Clinical effects of twin-block combined with maxillary expansion on the upper airway in adolescents with Class II malocclusion.

BACKGROUND: Class II malocclusion, particularly class II division 1, poses a significant orthodontic challenge with implications for both aesthetics and health. This study aimed to explore the impact of twin-block (TB) combined with maxillary expansion treatment (TB-ME) on upper airway dimensions and inflammatory profiles in adolescents with skeletal Class II Division 1 malocclusion in adolescent. METHODS: Ninety-two eligible patients were randomly assigned to two groups: TB-ME treatment and traditional McLaughlin Bennett Trevisi (MBT) straight-wire orthodontic treatment (Control). Cephalometric lateral X-ray scans were conducted before and after treatment to assess skeletal changes, including SNA, ANB, and SNB angles, which are essential to assess the anteroposterior relationships of the maxilla and mandible to the cranial base. We also measured the upper airway volumes and areas. Concentrations of inflammatory factors including intercellular adhesion molecule 1 (ICAM-1), matrix metallopeptidase 2 (MMP2), and interleukin 8 (IL-8) of gingival crevicular fluid analysis (GCF) were detected by enzyme-linked immunosorbent assay. RESULTS: TB-ME treatment induced significant improvement in cephalometric parameters, including a decrease in SNA and ANB angles and an increase in SNB angle. Upper airway volumes and areas increased significantly in both groups, with TB-ME showing greater improvements. GCF analysis revealed a reduction in ICAM-1, MMP2, and IL-8 concentrations in the TB-ME group compared to the Control group. CONCLUSIONS: TB-ME treatment demonstrates multifaceted improvements in skeletal malocclusion, upper airway dimensions, and inflammatory profiles in adolescents with class II division 1 malocclusion, showing the promise of TB-ME in addressing the complexities associated with class II malocclusion.

The effect of food on the pharmacokinetics of Sutetinib maleate capsule, an irreversible EGFR tyrosine kinase inhibitor, in healthy Chinese subjects.

Sutetinib is an irreversible inhibitor of epidermal growth factor receptor (EGFR) and showed favorable efficacy and safety in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring nondrug-resistant rare EGFR mutations. To evaluate the potential food effect, eighteen healthy Chinese subjects were enrolled in a single-centre, randomized, open-label, two-sequence, two-period crossover study. Sutetinib was administered as a single oral 100 mg under fasting or fed conditions, and pharmacokinetic sampling was performed following each dose and analysed by a validated liquid chromatography/mass spectrometry method. Safety and tolerability were also evaluated. Food intake slightly decreased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUC0 - inf) of sutetinib (geometric least-squares mean [GLSM] ratio, 80.94% and 86.11%; 90% confidence interval [CI], 68.43-95.72 and 75.88-97.73) and its active metabolite sutetinib N-Oxide (GLSM ratio, 75.58% and 84.00%; 90% CI, 65.69-86.95 and 75.42-93.56), respectively. In addition, the time to maximum plasma concentration (Tmax) of both sutetinib and its metabolite has been prolonged by 2 h under fed conditions. A total of 31 adverse events (AEs) occurred during the study, with no serious adverse events (SAE) reported, and no obvious difference was observed between the fasting and fed groups. Our results demonstrated that a high-fat and high-calorie diet caused a significant delay in drug absorption and a marginal reduction in drug exposure. Sutetinib was generally well tolerated in healthy Chinese subjects. (This trial was registered at http://www.chinadrugtrials.org.cn . The registration No. is CTR20201933, and the date of registration is 2020-10-16).

Treatment of Class II Malocclusion With Orthodontic Microimplant Anchorage.

INTRODUCTION: The objective of the study was to compare the effects of orthodontic microimplant anchorage (MIA) and conventional extraoral arch anchorage (EAA) on tooth structure and oral inflammatory response in patients with Class II Division I malocclusion. METHODS: A total of 104 patients with Class II malocclusion were enrolled and were randomly assigned to receive MIA or EAA treatments. Clinical efficacy was assessed at 6 months after treatment by measuring molar shift, convex distance, and hinge angle difference between maxillary and mandibular incisors. X-ray was performed for tissue evaluations. The levels of cell adhesion molecule-1 (CAM-1), matrix metalloproteinase-2 (MMP-2), and proinflammatory cytokines in gingival sulcus fluid were measured using enzyme-linked immunosorbent assay to assess inflammatory responses to the implants. RESULTS: Our study demonstrated superior efficacy of MIA compared to EAA in terms of overall efficacy, molar shift, convex distance between upper and middle incisors, as well as hinge angle difference between upper and middle incisors. MIA also showed greater efficacy in reducing tissue fix-point measurements, including saddle point-nasal root point-superior alveolar seat point (SNA), alveolar seat point-nasal root point-inferior alveolar seat point (ANB), overlying (OJ), and overbite (OB). CONCLUSIONS: MIA is a novel orthodontic treatment that showed stronger efficacy in inducing molar shift and correcting soft/hard tissue positions, whilst generating suppressed inflammatory responses. Our study could have significant implications for practice in the orthodontic treatment of Class II malocclusion.

Effects of N-acetyl-L-cysteine polysulfides on periodontitis in a mouse model.

BACKGROUND: Polysulfides are reported to be involved in various important biological processes. N-acetyl-l-cysteine polysulfide with 2 sulfane sulfur atoms (NAC-S2) regulates diverse toll-like receptor (TLR) signaling pathways. Here, we aimed to determine the role of NAC-S2 in periodontitis and explore the potential mechanism. METHODS: A periodontitis mouse model was established by ligating the subgingival between the first and second molars in wild-type, TLR4-/- , and Myd88-/- mice. RESULTS: NAC-S2 did not affect the proportion of macrophages (CD11b+ F4/80+ ) or neutrophils (CD11b+ GR-1+ ) in the bone marrow. Mechanically, lipopolysaccharides (LPS), Zymosan A, or poly I: C induced tumor necrosis factor (TNF), interleukin (IL)-6, and IL-1ß expression in bone marrow-derived macrophages (BMDMs) could be inhibited by NAC-S2. On the other hand, NAC-S2 suppressed the phosphorylation levels of IκB-α, p65, and IκB kinase (IKK)-ß induced by LPS in BMDMs, while LPS induced phosphorylation of ERK1/2, p38, and transforming growth factor ß-activated kinase 1 (TAK1) could not be affected by NAC-S2. In wild-type periodontitis mice, NAC-S2 administration decreased the cemento-enamel-junction-alveolar bone crest (CEJ-ABC) distance and the relative mRNA expression of TNF, IL-6, and IL-1ß, while such phenomena could not be observed in TLR4 deficiency or Myd88 deficiency mice. CONCLUSIONS: All of these results indicate that NAC-S2 ameliorates TLR4/NF-κB pathway mediated inflammation in mouse periodontitis model.

Relationship between microRNA expression and inflammatory factors in patients with both type 2 diabetes mellitus and periodontal disease.

OBJECTIVE: To investigate the expression of single-stranded microRNAs (miRNAs) in serum and gingival crevicular fluid of patients with type 2 diabetes mellitus (T2DM) complicated by periodontal disease and its correlation with inflammatory factors. METHODS: Twenty-six periodontitis patients without diabetes mellitus (periodontal group), 24 patients with T2DM (T2DM group), 22 patients with both T2DM and periodontal disease (comorbid group), and 25 healthy individuals without a history of periodontal disease (healthy group) were recruited respectively. Serum and gingival crevicular fluid specimens were collected to detect the expression levels of miRNAs and inflammatory factors including serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß), and their correlations were also investigated. RESULTS: Eleven miRNAs were detected in the gingival crevicular tissue of all subjects. The expression of miR-223 and miR-200b in serum and gingival crevicular fluid was elevated higher in the comorbid group than in the other three groups (P<0.05), and their expressions in gingival crevicular fluid contributed to the differential diagnosis of periodontal disease from diabetes mellitus comorbid with periodontal disease (P<0.05). Gingival crevicular fluid miR-223 expression was positively associated with TNF-α, clinical attachment loss (CAL), and probing pocket depth (PPD) in the periodontal group, while negatively associated with IL-10 (P<0.05), and so was gingival crevicular fluid miR-200b expression with TNF-α, CAL, and PPD (P<0.05). In the comorbid group, gingival crevicular fluid miR-223 expression showed a positive correlation with TNF-α, CAL, and PPD (P<0.05), and so did gingival crevicular fluid miR-200b expression with TNF-α, CAL, and PPD (P<0.05). CONCLUSIONS: Our findings indicate a close link between the levels of miR-223 and miR-200b in serum and gingival crevicular fluid and susceptibility to T2DM as well as the pathogenesis of periodontal disease.

Correlation between salivary HBD-2 and LL-37 expression levels with blood glucose and periodontal status in patients with type 2 diabetes mellitus.

OBJECTIVE: To examine the correlation between salivary human ß defensin-2 (HBD-2) and LL-37 expression levels and blood glucose in relationship to periodontal status in patients with type 2 diabetes mellitus (T2DM). METHODS: The trial is available at: https://clinicaltrials.gov/ with ClinicalTrials.gov Identifier: NCT03512675. A total of 89 patients with T2DM with chronic periodontitis (CP) enrolled in our hospital from January 2020 to December 2020 were selected. According to the degree of glycemic control and CP, the patients were randomly divided into four groups, namely the good glycemic control and mild CP group (n=26), good glycemic control with moderate to severe CP group (n=24), poor glycemic control with mild CP group (n=21), and poor glycemic control with moderate to severe CP group (n=18). The periodontal clinical parameters, blood glucose indicators, and saliva HBD-2 and LL-37 expression levels were determined. RESULTS: The expression levels of HBD-2 and LL-37 in the saliva of T2DM patients with moderate to severe CP and poor blood sugar control were significantly increased (P<0.05). Saliva HBD-2 and LL-37 levels were positively correlated with probing depth, clinical attachment loss, plaque index, and glycosylated hemoglobin. There was a synergistic interaction between blood glucose, periodontal status, and saliva HBD-2, LL-37 levels (P<0.05). CONCLUSION: There is a positively correlated relationship between blood glucose and periodontal status with salivary HBD-2 and LL-37 levels.

Correlation between salivary developmental endothelial locus-1, interleukin 17 expression level and severity of periodontal disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the correlation of the salivary expression levels of developmental endothelial locus-1 (Del-1) and interleukin 17 (IL-17) with the severity of periodontal disease in patients with type 2 diabetes mellitus (T2DM). METHODS: Fifty-seven patients with T2DM and fifty-seven patients with T2DM complicated with chronic periodontitis (CP) admitted to our hospital from March 2020 to March 2021 were enrolled as the research objects and assigned to the T2DM group and T2DM+CP group respectively. Additionally, 57 healthy controls from the hospital physical examination center during the same period were included as the healthy controls. General information of all the enrolled participants was collected to measure the levels of glycated hemoglobin (HbA1c), salivary inflammatory factors, and salivary Del-1 and IL-17, as well as homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: HbA1c in the T2DM group and T2DM+CP group was significantly higher than that in the healthy control group. Gingival index (GI), plaque index (PI), and probing depth (PD) were significantly higher in case groups than those in the health group. Compared with the healthy control group, salivary IL-17 expression level increased remarkably in the T2DM+CP group and T2DM group, with a higher level observed in the T2DM+CP group (P<0.05). The T2DM+CP group presented significantly higher levels of salivary tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) than the other two groups (P<0.05). Compared with the healthy control group, HOMA-IR and salivary Del-1 declined evidently in the T2DM+CP group and T2DM group, and the lowest values were observed in the T2DM+CP group (P<0.05). Salivary Del-1 and HbA1c were independent risk factors for CP in T2DM patients (P<0.05). CONCLUSION: Salivary Del-1 was downregulated and IL-17 was up-regulated in T2DM patients complicated with CP, indicating their correlation with the occurrence of CP in T2DM patients.

LncRNA FGD5-AS1 promotes tumor growth by regulating MCL1 via sponging miR-153-3p in oral cancer.

PURPOSE: To investigate the function of long noncoding RNA (lncRNA) FGD5-AS1 in oral cancer (OC) and to further clarify the regulation of FGD5-AS1 on miR-153-3p/MCL1 axis. RESULTS: FGD5-AS1 was significantly increased in OC tissues and cells. Loss of FGD5-AS1 inhibited the proliferation, migration and invasion of OC cells. FGD5-AS1 acted as a sponge of miR-153-3p, and MCL1 was direct target of miR-153-3p. Forced expression of miR-153-3p or inhibition of MCL1 reversed the promoted role of FGD5-AS1 on OC cells' migration and invasion. The in vivo tumor growth assay showed that FGD5-AS1 promoted OC tumorigenesis by regulating miR-153-3p/MCL1 axis. CONCLUSIONS: Our research revealed lncRNA FGD5-AS1 acted as an oncogene by regulating MCL1 via sponging miR-153-3p, thus providing some novel experimental basis for clinical treatment or prevention of OC. PATIENTS AND METHODS: The mRNA expression of FGD5-AS1, miR-153-3p and MCL1 was detected by qRT-PCR. CCK8 assay, Edu assay, wound healing assay and transwell assay were used to detect the FGD5-AS1/ miR-153-3p/MCL1 axis function on proliferation, migration and invasion in OC cells. Western blot was used to calculate protein level of MCL1. Luciferase assay was used to detect the binding of miR-153-3p and MCL1, FGD5-AS1and miR-153-3p.

Simultaneous determination of sutetinib and its active metabolite sutetinib N-oxide in human plasma by liquid chromatography-tandem mass spectrometry: Evaluation of plasma stability.

From the point of view of drug efficacy and safety, pharmacokinetic profiles of both In this work, a sensitive and reliable liquid chromatographic-tandem mass spectrometric method was established for simultaneous determination of sutetinib and N-oxide metabolite (SNO) in human plasma and further applied to a pharmacokinetic study. Analytes were extracted from plasma samples (100 µl) via acetonitrile-induced protein precipitation and separated on a C18 column using ammonium acetate with ammonium hydroxide and acetonitrile as the mobile phase. Positive electrospray ionization was carried out through multiple reaction monitoring with transitions of m/z 440.2 → 367.1 and 446.2 → 367.1 for sutetinib and SNO, respectively. The method was linear within the concentration range of 0.5-100 ng/ml for both analytes. The precision, accuracy, selectivity, recovery and matrix effect of this method all met the requirements of bioanalytical guidance. In addition, a plasma stability assessment demonstrated unexpected results. Sutetinib was prone to form covalent conjugates with plasma albumin in vitro. The degree of covalent binding increased with increasing temperature, resulting in a significant decrease in its plasma concentrations. However, SNO could not easily bind with albumin owing to steric hindrance or electronegativity. Furthermore, sutetinib and SNO remained stable when blood and plasma samples were kept on wet ice. The validated method was successfully employed for the pharmacokinetic evaluation of sutetinib in patients with advanced malignant solid tumors.

Downregulation of miR-24-3p promotes osteogenic differentiation of human periodontal ligament stem cells by targeting SMAD family member 5.

Osteogenic differentiation is a complicated process that depends on various regulatory factors and signal pathways. In our research, the osteogenic differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase activity, and protein levels of osteogenic differentiation markers including runt-related transcription factor 2, bone morphogenetic protein 2, and osteocalcin (OCN). We observed a notable decrease of miR-24-3p level in osteogenic-differentiated human periodontal ligament stem cells (hPDLSCs) by microarray analysis. In our gain- and loss-of-function experiments, we discovered that miR-24-3p has a suppression effect on hPDLSCs osteogenic differentiation. Moreover, SMAD family member 5 (Smad5), the critical osteogenic differentiation transcription factors, was predicted to be targets of miR-24-3p. In addition, luciferase reporter assay further proved that miR-24-3p directly targeted the 3'-untranslated region of Smad5. Similarly, we found that the overexpression of miR-24-3p significantly decreased the Smad5 messenger RNA level in hPDLSCs, which was detected by real-time quantitative polymerase chain reaction. Then hPDLSCs were transfected with miR-24-3p mimics to inhibit Smad5 expression; meanwhile, Smad5 RNA interference could significantly reverse the osteogenic differentiation inhibition effect of miR-24-3p. In brief, a series of data showed that miR-24-3p is a regulator of Smad5, playing an important role in osteogenic differentiation.

Molecular Targets and Associated Potential Pathways of Danlu Capsules in Hyperplasia of Mammary Glands Based on Systems Pharmacology.

Hyperplasia of mammary glands (HMG) is common in middle-aged women. Danlu capsules (DLCs) can effectively relieve pain and improve clinical symptoms and are safe for treating HMG. However, the active substances in DLCs and the molecular mechanisms of DLCs in HMG remain unclear. This study identified the bioactive compounds and delineated the molecular targets and potential pathways of DLCs by using a systems pharmacology approach. The candidate compounds were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Each candidate's druggability was analyzed according to its oral bioavailability and drug-likeness indices. The candidate proteins and genes were extracted in the TCMSP and UniProt Knowledgebase, respectively. The potential pathways associated with the genes were identified by performing gene enrichment analysis with DAVID Bioinformatics Resources 6.7. A total of 603 compounds were obtained from DLCs, and 39 compounds and 66 targets associated with HMG were obtained. Gene enrichment analysis yielded 10 significant pathways with 34 targets. The integrated HMG pathway revealed that DLCs probably act in patients with HMG through multiple mechanisms of anti-inflammation, analgesic effects, and hormonal regulation. This study provides novel insights into the mechanisms of DLCs in HMG, from the molecular level to the pathway level.

[Experimental study on anaphylactoid reactions induced by different components of shengmai injection (new production process) on Beagle dogs].

OBJECTIVE: To evaluate the sensitization effect of different components of Shengmai injection (new production process) on Beagle dogs. METHOD: Beagle dogs were randomly divided into 7 groups, 3 in each group. Each group was respectively injected with 5% glucose injection, Ginseng Radix et Rhizoma Rubra extract, Ophiopogonis Radix extract, Schisandrae Chinensis Fructus extract, Schisandrae Chinersis Fructus distillate, Shengmaifang, 0.2% tween 80. The changes of each dog were observed from injection before until 24 hours after injection, and the response level was determined according to the severity of the symptoms. Blood samples were collected before injection and at 10 min after injection for measuring histamine content in plasma by ELISA. Sensitization of the injection was comprehensively determined by combined the response level of symptoms and the histamine level. RESULT: One dog of Ginseng Radix et Rhizoma Rubra extract group showed untypical symptoms of anaphylactoid reactions, and serum histamine of two dogs increased more than doubled. The Beagle dogs administrated with 0.2% tween 80 showed typical symptoms of anaphylactoid reactions, while there was no significant increase of serum histamine. Other groups were observed with no typical anaphylactoid reactions. CONCLUSION: The sensitization effect of Shengmai injection (new production process) may be associated with Ginseng Radix et Rhizoma Rubra extract and 0.2% tween 80.

[Experimental study on anaphylactoid reactions induced by shengmai injection (new production process) on Cynomolgus monkey].

OBJECTIVE: To compare the anaphylactoid effect of old Shengmai injection and new Shengmai injection on Cynomolgus monkey. METHOD: Cynomolgus monkeys were randomly divided into 4 groups, and were respectively injected with 5% glucose injection, old Shengmai injection, new Shengmai injection, positive control drug. The changes of each monkey were observed from injection before until 24 hours after injection, and the response level was determined according to the severity of the symptoms. Blood samples were collected before injection and at 10 min after injection for measuring histamine content in plasma. Blood pressure and heart rates were detected before injection and at 10 min after injection. Sensitization of the injection was comprehensively determined by combined the response level of symptoms and the histamine level. RESULT: The Cynomolgus monkeys administrated with old Shengmai injection showed typical symptoms of anaphylactoid reactions and the content of serum histamine is not more than doubled. The Cynomolgus monkeys administrated with new Shengmai injection showed untypical symptoms of anaphylactoid reactions and the content of serum histamine did not rise. CONCLUSION: The old Shengmai injection can induce typical anaphylactoid reactions on Cynomolgus monkeys, and the sensitization ability is strong. The symptoms of anaphylactoid reactions induced by the new Shengmai injection appeared later and showed lesser degree with the sensitization lower.

[Comparative study on pseudoanaphylactoid reactions induced by medicinal tween 80 and injectable tween 80].

OBJECTIVE: To investigate the safety of different level of tween 80 by comparing the degree of pseudoanaphylactoid reactions (PR) induced by medicinal tween 80 and injectable tween 80. METHOD: The analysis of vascular permeability of the mice ears: ICR mouse were divided into different test groups, the mice were intravenously injected with solutions of medicinal tween 80 and injectable tween 80 with 0.2%, 1% and 5% concentration, positive control Compound 48/80 and 5% glucose injection. All test substances were mixed with 0.4% Evans blue. The reaction and vascular permeability of the ears were observed and measured 30 min after injection. The analysis of vascular permeability of the rat's skin: the rats were intravenous injected with 0. 6% Evans blue normal saline solution first, 10 minutes later, the same substances were intradermal administrated into the back of rats. The rats were sacrificed and the diameter of locus ceruleus and the content of Evans blue leak out were measured 20 min after injection. RESULT: Medicinal tween 80 and injectable tween 80 with 5% concentration caused obvious vascular hyper permeability in ICR mice, but the degree of vascular hyperpermeability caused by injectable tween 80 was lighter than by medicinal tween 80. Other tween 80 didn't cause obvious vascular hyper permeability in the ears of mouse. The solution of different concentration of tween 80 caused obvious locus ceruleus reaction in rat's back. As for the content Evans blue leak out, there was no statistical significance between each group except positive control Compound 48/80 group. CONCLUSION: Tween 80 can cause obvious vascular hyper permeability and the effect is dose dependent, which indicated that tween 80 can cause PR. On the other hand, injectable tween 80 is more security than medicinal tween 80, the dosage of tween 80 should be still controlled strictly so that to decrease the incidence of PR.