* ; Animals ; Cell Differentiation/genetics* ; Cells, Cultured ; Histone Deacetylases/metabolism* ; Humans ; Mice ; MicroRNAs/metabolism* ; Osteogenesis/genetics* ; RNA, Circular/metabolism* ; Repressor Proteins/metabolism* ; Signal Transduction ; Stem Cells/metabolism*

Orthodontic treatment for dentofacial deformity is fundamental throughout the entire management process of cleft lip and palate. Orthodontist is one of those who are indispensable in the comprehensive multidisciplinary cleft team. Cleft lip and palate patients have unique dentofacial characteristics which makes the treatment goals and strategies different from those of other patients in different stages. For newborns with cleft lip and palate, the main treatment includes presurgical orthopedics. For patients in their primary dentition stage, the treatment mainly focuses on the prevention of bad oral habits and severe malocclusion. For those in their mixed dentition stage, the treatment mainly consists of dentition preparation for alveolar bone grafting and skeletal growth modification. For patients in their permanent dentition stage, treatment strategies include orthodontic camaflouge treatment, combined orthodontic-orthognathic approach and segmental alveolar distraction osteogenesis. In addition to routine orthodontic treatment, orthodontists should pay special attention to managing the compliance of cleft lip and palate patients with unique psychological characteristics. By summarizing the state-of-art cleft lip and palate orthodontic care in the multidisciplinary team, this review aims to involve more orthodontic clinicians to join in the modern biopsychosocial medical practice of cleft lip and palate team approach and to improve the standard of care for cleft lip and palate patients.