Dentin ; Dentin-Bonding Agents ; Plant Extracts

NanoString nCounter Analysis System is a newly developed gene expression detection platform that directly measures multiplexed mRNA levels through digital counting of individual mRNA transcripts.This technology uses as little as 100 ng of RNA and can obtain accurate gene quantitative data from up to 800 genes in one reaction.It requires no reverse transcription,enzymes and amplifications,and its sensitivity and accuracy are comparable to real time quantitative PCR.NanoString technology has been more and more extensively used in frontiers of biomedical research and clinics such as in validation of data from high-throughput platforms,gene expression profiling,gene regulatory network,molecular subtyping,diagnosis and prognosis of diseases.

Objective:To summarize the clinical features and pathological changes of peripheral tissues from patients with neuronal intranuclear inclusion disease (NIID) diagnosed by genetic tests.Methods:Repeat-primed polymerase chain reaction was used to confirm the GGC repeated expansion in the 5′ untranslated region of the NOTCH2NLC gene in patients with suspected NIID who had visited the Department of Neurology of Peking University First Hospital from January 2018 to February 2020. The clinical data and pathological changes of peripheral tissues from patients with genetically diagnosed NIID were collected retrospectively and analysed. Immunostaining with anti-p62 and anti-ubiquitin antibody was performed on peripheral biopsy specimens.Results:Totally nine patients with NIID who had GGC repeated expansion in the NOTCH2NLC gene were found. Five patients were familial (from three faimilies), and four patients were sporadic. The age of onset was 36-61(51.33±7.12) years. The most common symptoms in this NIID group were episodic emotion and personality change (8/9), paroxysmal disturbance of consciousness (6/9) and intermitant head discomfort (6/9). Other symptoms included cognitive dysfunction, limb weakness, limb sensory disturbance, bladder dysfunction, ataxia, seizures and psychiatric symptoms. Brain magnetic resonance imaging showed high signals along the corticomedullary junction on diffusion-weighted image in eight out of nine patients. Skin biopsied samples from nine patients demonstrated the presence of eosinophilic intranuclear inclusions (IIs), appearing in the nucleus of fibroblasts, fat cells and ductal epithelial cells of sweat glands on hematoxylin-eosin staining. IIs were positive on anti-p62 and anti-ubiquitin immunostaining. Electron microscopy indicated the IIs were composed of a pile of filament materials without membrane. Muscle biopsies from two patients showed no obvious neurogenic or myogenic pathologic changes, except in one patient several rimmed vacuoles fibers were found. In one patient sural nerve biopsy showed severe demyelinating pathological changes. No IIs were found in the muscles and peripheral nerve tissue either by histological examination or by immunohistochemical staining with anti-p62 or anti-ubiquitin, while IIs were found by immunofluorescence staining with both anti-p62 and anti-ubiquitin in three patient′s tissue. Conclusions:The phenotype of this NIID patient group is adult-onset NIID, with episodic encephalopathy as the main clinical manifestation. Skin biopsy has high pathological diagnostic value for NIID. The immunofluorescence staining with anti-p62 and anti-ubiquitin is easier to detect the presence of IIs than histological staining and immumohistochemical staining.

Objective To investigate the clinical features of cutaneous adverse reactions to tyrosine kinase inhibitors.Methods Thirty patients with cutaneous adverse reactions to tyrosine kinase inhibitors were enrolled from the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2016,and their laboratory test results,histopathological findings and treatment response data were collected and analyzed retrospectively.Results Of the 30 patients,15 presented with acneiform eruptions,10 with eczematoid eruptions,2 with morbilliform rashes,1 with telangiectasia,1 with hand-foot skin reaction,9 with xerosis,7 with nail changes and 4 with hair changes.A patient with grade 4 acneiform eruptions showed a markedly elevated alanine transaminase (ALT) level (315 U/L).Mild ALT abnormalities (48.5-88.1 U/L) were found in 3 patients with grade 3 acneiform eruptions,1 with grade 2 acneiform eruptions,1 with grade 1 acneiform eruptions and 1 with eczematoid eruptions complicated by fever.Two patients with eczematoid eruptions and 1 with morbilliform rashes showed elevated proportions of peripheral blood eosinophils (0.057-0.303).Pathological changes of the acneiform eruptions included hyperkeratosis and dilation of hair follicles and neutrophilic infiltration.Pathological manifestations of eczematoid eruptions included different degrees of spongiosis,thickened spinous layer,irregular elongation of rete ridges and liquefaction degeneration of basal cells in the epidermis,and perivascular infiltration of lymphocytes and eosinophils in the superficial dermis.Patients with grade 1-3 acneiform eruptions received oral minocycline for 6 weeks,skin lesions gradually regressed,but relapse occurred after the withdrawal.After withdrawal of targeted antineoplastic agents and 2-week treatment with systemic glucocorticoids,skin lesions gradually regressed in patients with grade 4 acneiform eruptions,those with eczematoid eruptions complicated by fever,and those with morbilliform rashes.Skin rashes also resolved in patients with mild morbilliform rashes and those with mild eczematoid eruptions after 2 weeks of treatment with antianaphylactic agents and topical glucocorticoids.Oral antibiotics were effective for the treatment of periungual erythematous swelling or granulomas.Conclusion Tyrosine kinase inhibitor-related cutaneous adverse reactions include a constellation of disorders,and hepatic function can be impaired.

This study analyzed the current status of the cultivation process of professional postgraduates of clinical medicine, combining with the case of the auxiliary teaching model of Academic Salons on the WeChat platform in Xiangya Hospital of Central South University. We collected students' satisfaction evaluation of this auxiliary teaching model by questionnaire survey. Through analyzing the results and feedback, we found that the overall satisfaction of this auxiliary teaching model is 71.43%, and the model has a remarkable effect in broadening knowledge, inspiring thinking of clinical diagnosis and treatment, improving ability of scientific research, increasing learning interest, enhancing the ability to link theory with practice, and using the knowledge flexibly. However, there are still some shortcomings in early publicity, understanding students' interests and needs, and improving students' autonomous learning ability. Therefore, using the WeChat platform to carry out academic salons is a good auxiliary teaching model for cultivating the scientific research ability of professional postgraduates of clinical medicine.

Objective:To study the intervention effect of ganoderma triterpenoids combined with exogenous monosialotetrahexosyl ganglioside(GM1) on cognitive dysfunction and synaptic ultrastructure of hippocampal neurons in rats with epilepsy caused by pentylenetetrazol(PTZ).Methods:A total of 40 Sprague-Dawley rats were divided into blank control group, epileptic model group, ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group according to the random number table method( n=8 in each group). The rats were intraperitoneally injected with PTZ subconvulsant dose (35 mg·kg -1·d -1) once a day for 28 days to replicate the models of chronic epilepsy. And the rats in different medication groups were given corresponding administration based on daily intraperitoneal injection of PTZ(GM1: intraperitoneal injection of 30 mg·kg -1·d -1, ganoderma triterpenoids: gavage 1 000 mg·kg -1·d -1). Morris water maze was used to test the spatial exploration and learning and memory ability of epileptic rats.Transmission electron microscopy was used to observe the ultrastructure of hippocampal neurons in epileptic rats.Immunofluorescence staining was used to observe expression levels of cofilin and SYN protein in hippocampus CA1 of rats. In addition, Western blot was used to detect the expression levels of cofilin, p-cofilin and synaptophysin(SYN) protein in hippocampus of rats. SPSS 17.0 software was used for statistical analysis. Repeated one-way ANOVA was used for comparing among groups, LSD test was used for pairwise comparisons. Results:Morris water maze results showed that there were statistically significant differences in escape latency, times of crossing the platform and time spent in the target quadrant among the groups( F=5.259, 8.240, 5.961, all P<0.05). Compared with the epilepsy model group, the escape latencies((20.31±7.39) s, (21.81±6.05) s, (17.66±4.76) s) of the ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were shorter (all P<0.05), the numbers of crossing the platform ((4.63±1.41) times, (4.50±1.93) times, (5.50±1.77) times) were more (all P<0.05), the residence time in target quadrant ((31.91±5.00) s, (30.49±5.72) s, (35.70±5.34) s) were longer (all P<0.05). And the most obvious change was found in the GM1 combined with ganoderma triterpenoids group ( P<0.01). The results of transmission electron microscope showed that there were significant differences in the numbers of hippocampal neurons synapses, the synaptic gap, the density of postsynaptic membrane and length of active area of postsynaptic membrane among the groups( F=3.693, 7.201, 5.012, 4.033, all P<0.05). Compared with the epilepsy model group, the numbers of synapses ((8.00±1.79), (7.83±1.84), (8.50±1.87)) in the ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were all more (all P<0.05), synaptic gap ((33.83±3.81)nm, (32.43±4.14)nm, (30.23±3.08)nm)were narrower, and the postsynaptic dense substances ((57.50±6.03)nm, (58.10±2.40)nm, (60.73±3.81)nm) were all thicker (all P<0.05). The length of active region of postsynaptic membrane ((271.66±11.80) nm, (279.06±13.58) nm) in ganoderma triterpenoid group and GM1 combined with ganoderma triterpenoids group were longer than that in epilepsy model group (both P<0.05). Immunofluorescence results showed that the average fluorescence intensity of cofilin in the epilepsy model group was higher than that in the blank control group, and the average fluorescence intensity of SYN was lower than that in the blank control group (both P<0.05). The average fluorescence intensity of cofilin in GM1 group and GM1 combined with ganoderma triterpenoids group were lower than that in epilepsy model group (both P<0.05), and the average fluorescence intensity of SYN in ganoderma lucidum triterpenoids combined with GM1 group was higher than that in epilepsy model group ( P<0.05). Western blot showed that the expression levels of cofilin protein in the epilepsy model group was higher than that in the blank control group ((1.454±0.080), (1.092±0.099), P<0.05), and the expression of p-cofilin and SYN were lower than those in the blank control group ((1.103±0.120) vs (1.420±0.934), (1.650±0.062) vs (1.958±0.062), both P<0.05). The expression of cofilin protein ((1.227±0.071), (1.262±0.078), (1.162±0.129), P<0.05) in ganoderma triterpenoids group, GM1 group and GM1 combined with ganoderma triterpenoids group were lower than that in epilepsy model group, and the expression levels of p-cofilin(1.357±0.199) and SYN protein(1.873±0.010) in ganoderma triterpenoids combined with GM1 group were higher than that in epilepsy model group (both P<0.05). Compared with ganoderma lucidum triterpenoids group and GM1 group, there was no significant difference in each index of GM1 combined with ganoderma triterpenoids group (all P>0.05). Conclusion:GM1 combined with ganoderma triterpenoids may promote the synaptic plasticity of neurons, improve the learning and memory ability of epileptic rats.Combination medication is better than single medication in some observed indicators.

Objective To observe the inhibitory effect of quercetin on the biofilm formation of Streptococcus mutans(Sm),to preliminarily reveal the possible underlying mechanisms,and to evaluate the cytotoxicity of quercetion to human dental pulp cells so as to provide the theoretical basis for the application of quercetin in oral biomaterials.Methods Quercetin storage solution was diluted to 0,3.125,6.25,12.5,25,50,100,200,400 and 800 mg/L,and added into Sm medium for 4 h and 24 h,crystal violet staining was used to evaluate the biofilm volume.In subsequent detections,three groups were set:control(0 mg/L),200 mg/L quercetin and 400 mg/L quercetin.Confocal laser scanning microscopy was used to observe the morphology of the biofilm;qPCR for gtfB,gtfC,comD,comE,and luxS were assessed to preliminarily investigate the mechanisms.Finally,the methyl thiazolyl tetrazolium(MTT) test using human dental pulp cells was used to investigate cytotoxicity.Results Quercetin could significantly inhibit up to (86.16±0.45)％ of the biofilm formation of Sm (Compared with the control group P=0.00) and effectively removed (43.04±0.53)％ of the mature biofilm(Compared with the control group P=0.00).Confocal laser scanning microscopy photographs showed that after co-incubated for 24 h,the dense biofilm structures of the experimental group were destroyed by quercetin both at 200 mg/L and 400 mg/L.Quercetin suppressedover 50％ of the expression of gtfB,gtfC,comD,comE(compared with the control group P＜0.05) and promoted the expression of luxS up to 2.18 ±0.24 and 2.84±0.26 after 4 h and 24 h,respectively(compared with the control group P＜0.05).Quercetin also exhibited acceptable compatibility for human dental pulp cells.Conclusions Quercetin could effectively reduce the biofilm formation of Sm by inhibiting the expression of the related genes,and exhibited no cytotoxicity for human dental pulp cells.Quercetin has good potential to be applied in oral biological materials.

Objective To systematically retrieve,evaluate and integrate evidences about the assessment and management of perioperative pain in patients with acute aortic dissection.Methods PIPOST model was used to identify themes of assessment and management of perioperative pain.The literatures in the themes was systematically searched through the databases of UpToDate,JBI,BMJ Best Practice,practice guide REgistration for trans RAREncy(PREPARE),Guidelines International Network(GIN),National Guideline Clearinghouse(NGC),National Institute for Health and Care Excellence(NICE),Scottish Intercollegiate Guidelines Network(SIGN),New Zealand Guidelines Group(NZGG),Registered Nurses'Association of Ontario(RNAO),Australian Clinical Practice Guidelines(ACPG),American Heart Association(AHA),European Society of Cardiology(ESC),the Chinese Cochrane Center,Medlive,Cochrane library,PubMed,SinoMed,CNKI,Wangfan Data,and VIP.The retrieved literatures were evaluated and the evidences that met the inclusive criteria were extracted from the literatures by researchers who had trained for evidence-based study.Results A total of 17 studies,including 5 guidelines,3 expert consensus,6 systematic reviews and 3 randomised controlled trials were included in this study.Totally,29 pieces of best evidence were extracted in the assessment and management of pain in perioperative patients with acute aortic dissection,including pain assessment,basic principles of pain management,medication intervention strategies of pain management,non-medication intervention strategies of pain management,pain evaluation,education of pain management and organising pain management.Conclusion Evidences in assessment and management of pain in perioperative patients with acute aortic dissection can provide references and guidance for clinical practice.

Objective: To explore the molecular biological mechanism of curcumol in regulating ferroptosis and autophagy. Methods: The Pharm Mapper database was used to screen out curcumol targets, various known related databases were used to establish a database of ferroptosis and autophagy related targets, and the String database was used to construct a protein-protein interaction network. The key targets were enriched and analyzed using DAVID database. Results: 152 curcumol targets, 259 ferroptosis targets, and 796 autophagy targets were obtained; curcumol mainly regulated the ferroptosis process through PTGS2, ALB, MAPK1, MAPK8, and MAPK14 targets, and curcumol mainly through HSP90 AA1, MAPK1, MAPK8, ALB, NOS3 targets regulated the autophagy process, and curcumol mainly regulated the ferroptosis and autophagy process through ALB, MAPK1, MAPK8 targets. Conclusion Curcumol can exert pharmacological effects by regulating ferroptosis and autophagy.

Objective    To explore the efficacy of a novel detection technique of circulating tumor cells (CTCs) to identify benign and malignant lung nodules. Methods     Nanomagnetic CTC detection based on polypeptide with epithelial cell adhesion molecule (EpCAM)-specific recognition was performed on enrolled patients with pulmonary nodules. There were 73 patients including 48 patients with malignant lesions as a malignant group and 25 patients with benign lesion as a benign group. There were 13 males and 35 females at age of 57.0±11.9 years in the malignant group and 11 males and 14 females at age of 53.1±13.2 years in the benign group. e calculated the differential diagnostic efficacy of CTC count, and conducted subgroup analysis according to the consolidation-tumor ratio, while compared with PET/CT on the efficacy. Results     CTC count of the malignant group was significantly higher than that of the benign group  (0.50/ml vs. 0.00/ml, P<0.05). Subgroup analysis according to consolidation tumor ratio (CTR) revealed that the difference was statistically significant in pure ground glass (pGGO) nodules 1.00/ml vs. 0.00/ml, P<0.05), but not in part-solid or pure solid nodules. For pGGO nodules, the area under the receiver operating characteristic (ROC) curve of CTC count was 0.833, which was significantly higher than that of maximum of standardized uptake value (SUVmax) (P<0.001). Its sensitivity and specificity was 80.0% and 83.3%, respectively. Conclusion     The peptide-based nanomagnetic CTC detection system can differentiate malignant tumor and benign lesions in pulmonary nodules presented as pGGO. It is of great clinical potential as a noninvasive, nonradiating method to identify malignancies in pulmonary nodules.