Treatment effects after maxillary expansion using tooth-borne vs tissue-borne miniscrew-assisted rapid palatal expansion appliance.

INTRODUCTION: The study investigated the skeletal effects and root resorption in young adults with maxillary transverse deficiency after tissue-borne or tooth-borne mini-implant anchorage maxillary expansion. METHODS: Ninety-one young adults with maxillary transverse deficiency, aged 16-25 years, were divided into 3 groups according to the treatment method: group A (n = 29) comprising patients treated with tissue-borne miniscrew-assisted rapid palatal expansion (MARPE), the group B (n = 32) comprising patients treated with tooth-borne MARPE, and the control group (n = 30) comprising patients only treated with fixed orthodontic therapies. Pretreatment and posttreatment cone-beam computed tomography images were used to assess the change of maxillary width, nasal width, first molar torque and root volume by paired t test in the 3 groups, respectively. Analysis of variance and Tukey least significant difference analysis were used to detect the changes of all descriptions among the 3 groups P <0.05. RESULTS: In the 2 experimental groups, we observed significant increases in the width of the maxilla, nasal, and arch width, as well as the molar torque. In addition, the height of the alveolar bone and the root volume decreased significantly. There were no significant differences in the maxilla, nasal, and arch width change between the 2 groups. Group B displayed more increases in buccal tipping, alveolar bone loss, and root volume loss than group A (P <0.05). Compared with groups A and B, the control group showed negligible tooth volume loss, with no expansion effect in both skeletal and dental descriptions. CONCLUSIONS: Tissue-borne MARPE produced the same expansion efficiency as tooth-borne MARPE. However, tooth-borne MARPE causes more dentoalveolar side effects in buccal tipping, root resorption and alveolar bone loss.

Factors related to microimplant-assisted rapid palatal expansion in teenagers and young adults: A cone-beam computed tomography study.

INTRODUCTION: For patients with maxillary transverse deficiency, selecting an appropriate therapeutic method is important for the treatment effect and prognosis. Our study aimed to explore factors related to microimplant-assisted rapid palatal expansion (MARPE) in teenagers and young adults using cone-beam computed tomography. METHODS: Twenty-five patients who underwent MARPE were included in this retrospective study from February 2014 to June 2019. Midpalatal suture density (MPSD) ratio, midpalatal suture maturation (MPSM), bone effect, dentoalveolar effect, and dental effect in maxillary first molar were evaluated using cone-beam computed tomography. Spearman correlation analysis was used to analyze the correlation between the MPSD ratio, MPSM, age, and the expansion amount generated by MARPE. RESULTS: Twenty-five patients (mean age, 19.84 ± 3.96 years; range, 15-29 years) with maxillary transverse deficiency were analyzed. Age was negatively correlated with bone expansion, alveolar expansion, and alveolar change (all P <0.05). There was a negative correlation between MPSM and nasal cavity variation, bone expansion, and alveolar change (all P <0.05). The bone expansion was negatively correlated with MPSD ratio 3 (r = -0.417; P <0.05) and MPSD ratio 4 (all P <0.05). CONCLUSIONS: Age, MPSM, and MPSD ratio were significantly related to the MARPE effect. Age, MPSM, and MPSD ratio should be considered when choosing MARPE.

Obstructive sleep apnea: a follow-up program in its relation to temporomandibular joint disorder, sleep bruxism and orofacial pain.

OBJECTIVE: To evaluate the correlation between obstructive sleep apnea (OSA) and temporomandibular joint (TMJ) morphology, tooth wear condition, orofacial pain through a follow-up program. MATERIALS AND METHODS: Seventy one OSA patients were divided into three groups according to their (apnea hypopnea index) AHI: mild group (n = 23), moderate group (n = 24), and severe group (n = 24). All patients had OSA therapies around six months after confirm the diagnosis of OSA. The tooth wear score and orofacial pain condition of all patients were recorded via clinical examination. Cone beam computed tomography (CBCT) images were also taken when confirm the diagnosis of OSA (T0), 6 months after the diagnosis (T1), and 6 months after the OSA treatment (T2). Parameters indicating the condylar morphology and joint space were evaluated. The differences of clinical symptoms and TMJ conditions among T0, T1 and T2 time point were detected in the three groups respectively. The changes in T1-T0 and T2-T1 of all descriptions among three groups were also compared. The correlations between AHI and clinical symptoms were detected with Spearman correlation analysis. RESULTS: In mild group, there was no difference in all clinical symptoms and TMJ morphology among the three time points. Both in moderate and severe group, the condylar volume, superficial area, wear score, visual analogue scales (VAS), and R value (indicating condyle position) displayed significant differences among the three time points (P < 0.05). From T0 to T1, mild group displayed fewer decreases in the condylar volume and superficial area and fewer increases in wear score than that in moderate and severe group (P < 0.05). From T1 to T2, there was a greatest reduction in severe group for R value, and significant difference in the description of VAS and R value were found among the three groups. AHI was negatively correlated condylar volume and condylar superficial area, and was positively correlated with tooth wear score and VAS (P < 0.05). CONCLUSION: Moderate to severe OSA will aggravate orofacial pain and tooth wear, affect TMJ volume and superficial area, even change the location of condyles. Appropriate OSA therapies may be effective ways to alleviate these adverse effects in long-term.

Treatment effects after maxillary expansion using invisalign first system vs. acrylic splint expander in mixed dentition: a prospective cohort study.

BACKGROUND: Invisalign First System (First) is a new type of orthodontic appliance for maxillary arch expansion in mixed dentition children. Till now, few studies have evaluated the expansion effects of First versus other appliances. What's more, most studies of arch expansion did not include a natural group to rule out growth effects. This prospective cohort study aimed to evaluate the dental and dentoalveolar effects using First or acrylic splint rapid maxillary expander (RME) in adolescents excluding growth factors. MATERIALS AND METHODS: After screening by strict inclusion criteria and propensity score matching (PSM), fifty-one patients were included: First group (n = 17), RME group (n = 17), and natural growth (NG) group (n = 17). Nine indicators including dental arch width, dentoalveolar arch width, and inclination of the molars were measured on digital dental casts at baseline (T0) and six-month follow-up (T1). Paired t-tests were used for intra-group results, and two-sample independent t-tests were used for inter-group comparisons. RESULTS: There was no significant increase in all indicators within six months in the NG group (p > 0.05). In the First group and RME group, all width indicators were significantly increased after treatment (p < 0.05). The RME group exhibited greater expansion than the First group in intercanine width, first interpremolar width, second interdeciduous molar width, first intermolar width, arch perimeter, intercanine dentoalveolar width, intermolar dentoalveolar width, and inclination of the molars (p < 0.05). Whereas, there was no significant difference in arch depth between the two treated groups. CONCLUSIONS: Both First and RME can expand the maxillary arch in mixed dentition. In case of mild to moderate maxillary transverse deficiency (MTD), Invisalign First System could be a reasonable option. RME shows significant better efficiency of dental arch expansion than First, recommended for patients with severe MTD. TRIAL REGISTRATION: This prospective study was registered on ClinicalTrials.gov (01/02/2022, registration number: ChiCTR2200056220). The trial was approved by the Ethical Committee of the Hunan Xiangya Stomatological Hospital Central South University (20,200,088), and informed consent was obtained from all subjects and their legal guardian(s).

Morphological changes in alveolar bone thickness and height after orthodontic proclination or labial movement combined with autogenous soft tissue grafting: a CBCT evaluation.

BACKGROUND: Autogenous soft tissue grafting is indicated in thin gingival biotypes before orthodontic proclination or labial movements to increase the keratinized gingiva and prevent gingival recession. However, its effect on local alveolar bone remodeling is unclear. The aim of this study was to investigate the effects of autogenous soft tissue grafting on local alveolar bone after orthodontic proclination or labial movements. METHODS: Sixteen patients with a thin scalloped gingival biotype, narrow keratinized gingiva, or thin cortical bone requiring orthodontic proclination or labial movement of teeth were included. Cone-beam computed tomography (CBCT) images were obtained before grafting and at least 6 months after surgery. Sixty mandibular teeth were included, and the vertical bone level and horizontal labial bone thickness were measured. The results were compared using paired t-tests or Wilcoxon signed-rank test. RESULTS: The horizontal labial bone thickness increased, especially at 6 mm below the cementoenamel junction (CEJ) in the mandibular central and lateral incisors (P < 0.05). The total alveolar bone area of the canines, first premolars, and second premolars increased at 3, 6, and 9 mm below the CEJ, respectively, and the differences were statistically significant (P < 0.05). Additionally, vertical bone height increased minimally on the labial side, but the differences were not statistically significant (P > 0.05). CONCLUSIONS: New bone regeneration was observed on the labial (pressure) side after autogenous soft tissue grafting, which may represent a mechanism to effectively prevent gingival recession and maintain periodontal health. IRB APPROVAL: All the experimental procedures involving humans in this study were approved by the Medical Ethics Committee of Xiangya Stomatological Hospital, Central South University ( No. 20190048).

Effects of occlusal splint and exercise therapy, respectively, for the painful temporomandibular disorder in patients seeking for orthodontic treatment: a retrospective study.

OBJECTIVE: To evaluate the effect of hard stabilization splints (HSS), counselling and exercise therapies, respectively, for the painful temporomandibular disorder (TMD) in patients seeking for orthodontic treatment through magnetic resonance imaging (MRI) and clinical examination. MATERIALS AND METHODS: Eighty-seven TMD patients were divided into two groups according to their therapies: the HSS group (n = 43) comprising of patients treated with HSS, counselling and masticatory muscle exercises; the control group (n = 44) comprising of patients treated with counselling and masticatory muscle exercises alone. All patients had orthodontic therapies after the first treatment phase. The joint pain and clicking of all patients were recorded via clinical examination. MRIs of HSS groups were taken before (T0), after the first phase (T1), and after the orthodontic treatment (T2). Parameters indicating the condyles and articular discs were evaluated. Clinical symptom (pain and clicking) changes among T0, T1 and T2 time point were detected in the two groups respectively. The significant differences between HSS and control groups, as well as between male and female were tested at T1 and T2. Position changes of condyles and discs in HSS group among T0, T1 and T2 were detected in male and female respectively. RESULTS: After the first treatment phase, there was no difference in the decrease of facial pain between the two group, as well as between male and female in the two groups (P > 0.05). Clicking decreasing was not statistically significant. After the whole orthodontic periods, the TMJ pain relapsed in female of the control group, and the number of female's pain joints was more than male's (P < 0.05). In the HSS group, the posterosuperior movements of discs and the anteroposterior movements of condyles were recorded in closing position (P < 0.05). After the whole orthodontic periods, female's disc-condyle angles increased, the discs to HRP distance decreased and condyles to VRP distance increased when compared with the data of T1 (P < 0.05). CONCLUSIONS: For the orthodontic patients with painful TMD, HSS combined with counselling and exercise therapies before orthodontic treatment could provide pain relief. HSS is helpful to improve the position and relation of discs and condyles. In addition, male's prognosis is better than female's in terms of stability.

Displacement and stress distribution of the craniomaxillofacial complex under different surgical conditions: a three-dimensional finite element analysis of fracture mechanics.

OBJECTIVE: To provide a simplified treatment strategy for patients with maxillary transverse deficiency. We investigated and compared the fracture mechanics and stress distribution of a midline palatal suture under dynamic loads during surgically-assisted rapid palatal expansion. METHODS: Based on the cone-beam computed tomography (CBCT) data of a 21-year-old female volunteer, a three-dimensional model of the cranio-maxillofacial complex (including the palatal suture) was constructed. A finite element analysis model was constructed based on meshwork. After the yield strength of the palatal suture was set, an increasing expansion force (0-500 N) was applied within 140 ms to calculate the time-load curve, which mimicked nonsurgical bone expansion (model A). The same method was used to evaluate the fracture process, time and stress distribution of the palatal suture in maxillary lateral osteotomy-assisted (model B) and LeFort osteomy I (LFIO)-assisted expansion of the maxillary arch (model C). RESULTS: Compared with model A, the palatal suture of model B and model C showed a faster stress accumulation rate and shorter fracture time, and the fracture time of model B and model C was almost identical. Compared with model A, we discovered that model B and model C showed greater lateral extension of the maxilla, and the difference was reflected mainly in the lower part of the maxilla, and there was no difference between model B and model C in lateral extension of the maxilla. CONCLUSIONS: Compared with arch expansion using nonsurgical assistance (model A), arch expansion using maxillary lateral wall-osteotomy (model B) or LFIO had a faster rate of stress accumulation, shorter time of fracture of the palatal suture and increased lateral displacement of the maxilla. Compared with arch expansion using LFIO (model C), arch expansion using lateral osteotomy (model B) had a similar duration of palatal suture rupture and lateral maxillary extension. In view of the trauma and serious complications associated with LFIO, maxillary lateral wall-osteotomy could be considered a substitute for LFIO.

Effects of occlusion modification on the remodelling of degenerative mandibular condylar processes.

OBJECTIVE: The temporomandibular joint (TMJ) displays a high remodelling capability in response to occlusion changes. The purpose of the current study was to investigate the responses of TMJ condyles of growing mice to the installation of a unilateral anterior crossbite (UAC) prosthesis and the replacement of the UAC prothesis with a bilateral anterior elevation (BAE) prosthesis. MATERIALS AND METHODS: C57BL/6J mice were randomly assigned to the blank control and experimental groups. In mice in the experimental groups, UAC was created, while in others, BAE was created after the creation of UAC or removal of UAC. Changes in TMJ condylar cartilage and subchondral bone were assessed. RESULTS: The degradation of condylar cartilage induced by UAC was reversed by BAE, as evaluated by cartilage histochemical changes, collagen II-positive area, collagen X-positive chondrocytes and expression levels of Adamts-5, Mmp13, Tnf-α and Il-1ß. Subchondral bone was assessed based on the subchondral bone volume, the number of TRAP-positive cells and the Opg/Rankl ratio. CONCLUSION: The growing mouse TMJ condyle displays a high remodelling capability, which can be degenerative or rehabilitative in response to the creation of UAC and the replacement of UAC with BAE. Early correction of occlusion is beneficial for the recovery of degenerative condyles.

Changes of the upper airway and bone in microimplant-assisted rapid palatal expansion: A cone-beam computed tomography (CBCT) study.

OBJECTIVE: To evaluate the changes of maxillary expansion and upper airway structure after microimplant assisted rapid palatal expansion (MARPE) using cone-beam computed tomography (CBCT). METHODS: This retrospective study included 19 subjects (15 females and 4 males) aged 15-29 years old (mean, 19.95±4.39 years) with maxillary transverse deficiency treated with MARPE. CBCT was performed at the initial diagnosis and 3 months after MARPE treatment. Measurements were taken to evaluate the amount of total expansion, skeletal expansion, and dental expansion at the maxillary first premolar (P1), second premolar (P2), first molar (M1), second molar (M2) regions and upper airway changes. RESULTS: After MARPE treatment, the maxillary skeletal base expansion, skeletal expansion, alveolar expansion and dental expansion were achieved at the P1, P2, M1, M2 region. The nasopharyngeal volume significantly increased 8.48% after MARPE treatment compared with that before the treatment (P < 0.05). The change of nasal lateral width (NLW) was also significantly different before and after MARPE (P < 0.05). However, there were no statistically significant change in the oropharyngeal, palatopharyngeal, glossopharyngeal and airway total volume (all P > 0.05). CONCLUSIONS: MARPE can produce more transverse bone expansion, relieve maxillary transverse deficiency and improve upper airway ventilation.

A protocol for isolation and identification and comparative characterization of primary osteoblasts from mouse and rat calvaria.

Calvaria from neonatal mouse and rat is ideal resource for osteoblasts but can be easily contaminated by other cells such as fibroblasts. Here, we established a protocol for isolation and purification of primary osteoblast by enzyme sequential digestion and differential adhesion. In addition, we compared the phenotypic and functional traits of osteoblasts from mouse and rat which are commonly employed in studies. The method applied equally to rat and mouse in osteoblasts isolation and was corroborated its feasibility and validity. The results also provided us evidences for other experiments such as choosing a certain time point to give intervention and do the relevant tests.

Comparison of the prevalence of respiratory viruses in patients with acute respiratory infections at different hospital settings in North China, 2012-2015.

BACKGROUND: Acute respiratory infections (ARIs) are a great public health challenge globally. The prevalence of respiratory viruses in patients with ARIs attending at different hospital settings is fully undetermined. METHODS: Laboratory-based surveillance for ARIs was conducted at inpatient and outpatient settings of 11 hospitals in North China. The first 2-5 patients with ARIs were recruited in each hospital weekly from 2012 through 2015. The presence of respiratory viruses was screened by PCR assays. The prevalence of respiratory viruses was determined and compared between patients at different hospital settings. RESULTS: A total of 3487 hospitalized cases and 6437 outpatients/Emergency Department (ED) patients were enrolled. The most commonly detected viruses in the hospitalized cases were respiratory syncytial virus (RSV, 33.3%) in children less than two years old, adenoviruses (13.0%) in patients 15-34 years old, and influenza viruses (IFVs, 9.6%) in patients ≥65 years. IFVs were the most common virus in outpatient/ED patients across all age groups (22.7%). After controlling for the confounders caused by other viruses and covariates, adenoviruses (adjusted odds ratio [aOR]: 3.97, 99% confidence interval [99% CI]: 2.19-7.20) and RSV (aOR: 2.04, 99% CI: 1.34-3.11) were independently associated with increased hospitalization in children, as well as adenoviruses in adults (aOR: 2.14, 99% CI: 1.19-3.85). Additionally, co-infection of RSV with IFVs was associated with increased hospitalization in children (aOR: 12.20, 99% CI: 2.65-56.18). CONCLUSIONS: A substantial proportion of ARIs was associated with respiratory viruses in North China. RSV, adenoviruses, and co-infection of RSV and IFVs were more frequent in hospitalized children (or adenoviruses in adults), which might predict the severity of ARIs. Attending clinicians should be more vigilant of these infections.

Analysis of Senescence-Related Differentiation Potentials and Gene Expression Profiles in Human Dental Pulp Stem Cells.

INTRODUCTION: Dental pulp stem cell (DPSC)-mediated dental pulp regeneration is considered a promising method for the treatment of deep caries with pulpitis. However, mesenchymal stem cell (MSC) senescence is an adverse factor from the perspective of cell-based therapies. In this study, we investigated the characteristics and expression profiles of DPSCs from young and old donors. METHODS: DPSCs from young and old donors were cultured in differentiation medium, and their differentiation potentials were assessed. Long noncoding RNA (LncRNA) microarray assays and a bioinformatic analysis were performed to investigate differences in LncRNA and mRNA expression profiles between DPSCs from young and old donors. RESULTS: We found that DPSCs from young donors exhibited more powerful proliferation ability and greater osteogenic and adipogenic differentiation potentials than DPSCs from old donors. In DPSCs from young donors, numerous LncRNAs were significantly up- (n = 389) or down-regulated (n = 172) compared to DPSCs from old donors. Furthermore, 304 mRNAs were differentially expressed, including 247 up-regulated genes and 57 down-regulated genes in DPSCs from young donors. The bioinformatic analysis identified that several pathways may be associated with DPSC characteristics, such as those involved in the cell cycle and RNA transport, and revealed nuclear transcription factor Y subunit ß, general transcription factor IIB, and nuclear receptor subfamily 3 group C member 1 as core regulatory factors and FR249114, FR299091, and ENST00000450004 as core LncRNAs. CONCLUSIONS: Our results indicated that senescence impaired the proliferation and differentiation potentials of DPSCs and that donor age is an important factor that affects their use for tooth regeneration. We also provide insight into the mechanisms responsible for senescence in DPSCs.

Mutational and structural characteristics of four novel heterozygous C-propeptide mutations in the proα1(I) collagen gene in Chinese osteogenesis imperfecta patients.

OBJECTIVE: Osteogenesis imperfecta (OI) with C-propeptide mutations in proα1(I) collagen gene are rarely reported. We report four novel C-propeptide mutations in COL1A1 gene from Chinese OI patients. METHODS: Clinical characteristics and radiographic findings were described for four OI patients with C-propeptide mutations in proα1(I) collagen gene. Mutations were identified by traditional DNA sequencing based on PCR. The locations of mutations were mapped, and in silico prediction was conducted to analyse their effects on protein structure. Histology studies of skin, bone and muscle tissues were performed. RESULTS: All four C-propeptide heterozygous mutations identified were in the COL1A1 gene. Heterozygous mutation of c.4021C>T (p.Q1341X) disrupted the chain recognition sequences and was found in patients with type IV OI. Mutations of c.3893C>A (p.T1298N) and c.3897C>A (p.C1299X) impeded the formation of disulphide bonds and were associated with type IV OI phenotype. Missense mutation of c.3835A>C (p.N1279H) disrupted Ca(2+) binding and led to a severe type III OI phenotype. In silico programs predicted damaging effects for the patients with type III OI and the creation of an exonic splicing enhancer hexamer sequence for the type IV patients. Expansion of the bone marrow cavity and disorganization of osteocyte alignment was evident in bone specimens; and muscle atrophy and enlargement of intramuscular connective tissue were found in muscle specimens. CONCLUSIONS: Four novel C-propeptide mutations in proα1(I) collagen gene were identified in Chinese OI patients, and their clinical severity ranged from moderate type IV to severe type III. In silico prediction of the mutation effect and histological characteristics of tissue specimens was in accordance with the OI phenotypes.

A novel deletion mutation and structural abnormality in the Bruton's tyrosine kinase gene identified in a Chinese patient with X-linked agammaglobulinemia.

BACKGROUND: X-linked agammaglobulinemia (XLA) is a heritable primary immune deficiency disorder caused by mutation of Bruton's tyrosine kinase (BTK) gene. The main clinical characteristics of XLA are recurrent respiratory tract infections and profoundly low serum immunoglobulin levels and B cells. METHODS: The clinical characteristics of a five-year-old Chinese boy with XLA were described. Mutations of BTK genes were identified by traditional DNA sequencing based on PCR. A three-dimensional model of the truncated BTK protein was constructed. RESULTS: Molecular analysis showed a point deletion of an adenine nucleotide at position 1427 (p.Tyr476Ser), which would cause a frameshift and premature termination at codon 484. Three-dimensional analysis showed that the truncated protein had lost the functional region for both ATP and substrate binding such that tyrosine kinase activity would be affected. CONCLUSIONS: The study identified a novel BTK mutation of one Chinese XLA patient. The truncated BTK model identified the loss of a functional domain.

Orphan drug policy analysis in China.

Rare diseases have various types, low incidence rates, complex conditions, and are often difficult to diagnose. Due to China's large population, there is a significant number of rare disease patients, but there is a shortage of orphan drugs. Consequently, these patients often find themselves in a situation where necessary medications are either unavailable or unaffordable. To address this urgent clinical need, China has implemented a series of orphan drug policies aimed at improving drug accessibility and affordability. In terms of drug accessibility, companies are encouraged to expedite drug development through the implementation of tax incentives, guidance for clinical research on rare diseases, and the provision of data protection periods of 6 years, along with market exclusivity periods limited to a maximum of 7 years. Moreover, exemptions for clinical trials, acceptance of overseas clinical trial data, and the creation of a list prioritizing clinically urgent new drugs from overseas have been introduced to expedite the drug registration application, review, inspection, and approval processes. In terms of drug affordability, the import value-added tax on rare disease drugs has been reduced by 3%, and various provinces and cities have established a representative rare disease protection model, which includes special funds, medical assistance programs, and serious disease insurance. The national medical insurance catalog has been adjusted to reduce the financial burden on rare disease patients, resulting in an increase in the number of orphan drugs covered by the catalog to 95 as of March 2024. By comparing orphan drug policies in the United States, the European Union, Japan, Australia, and other countries (or regions), we will provide relevant suggestions to further improve orphan drug policies in China, thus bringing more treatment options and hope to patients with rare diseases.

Role of IFITM2 in osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.

Interferon-inducible transmembrane (IFITM) are a family of small proteins localized to plasma and endolysosomal membranes. Their functions beyond restricting viral entry and replication have been revealed in recent years. IFITM5 is involved in bone mineralization and is an osteogenic cell surface marker. IFITM1 and 3 interact with desmin and myosin, and are involved in myogenic differentiation. This study found upregulation of Ifitm2 during osteogenic differentiation of C3H10T1/2 cells. This positively correlated to the expression of osteogenic differentiation markers Col1a1, Alp, Runx2, and Ocn. Knockdown of Ifitm2 by siRNAs inhibited osteogenic differentiation, calcium deposition, and osteogenic marker expression of C3H10T1/2 cells. The osteoblast transcriptome revealed that knocking down Ifitm2 affected the expression Wnt signaling pathway-related genes, including Wnt family members, their receptors Lrp, Frizzled, and Lgr, and transmembrane molecule Rnf43 that suppresses the Wnt signaling pathway. Luciferase assays indicated enhancement of canonical Wnt signaling pathways by Ifitm2 overexpression. Furthermore, IFITM2 was colocalized in the metaphyseal bone and growth plate of the mouse tibial bone with SP7, a transcription factor essential for osteoblast differentiation and bone formation. These findings reveal a possible novel function and potential mechanisms of Ifitm2 in osteogenic differentiation.

[Occurrence and Risk Assessment of N-nitrosamines and Their Precursors in Qingjiang River Basin].

N-nitrosamines are a type of nitrogen-containing organic pollutant with high carcinogenicity and mutagenicity. In the main drinking water sources of small and medium-sized towns in China, the contamination levels of N-nitrosamines remain unclear. In addition, there is still lack of research on the concentration of N-nitrosamines and their precursors in tributary rivers. In this study, eight N-nitrosamines and their formation potentials （FPs） were investigated in the Qingjiang River, which is a primary tributary of the Yangtze River. The sewage discharge sites were also monitored, and the environmental influencing factors, carcinogenic and ecological risks caused by N-nitrosamines, and their precursors were evaluated. The results showed that six N-nitrosamines were detected in water samples of the Qingjiang River, among which NDMA [（10 ±15） ng·L-1], NDEA [（9.3 ±9.3） ng·L-1], and NDBA [（14 ±7.8） ng·L-1] were the dominant N-nitrosamines, whereas seven N-nitrosamines were detected in chloraminated water samples, among which NDMA-FP [（46 ±21） ng·L-1], NDEA-FP [（26 ±8.3） ng·L-1], and NDBA-FP [（22 ±13） ng·L-1] were the dominant N-nitrosamine FPs. The concentrations of N-nitrosamines in the middle reaches of the Qingjiang River were higher than those in the upper and lower reaches. Furthermore, the concentrations of N-nitrosamines in the sample sites of sewage discharge and tributaries were significantly higher than those in other sampling sites. The monitoring results at the direct sewage discharge points indicated that the main source of N-nitrosamines in river water was the sewage carrying N-nitrosamines and their precursors. In addition, the concentrations of the three dominant N-nitrosamines including NDMA, NDBA, and NDEA were positively correlated with each other, mainly because of their similar sewage sources. The average carcinogenic risk to residents due to N-nitrosamine in drinking water sources was 2.4×10-5, indicating a potential carcinogenic risk. Moreover, due to the high concentrations of N-nitrosamine formation potentials in the Qingjiang River, the carcinogenic risk of drinking water may be even higher. The ecological risk assessment showed that the ecological risk quotient values of N-nitrosamines in the Qingjiang River watershed were lower than 0.002, which was negligible.

Clinical research progress of ridaforolimus (AP23573, MK8668) over the past decade: a systemic review.

Rapamycin, an established mTOR inhibitor in clinical practice, is widely recognized for its therapeutic efficacy. Ridaforolimus, a non-prodrug rapalog, offers improved aqueous solubility, stability, and affinity compared to rapamycin. In recent years, there has been a surge in clinical trials involving ridaforolimus. We searched PubMed for ridaforolimus over the past decade and selected clinical trials of ridaforolimus to make a summary of the research progress of ridaforolimus in clinical trials. The majority of these trials explored the application of ridaforolimus in treating various tumors, including endometrial cancer, ovarian cancer, prostate cancer, breast cancer, renal cell carcinoma, and other solid tumors. These trials employed diverse drug combinations, incorporating agents such as ponatinib, bicalutamide, dalotuzumab, MK-2206, MK-0752, and taxanes. The outcomes of these trials unveiled the diverse potential applications of ridaforolimus in disease treatment. Our review encompassed analyses of signaling pathways, ridaforolimus as a single therapeutic agent, its compatibility in combination with other drugs, and an assessment of adverse events (AEs). We conclude by recommending further research to advance our understanding of ridaforolimus's clinical applications.

Viral aetiology in adults with acute upper respiratory tract infection in Jinan, Northern China.

Our study investigated the epidemiology of respiratory viruses in adult patients with upper respiratory tract infection (URTI) between August 2009 and September 2010 in Jinan, northern China. Nasal and throat swabs (n = 596) were collected from adult patients with URTIs. Nine respiratory-related viruses, including IFV, PIV, HRV, HMPV, HBoV, HCoV, ADV, RSV, and EV, were detected in all samples by conventional and reverse transcription polymerase chain reactions. Positive detection rate for respiratory virus was 38.76% and codetection rate was 4.70% in adults with acute respiratory tract infections. IFV (20.81%) was the dominant agent detected and IFVB had a higher incidence (12.58%) than IFVA (7.72%). Detection rates of 8.22%, 5.03%, 3.69%, and 2.52% were observed for HBoV, HRV, EV, and RSV, respectively. HCoV had the lowest detection rate of 0.50%. HBoV, HRV, EV, and ADV infection rates were higher in the 14-25-year-old group than in the 26-65-year-old group. Codetection rates were higher (7.52%) in the 14-25-year-old group than in the older age group (2.64%). The spectrum of respiratory virus infection in adult patients with URTIs was different in Jinan compared with other cities in China.