LncRNA DDX11-AS1 promotes cell growth, migration and invasion through regulating epithelial-mesenchymal transition in breast cancer.

This study aimed to investigate the expression of long non-coding ribonucleic acid (lncRNA) DDX11 antisense RNA 1 (DDX11-AS1) in breast cancer (BC) tissues and cells and investigate its biological function and potential molecular mechanism through in vitro experiments. Tissue specimens were obtained from 44 BC patients. TRIzol method was used to extract RNAs from the tissues. The relative expression of DDX11-AS1 in BC tissues and the expression of DDX11-AS1 in BC cells were detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The effect of DDX11-AS1 on the proliferation ability of BC cells was detected via cell counting kit-8 (CCK-8) assay. Flow cytometry was adopted to study the effect of DDX11-AS1 on the distribution of BC cell cycle. Transwell assays were performed to analyze the effects of DDX11-AS1 on the migration and invasion abilities of BC cells. Finally, after interfering with the expression of DDX11-AS1 in BC cells, changes in the expressions of molecular markers for epithelial-mesenchymal transition (EMT) were detected via Western blotting. According to the results of qRT-PCR, the expression of DDX11-AS1 was up-regulated in 38 out of 44 cases of BC tissues compared with that in the para-carcinoma tissues, and the expression of DDX11-AS1 in BC cells was up-regulated as well. After interference with the expression of DDX11-AS1 in BC cells, it was found via CCK-8 assay that the proliferation ability of BC cells was restrained, flow cytometry results showed that the BC cell cycle was arrested at G1/G0 phase, and the results of transwell assays revealed that the cell invasion and migration abilities were suppressed in experimental group compared with those in control group. According to the results of Western blotting, after interfering with the expression of DDX11-AS1 in BC cells, there were changes in the expressions of molecular markers for EMT. In BC, the expression of lncRNA DDX11-AS1 is up-regulated, which promotes the proliferation, migration and invasion of BC cells by regulating EMT.

Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/D2R heterodimers.

Growth hormone secretagogue receptor 1a (GHS-R1a) is an important G protein-coupled receptor (GPCR) that regulates a variety of functions by binding to ghrelin. It has been shown that the dimerization of GHS-R1a with other receptors also affects ingestion, energy metabolism, learning and memory. Dopamine type 2 receptor (D2R) is a GPCR mainly distributed in the ventral tegmental area (VTA), substantia nigra (SN), striatum and other brain regions. In this study we investigated the existence and function of GHS-R1a/D2R heterodimers in nigral dopaminergic neurons in Parkinson's disease (PD) models in vitro and in vivo. By conducting immunofluorescence staining, FRET and BRET analyses, we confirmed that GHS-R1a and D2R could form heterodimers in PC-12 cells and in the nigral dopaminergic neurons of wild-type mice. This process was inhibited by MPP+ or MPTP treatment. Application of QNP (10 µM) alone significantly increased the viability of MPP+-treated PC-12 cells, and administration of quinpirole (QNP, 1 mg/kg, i.p. once before and twice after MPTP injection) significantly alleviated motor deficits in MPTP-induced PD mice model; the beneficial effects of QNP were abolished by GHS-R1a knockdown. We revealed that the GHS-R1a/D2R heterodimers could increase the protein levels of tyrosine hydroxylase in the SN of MPTP-induced PD mice model through the cAMP response element binding protein (CREB) signaling pathway, ultimately promoting dopamine synthesis and release. These results demonstrate a protective role for GHS-R1a/D2R heterodimers in dopaminergic neurons, providing evidence for the involvement of GHS-R1a in PD pathogenesis independent of ghrelin.

Three-dimensional (3D) quantitative evaluation of the morphological changes of the upper anterior alveolar bone after retraction of a maxillary incisor.

BACKGROUND: The purpose of this study was to assess morphological changes of the upper anterior alveolus after retraction of a maxillary incisor by applying three-dimensional (3D) superimposition of pretreatment (T1) and posttreatment (T2) cone-beam computed tomography (CBCT) data. METHODS: The study group was comprised of 28 patients with skeletal Class II malocclusion who underwent incisor retraction. CBCT data were acquired before (T1) and after (T2) orthodontic treatment. Labial and palatal alveolar thickness were assessed at the crestal, midroot and apical levels of the retracted incisors. Following three-dimensional (3D) cranial base superimposition, we performed surface modeling and inner remodeling of the labial and palatal alveolar cortex of the maxillary incisors. Paired t-tests were used to compare T0 and T1 bone thickness and volume measurements. Comparisons between labial and palatal surface modeling, inner remodeling and outer surface modeling were performed with paired t-tests in SPSS 20.0 version. RESULTS: We observed controlled tipping retraction of the upper incisor. After treatment, the alveolar thickness on the labial sides increased and the palatal alveolar thickness decreased. The labial cortex showed a wider range of modeling area with a larger bending height and a smaller bending angle than the palatal side. The extent of inner remodeling was more prominent than the outer surface on both the labial and palatal sides. CONCLUSIONS: Adaptive alveolar surface modeling occurred in response to incisor tipping retraction on both the lingual and labial sides although these changes occurred in an uncoordinated manner. Tipping retraction of the maxillary incisors led to a reduction in alveolar volume.

Cellular communication network factor 1 interlinks autophagy and ERK signaling to promote osteogenesis of periodontal ligament stem cells.

OBJECTIVES: To investigate the effects of cellular communication network factor 1 (CCN1), a critical matricellular protein, on alveolar bone regeneration, and to elucidate the underlying molecular mechanism. BACKGROUND: In the process of orthodontic tooth movement, bone deposition on the tension side of human periodontal ligament stem cells (hPDLSCs) ensured high efficiency and long-term stability of the treatment. The matricellular protein CCN1 is responsive to mechanical stimulation, exhibiting important tasks in bone homoeostasis. However, the role and mechanism of CCN1 on alveolar bone remodeling of hPDLSCs remains unclear. METHODS: The expression and distribution of CCN1 in rat periodontal ligament were detected by immunofluorescence staining and immunohistochemical staining. ELISA verified the secretion of CCN1 triggered by stretch loading. To examine the mineralization ability of hPDLSCs induced by CCN1, Western blotting, qRT-PCR, ARS, and ALP staining were performed. CCK-8 and cell migration assay were performed to detect the cell proliferation rate and the wound healing. PI3K/Akt, MAPK, and autophagy activation were examined via Western blotting and immunofluorescence. RESULTS: Mechanical stimuli induced the release of CCN1 into extracellular environment by hPDLSCs. Knockdown of CCN1 attenuated the osteogenesis of hPDLSCs while rhCCN1 enhanced the expression of Runx2, Col 1, ALPL, and promoted the mineralization nodule formation. CCN1 activated PI3K/Akt and ERK signaling, and blockage of PI3K/Akt signaling reversed the accelerated cell migration triggered by CCN1. The enhanced osteogenesis induced by CCN1 was abolished by ERK signaling inhibitor PD98059 or autophagy inhibitor 3-MA. Further investigation demonstrated PD98059 abrogated the activation of autophagy. CONCLUSION: This study demonstrated that CCN1 promotes osteogenesis in hPDLSCs via autophagy and MAPK/ERK pathway.

Nrf2 activation is involved in osteogenic differentiation of periodontal ligament stem cells under cyclic mechanical stretch.

During orthodontic treatment, mechanical stretch serves a crucial function in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Up-regulated reactive oxygen species (ROS) level is a result of cyclic mechanical stretch in many cell types. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator in various antioxidants expression. However, it is not known whether cyclic mechanical stretch could induce the ROS generation in PDLSCs and whether Nrf2 participated in this process. The present study was aimed to investigate the role of Nrf2 in PDLSCs under cyclic mechanical stretch. Our results showed that cyclic mechanical stretch increased ROS level and the nuclear accumulation of Nrf2 during osteoblast differentiation. Knocking down Nrf2 by siRNA transfection increased ROS formation and suppressed osteogenic differentiation in PDLSCs. T-BHQ, a Nrf2 activator, promoted the osteogenic differentiation in PDLSCs under cyclic mechanical stretch, and improved the microstructure of alveolar bone during orthodontic tooth movement in rats by employing micro-CT system. Taken together, Nrf2 activation was involved in osteogenic differentiation under cyclic mechanical stretch in PDLSCs. T-BHQ could promote the osteogenic differentiation in vitro and in vivo, suggesting a promising option for the remodeling of the alveolar bone during orthodontic tooth movement.

miR-301b and NR3C2 co-regulate cells malignant properties and have the potential to be independent prognostic factors in breast cancer.

This study intends to address the function of miR-301b/nuclear receptor subfamily 3 group C member 2 (NR3C2) in breast cancer. The Cancer Genome Atlas database was processed to investigate the expression of miR-301b/NR3C2 in breast cancer samples, as well as the relationship between their expression and the prognosis of the patients. Cox regression analysis was performed to determine whether miR-301b/NR3C2 was an independent predictor of the patient's prognosis. Associations between miR-301b and NR3C2 were analyzed by prediction website, dual-luciferase assay, and Pearson correlation coefficient. Quantitative polymerase chain reaction and Western blot analyses were implemented to detect gene expression. The relevant biological characteristics of MCF7 and BCAP-37 cells were tested by cell counting kit-8, colony formation, and transwell assays. Lower expression of NR3C2, which was closely related to the bad prognosis of breast cancer patients, was presented in breast cancer samples and can be used as an independent predictor. miR-301b, as an upstream regulator of NR3C2, was highly expressed in breast cancer samples and can be used as an independent predictor as well. Notably, a higher level of miR-301b and lower level of NR3C2 were related to the reduced overall survival in patients with breast cancer. The proliferative and migratory behaviors of cells were elevated or blocked after overexpression of miR-301b or NR3C2, respectively. However, the above situation was attenuated after together upregulation of miR-301b and NR3C2. The present data afforded evidence that miR-301b may be a tumor-promoting miRNA in breast cancer, and that miR-301b/NR3C2 axis mediated tumor development from cell proliferation and migration.

TRIM16 protects human periodontal ligament stem cells from oxidative stress-induced damage via activation of PICOT.

Periodontitis is a chronic inflammatory disease that result in severe loss of supporting structures and substantial tooth loss. Oxidative stress is tightly involved in the progression of periodontitis. Tripartite Motif 16 (TRIM16) has been identified as a novel regulatory protein in response to oxidative and proteotoxic stresses. The present study aimed to investigate the role of TRIM16 in human periodontal ligament stem cells (hPDLSCs) under oxidative stress. First, we found that the expression of TRIM16 decreased after exposure to H2O2. Then TRIM16 overexpression alleviated H2O2-induced oxidative stress by enhancing antioxidant capacity and reducing the amount of intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS). TRIM16 increased cell viability, inhibited cell apoptosis and the depolarization of the mitochondrial membrane potential in hPDLSCs. Furthermore, TRIM16 attenuated H2O2-induced suppression of osteogenic differentiation. Mechanistically, TRIM16 promoted the activation of protein kinase C (PKC)-interacting cousin of thioredoxin (PICOT), p-Akt and Nrf2, while knockdown of PICOT reversed TRIM16-mediated ROS resistance and decreased the expression of p-Akt and Nrf2. In conclusion, TRIM16 alleviated oxidative damage in hPDLSCs via the activation of PICOT/Akt/Nrf2 pathway, suggesting that TRIM16 could be a promising target to develop effective therapies for periodontitis.

Histogram analysis of diffusion kurtosis imaging derived maps may distinguish between low and high grade gliomas before surgery.

OBJECTIVE: To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the evaluation of glioma grading. METHODS: A total of 39 glioma patients who underwent preoperative magnetic resonance imaging (MRI) were classified into low-grade (13 cases) and high-grade (26 cases) glioma groups. Parametric DKI maps were derived, and histogram metrics between low- and high-grade gliomas were analysed. The optimum diagnostic thresholds of the parameters, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were achieved using a receiver operating characteristic (ROC). RESULT: Significant differences were observed not only in 12 metrics of histogram DKI parameters (P<0.05), but also in mean diffusivity (MD) and mean kurtosis (MK) values, including age as a covariate (F=19.127, P<0.001 and F=20.894, P<0.001, respectively), between low- and high-grade gliomas. Mean MK was the best independent predictor of differentiating glioma grades (B=18.934, 22.237 adjusted for age, P<0.05). The partial correlation coefficient between fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA) was 0.675 (P<0.001). The AUC of the mean MK, sensitivity, and specificity were 0.925, 88.5% and 84.6%, respectively. CONCLUSIONS: DKI parameters can effectively distinguish between low- and high-grade gliomas. Mean MK is the best independent predictor of differentiating glioma grades. KEY POINTS: • DKI is a new and important method. • DKI can provide additional information on microstructural architecture. • Histogram analysis of DKI may be more effective in glioma grading.

[Cas9 protein variant VQR recognizes NGAC protospacer adjacent motif in rice].

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system is the third-generation genome editing tools that was developed and widely used in recent years. However, Streptococcus pyogenes Cas9 (SpCas9) in this system could only recognize NGG PAM (protospacer adjacent motif), which largely restricts the range of genome editing. The VQR (D1135V/R1335Q/T1337R) variant of SpCas9 could recognize NGAA, NGAG and NGAT PAMs in rice. However, whether VQR variant could recognize NGAC PAM remains unclear. In this study, three low editing efficiency sites of the VQR variant, NAL1-Q1, NAL1-Q2 and LPA1-Q, were selected for genome editing using the improved CRISPR/VQR system. The improved CRISPR/VQR system effectively edited these target sites, and the gene editing efficiency was 9.75%, 43.90% and 29.26% respectively. To ensure the recognition of NGAC PAM by the improved CRISPR/VQR system, two NGAC PAM containing sites (NAL-C and GL1-C) in the NARROW LEAF 1 (NAL1) for leaf length and GLOSSY1 (GL1) genes for wax biosynthesis were selected for genome editing in rice in this study, and 57 transgenic plants were obtained. The PCR amplification and sequencing results showed that 27 plants (47.36%) had mutation in the NAL1-C site, 44 plants (77.19%) had mutation in the GL1 gene, and 26 plants (45.61%) had mutation in the NAL-C and GL1-C sites. Further analysis revealed that there were four types of mutations caused by the CRISPR/VQR system, respectively for the hybrid mutation, biallelic mutation, chimeric mutation and homozygous mutations. Among them, heterozygous mutation and biallelic mutation were dominant changes. These results indicated that the improved CRISPR/VQR system could efficiently edit the NGAC PAM sites of the rice and produce abundant mutant types. This study provides a theoretical basis for NGAC PAM editing in rice and other related plants.

Influence of sodium nitroprusside on expressions of FBXL5 and IRP2 in SH-SY5Y cells.

Iron accumulation in the brain is associated with the pathogenesis of Parkinson's disease (PD). Misexpression of some iron transport and storage proteins is related to iron dyshomeostasis. Iron regulatory proteins (IRPs) including IRP1 and IRP2 are cytosolic proteins that play important roles in maintaining cellular iron homeostasis. F-box and leucine-rich repeat protein 5 (FBXL5) is involved in the regulation of iron metabolism by degrading IRP2 through the ubiquitin-proteasome system. Nitric oxide (NO) enhances the binding activity of IRP1, but its effect on IRP2 is ambiguous. Therefore, in the present study, we aim to determine whether sodium nitroprusside (SNP), a NO donor, regulates FBXL5 and IRP2 expression in cultured SH-SY5Y cells. MTT assay revealed that treatment of SNP attenuated the cell viability in a dose-dependent manner. Flow cytometry test showed that 100 and 300 µmol/L SNP administration significantly reduced the mitochondrial membrane potential by 45% and 60%, respectively. Moreover, Western blotting analysis demonstrated that 300 µmol/L SNP significantly increased FBXL5 expression by about 39%, whereas the expression of IRP2 was decreased by 46%, correspondingly. These findings provide evidence that SNP could induce mitochondrial dysfunction, enhance FBXL5 expression and decrease IRP2 expression in SH-SY5Y cells.

The operation experience of endoscopic thyroidectomy by areola and axilla approach.

To explore the feasibility of endoscopic thyroidectomy via breast areola and axilla approach. The clinical data of 36 cases that underwent endoscopic thyroidectomy via breast areola and axilla approach from February 2012 to December 2013 were reviewed. All cases were completed, the mean operation time was 136.3 min (95-183 min), intraoperative blood loss was 15.8 ml (5-60 ml). The average hospitalization time was 5 days (4-6 days). There were no conversions to open surgery, no permanent nerve injuries, and no cases of hypoparathyroidism. Three patients had postoperative subcutaneous ecchymosis who were cured spontaneously after 1 month. Endoscopic thyroidectomy is safe and feasible for patients with thyroid diseases with good cosmetic results, and is worthy of being widely applied for patients who have cosmetic demand.

[An overview on autophagy in neural stem cells].

Neural stem cells (NSCs) offer great promise for the treatment of multiple neurodegenerative diseases. However, the survival and differentiation rates of grafted cells in the host brain need to be enhanced. In this regard, understanding of the underlying mechanism of NSCs survival and death is of great importance for the implications of stem cell-based therapeutic application in the treatments of neurological disorders. Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis, which can affect NSCs fate through regulating their biological behaviors, such as survival and proliferation. In this mini-review, we will summarize the effects of autophagy on NSCs fate including survival, apoptosis, proliferation and differentiation, as well as the underlying mechanisms.

[Advances in the association of ATP-sensitive potassium channels and Parkinson's disease].

ATP-sensitive potassium channels (KATP), as an inward rectifying potassium channel, are widely distributed in many types of tissues. KATP are activated by the depletion of ATP level and the increase in oxidative stress in cells. The activity of KATP couples cell metabolism with electrical activity and results in membrane hyperpolarization. KATP are ubiquitously distributed in the brain, including substantia nigra, hippocampus, hypothalamus, cerebral cortex, dorsal nucleus of vagus and glial cells, and participate in neuronal excitability, mitochondria homeostasis and neurotransmitter release. Accumulating lines of evidence suggest that KATP are the major contributing factors in the pathogenesis of Parkinson's disease (PD). This review discussed the association of KATP with the pathogenic processes of PD by focusing on the roles of KATP on the degeneration of dopaminergic neurons, the functions of mitochondria, the firing pattern of dopaminergic neurons in the substantia nigra, the α-synuclein secretion from striatum, and the microglia activation.

Tumor Cell-Derived Exosomal miR-191-5p Activates M2-Subtype Macrophages Through SOCS3 to Facilitate Breast Cancer.

Differential activation of macrophages is associated with poor progression of breast cancer (BC). Many reports have elucidated the important involvement of exosomes produced by cancer cells in remodeling the macrophage activation phenotype to promote tumor expansion and invasion. However, the underlying mechanisms by which exosomes secreted by BC cells facilitate macrophage M2 polarization remain enigmatic and worth exploring. In this study, quantitative real-time PCR (RT-qPCR) was used to investigate miR-191-5p expression in BC tumor tissues and cells. Cell counting kit 8 (CCK-8), transwell, and flow cytometry were applied to assess the functional role of miR-191-5p in BC. Isolated nano-vesicles were identified using transmission electron microscopy and western blotting. We also observed that miR-191-5p was significantly elevated in BC clinical samples and that inhibition of miR-191-5p hindered the growth and metastasis of BC cells. Importantly, BC cells successfully accelerated macrophage M2-like polarization by directly transferring exosomes to macrophages, resulting in increased miR-191-5p levels in macrophages. Mechanistically, exosomal miR-191-5p directly inhibited the suppressors of cytokine signaling 3 (SOCS3) expression in macrophages and aggravated macrophage M2 polarization. Similarly, si-SOCS3 transfected macrophages boosted BC cell migration and invasion in a positive feedback manner. Overall, our results manifested a pro-growth and pro-metastatic role between the two cells by elucidating the crucial role of exosomal miR-191-5p in stimulating M2 macrophage polarization and mediating communication between BC cells and macrophages. These findings opened up new horizons for the development of BC therapeutic strategies.

Effect of fast-track surgery model on postoperative pain and hospital stay of patients undergoing thyroid surgery.

OBJECTIVE: To investigate the effect of fast-track surgery on emotions, pain, and length of hospital stay during the preoperative period for thyroid disease. STUDY DESIGN AND METHODS: From June 2020 to September 2020, 43 patients who received routine perioperative nursing for thyroid disease in Ganzhou People's Hospital were retrospectively included as a control group, and 51 patients who received nursing care on the basis of fast-track surgery strategy from June 2020 to September 2020 in Ganzhou People's Hospital were retrospectively included as an experimental group. Time spent out of bed, length of hospital stay, medical expenses, and time of indwelling catheter use were compared between the two groups. Visual analogue scale (VAS) was used to evaluate the variations in intensity of pain postoperatively. The incidence of adverse reactions was recorded and compared. The risk factors affecting complications in patients undergoing surgery for thyroid disease were evaluated. RESULTS: Patients in the experimental group had shorter time spent out of bed, shorter length of hospital stay, less medical expenses, and shorter time of indwelling catheter use than those in the control group (all P < 0.05). The experimental group exhibited lower VAS scores than control group at 3 to 5 days after surgery (both P < 0.05). The total incidence of adverse reactions in the experimental group was lower than that in the control group (P < 0.05). Univariate analysis showed that gender, reoperation, intraoperative blood loss, and the use of recurrent laryngeal nerve detector were single factors affecting perioperative complications, while Logistic regression analysis showed that reoperation, intraoperative blood loss and the use of recurrent laryngeal nerve detector were highly correlated with perioperative complications (all P < 0.05). CONCLUSION: Fast-track surgery can significantly accelerate the rehabilitation of patients, alleviate postoperative pain and adverse emotions, and reduce the incidence of adverse reactions in patients with thyroid disease, which has positive significance to improve the prognosis of patients, and thus it is recommended for clinical promotion.

Study on Hydro-Mechanical Coupling Failure and Permeability Enhancement Mechanisms for Sandstone with T-Shaped Fractures.

The rise in the connectivity of the fractures is a key task in oil/gas and geothermal exploitation systems. Natural fractures widely exist in underground reservoir sandstone, while the mechanical behavior of rock with fractures subjected to hydro-mechanical coupling loads is far from clear. This paper employed comprehensive experiments and numerical simulations to investigate the failure mechanism and permeability law for sandstone specimens with T-shaped faces subjected to hydro-mechanical coupling loads. The effects of crack closure stress, crack initiation stress, strength, and axial strain stiffness of the specimens under different fracture inclination angles are discussed, and the evolution processes of permeability are obtained. The results show that secondary fractures are created around the pre-existing T-shaped fractures through tensile, shear, or mixed modes. The fracture network causes an increase in the permeability of the specimen. T-shaped fractures have a more significant effect on the strength of the specimens than water. The peak strengths of T-shaped specimens decreased by 34.89%, 33.79%, 46.09%, 39.32%, 47.23%, 42.76%, and 36.02%, respectively, compared with intact specimen without water pressure. With the increase in deviatoric stress, the permeability of T-shaped sandstone specimens decreases first, then increases, reaching its maximum value when macroscopic fractures are formed, after which the stress suddenly decreases. When the prefabricated T-shaped fracture angle is 75°, the corresponding permeability of the sample at failure is maximum, with a value of 15.84 × 10-16 m2. The failure process of the rock is reproduced through numerical simulations, in which the influence of damage and macroscopic fractures on permeability is discussed.

Efficacy of Sequential Capecitabine on Adjuvant Chemotherapy of Triple-Negative Breast Cancer.

This paper aims to evaluate the efficacy of capecitabine as extended adjuvant treatment after anthracycline and paclitaxel combined adjuvant chemotherapy for women with early triple-negative breast cancer (TNBC). The patients with early TNBC were randomly assigned to capecitabine sequential treatment for 4 cycles and without any sequential treatment in the control group after anthracycline and paclitaxel combined adjuvant chemotherapy. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). One hundred patients were enrolled in this study between June 2013 and February 2015. Median age was 49 years ranging from 25 to 66 years and treatment was well tolerance. The median follow-up time after random allocation was 58 months (range: 11-62 months). There was no significant difference in DFS and OS between the two groups (hazard ratio (HR) of DFS was 0.50; 95% CI, 0.24-1.05; P=0.066). Our study shows that although the addition of four cycles capecitabine after anthracycline and paclitaxel combining adjuvant chemotherapy does not improve DFS and OS, but the trend of DFS is improved. The possible reason is that the four-cycle treatment of capecitabine is not enough, and another possible reason is that the number of cases is not enough.

Condylar morphology and position changes after miniscrew-assisted rapid palatal expansion in skeletal Class III malocclusion adult patients with mandibular deviation and unilateral posterior crossbite.

BACKGROUND: To evaluate the morphological and positional changes of mandibular condyle after miniscrew-assisted rapid palatal expansion (MARPE) in skeletal Class III malocclusion adult patients with horizontal mandibular deviation (MD). METHODS: The sample consisted of 15 patients with MD (6 males and 9 females, mean age 21.58 ± 3.12 years). The CBCT scans were taken before and after MARPE immediately. The pre- and post-registered images of the cranial base and mandible were measured, respectively, by Mimics. RESULTS: After expansion, the distance between superior condylar point and the Frankfort horizontal plane on the deviated side and the non-deviated side increased by 0.96 ± 0.60 mm (P = 0.011) and 0.70 ± 0.65 mm (P = 0.046); coronal condylar angle of the deviated side increased by 0.39° ± 0.34 (P = 0.028) and 0.06° ± 0.49 (P = 0.917) on the non-deviated side. No statistically significant differences were found when comparing the condylar position on both sides before and after treatment. The degree of mandibular deviation decreased 0.43 mm (P = 0.270). CONCLUSIONS: This study suggested that for skeletal Class III malocclusion adult patients with horizontal MD, the condyle on the deviated side rotated toward the non-deviated side in the coronal direction; the condylar remodeling occurred mainly on the deviated side after MARPE in the vertical direction.

N-acetylcysteine promotes cyclic mechanical stress-induced osteogenic differentiation of periodontal ligament stem cells by down-regulating Nrf2 expression.

Background/purpose: Mechanical stress plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Cyclic mechanical stress may up-regulate reactive oxygen species (ROS) level. N-acetylcysteine (NAC) possesses powerful antioxidant capacity. However, it is undefined the impact of NAC on osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs. The aim of our research was to study the effect of NAC on PDLSCs during osteogenic differentiation under cyclic mechanical stress. Materials and methods: The expression levels of osteogenesis markers were used to examine the osteogenic differentiation of PDLSCs. ROS production were measured by flow cytometry. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were analyzed. We also examined the changes of alveolar bone and periodontal ligament (PDL) tissues in orthodontic rats by micro-computed tomography (micro-CT) system and immunohistochemistry (IHC) staining. The nuclear factor erythroid-2-related factor-2 (Nrf2) expression was examined. Results: NAC could enhance the osteogenic differentiation and up-regulate the GSH level as well as the ratio of GSH/GSSG, while down-regulate ROS generation and Nrf2 expression induced by cyclic mechanical stress in PDLSCs. NAC had beneficial effects on the microstructure of alveolar bone and enhanced the expression levels of osteogenesis markers, such as alkaline phosphatase (ALP) and collagen type 1 (COL1) in PDL in orthodontic rats at the tension side. Conclusion: NAC could improve the osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs and in orthodontic rats, suggesting a potential therapeutic approach for alveolar bone remodeling in orthodontics.

Spatiotemporal evolution of online attention to vaccines since 2011: An empirical study in China.

Since the outbreak of Coronavirus Disease 2019 (COVID-19), the Chinese government has taken a number of measures to effectively control the pandemic. By the end of 2021, China achieved a full vaccination rate higher than 85%. The Chinese Plan provides an important model for the global fight against COVID-19. Internet search reflects the public's attention toward and potential demand for a particular thing. Research on the spatiotemporal characteristics of online attention to vaccines can determine the spatiotemporal distribution of vaccine demand in China and provides a basis for global public health policy making. This study analyzes the spatiotemporal characteristics of online attention to vaccines and their influencing factors in 31 provinces/municipalities in mainland China with Baidu Index as the data source by using geographic concentration index, coefficient of variation, GeoDetector, and other methods. The following findings are presented. First, online attention to vaccines showed an overall upward trend in China since 2011, especially after 2016. Significant seasonal differences and an unbalanced monthly distribution were observed. Second, there was an obvious geographical imbalance in online attention to vaccines among the provinces/municipalities, generally exhibiting a spatial pattern of "high in the east and low in the west." Low aggregation and obvious spatial dispersion among the provinces/municipalities were also observed. The geographic distribution of hot and cold spots of online attention to vaccines has clear boundaries. The hot spots are mainly distributed in the central-eastern provinces and the cold spots are in the western provinces. Third, the spatiotemporal differences in online attention to vaccines are the combined result of socioeconomic level, socio-demographic characteristics, and disease control level.