OBJECTIVETo modify biomacromolecules, such as chitosan and collagen, to synthesize a mineralized template that will induce self-growing remineralization of tooth enamel.

METHODSNatural polycation polysaccharide chitosan was modified through phosphorylation to synthesize the polyanion derivative ofphosphorylated chitosan. Parent hydrogels com- bined with chitosan and collagen I were built through peptide binding reaction using genipin as a crosslinker. The gels self- assembled on the tooth's inert surface, which was stimulated by ultraviolet radiation. The bionic saliva provided mineralized ion, and then the hydroxyapatite assembled and grew in situ on the tooth.

RESULTSThe functional group P04(3-) (3,446 cm(-1)) was grafted on chitosan as confirmed by the Fourier transform infrared spectroscopy. The porous polyelectrolyte complex hydrogel formed by the interaction between the polycation chitosan and the polyanion phosphorylated chitosan could induce hydroxyapatite crystal nucleation and growth on the hydrogel fiber surfaces. The neonatal crystal was hydroxyapatite as confirmed by X-ray diffraction and was tightly connected to the tooth. A continuous structure of column crystals with sizes ranging from 30 nm to 60 nm was observed. The structure was in parallel direction similar to the direction of the enamel rod, and its hardness was close to dentin.

CONCLUSIONThe parent hydrogels that were easily obtained and controlled could mimic the template of the enamel mineralization and induce a self-growing hydroxyapatite, which is an important step in the structural bionics of enamel.

Biocompatible Materials ; Chitosan ; Collagen ; Dental Enamel ; Durapatite ; Microscopy, Electron, Scanning ; Polymers ; Spectroscopy, Fourier Transform Infrared ; Tooth ; Tooth Remineralization ; Ultraviolet Rays ; X-Ray Diffraction

Traditional Chinese medicine Polygoni Multiflori Radix is dried roots of Polygonaceae Polygortum multiflorum Thunb. Its clinical application records were first discovered in literatures of the Tang dynasty. The origins, efficacy, toxicity, processing and taboos of Polygoni Multiflori Radix have been discussed in many ancient herb literatures. In recent years, with the increase in the public awareness in health, Polygoni Multiflori Radix admits preparations have been more widely applied in the treatment and prevention of diseases. However, there have been more and more reports about Polygoni Multiflori Radix induced liver injury, the safety of Polygoni Multiflori Radix has increasingly attracted attention of the society. In this paper, the authors summarized and analyzed the toxicity and medication risk factors of Polygoni Multiflori Radix recorded in ancient herb literatures, and proposed that more attention shall be given to the effect of the planting and processing methods on the components and toxicity of Polygoni Multiflori Radix in safety studies, which provides clues for the further studies.
China ; Drugs, Chinese Herbal ; adverse effects ; history ; History, Ancient ; Humans ; Medicine in Literature ; Medicine, Chinese Traditional ; history ; Polygonum ; adverse effects ; Risk Assessment

The renal toxicity and mutagenicity of aristolochic acid (AA) as well as its carcinogenicity on upper urinary tract transitional epithelial cells have been widely known. Since 2003, drug regulatory departments have successively cancelled the quality standards for AA-containing medicines such as Aristolochiae Radix, Aristolochiae Manshuriensis Caulis and Aristolchiae Fangchi Radix, and adopted measures for strengthening regulation and revising package insert or quality standards for other AA-containing medicines, including Aristolochia Cinnabarina Radix, Aristolochiae Fructus, Aristolochiae Mollissimae Herba, in order to control its safety risk. In recent years, domestic and foreign studies on AA have mainly involved action mechanism and clinical performance of AA toxicity, early-stage diagnosis and treatment method. In this paper, authors gave a brief summary and evaluation on risk factors for using AA-containing medicines, and offered measures and suggestions for preventing and controlling AA toxicity.
Animals ; Aristolochia ; adverse effects ; chemistry ; Aristolochic Acids ; analysis ; therapeutic use ; toxicity ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; toxicity ; Humans

The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines.
China ; epidemiology ; Drug Evaluation ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Product Surveillance, Postmarketing

Post-marketing evaluation is a process which evaluate the risks and benefits of drug clinical application comprehensively and systematically, scientific and systematic results of post-marketing evaluation not only can provide data support for clinical application of traditional Chinese medicine, but also can be a reliable basis for the supervision department to develop risk control measures. With the increasing demands for treatment and prevention of disease, traditional Chinese medicine has been widely used, and security issues are also exposed. How to find risk signal of traditional Chinese medicine in the early stages, carry out targeted evaluation work and control risk timely have become challenges in the development of traditional Chinese medicine industry.
Drug Evaluation ; methods ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional

Objective:Study on the feature of thrombin-antithrombin complex (TAT) during traumatic brain injury and the predicting performance with adverse clinical outcomes.Methods:From January 2018 to December 2019, 147 patients with traumatic brain injury(TBI) were enrolled, including 112 males and 35 females, aged 36 (26-48) years old. The plasma levels of TAT were detected on the 0th, 1st, 3rd and 7th day after TBI attack. Kruskal-Wallis H test was used for comparison among multiple groups; Mann-Whitney U test was used for data comparison between the two groups; continuous comparison of patient data in the same group using Friedman rank test; the diagnostic performance of TAT with adverse event risk predicting was evaluated by ROC analysis; Kaplan-Meier curve was used to analyze the survival curve; the risk ratio (HR) was obtained by Cox proportional hazard regression model.Results:Among the patients groups with mild, moderate and severe phenotype, the TAT levels were gradually decreased on the 0th, 1st, 3rd and 7th day after TBI attack(χ 2 values were 95.612, 133.555, and 132.453, respectively, all P values<0.001). The TAT levels on the 0th, 1st, 3rd and 7th day in the adverse event group were higher than in the group of patients with stable condition ( U values were 959.0, 321.0, 36.0 and 1.0 respectively, all P values<0.001). In the stable condition group, the TAT levels on the 0th and 1st day in the severe group were higher than in the mild group ( U values were 0 and 1.0 respectively, both P values<0.001), while there was no statistically significant difference of TAT levels between the 3rd and 7th day in the severe group ( U values were 342.5 and 272.5, P values were 0.486 and 0.065 respectively). The TAT levels of the moderate group on 0th and 1st day were higher than those of the mild group ( U values were 0 and 280.0, respectively, both P<0.001), while there was no significant difference between the TAT levels on the 3rd and 7th day ( U values were 628.0 and 647.0, P values were 0.826 and 0.996, respectively). ROC curves analysis showed that when the TAT diagnostic thresholds were 68.75 ng/ml, 29.05 ng/ml, 17.25 ng/ml and 13.85 ng/ml on the 0th, 1st, 3rd and 7th day, the diagnostic sensitivities of predicting adverse events were 86.8%, 94.3%, 100% and 100%; while the diagnostic specificities were 71.3%, 78.7%, 91.5% and 96.8%, respectively. Survival analysis showed that the cumulative probability of adverse outcomes was significantly higher in patients above the critical value. Cox analysis showed that the HR on the 0th, 1st, 3rd and 7th day to predict adverse clinical outcomes by TAT levels were 1.818, 2.257, 3.526 and 4.813, respectively ( P value<0.001). Conclusion:There was strong relationship between the plasma TAT level and the severity of the patient′s condition, and persistent increasing with TAT level could reflect the risk of adverse events, which could be used as an effective index to comprehensively predicting the development tendency of the TBI patient′s condition.

Objective: To identify Tongren Wujibaifeng Pills and Xiaoshuanzaizao Pills respectively by analysis of IR fingerprint. Methods: Both drugs were extracted with hexane, ether and butanone and then the extracts obtained were measured with FT IR spectrometer. Results: By analizing IR fingerprint of 25 batches Tongren Wujibaifeng Pills and 31 batches Xiaoshuanzaizao Pills, we found that different batches of the same drug have stable and repeatable fingerprint. Conclusion: By using IR fingerprint, either Tongren Wujibaifeng Pills and Xiaoshuanzaizao Pills can be identified. It provides a rapid method for drug identification and quality control.

Objective: To study the effect of cardiac autonomic nerve function on body function and weakness in elderly diabetic patients. Methods: A total of 100 patients diagnosed as diabetic autonomic neuropathy in the endocrine ward of Dalian Friendship Hospital from August 2017 to August 2018 were enrolled. The demographics, clinical data, and Activities of Daily Living (ADL) scale of each patient were recorded, and the Instrument Activities of Daily Living (IADL) and the weak score were used to record heart rate variability in each patient. Aweak score of 5 was used as boundaries. Patients with weak score greater than or equal to 5 were divided into weak group, and those less than 5 were divided into non-weak groups. Each indicators were compared between the two groups. The statistically significant variables were used as covariates, and the weak scores were used as dependent variables to perform direct and indirect Logistic regression analysis of covariates and dependent variables and the receiver operation characteristic (ROC) curve. Results: There were significant differences between the two groups in age, diabetes history, heart rate variability, standard deviation of NN intervals (SDNN), standard deviation of sinus RR interval every 5 min (SDANN), triangle index, ultralow frequency (ULF), very low frequency (VLF), activities of daily living (ADL), instrument activities of daily living (IADL) (t=13.45, U=1700, t=-17.52, t=-18.34, U =1204.00, U=3407.56, t=17.90, t=21.89, t=12.21, P< 0.05). Age, diabetes history, heart rate variability, SDNN, SDANN, triangle index, ULF, VLF, ADL, IADL were independent factors of weakness (B=1.14, 0.98, - 0.46, -0.45, -0.79, 0.57, 0.53, -0.67, -0.79, P<0.05). Age, history of diabetes, SDNN, SDANN, ULF, VLF could affect the weak score by indirectly affecting ADL/IADL (B=0.54/0.23, 0.16/0.07, -0.34/-0.04,, -0.54/-0.03, 0.99/0.21, 0.47/0.22, P< 0.05). SDNN, SDANN and ULF could significantly predict weakness, and the sensitivity values of the Yuedeng index maximum were 98ms, 97ms and 236 ms²/Hz, respectively. Conclusions Week score needs to be assessed in patients with diabetic autonomic neuropathy who have a long history of diabetes, and a DANN greater than 98 ms, a SDANN greater than 97 ms, and a ULF greater than 236 ms²/Hz in the heart rate variability index.

Objectives:To observe the changes of the tongues in rats with blood-stasis syndrome induced mainly by cold. To explore the evidence that tongues were the target of blood stasis syndrome and the target of medication. Methods: Rats with blood-stasis syndrome induced by cold (BSC group) were dipped into ice water (0 ℃) for 5 minutes every day and lasted 20d individually. Different drugs were given orally after the model establishment. And then we took photos of tongues of all rats by digital camera, analyzed the gray scale value of all rats' tongues using image analysis software, and observed the capillaries in tongues by electron microscope. Results: The tongues of rats which had been frozen in ice water for 20 d (once a day) were dark purple, the same as that of models induced by chemical materials .While as for the normal rats, the tongues were lustrous and ruddy. The changes of color of the tongues persisted about 1 week and were great obvious at the 3rd day after the model establishment among different time-points. After given different drugs, the degree of dark purple tongue degraded, showed significant difference (P < 0.01) from that of model rats. The capillary stegnosis and nucleus turgescence of vascular endothelial cell were observed in tongues in BSC group by using electron microscope. After medication, the above changes recovered. Conclusion: The degree of dark purple tongue indicates the degree of diseases with blood-stasis syndrome. The tongue probably is a target of drug treatment.

ObjectiveTo construct one recombinant adenovirus AdE7E6 expressing HPV16 E6 and E7 fusion protein as candidate for HPV16 therapeutic vaccine.MethodsThe codon-optimized E6 and E7 gene,were fused to create one open reading frame,then inserted into adenovirus vector pCD316.A strain of recombinant adenovirus was constructed through homologous recombinant in 293 cells,and identified by PCR and Western blot.Finally,it was employed to study it's immunogenicity and the activity of the tumor growth regression.ResultsThe PCR result showed that E6E7 fusion gene had been integrated in recombinant Ad5 DNA.Western blot test confirmed that the E6E7 fusion protein was highly expressed in 293 cells infected with Ad5E7E6 recombinant adenovirus.The recombinant adenovirus elicited significant E7 specific CD8+ T lymphocyte response in vaccinated mice.These responses could completely prevent the TG-1 tumor cell bearing mice treated with AdE7E6 from developing into tumor.ConclusionThese results suggested that rAd5E7E6 could be a potent vaccine candidate for the treatment of HPV16-associated tumors and their precancerous transformations.