Transformation and Prospects of Dentistry Innovations in China.

The burden of dental diseases is increasing in the Chinese population. However, the development of the dental industry falls behind the average development level of medical industry in China. The emergence of digital dental technologies has created significant opportunities for the development of the dental industry in China. This article explores the innovative development background of the Chinese dental industry, describes the current innovation status in Chinese medical colleges and enterprises, highlights key problems faced by the nation, enterprises, and hospitals, proposes solutions to these issues, and puts forwards a new concept of building an open and collaborative service system, a transformation path, and a whole-chain support system for innovations in dentistry.

Copper-Catalyzed Intermolecular Alkynylation and Allylation of Unactivated C(sp3)-H Bonds via Hydrogen Atom Transfer.

We describe Cu-catalyzed intermolecular alkynylation and allylation of unactivated C(sp3)-H bonds with singly occupied molecular orbital-philes (SOMO-philes) via hydrogen atom transfer (HAT). Employing N-fluoro-sulfonamide as a HAT reagent, a set of substituted alkene and alkyne compounds were synthesized in high yields with good regioselectivity and functional-group compatibility. Late-stage functionalization of natural products and drug molecules is also demonstrated.

Single-pixel imaging with neutrons.

Neutron imaging is an invaluable tool for noninvasive analysis in many fields. However, neutron facilities are expensive and inconvenient to access, while portable sources are not strong enough to form even a static image within an acceptable time frame using traditional neutron imaging. Here we demonstrate a new scheme for single-pixel neutron imaging of real objects, with spatial and spectral resolutions of 100 µm and 0.4% at 1 Å, respectively. Low illumination down to 1000 neutron counts per frame pattern was achieved. The experimental setup is simple, inexpensive, and especially suitable for low intensity portable sources, which should greatly benefit applications in biology, material science, and industry.

Repressed Gene Expression of Photosynthetic Antenna Proteins Associated with Yellow Leaf Variation as Revealed by Bulked Segregant RNA-seq in Tea Plant Camellia sinensis.

The young leaves and shoots of albino tea cultivars are usually characterized as having a yellow or pale color, high amino acid, and low catechin. Increasing attention has been paid to albino tea cultivars in recent years because their tea generally shows high umami and reduced astringency. However, the genetic mechanism of yellow-leaf variation in albino tea cultivar has not been elucidated clearly. In this study, bulked segregant RNA-seq (BSR-seq) was performed on bulked yellow- and green-leaf hybrid progenies from a leaf color variation population. A total of 359 and 1134 differentially expressed genes (DEGs) were identified in the yellow and green hybrid bulked groups (Yf vs Gf) and parent plants (Yp vs Gp), respectively. The significantly smaller number of DEGs in Yf versus Gf than in Yp versus Gp indicated that individual differences could be reduced within the same hybrid progeny. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed that the photosynthetic antenna protein was most significantly enriched in either the bulked groups or their parents. Interaction was found among light-harvesting chlorophyll a/b -binding proteins (LHC), heat shock proteins (HSPs), and enzymes involved in cuticle formation. Combined with the transcriptomic expression profile, results showed that the repressed genes encoding LHC were closely linked to aberrant chloroplast development in yellow-leaf tea plants. Furthermore, the photoprotection and light stress response possessed by genes involved in HSP protein interaction and cuticle formation were discussed. The expression profile of DEGs was verified via quantitative real-time PCR analysis of the bulked samples and other F1 individuals. In summary, using BSR-seq on a hybrid population eliminated certain disturbing effects of genetic background and individual discrepancy, thereby helping this study to intensively focus on the key genes controlling leaf color variation in yellow-leaf tea plants.

Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via Wnt/ß-catenin signaling to prevent differentiation of dental mesenchymal cells during the late bell stage.

Homeobox protein MSX-1 (hereafter referred to as MSX-1) is essential for early tooth-germ development. Tooth-germ development is arrested at bud stage in Msx1 knockout mice, which prompted us to study the functions of MSX-1 beyond this stage. Here, we investigated the roles of MSX-1 during late bell stage. Mesenchymal cells of the mandibular first molar were isolated from mice at embryonic day (E)17.5 and cultured in vitro. We determined the expression levels of ß-catenin, bone morphogenetic protein 2 (Bmp2), Bmp4, and lymphoid enhancer-binding factor 1 (Lef1) after knockdown or overexpression of Msx1. Our findings suggest that knockdown of Msx1 promoted expression of Bmp2, Bmp4, and Lef1, resulting in elevated differentiation of odontoblasts, which was rescued by blocking the expression of these genes. In contrast, overexpression of Msx1 decreased the expression of Bmp2, Bmp4, and Lef1, leading to a reduction in odontoblast differentiation. The regulation of Bmp2, Bmp4, and Lef1 by Msx1 was mediated by the Wnt/ß-catenin signaling pathway. Additionally, knockdown of Msx1 impaired cell proliferation and slowed S-phase progression, while overexpression of Msx1 also impaired cell proliferation and prolonged G1-phase progression. We therefore conclude that MSX-1 maintains cell proliferation by regulating transition of cells from G1-phase to S-phase and prevents odontoblast differentiation by inhibiting expression of Bmp2, Bmp4, and Lef1 at the late bell stage via the Wnt/ß-catenin signaling pathway.

Efficacy and Tolerability of Gabapentin in Adults with Sleep Disturbance in Medical Illness: A Systematic Review and Meta-analysis.

BACKGROUND AND PURPOSE: The aim of this study was to systematically review the efficacy and tolerability of gabapentin in the treatment of sleep disturbance in patients with medical illness. METHODS: PubMed was searched for randomized, double-blinded, placebo-controlled trials that reported sleep changes during gabapentin treatment up to November 2015. FINDINGS: This review included 26 studies involving 4,684 participants. Except for Composite Endpoint 3 [standardized mean difference (SMD) = 0.09, 95% confidence interval (CI): -0.05-0.22] compared with the placebo group, the gabapentin group showed superior outcomes on our endpoints: Composite Endpoint 1 (SMD = 0.50, 95% CI: 0.28-0.71), Composite Endpoint 2 (SMD = -0.53, 95% CI: -0.77 to -0.30), Composite Endpoint 4 (SMD = -0.38, 95% CI: -0.58 to -0.19), Composite Endpoint 5 [risk ratio (RR) = 1.79, 95% CI: 1.24-2.58], and Composite Endpoint 6 (RR = 0.48, 95% CI: 0.32-0.72). However, the patients in the gabapentin group showed worse tolerance than those in the placebo group (RR = 1.38, 95% CI: 1.08-1.76). IMPLICATIONS: This study is the first to systematically assess the clinical value of gabapentin for the treatment of sleep disorders. We found that regardless the type of sleep outcomes, gabapentin displayed stable treatment efficacy for sleep disturbance in patients with medical illness. However, when an average dose of approximately 1,800 mg/day was used, the risk of treatment discontinuation or drug withdrawal was relatively high. We recommend that further studies confirm these findings in patients with primary sleep disorders.

Incidence of Augmentation in Primary Restless Legs Syndrome Patients May Not Be That High: Evidence From A Systematic Review and Meta-Analysis.

Augmentation is a common complication of primary restless legs syndrome (RLS) during treatment; however, its incidence rate remains unclear.The aim of this study is investigate the rate of augmentation during RLS treatment.We searched 6 databases, including PubMed, OVID, Embase, Wiley citations, Web of Science research platform (including SciELO Citation Index, Medline, KCI Korean Journal Database, the Web of Science™ Core Collection), and the Cochrane library, and screened the reference lists of the included trials and recently published reviews.Randomized controlled trials and observational studies that reported augmentation events during RLS treatment.Primary RLS patients older than 18 years.No restrictions regarding intervention types were applied.Three investigators independently extracted and pooled the data to analyze the augmentation rate of the total sample and of patient subgroups with different interventions, treatment durations and drug regimens and different geographic origins. Fixed-effects or random-effects model was used for pooled analysis.A total of 60 studies involving 11,543 participants suggested an overall augmentation rate of 5.6% (95% confidence intervals (CI), 4.0-7.7). The augmentation incidence was 6.1% (95% CI, 4.1-9.1) for long-term treatment and 3.3% (95% CI, 1.4-7.3) for short-term treatment. In addition, 27.1% (95% CI, 12.3-49.5) of the levodopa-treated patients, 6.0% (95% CI, 4.1-8.8) of the patients treated with dopamine agonists, and 0.9% (95% CI, 0.2-3.3) of the patients taking pregabalin or gabapentin developed augmentation. Augmentation occurred in 7.2% (95% CI, 5.0-10.3) of the patients taking immediate-release drugs and in 1.7% (95% CI, 0.6-5.0) of the patients taking transdermal application.The main limitations are that the augmentation rates were not evaluated according to drug dosage, gender, and age and symptom severity.Approximately 5 to 6 in 100 RLS patients developed augmentation during treatment.

Histone demethylase KDM2B inhibits the chondrogenic differentiation potentials of stem cells from apical papilla.

Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. Histone methylation, controlled by histone methyltransferases and demethylases, may play a key role in MSCs differentiation. Previous studies determined that KDM2B can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2B is involved in the other cell lineages differentiation of MSCs. Here we used the stem cells from apical papilla (SCAPs) to study the role of KDM2B on the chondrogenic differentiation potentials in MSCs. In this study, Gain- and loss-of-function assays were applied to investigate the role of KDM2B on the chondrogenic differentiation. Alcian Blue Staining and Quantitative Analysis were used to investigate the synthesis of proteoglycans by chondrocytes. Real-time RT-PCR was used to detect the expressions of chondrogenesis related genes. The Alcian Blue staining and Quantitative Analysis results revealed that overexpression of KDM2B decreased the proteoglycans production, and real-time RT-PCR results showed that the expressions of the chondrogenic differentiation markers, COL1, COL2 and SOX9 were inhibited by overexpression of KDM2B in SCAPs. On the contrary, depletion of KDM2B increased the proteoglycans production, and inhibited the expressions of COL1, COL2 and SOX9. In conclusion, our results indicated that KDM2B is a negative regulator of chondrogenic differentiation in SCAPs and suggest that inhibition of KDM2B might improve MSC mediated cartilage regeneration.

[Chromatographic Fingerprinting Study of Zhenyuan Granules Dry Extract by HPLC-DAD and HPLC-MS/MS].

OBJECTIVE: To establish a novel, accurate and valid fingerprint method of Zhenyuan granules dry extract by using HPLC-DAD method, to study herbs belonging of fingerprint peaks and to identify some of the chromatographic peaks by HPLC-MS/MS analysis, for providing the basis for scientific evaluation of the quality. METHODS: The sample solutions were analyzed by an Agilent SB C18 (250 mm x 4.6 mm, 5 µm) column, and gradiently eluted with acetonitrile (containing 0.1% formic acid) and aqueous phase (containing 0.1% formic acid) as the mobile phase. The flow rates were 1.2 mL/min (0~70 min) and 0.8 mL/min (70~150 min); the column temperature was 30 °C; and the detection wavelength was 254 nm. RESULTS: 40 peaks were selected as fingerprint peaks under the optimal chromatographic condition, and the similarity coefficients of 10 batches of Zhenyuan granules dry extract were all greater than 0.98. 27 peaks were tentatively identified with reference to literature data based on their mass spectrometry. CONCLUSION: The chromatographic fingerprint of Zhenyuan granules is proved to be a reliable method for comprehensive quality control and assessment.

Enriched trimethylation of lysine 4 of histone H3 of WDR63 enhanced osteogenic differentiation potentials of stem cells from apical papilla.

INTRODUCTION: Dental tissue-derived mesenchymal stem cells (MSCs) are a reliable cell source for dental tissue regeneration. However, the molecular mechanisms underlying their directed differentiation remain unclear, thus limiting their use. Trimethylation of lysine 4 of histone H3 (H3K4Me3) correlates with gene activation and osteogenic differentiation. We used stem cells from apical papilla (SCAPs) to investigate the effects of genomic changes in H3K4Me3 modification at gene promoter regions on MSC osteogenic differentiation. METHODS: ChIP-on-chip assays were applied to compare the H3K4Me3 profiles at gene promoter regions of undifferentiated and differentiated SCAPs. Alkaline phosphatase activity assay, alizarin red staining, quantitative analysis of calcium, the expressions of osteogenesis-related genes, and transplantation in nude mice were used to investigate the osteogenic differentiation potentials of SCAPs. RESULTS: In differentiated SCAPs, 119 gene promoters exhibited >2-fold increases of H3K4Me3; in contrast, the promoter regions of 21 genes exhibited >2-fold decreases of H3K4Me3. On the basis of enriched H3K4Me3 and up-regulated gene expression on the osteogenic differentiation of SCAPs, WDR63 may be a potential regulator for mediating SCAP osteogenic differentiation. Through gain-of-function and loss-of-function studies, we discovered that WDR63 enhances alkaline phosphatase activity, mineralization, and the expression of BSP, OSX, and RUNX2 in vitro. In addition, transplant experiments in nude mice confirmed that SCAP osteogenesis is triggered by activated WDR63. CONCLUSIONS: These results indicate that WDR63 is a positive enhancer for SCAP osteogenic differentiation and suggest that activation of WDR63 signaling might improve tissue regeneration mediated by MSCs of dental origin.

Clinical significance of tumor necrosis factor-α inhibitors in the treatment of sciatica: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Currently, no satisfactory treatment is available for sciatica caused by herniated discs and/or spinal stenosis. The objective of this study is to assess the value of tumor necrosis factor (TNF)-α inhibitors in the treatment of sciatica. METHODS: Without language restrictions, we searched PubMed, OVID, EMBASE, the Web of Science, the Clinical Trials Registers, the Cochrane Central Register of Controlled Trials and the China Academic Library and Information System. We then performed a systematic review and meta-analysis on the enrolled trials that met the inclusion criteria. RESULTS: Nine prospective randomized controlled trials (RCTs) and two before-after controlled trials involving 531 patients met our inclusion criteria and were included in this study. Our systematic assessment and meta-analysis demonstrated that in terms of the natural course of the disease, compared with the control condition, TNF-α inhibitors neither significantly relieved lower back and leg pain (both p > 0.05) nor enhanced the proportion of patients who felt overall satisfaction (global perceived effect (satisfaction)) or were able to return to work (return to work) (combined endpoint; p > 0.05) at the short-term, medium-term and long-term follow-ups. In addition, compared with the control condition, TNF-α inhibitors could reduce the risk ratio (RR) of discectomy or radicular block (combined endpoint; RR = 0.51, 95% CI 0.26 to 1.00, p = 0.049) at medium-term follow-up, but did not decrease RR at the short-term (RR = 0.64, 95% CI 0.17 to 2.40, p = 0.508) and long-term follow-ups (RR = 0.64, 95% CI 0.40 to 1.03, p = 0.065). CONCLUSION: The currently available evidence demonstrated that other than reducing the RR of discectomy or radicular block (combined endpoint) at medium-term follow-up, TNF-α inhibitors showed limited clinical value in the treatment of sciatica caused by herniated discs and/or spinal stenosis.

Effect of same-dose single or dual field irradiation on damage to miniature pig parotid glands.

AIM: To evaluate the effect of single or dual field irradiation (IR) with the same dose on damage to miniature pig parotid glands. METHODOLOGY: Sixteen miniature pigs were divided into two IR groups (n=6) and a control group (n=4). The irradiation groups were subjected to 20 Gy X-radiation to one parotid gland using single-field or dual-field modality by linear accelerator. The dose-volume distributions between two IR groups were compared. Saliva from parotid glands and blood were collected at 0, 4, 8 and 16 weeks after irradiation. Parotid glands were removed at 16 weeks to evaluate tissue morphology. RESULTS: The irradiation dose volume distributions were significantly different between single and dual field irradiation groups (t=4.177, P=0.002), although dose volume histogramin (DVH) indicated the equal maximal dose in parotid glands. Saliva flow rates from IR side decreased dramatically at all time points in IR groups, especially in dual field irradiation group. The radiation caused changes of white blood cell count in blood, lactate dehydrogenase and amylase in serum, calcium, potassium and amylase in saliva. Morphologically, more severe radiation damage was found in irradiated parotid glands from dual field irradiation group than that from single field irradiation group. CONCLUSION: Data from this large animal model demonstrated that the radiation damage from the dual field irradiation was more severe than that of the single field irradiation at the same dose, suggesting that dose-volume distribution is an important factor in evaluation of the radiobiology of parotid glands.

Antimicrobial effect of acidified nitrate and nitrite on six common oral pathogens in vitro.

BACKGROUND: Salivary nitrate is positively correlated with plasma nitrate and its level is 9 times the plasma level after nitrate loading. Nitrate in saliva is known to be reduced to nitrite by oral bacteria. Nitrate and nitrite levels in saliva are 3 - 5 times those in serum in physiological conditions respectively in our previous study. The biological functions of high salivary nitrate and nitrite are still not well understood. The aim of this in vitro study was to investigate the antimicrobial effects of nitrate and nitrite on main oral pathogens under acidic conditions. METHODS: Six common oral pathogens including Streptococcus mutans NCTC 10449, Lactobacillus acidophilus ATCC 4646, Porphyromonas gingivalis ATCC 33277, Capnocytophaga gingivalis ATCC 33624, Fusobacterium nucleatum ATCC 10953, and Candida albicans ATCC 10231 were cultured in liquid medium. Sodium nitrate or sodium nitrite was added to the medium to final concentrations of 0, 0.5, 1, 2, and 10 mmol/L. All of the microorganisms were incubated for 24 to 48 hours. The optical densities (OD) of cell suspensions were determined and the cultures were transferred to solid nutrient broth medium to observe the minimum inhibitory concentration and minimum bactericidal/fungicidal concentration for the six tested pathogens. RESULTS: Nitrite at concentrations of 0.5 to 10 mmol/L had an inhibitory effect on all tested organisms at low pH values. The antimicrobial effect of nitrite increased with the acidity of the medium. Streptococcus mutans NCTC 10449 was highly sensitive to nitrite at low pH values. Lactobacillus acidophilus ATCC 4646 and Candida albicans ATCC 10231 were relatively resistant to acidified nitrite. Nitrate at the given concentrations and under acidic conditions had no inhibitory effect on the growth of any of the tested pathogens. CONCLUSION: Nitrite, at a concentration equal to that in human saliva, is both cytocidal and cytostatic to six principal oral pathogens in vitro, whereas nitrate at a similar concentration has no antimicrobial effect on these organisms.