Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; drug therapy ; therapy ; Young Adult

Objective To investigate the radiosensitiation effect of berberine on human nasopharyngeal carcinoma ( NPC) in hypoxia condition and explore the underlying mechanisms. Methods MTT assay, clonogenic assay and flow cytometry were performed to analyze cell proliferation, colony formation and apoptosis, respectively. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the radiosensitization effect of berberine in vivo. The expressions of HIF-1α and VEGF were assessed by Western blot. Results Berberine efficiently inhibited the proliferation of CNE-2 cells in time-dependent and dose-dependent fashions with an IC50 of ( 14?9 ± 2?2 ) μmol/L. Clonogenic survival assay showed that berberine ( 5 μmol/L ) sensitized CNE-2 cells to ionizing radiation in hypoxia and its SERD0 was 1?27. Under hypoxic condition, berberine alone (5, 15 μmol/L) could induce apoptosis (t=5?01, 9?02,P<0?05) and it further promoted 8 Gy radiation-induced apoptosis (t =5?31, 9?91,P <0?05). Moreover, berberine significantly delayed the tumor growth in the combination group (berberine +irradiation) compared with the mice received irradiation alone or PBS (t =2?96, 14?52, P <0?05). Immunobloting assay showed that berberine inhibited the upregulation of HIF-1α and VEGF induced by hypoxia in CNE-2 cells. Conclusion Berberine confers radiosensitivity on hypoxic NPC in vitro and in vivo, which is probably associated with the downregulation of HIF-1α and VEGF expressions.

Objective:To compare the prediction efficiency of traditional linear regression model and four machine learning models on the learning behavior of clinical medical postgraduates, and to explore the pros and cons and applicability of different prediction models.Methods:A total of 6,922 clinical medical postgraduates were surveyed, their comprehensive learning behavior scores were obtained through the learning behavior scale. In the training set, Lasso linear regression and artificial neural network, decision tree, Bootstrap random forest, and lifting tree were used to build prediction models respectively. The above models were used to predict the validation set data and compare the prediction efficiency.Results:The comprehensive learning behavior score of clinical medical postgraduates was (3.31±0.54) points, and the overall compliance rate was 74.02%. In the linear regression model, the influence of age, school level, degree type, learning interest, pressure and satisfaction on learning behavior were statistically significant. In the prediction of validation set, the sensitivity, specificity, and accuracy of the linear regression model were 0.484, 0.914, and 0.801, respectively. The indexes of the four machine learning models were higher than those of the traditional linear regression model, and the Bootstrap random forest had the highest elevation.Conclusion:The linear regression model has a good prediction effect on learning behavior, and machine learning is superior to linear regression model in terms of accuracy of prediction. However, traditional linear regression models are superior to machine learning models in computational efficiency and interpretability.

Objective:To review the development and progress of geriatric research in China from the perspective of funding from the National Natural Science Foundation of China, and to provide supporting data for further development of the field.Methods:Based on project funding data of the National Natural Science Foundation of China for geriatric medicine from 2008 to 2017, the number and composition of projects, funding amount and funded institutions were statistically analyzed, and the overall trend of change was examined.The research hotspots in recent years were summarized by using word frequency analysis.Results:From 2008 to 2017, a total of 446 projects were approved in the field of geriatric medicine.Both the number of projects and the amount of funding showed an increasing trend.Project types were gradually expanded and the composition was constantly optimized.Since 2014, the fund types each year included 6 or more and breakthroughs in major projects were achieved.East China remained the leading region in the number of projects and amount of funding, with Beijing, Shanghai and Zhejiang receiving the highest numbers of project approvals and accounting for more than 10% of the national total in the number of project approvals and the amount of funding.During this period, 114 institutions received funding, with 74 winning 2 or more projects.In word frequency analysis, senescence(229 times), cell(161 times)and protein(120 times)were the three most frequently used keywords.Conclusions:In the field of geriatric medicine, the project approval level from the National Natural Science Foundation of China has significantly improved in quantity and quality, but it has always been under-represented in the branch of medical sciences.The regional and institutional distribution of projects is unbalanced and tends to skew in favor of institutions with prominent academic disciplines.Basic research is the main type of funded projects.Geriatric research is centered on the mechanisms of aging.

The antisense transcript long non-coding RNA (1ncRNA) (antisense non-coding RNA in the INK4 locus,ANRIL) is an antisense of the cyclin-dependent kinase inhibitor 2B (CDKN2B) gene on chromosome 9p21 that contains an overlapping 299-bp region and shares a bidirectional promoter with alternate open reading frame (ARF).In the context of gene regulation,ANRIL is responsible for directly recruiting polycomb group (PcG) proteins,including polycomb repressive complex-1 (PRC-1) and polycomb repressive complex-2 (PRC-2),to modify the epigenetic chrornatin state and subsequently inhibit gene expression in cis-regulation.On the other hand,previous reports have indicated that ANRIL is capable of binding to a specific site or sequence,including the Alu element,E2F transcription factor 1 (E2F1),and CCCTC-binding factor (CTCF),to achieve trans-regulation functions.In addition to its function in cell proliferation,adhesion and apoptosis,ANRIL is very closely associated with atherosclerosis-related diseases.The different transcripts and the SNPs that are related to atherosclerotic vascular diseases (ASVD-SNPs) are inextricably linked to the development and progression of atherosclerosis.Linear transcripts have been shown to be a risk factor for atherosclerosis,whereas circular transcripts are protective against atherosclerosis.Furthermore,ANRIL also acts as a component of the inflammatory pathway involved in the regulation of inflammation,which is considered to be one of the causes of atherosclerosis.Collectively,ANRIL plays an important role in the formation of atherosclerosis,and the artificial modification of ANRIL transcripts should be considered following the development of this disease.

OBJECTIVETo present a method of quantitative diagnosis of craniofacial skeleton deformities based on three-dimensional computed tomography (3D CT).

METHODS20 cases with facial asymmetric deformities underwent 3D CT and the 3D images were reconstructed by Mimics 10.0 (Belgium). Anatomical landmarks were located and the coordinate of the landmarks obtained. Axial images of 1 patient with Romberg disease was used as representative case. The differences in the distance between the right landmarks and the left were calculated and analyzed.

RESULTSThe measurement results were not significantly different between two stages with an interval of 4 weeks ( P > 0.05), showing a reproducible resutls. The deviation of landmarks at facial midline increased gradually from upward to downward, reaching (2.63 +/- 0.54) mm at menton point. Paired landmarks showed asymmetry in three dimensions, especially gonion point on the left side, which was deviated 10.21 mm inward, 9.26 mm forward, 6.30 mm upward, compared to the opposite side.

CONCLUSIONSThe method of 3D CT quantitative analysis can provide precise information in the diagnosis and treatment planning of facial asymmetry deformity.

Anatomic Landmarks ; diagnostic imaging ; Cephalometry ; Craniofacial Abnormalities ; diagnostic imaging ; Facial Asymmetry ; diagnostic imaging ; Humans ; Imaging, Three-Dimensional ; methods ; Tomography, X-Ray Computed ; methods

AIMTo explore the role of humoral immunity in the pathophysiological process of freezing injury and the possible immune interference in the preventation and treatment of frostbite.

METHODSSevere experimental freezing injury model was made in Wistar rats( n = 20). The concentration of three types of immunoglobulin (IgG, IgA and IgM), two types of complement components (C3 and C4), and circulating immune complex (CIC) were measured respectively before and at 4h, 1d, 3d, and 5d after frostbite. At the same time, the tissue immune complex (TIC) in skeletal muscle and the contents of the red blood cell immune complex (RBC-IC) were also observed and then was the red blood cell immune adherence activity (RCIA).

RESULTSSerum IgG concentration decreased rapidly to the lowest level at 4 h after frostbite IgA concentration dropped to the nadir on 1 day after freezing. Decreases of both immunoglobulins were maintained during the 5 days after frostbite. The fate of both C3 and C4 were the same as those immunoglobulins. Freezing had rather less effect on IgM level. CIC concentration in serum, expressed as the percent of prefreezing increased rapidly and to the zenith on the 3 days post-freezing. By immunofluorescence microscopy, thin continuous linear pattern (IgG) was demonstrated along the SM on the first day post-freezing. Granular and nodular deposits (IgG) appeared along the SM as the time proceeded after frostbite. RBC-IC contents, expressed as the erythrocyte IC rosette rate, increased significantly and to the zenith on the 3 d post-freezing, while RCIA depressed to the nadir at the same time.

CONCLUSIONThe freezing frostbite is an immune complex related disease which have not been reported by others before.

Animals ; Antigen-Antibody Complex ; analysis ; immunology ; Frostbite ; blood ; immunology ; Immunoglobulin A ; immunology ; Immunoglobulin G ; immunology ; Immunoglobulin M ; immunology ; Immunoglobulins ; immunology ; Male ; Rats ; Rats, Wistar

Differentiation, the stepwise specialization of cells, and transdifferentiation, the apparent switching of one cell type into another, capture much of the stem cell spotlight. But dedifferentiation, the developmental reversal of a cell before it reinvents itself, is an important process too. In multicellular organisms, cellular dedifferentiation is the major process underlying totipotency, regeneration and formation of new stem cell lineages. In humans, dedifferentiation is often associated with carcinogenesis. The study of cellular dedifferentiation in animals, particularly early events related to cell fate-switch and determination, is limited by the lack of a suitable, convenient experimental system. The classic example of dedifferentiation is limb and tail regeneration in urodele amphibians, such as salamanders. Recently, several investigators have shown that certain mammalian cell types can be induced to dedifferentiate to progenitor cells when stimulated with the appropriate signals or materials. These discoveries open the possibility that researchers might enhance the endogenous regenerative capacity of mammals by inducing cellular dedifferentiation in vivo.
Animals ; Cell Differentiation ; Cells, Cultured ; Epidermal Growth Factor ; physiology ; Humans ; Regeneration ; Salamandridae ; physiology ; Serum ; physiology ; Thrombin ; pharmacology

OBJECTIVETo observe the differentiation and distribution of epidermal stem cell (ESC) after skin soft tissue expansion, and to initially probe into the growth mechanism of expanded skin tissue.

METHODSSamples of normal skin and expanded skin (mean effusion period 45 days) were harvested from head and cervical region in 15 patients who underwent II stage surgery after skin expansion. Samples were divided into scalp adjacent to the center of expander group (expanded scalp, 3 cm from the vertical axis of the expander), scalp from lateral part of the expander group (expanded scalp, 5 - 7 cm lateral to the vertical axis of the expander), cervical skin expansion group, un-expanded scalp control group, and un-expanded cervical skin control group, according to the position of skin harvested. The tissue structure of skin in each group was observed with HE staining, and the differentiation and distribution characteristics of cytokeratin 19 (CK19) positive cells were observed with immunohistochemical staining.

RESULTSCompared with those in the un-expanded control groups, uneven, relatively thickened and obviously folded epidermis with more cell layers and cells with obvious aggregation close to the basal layer were observed in the expanded groups, but those cells were not well-arranged and the transition of polarity was not obvious. The continuity of CK19 positive cells in the basal layer of skin was observed in each of the expanded group with immunohistochemical staining, and positive cells increased obviously and arranged in multilayer in certain parts of basal layer. Clustered or dispersed CK19 positive cells were also observed outside the basal layer. No above-mentioned phenomenon was observed in the un-expanded control group.

CONCLUSIONSThe proliferation and differentiation of ESC with ectopic distribution may enhance the repair process after skin soft tissue expansion.

Cell Proliferation ; Dermis ; cytology ; Epidermis ; cytology ; Humans ; Stem Cells ; cytology ; Tissue Expansion ; Wound Healing

OBJECTIVETo examine the effect of RhoA/Rho kinase signal pathway on TGF-beta1-induced phenotypic differentiation of human dermal fibroblasts.

METHODSThe 4th generation of primary cultured human dermal fibroblasts were stimulated with TGF-beta1, (10 ng/ml). The expression of alpha-SMA was detected after treatment with TGF-beta1, for 0, 3, 6, and 24 h. The expression of alpha-SMA was also detected after treatment with different concentration of TGF-beta1 (0, 2, 10, 50 ng/ml). Then the human dermal fibroblasts (4th generation) were stimulated with TGF-beta1, (10 ng/ml) after being treated with the RhoA/Rho kinase signaling pathway inhibitor Y-27632 (10 umol/ml). The fibroblasts were treated with nothing as sham control, or with Y-27632 (10 umol/L) only as negative control group, or with TGF-beta1 (10 ng/ml) only as positive control group. The expression of alpha-SMA was detected in all the groups. Protein expression was analyzed with ANOVA statistical method.

RESULTSalpha-SMA expression in fibroblasts with 10 ng/ml TGF-beta1 stimulation for 0, 3, 6, 24 h was 1.0, 1.9 0.2, 2.1 +/- 0. 1, 3. 1 +/- 0.1, respectively. Alpha-SMA expression in 24 h group was significantly higher than that in other three groups (n = 4, P < 0.05). alpha-SMA expression in human dermal fibroblasts after stimulation with different concentration of TGF-beta1 (0, 2, 10, 50 ng/ml) was 1.0, 1.4 +/- 0.2, 3.2 + 0.1, 3.1 +/- 0.2, respectively. alpha-SMA expression in 10 ng/ ml group was significantly higher than that in 2 ng/ml group and control group (n = 4, P < 0.05). There was no statistical difference in alpha-SMA expression between 10 ng/ml group and 50 ng/ml group (n = 4, P > 0.05). With both Y-27632 (10 micromol/L) and TGF-beta1 stimulation, the cell phenotype differentiation was inhibited. Alpha-SMA expression in experimental group (1.2 +/- 0.2) was significantly reduced, when compared with that in positive control group (2.9 +/- 0.1) (n = 5, P < 0.05). There was no significant difference (n = 5, P > 0.05) in alpha-SMA expression between control group (1.0) and negative control group (1.1 +/- 0.1).

CONCLUSIONSRhoA/Rho kinase signaling pathway should be involved in TGF-beta1-induced phenotypic differentiation of human dermal fibroblasts.

Actins ; metabolism ; Adolescent ; Cell Differentiation ; Cells, Cultured ; Fibroblasts ; cytology ; Humans ; Male ; Signal Transduction ; Skin ; cytology ; Transforming Growth Factor beta1 ; pharmacology ; rho-Associated Kinases ; metabolism ; rhoA GTP-Binding Protein ; metabolism