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1.
Article in Chinese | WPRIM | ID: wpr-847161

ABSTRACT

BACKGROUND: Whether remnant preservation can improve tendon-bone healing remains a controversy. Experiments were designed to evaluate whether remnant preservation has the biological advantage of promoting tendon-bone healing by histology and imaging. OBJECTIVE: To investigate the effect of preservation of ligament stump on tendon-bone healing in anterior cruciate ligament reconstruction. METHODS: Forty New Zealand rabbits were randomly divided into two groups: anterior cruciate ligament reconstruction group without remnant preservation (group A) and anterior cruciate ligament reconstruction group with remnant preservation (group B), with 20 rabbits in each group. Achilles tendon was selected as the graft, and the bilateral anterior cruciate ligaments of all the rabbits were cut off. In group A, the anterior cruciate ligament stump was completely removed. In group B, the tibia stump was cut off from the femoral stop, and the tibia stump was retained. According to the position of the anterior cruciate ligament of the normal rabbits, the tibia and the femoral canal were selected for reconstruction. At 6 and 12 weeks after surgery, the expression of vascular endothelial growth factor and hypoxia inducible factor-1α was detected by immunohistochemistry. Graft microvessel density was detected by CD34 immunohistochemical staining. The signal intensity of tendon and the width of bone tunnel were observed by MRI and CT. RESULTS AND CONCLUSION: (1) The percentage of hypoxia inducible factor-1α and vascular endothelial growth factor positive cells in group B was significantly higher than that in group A at 6 weeks after operation (P 0.05). (2) At 6 weeks after operation, the expansion of bone tunnel in group B was significantly lower than that in group A, and the signal intensity of tendon graft was lower in group B than that in group A (P 0.05). (3) In this experiment, in the early stage of ligament reconstruction, the anterior cruciate ligament reconstruction with remnant preservation is superior to the anterior cruciate ligament reconstruction without remnant preservation in terms of graft revascularization and reduction of bone tunnel expansion, showing some biological advantages.

2.
Article in English | WPRIM | ID: wpr-902407

ABSTRACT

Objective@#To evaluate the feasibility of texture analysis on non-contrast-enhanced T1 maps of cardiac magnetic resonance (CMR) imaging for the diagnosis of myocardial injury in acute myocardial infarction (MI). @*Materials and Methods@#This study included 68 patients (57 males and 11 females; mean age, 55.7 ± 10.5 years) with acute ST-segment-elevation MI who had undergone 3T CMR after a percutaneous coronary intervention. Forty patients of them also underwent a 6-month follow-up CMR. The CMR protocol included T2-weighted imaging, T1 mapping, rest first-pass perfusion, and late gadolinium enhancement. Radiomics features were extracted from the T1 maps using open-source software. Radiomics signatures were constructed with the selected strongest features to evaluate the myocardial injury severity and predict the recovery of left ventricular (LV) longitudinal systolic myocardial contractility. @*Results@#A total of 1088 segments of the acute CMR images were analyzed; 103 (9.5%) segments showed microvascular obstruction (MVO), and 557 (51.2%) segments showed MI. A total of 640 segments were included in the 6-month follow-up analysis, of which 160 (25.0%) segments showed favorable recovery of LV longitudinal systolic myocardial contractility.Combined radiomics signature and T1 values resulted in a higher diagnostic performance for MVO compared to T1 values alone (area under the curve [AUC] in the training set; 0.88, 0.72, p = 0.031: AUC in the test set; 0.86, 0.71, p = 0.002).Combined radiomics signature and T1 values also provided a higher predictive value for LV longitudinal systolic myocardial contractility recovery compared to T1 values (AUC in the training set; 0.76, 0.55, p < 0.001: AUC in the test set; 0.77, 0.60, p < 0.001). @*Conclusion@#The combination of radiomics of non-contrast-enhanced T1 mapping and T1 values could provide higher diagnostic accuracy for MVO. Radiomics also provides incremental value in the prediction of LV longitudinal systolic myocardial contractility at six months.

3.
Article in English | WPRIM | ID: wpr-894703

ABSTRACT

Objective@#To evaluate the feasibility of texture analysis on non-contrast-enhanced T1 maps of cardiac magnetic resonance (CMR) imaging for the diagnosis of myocardial injury in acute myocardial infarction (MI). @*Materials and Methods@#This study included 68 patients (57 males and 11 females; mean age, 55.7 ± 10.5 years) with acute ST-segment-elevation MI who had undergone 3T CMR after a percutaneous coronary intervention. Forty patients of them also underwent a 6-month follow-up CMR. The CMR protocol included T2-weighted imaging, T1 mapping, rest first-pass perfusion, and late gadolinium enhancement. Radiomics features were extracted from the T1 maps using open-source software. Radiomics signatures were constructed with the selected strongest features to evaluate the myocardial injury severity and predict the recovery of left ventricular (LV) longitudinal systolic myocardial contractility. @*Results@#A total of 1088 segments of the acute CMR images were analyzed; 103 (9.5%) segments showed microvascular obstruction (MVO), and 557 (51.2%) segments showed MI. A total of 640 segments were included in the 6-month follow-up analysis, of which 160 (25.0%) segments showed favorable recovery of LV longitudinal systolic myocardial contractility.Combined radiomics signature and T1 values resulted in a higher diagnostic performance for MVO compared to T1 values alone (area under the curve [AUC] in the training set; 0.88, 0.72, p = 0.031: AUC in the test set; 0.86, 0.71, p = 0.002).Combined radiomics signature and T1 values also provided a higher predictive value for LV longitudinal systolic myocardial contractility recovery compared to T1 values (AUC in the training set; 0.76, 0.55, p < 0.001: AUC in the test set; 0.77, 0.60, p < 0.001). @*Conclusion@#The combination of radiomics of non-contrast-enhanced T1 mapping and T1 values could provide higher diagnostic accuracy for MVO. Radiomics also provides incremental value in the prediction of LV longitudinal systolic myocardial contractility at six months.

4.
Chinese Journal of Radiology ; (12): 961-967, 2021.
Article in Chinese | WPRIM | ID: wpr-910259

ABSTRACT

Objective:To investigate the value of logistic regression model based on the features of cone-beam breast CT (CBBCT) for the identification of benign and malignant masses in dense breast.Methods:The data of 106 patients (130 masses) with dense breast who underwent contrast-enhanced CBBCT examination and obtained pathological results from May 2011 to August 2020 were retrospectively analyzed as the training set. From August 2020, the data of 49 patients (54 masses) who met the same criteria were prospectively and consecutively collected and used as the validation set. Taking pathological results as the gold standard, the training set was divided into benign and malignant groups. The t-test, χ 2 test and Fisher′s exact test were used to compare the differences in CBBCT image characteristics between the two groups in the training set. A binary logistic regression model was established by multivariate analysis. ROC curves were used to assess the diagnostic efficacy of the model as a whole in the training and validation sets and the diagnostic efficacy of each feature in the model, and the cut-off value of the intensity (ΔCT) value was determined. The H-L method was used to test the goodness of fit of the model. Decision curve analysis (DCA) was drawn to validate the clinical power of the model. Results:Univariate analysis showed that the breast parenchymal background enhancement (BPE), shape, margin, lobulation, spiculation, density, calcifications, ΔCT value, enhancement pattern, non-mass enhancement, ipsilateral increased vascularity (IIV), and peripheral vascular signs had statistical difference between benign group and malignant group ( P<0.05). BPE, margin, ΔCT value and IIV were included in the multivariate analysis, the equation was logit( P′)=-8.510+0.830×BPE+0.822×margin+1.919× ΔCT+1.896 × IIV. The are a under curve of the model in the training set was 0.879 ( P<0.001) and in the validation set was 0.851 ( P=0.001). The are a under curve of BPE, margin, ΔCT value, and IIV in the diagnosis of malignant mass were 0.645, 0.711, 0.712, 0.775 (all P<0.05); the best cut-off value of ΔCT was 50.38 HU. The fit of this model was good ( P = 0.776). The DCA curve showed that when the risk threshold was 0.05-0.97, the net benefit rate was>0, and this model had some clinical value. Conclusion:The logistic regression model based on the features of CBBCT is helpful to distinguish benign and malignant masses in dense breasts.

5.
China Pharmacy ; (12): 1885-1893, 2021.
Article in Chinese | WPRIM | ID: wpr-886284

ABSTRACT

OBJECTIVE:To provide reference for the selection of more economical programmed death- 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitors for National Medical Insurance List and the quality improvement of related economic evaluation. METHODS:Retrieved from CNKI ,VIP,Wanfang database ,PubMed,Web of Science and Ovid Embase ,economic evaluation studies including listed PD- 1/PD-L1 inhibitors of China were collected during the inception to Oct. 2020. CHEERS checklist was used to evaluate the quality of the included literatures ,and the methodological characteristics and economic evaluation results of the included studies were analyzed systematically. RESULTS :A total of 14 literatures were included ,all of which were model-based and with moderate or high quality. However ,there were still some deficiencies in the included literatures ,mainly manifesting as the insufficient reports on the reasons for setting or selecting model parameters ,as well as the great uncertainty of clinical effect data and utility value. Only 3 of the 8 PD-1/PD-L1 inhibitors listed in China were involved in the included literatures. Compared with chemotherapy or targeted therapy plan ,9 literatures(64.29%)showed that the therapy plan containing PD- 1/PD-L1 inhibitors was not cost-effective. CONCLUSIONS :The economic evidence of domestic PD- 1/PD-L1 inhibitors is lacking ,the higher price of imported PD- 1/PD-L1 inhibitors lead to poor economic performance. The existing economic evaluations has some shortcomings in methodological application and parameter selection. Pharmaceutical enterprises should fill in the data gaps and adjust the pricing strategy,researchers should improve the standardization of research ,and medical insurance decision-making departments should improve the judgment on the quality of economic evidences ,so as to promote more economical drugs to be included in the National Medical Insurance List.

6.
Article in Chinese | WPRIM | ID: wpr-883007

ABSTRACT

Objective:To collect and summarize evidence for improvement of readiness for hospital discharge of patients after PCI.Methods:BMJ Best Practice, UpToDate, Joanna Briggs Institute (JBI) evidence-based health care center database, National Institutes of Health and Clinical Optimization Guidelines Network, Scotland Inter Hospital Guidelines Network, Ontario Registered Nurses Association, International Guidelines Collaboration Network, American Heart Association website, European Heart Association website, Cochrane The literatures about improving the discharge readiness of patients after PCI in library, PubMed, CINAHL, CNKI and Wanfang databases included guidelines, system reviews, best practice information books, evidence summary, expert consensus, and randomized controlled studies. The retrieval time limit was from the establishment of the database to October 2019. Four researchers evaluated the quality of the literature, and extracted evidence from the literature that met the quality standards.Results:A total of 5 articles were included, including 2 guidelines, 2 expert consensus, 1 systematic reviews,3 randomized controlled trials. The best evidence included evaluation of discharge readiness, education of knowledge and skills to patients and caregivers, improvement of self-efficacy of patients and caregivers in disease management, and assurance of social support and health resources for patients and caregivers after discharge.Conclusion:It is suggested that in clinical practice, medical personnel should use the discharge readiness assessment tool to comprehensively evaluate patients after PCI, carry out programmed health education, improve patients' self-efficacy in disease management, and ensure social and medical support for patients and caregivers after discharge as much as possible.

7.
Article in English | WPRIM | ID: wpr-881086

ABSTRACT

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or α

8.
Article in English | WPRIM | ID: wpr-922768

ABSTRACT

Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT


Subject(s)
Animals , Bufanolides , Edema/drug therapy , Inflammation , Lipidomics , Molecular Docking Simulation , Rats , Water
9.
Article in Chinese | WPRIM | ID: wpr-878920

ABSTRACT

This study was to investigate the chemical constituents from the aerial parts of Thymus przewalskii. The chemical consti-tuents were separated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and semi-prepared HPLC, and their structures were determined by physicochemical properties and spectroscopic data. Four flavanones were isolated from the ethanol extract of the aerial parts of T. przewalskii, and identified as(2S)-5,6-dihydroxy-7,8,4'-trimethoxyflavanone(1), 5,4'-dihydroxy-6,7-dimethoxyflavanone(2),(2S)-5,4'-dihydroxy-7,8-dimethoxyflavanone(3), sakuranetin(4), respectively. Compound 1 was a new compound and its configuration was determined by CD spectrum, compound 3 was natural product which was isolated for the first time and their configurations were determined by CD spectra. Compound 2 was isolated from the genus Thymus for the first time and compound 4 was isolated from T. przewalskii for the first time. Furthermore, cytotoxicity test was assayed for the four flavanones. They exhibited weak cytotoxicity against human lung cancer cells(A549), with the IC_(50) from 74.5 to 135.6 μmol·L~(-1).


Subject(s)
Chromatography, High Pressure Liquid , Flavanones , Humans
10.
Article in Chinese | WPRIM | ID: wpr-908077

ABSTRACT

Objective:To understand the attitudes of obstetricians and midwives towards the development of nurse practitioner in China.Methods:The phenomenological method in qualitative research was used to conduct semi-structured interviews with 24 medical staff in the third-A general hospitals and women and children's hospitals in Guangzhou and Dongguan City. The interview data were analyzed by Colaizzi's 7-step analysis method.Results:Four themes were extracted, namely, unanimous approval attitude, imperfect midwifery discipline and management system, insufficient independent practice capacity, low support and recognition in midwifery area.Conclusions:Obstetricians and midwives hold a positive attitude towards the development of midwifery nurse practitioner. At the same time,its development is restricted in many aspects. They can gradually develop midwife′s legislation, improve the management system, try some prescription rights, and increase the education and talents of midwifery subjects. Cultivation and promotion of social recognition will help gradually train midwifery nurse practitioner in China.

11.
Chinese Journal of Radiology ; (12): 948-953, 2020.
Article in Chinese | WPRIM | ID: wpr-868363

ABSTRACT

Objective:To investigate the correlation between venous collateral circulation and clinical data such as symptoms, parenchymal injury, and prognosis in patients with cerebral venous thrombosis(CVT).Methods:The clinical and imaging data of patients with CVT diagnosed in the department of Neurosurgery of the Third Affiliated Hospital of Southern Medical University from December 2011 to August 2018 were retrospectively analyzed. A total of 32 patients with CVT were included, 19 males and 13 females, aged from 20 to 60 (39±12) years. All patients underwent cerebral angiography, individualized delayed rotational phlebography. According to the number and diameter of collateral circulation and the phenomenon of flow delay of contrast medium, the collateral venous circulation scale (CVCS) was developed and divided into 3 levels. The clinical data (risk factors, course of disease, clinical symptoms), imaging data (parenchymal injury, thrombus site), treatment (endovascular treatment, decompressive craniectomy) and prognosis of all patients were recorded. The differences in clinical data, imaging appearances, parenchymal injury, and prognosis between patients with different CVCS were compared, and the correlation between variables with statistically significant differences and CVCS was compared using the Gamma method or Spearman correlation analysis.Results:Among the 32 patients with CVT, 9 were CVCS 0, 13 were CVCS 1 and 10 were CVCS 2. Among them, there were 19 cases of neurological deficit and 17 cases of brain parenchymal injury. There were significant differences in course of disease, neurological deficit, focal dyskinesia, language dysfunction, consciousness disorder, isolated headache, deep vein thrombosis, cortical vein thrombosis and prognosis across different CVCS ( P<0.05). Correlation analysis showed that CVCS was positively correlated with course of disease and isolated headache ( r=0.724, 0.637, P<0.001), and negatively correlated with neurological deficit symptoms, focal dyskinesia, disturbance of consciousness, brain parenchymal injury and deep vein thrombosis ( r=-0.797, -0.451, -0.782, -0.697, -0.427, P<0.05). The results of 90 days follow-up showed that there were 18 cases with mRS 0, 6 cases with mRS 1, 2 cases with mRS 2-4, and 1 case with mRS 5-6 points. There was a negative correlation between CVCs grading and mRS score at 90 days ( r=-0.732, P<0.001). Conclusion:Lower cerebral venous collateral circulation grade is associated with higher incidence of brain parenchymal injury, neurological deficit symptoms, and worse clinical prognosis.

12.
Chinese Journal of Radiology ; (12): 521-526, 2020.
Article in Chinese | WPRIM | ID: wpr-868320

ABSTRACT

Objective:To investigate the optimal monoenergetic level of spectral reconstructions and contrast agent concentration for the structure and lumen of isolated coronary stents on a dual-layer spectral detector CT (DLCT).Methods:Eighteen scaffolds of different materials were implanted into the artificial simulated coronary artery, and were filled with conventional and low concentration contrast agents (1/2 of the conventional dose). Spectral CT scan was performed, and 50-100 keV (interval 10 keV) and 120 keV single-level reconstruction were performed at the conventional concentration and low concentration, which were recorded as A 50-100, 120 keV group and B 50-100, 120 keV group respectively; Another group of conventional concentration data was reconstructed with conventional iDose 4, which was recorded as conv group. The image was evaluated subjectively, including stent structure score (Likert 5-score) and stent lumen score (Likert 4-score); objective evaluation, including background noise, contrast noise ratio (CNR) and stent inner diameter difference (AlN). The differences of subjective and objective evaluation indexes were analyzed. Results:The stent structure scores of A 80, 90 keV group [(3.56±0.64), (4.11±0.58) points] and B 90 keV group [(3.61±0.50) points] were significantly better than those of other groups ( P<0.01), and the A 90 keV group had the highest score. The scores of stent lumen in A 70 keV group [(3.61±0.50) points] and B 70 keV group [(3.47±0.63) points] were significantly better than other groups ( P<0.01), and the score of A 70 keV group was the highest. There was no significant difference in noise, CNR and AlN ( F=1.67, 0.15, 1.16, P>0.05). The main effect analysis was energy level, there were significant differences in noise, CNR and AlN between groups a, B and conv ( F=83.74, 23.95, 24.63, P<0.01). A 70, 80, 90 keV group [(11.43±0.48), (11.81±0.34), (12.01±0.33) HU] and B 70, 80, 90 keV group [(11.50±0.31), (11.58±0.18), (12.13±0.30) HU], image background noise was significantly lower than other groups ( P<0.01). There was no significant difference between the six groups ( P>0.05). The noise of A 70 keV group was the least. The CNR in stent lumen of A 50, 60, 70 keV groups (26.85±5.19, 26.03±4.29, 24.46±5.40) and B 50, 60, 70 keV groups (25.88±5.67, 24.18±5.46, 24.91±7.67) was significantly higher than that of other groups ( P<0.01). The highest CNR value was found in A 50 keV group. The AlN value of A 90, 100, 120 keVgroup [(32.22±6.16) %, (30.79±5.55) %, (27.05±4.47)%] was higher than that of conv group [(41.76±6.00)%], the difference was statistically significant ( P<0.01). The AlN values of A 90, 100, 120 keV group and B 90, 100, 120 keV group [(34.34±5.73)%, (33.95±5.46)%, (33.92±5.45)%] were lower than those of other subgroups, and the differences were statistically significant ( P<0.01). There was no statistically significant difference between the six groups ( P>0.05). The AlN of A 120 keV group was the lowest. Conclusions:Regarding stent phantom imaging, DLCT monoenergetic imaging was better than conventional mixed energy imaging. When DLCT scanning was performed, 90 keV (structure) and 70 keV (lumen) combined reconstruction could not reduce the imaging quality when the concentration was halved.

13.
Article in Chinese | WPRIM | ID: wpr-865376

ABSTRACT

Objective:To analyze the stability of different internal fixation methods for zygomaticomaxillary complex fracture using finite element biomechanical analysis and to provide a quantitative basis for the option of optimal internal fixation methods.Methods:One patient with zygomaticomaxillary complex ZMC fracture (Zingg B type) was enrolled from the Second Hospital of Dalian Medical University in October 2016.The zygomaticofrontal suture and the inferior orbital rim were fixed during the surgery, and the postoperative function was well recovered with no mouth opening restriction, diplopia or implant displacement, and had a symmetrical facial appearance.The preoperative orbital CT images were collected.The normal craniofacial bones finite element model (FEM/intact) was reconstructed through Mimics, Geomagic, Solidworks and Abaqus softwares based on the non-fractured side and verified.Based on the verified model, the segmentation and assembling was performed according to the fracture location, and the internal fixation models were established according to the methods of surgery, including fixed zygomaticofrontal suture model (FEM/ZFS), fixed inferior orbital rim model(FEM/IOR), fixed zygomaticofrontal suture and inferior orbital rim model (FEM/ZFS+ IOR), fixed ZFS and IOR and zygomaticomaxillary suture model (FEM/ZFS+ IOR+ ZMS). The masseter muscle strength was applied to the model.The stress and displacement were analyzed and the rotation angle of zygoma was calculated to compare the stability of different operative methods.The postoperative model (FEM/post) was established according to the actual operative method and was compared with FEM/ZFS+ IOR.This study protocol was approved by the Ethic Committee of The Second Hospital of Dalian Medical University (2020-33), and written informed consent was obtained from the subject before entering the study.Results:The established FEM/intact had a realistic appearance and good geometric similarity, and the validity and accuracy of model was verified.In the FEM/ZFS+ IOR and FEM/ZFS+ IOR+ ZMS, the maximal stress of the titanium plate was 396 MPa and 426 MPa, respectively, which was lower than the yield strength 483 MPa of pure titanium, and the maximal displacement of the fracture line was 0.10 mm and 0.06 mm, respectively, which was both≤0.1 mm, and the rotation angle of zygoma was both<2°.In the FEM/ZFS and FEM/IOR, the maximal stress of the titanium plate was 730 MPa and 501 MPa, respectively, which was higher than the yield strength of pure titanium; the maximal displacement of fracture line was 0.27 mm and 0.15 mm, respectively, which was >0.1 mm, and the rotation angle of zygoma was <2°.The results of FEM/post were consistent with those of FEM/ZFS+ IOR.Conclusions:The finite element analysis can perform digital analysis and evaluation of the stability of different internal fixation methods before surgery, which is available for the selecting of the optimal fixation methods.Finite element analysis can provide an objective quantitative basis for the precise treatment of zygomaticomaxillary complex fractures.

14.
Acta Pharmaceutica Sinica ; (12): 2298-2305, 2020.
Article in Chinese | WPRIM | ID: wpr-829377

ABSTRACT

Malignant tumor is a disease that severely threaten human health. Common chemotherapeutical drugs currently used in clinical practice have some problems in severe side effects and chemoresistance. In contrast, natural venom peptides and artificially designed targeting peptides have excellent biological activities and potential druggability due to their small molecular weights and high affinity to tumor tissues. Thus, the methods for the discovery of anti-tumor peptides have attracted much attention. In this paper, we summarized the types of anti-tumor peptides from recent literatures. Then, we systematically reviewed screening theories, methods and applications based on traditional chromatographic separation, peptidomics, phage display, phenotypic screening, and artificial intelligence. These strategies and technologies will provide a methodological reference for accelerating anti-tumor peptides research.

15.
Chinese Journal of Biotechnology ; (12): 891-898, 2020.
Article in Chinese | WPRIM | ID: wpr-826887

ABSTRACT

Unnatural amino acid orthogonal translation machinery can insert unnatural amino acids at desired sites of protein through stop codon by means of foreign orthogonal translation system composed of aminoacyl-tRNA synthetase and orthogonal tRNA genes. This new genetic engineering technology is not only a new tool for biochemical researches of proteins, but also an epoch-making technology for the development of new-type live viral vaccines. The mutated virus containing premature termination codon in genes necessary for replication can be propagated in transgenic cells harboring unnatural amino acid orthogonal translation machinery in media with corresponding unnatural amino acid, but it cannot replicate in conventional host cells. This replication-deficient virus is a new-type of live viral vaccine that possesses advantages of high efficacy of traditional attenuated vaccine and high safety of killed vaccine. This article reviews the application and prospect of unnatural amino acid orthogonal translation machinery in the development of novel replication-deficient virus vaccines.


Subject(s)
Amino Acids , Genetics , Amino Acyl-tRNA Synthetases , Genetic Engineering , Protein Engineering , RNA, Transfer , Viral Vaccines
16.
Acta Pharmaceutica Sinica ; (12): 566-574, 2020.
Article in Chinese | WPRIM | ID: wpr-820855

ABSTRACT

Hepatitis B has become one of the major diseases which seriously affect people's health and social development. Hepatitis B, with high incidence and long disease course, cannot be cured by approved drugs such as the nucleoside analogues. Therefore, the discovery of safe and efficient novel HBV inhibitors is of great significance. From the point of view of medicinal chemistry, we summarized and discussed current endeavours towards the discovery and development of anti-HBV agents of RNase H and other novel target inhibitors with various scaffolds or distinct mechanisms of action, besides the existing capsid protein inhibitors.

17.
Acta Pharmaceutica Sinica ; (12): 554-565, 2020.
Article in Chinese | WPRIM | ID: wpr-820854

ABSTRACT

Hepatitis B virus (HBV) capsid protein plays an important role in the life cycle, thus becoming an ideal target for drug design. Capsid protein inhibitors can exert a synergistic antiviral effect with nucleoside drugs by inhibiting the replication of HBV. This paper reviews the research progress of capsid protein inhibitors with different structural types from the perspective of medicinal chemistry.

18.
Chinese Journal of Pathology ; (12): 122-128, 2020.
Article in Chinese | WPRIM | ID: wpr-787658

ABSTRACT

To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL). Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People's Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases. This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma. BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.

19.
China Pharmacy ; (12): 2882-2888, 2020.
Article in Chinese | WPRIM | ID: wpr-837543

ABSTRACT

OBJECTIVE:To systematically evaluate the pharmacoeconomic research of the second-generation direct-acting antiviral agents (DAAs)in the treatment of hepatitis C ,and to provide methodological suggestions for economic research ,and to provide decision-making reference for the adjustment of medical insurance catalogues and market access. METHODS :Retrieved from PubMed ,EMbase,the Cochrane library ,CNKI,Wanfang database and VIP ,the pharmacoeconomic researches of the second-generation DAAs for hepatitis C were collected during Jan. 2015-Jan. 2020. The quality of included studies were evaluated with the checklist about Consolidated Health Economics Evaluation Reporting Standards (CHEERS),and the data were extracted and analyzed quantitatively. RESULTS :A total of 14 studies were included ,and the standard coincidence rate ranged from 79.2% to 95.8%;the overall quality was relatively high. Thirteen (92.9%)studies had compared the economics of different treatment schemes from the perspective of the payer by using the Markov model and the lifetime study time limit. Compared with the second-generation DAAs treatment schemes based on sofosbuvir ,all the research results showed that Ombitasvir combined with Dasabuvir(3D),EBR/GZR and GLE/PIB were more economical in the target countries ;single factor sensitivity analysis showed that the research results were more sensitive to the three parameters of drug price ,drug SVR rate and health status utility value. CONCLUSIONS:Among the second-generation DAAs for hepatitis C ,the three regimens of 3D,EBR/GZR and GLE/PIB are more economical. It is recommended that future research on the economics of medicines for hepatitis C adopted dynamic model and the research perspective of the whole society to carry out direct high-quality economic research on a variety of DAAs ;at the same time,considered the effects of drug price ,drug SVR rate and health status utility value on the robustness of basic analysis results in sensitivity analysis in order to increase the credibility of the research results.

20.
Chinese Critical Care Medicine ; (12): 1133-1136, 2019.
Article in Chinese | WPRIM | ID: wpr-797533

ABSTRACT

Objective@#To investigate the expressions of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells in peripheral blood of patients with acute coronary syndrome (ACS) and their significance.@*Methods@#A case-control study was conducted. Ninety-four patients receiving coronary angiography (CAG) admitted to Tianjin Chest Hospital from March 5th to April 27th in 2018 were enrolled. They were divided into non-coronary heart disease (CHD) group (n = 12), unstable angina pectoris (UAP) group (n = 27), acute non-ST elevation myocardial infarction (NSTEMI) group (n = 27) and acute ST elevation myocardial infarction (STEMI) group (n = 28) according to the patients' symptoms, electrocardiogram, troponin test and angiographic results. General data, blood routine parameters, and biochemical indicators were collected. The ratios of CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were determined by flow cytometry. Multivariate Logistic regression was used to evaluate whether CD4+CD45RA+ T cells and CD4+CD45RO+ T cells were associated with STEMI.@*Results@#Ninety-four patients were included initially. After excluding the patients who died during the intervention, 93 patients were enrolled in the data analysis finally, with 12 patients in the non-CHD group, 27 patients in the UAP group, and the same as the NSTEMI group and the STEMI group. Compared with the non-CHD group, white blood cell count (WBC) was decreased (×109/L: 6.03±1.30 vs. 6.60±1.30, P > 0.05), and lymphocyte ratio was increased (0.273±0.059 vs. 0.269±0.070, P > 0.05) in patients of the UAP group; however, in the NSTEMI group and STEMI group, WBC was increased (×109/L: 8.29±2.28, 9.86±2.76 vs. 6.60±1.30, both P < 0.05), and lymphocyte ratio was decreased (0.236±0.076, 0.173±0.094 vs. 0.269±0.070, P > 0.05 and P < 0.05), especially in the STEMI group [WBC (×109/L): 9.86±2.76 vs. 6.60±1.30, lymphocyte ratio: 0.173±0.094 vs. 0.269±0.070, both P < 0.05]. There was no significant difference in biochemical indicators among all of the groups. Flow cytometry results showed that the ratios of CD4+CD45RO+ T cells in the UAP group and NSTEMI group were higher than those in the non-CHD group (0.323±0.074, 0.319±0.078 vs. 0.314±0.058, both P > 0.05); however, the ratio of CD4+CD45RO+ T cells in the STEMI group showed a decreased tendency (0.270±0.057 vs. 0.314±0.058, P > 0.05), and it was significantly lower than that in the UAP group and the NSTEMI group (0.270±0.057 vs. 0.323±0.074, 0.319±0.078, both P < 0.05). There was no significant difference in the ratio of CD4+CD45RA+ T cells among all of the groups. Multivariate Logistic regression analysis showed that CD4+CD45RA+ T cells ratio was not significantly correlated with the occurrence of STEMI [odds ratio (OR) = 0.976, 95% confidence interval (95%CI) was 0.907-1.050, P = 0.518], but CD4+CD45RO+ T cells ratio was significantly correlated with the occurrence of STEMI (OR = 0.888, 95%CI was 0.821-0.961, P = 0.003).@*Conclusions@#There was no significant difference in the ratio of CD4+CD45RA+ T cells among UAP, NSTEMI and STEMI patients, and CD4+CD45RO+ T cells ratio in the STEMI group was significantly lower than that in the UAP group and NSTEMI group. CD4+CD45RO+ T cells ratio may be risk factor of STEMI.

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