ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

Oral submucous fibrosis(OSF)is a chronic and inflammatory mucosal disease caused by betel quid chewing,which belongs to oral potentially malignant disorders.Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development.The epithelium,which is the first line of defense against the external environment,can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment.However,the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear.In this study,we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes.MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts,where it promoted cell secretion,contraction,migration and fibrogenic marker(α-SMA and collagen type I)expression.The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1(TGFBR1)through the E3 ubiquitination ligase WWP1,thus facilitating downstream TGF-β pathway signaling.Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes.Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts.In conclusion,we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway,which provided a new perspective and strategy for the diagnosis and treatment of OSF.

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.
Consensus ; Humans ; Oral Ulcer/therapy*

It has been reported that ACE2 is the main host cell receptor of 2019-nCoV and plays a crucial role in the entry of virus into the cell to cause the final infection. To investigate the potential route of 2019-nCov infection on the mucosa of oral cavity, bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA and 14 organ types with normal tissues from FANTOM5 CAGE were analyzed in order to explore and validate the expression of ACE2 on the mucosa of oral cavity. Further, single-cell transcriptomes from an independent data generated in-house were used to identify and confirm the ACE2-expressing cell composition and proportion in oral cavity. The results demonstrated that the ACE2 expressed on the mucosa of oral cavity. Interestingly, this receptor was highly enriched in epithelial cells of tongue. Preliminarily, those findings have explained the basic mechanism that the oral cavity is a potentially high risk for 2019-nCoV infectious susceptibility and provided a piece of evidence for the future prevention strategy in dental clinical practice as well as daily life.

Holistic integrative medicine (HIM), as one of the important ideas in the field of medicine, arouses great concern recently. HIM regards the human body as a whole, turns data and evidence in medical research back to facts, integrates technologies and experience developed in clinical research into medical skills. The repeated practices at the levels of fact, experience, and medical skills will generate true knowledge to solve the wide spread problems brought by linearized thinking and fragmented knowledge. With the development of highly divided medical disciplines, how to utilize and practice HIM has become a common concern of the medical community. Specialization of stomatology, which is a first level discipline like medicine, has also become a trend for years. However, holistic concept cannot be overlooked, especially in the development of oral medicine. This article aims at the communication and exchange of knowledge about HIM among dental professionals. In order to serve the patients better, the authors look forward to practicing the HIM concept in the field of oral medicine through the efforts of us all.

Objective To investigate the effect of high viscosity bone cement in percutaneous vertebroplasty to treat osteoporotic vertebral compression fracture(OVCF) and veterbral metastasis tumor(VMT) .Methods 102 cases of OVCF(OVCF group) and 16 cases of VMT(VMT group) in our hospital from March 2010 to December 2012 were performed percutaneous vertebroplasty under local anesthesia ,through the vertebral pedicle approach by conducting puncture at bilateral vertebral pedicle into the vertebra , 3-6 mL high viscosity bone cement was injected to each vertebra .The pain intensity was detected by the McGill pain questionnaire score before operation ,on postoperative 3 d ,1 month and 6 -18 months last follow-up .The preoperative and postoperative MPQ scores were statistically analyzed .Results Postoperative patients′s back pain was significantly alleviated or disappeared .Compared with before operation ,the MPQ scores on postoperative 3 d ,in 1 month and 6 -18 months last follow-up in the OVCF group and the VMT group were significantly decreased(P<0 .05) .The postoperative CT scanning revealed that the cement leakage rates in the OVCF group and the VM T group were 11 .76% and 6 .25% respectively .But no complications of bone cement toxicity ,pulmo-nary embolism ,infection and nerve damage occurred .Conclusion High viscosity bone cement injection has the advantages of strongly controllable injection due to high viscosity ,low bone cement leakage and high surgical safety ,which is suitable for the treatment of OVCF and VM T .

OBJECTIVETo search for low-molecular-weight neuritogenic compounds from the traditional Chinese medicine (TCM).

METHODAn extract library of TCM was prepared. Targeted isolation guided by biological screening led to the discovery of compound 1, and its structure was elucidated by analysis of spectroscopic methods and comparison of spectroscopic data with these reported from the literature.

RESULTA neuritogenic compound 1, 3-O-beta-D-glucopyranosyl-22E, 24R-5alpha, 8alpha-epidioxyergosta-6, 22-diene, was isolated and identified from the methanol extract of T. fuciformis. This compound showed a significant neuritogenic activity against PC12 cells at 3 micromol x L(-1)).

CONCLUSIONMethonal extract of T. fuciformis and targeted compound 1 both showed significant neuritogenic activity against PC12 cells. These results suggested that the extract and compound 1 might be used to prevent and treat neurodegenerative disease such as Alzheimer's disease.

Animals ; Basidiomycota ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Nerve Growth Factor ; chemistry ; isolation & purification ; pharmacology ; Neurites ; drug effects ; PC12 Cells ; Rats

To establish a highly sensitive and specific method to detect the presence of Cryptosporidium homini, the RT-PCR-ELISA assay was tried, in which the primer with a biotin-labeled probe was designed to amplify fragment containing the highly variable region by multiple alignment between p23 gene of C.hominis and other Cryptosporidium spp. The RT-PCR was used to amplify the target fragment, and the amplified product was used to hybridize with the probe primer. The hybridized product was then captured on micro-plate wells coated with streptavidin and reacted with anti-digoxin antibody labeled with horse-radish peroxidase. This method of testing was then used for the detection of C.hominis in 22 clinical specimens and compared with the conventional methods of testing. It was demonstrated that the RT-PCR--ELISA for the detection of C.hominis was proved to be quite sensitive and specific. Its sensitivity was 100 times higher than that of the general PCR. From the result of clinic detection, the detection rate of RT-PCR-ELISA assay attained to 86%(19/22), while those of RT-PCR, sucrose floating method and anti-acid staining were 27%, 27% and 50% respectively. This result indicates that the RT-PCR-ELISA assay is more sensitive to detect C.hominis than the other three methods of testing.