Presynaptic dopaminergic PET imaging is a useful method for the diagnosis of parkinsonism. Based on the expert consensus on operation and clinical application of dopamine transporter brain PET imaging technology published in 2020, this paper further recommends the relevant elements of result interpretation of presynaptic dopaminergic PET imaging.

Glycogen synthase kinase-3β (GSK-3β) is an important serine/threonine kinase that implicates in multiple cellular processes and links with the neurodegenerative diseases including Alzheimer’s disease (AD). In this study, structure-based virtual screening was performed to search database for compounds targeting GSK-3β from Enamine’s screening collection. Of the top-ranked compounds, 7 primary hits underwent a luminescent kinase assay and a cell assay using human neuroblastoma SH-SY5Y cells expressing Tau repeat domain (TauRD) with pro-aggregant mutation ΔK280. In the kinase assay for these 7 compounds, residual GSK-3β activities ranged from 36.1% to 90.0% were detected at the IC50 of SB-216763. In the cell assay, only compounds VB-030 and VB-037 reduced Tau aggregation in SH-SY5Y cells expressing ΔK280 TauRD-DsRed folding reporter. In SH-SY5Y cells expressing ΔK280 TauRD, neither VB-030 nor VB-037 increased expression of GSK-3α Ser21 or GSK-3β Ser9. Among extracellular signal-regulated kinase (ERK), AKT serine/threonine kinase 1 (AKT), mitogen-activated protein kinase 14 (P38) and mitogenactivated protein kinase 8 (JNK) which modulate Tau phosphorylation, VB-037 attenuated active phosphorylation of P38 Thr180/ Tyr182, whereas VB-030 had no effect on the phosphorylation status of ERK, AKT, P38 or JNK. However, both VB-030 and VB-037 reduced endogenous Tau phosphorylation at Ser202, Thr231, Ser396 and Ser404 in neuronally differentiated SH-SY5Y expressing ΔK280 TauRD. In addition, VB-030 and VB-037 further improved neuronal survival and/or neurite length and branch in mouse hippocampal primary culture under Tau cytotoxicity. Overall, through inhibiting GSK-3β kinase activity and/or p-P38 (Thr180/Tyr182), both compounds may serve as promising candidates to reduce Tau aggregation/cytotoxicity for AD treatment.

Objective: To analyze the safety, effectiveness, economics, innovation, suitability and accessibility of tetrandrine in the treatment of pneumoconiosis, and provide evidence-based basis for health policy decision-making and clinical practice. Methods: In July 2022, the system searched PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed databases (the retrieval time was from the establishment of the database to June 30, 2022), screened the documents that meet the standards, extracted and evaluated the data, and used the "HTA checklist" developed by the International Network of Agencies for Health Technology Assessment (INAHTA) to evaluate the HTA report. AMSTAR-2 Scale was used to evaluate the quality of systematic evaluation/Meta analysis. CHEERS Scale was used to evaluate the quality of pharmacoeconomics research. The included cohort study or case-control study was evaluated with the Newcastle-Ottawa Scale. The included randomized controlled trial (RCT) studies were evaluated using the Cochrane Risk Bias Assessment Tool (Cochrane RCT) quality evaluation criteria. Comprehensive comparison and analysis based on the characteristics of the data included in the study. Results: A total of 882 related literatures were detected from the initial screening. According to relevant standards, 8 RCT studies were finally selected for analysis. Statistical results showed that basic treatment with tetrandrine could better improve FEV(1) (MD=0.13, 95%CI: 0.06-0.20, P<0.001), FEV(1)/FVC (MD=4.48, 95%CI: 0.61-8.35, P=0.02) and clinical treatment efficiency. Tetrandrine had a low incidence of adverse reactions. The affordability coefficient of tetrandrine tablets was 0.295-0.492. Conclusion: Tetrandrine can improve the clinical symptoms and pulmonary ventilation function of pneumoconiosis patients, most of the adverse reactions are mild, and the clinical application is safe.
Humans ; Pneumoconiosis/drug therapy* ; Benzylisoquinolines/therapeutic use* ; Drugs, Chinese Herbal ; Case-Control Studies

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.
Male ; Humans ; Stroke Volume ; Ventricular Function, Left ; Extracorporeal Membrane Oxygenation ; Percutaneous Coronary Intervention ; Heart ; Vascular Diseases

Humans ; Nasal Obstruction/surgery* ; Nasal Septum/surgery* ; Rhinoplasty

OBJECTIVE: To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs). METHODS: Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133⁺ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133), paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40. RESULTS: Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133⁺ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days, P=0.001) and high expressions of tumor stem cell markers OV6(P < 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P < 0.001) and significantly reduced the formation of tumor spheres (P < 0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133 showed the strongest effects in reducing the tumor mass among all the treatments (P < 0.001). CONCLUSION CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133⁺ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.
Animals ; Cell Line, Tumor ; Drug Carriers ; Lung ; Mice ; Mice, SCID ; Nanoparticles ; Neoplasms ; Neoplastic Stem Cells ; Paclitaxel/pharmacology* ; Polyethylene Glycols/pharmacology*

Chemical constituents from aerial parts of Glycyrrhiza uralensis were analyzed and identified using ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS). The chromatographic column of Waters Acquity UPLC BEH-C_(18)(2.1 mm×100 mm, 1.7 μm) was adopted, with acetonitrile-water(0.5% formic acid) as mobile phase at a flow rate of 0.2 mL·min~(-1). Data was collected in positive and negative modes of electrospray ionization(ESI). A total of 55 compounds, including 42 flavonoids, 9 stilbenes, 2 coumarins, 1 lignin and 1 phenolic acid, which were characterized in the aerial parts of G. uralensis based on accurate molecular mass information of molecular and product ions provided by UPLC-Q-Exactive Orbitrap-MS based on comparison with standard substances and references. It is an effective and accurate method to provide chemical information of constituents in aerial parts of G. uralensis, and can provide a reference for further study on pharmacodynamic material basis and resources development and utilization.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Glycyrrhiza uralensis ; Mass Spectrometry ; Plant Components, Aerial

Objective:To investigate the effect of different extracts of Lysimachiae Herba on the main toxicity induced by Tripterygii Radix et Rhizoma. Method:Ninety male SPF Kunming mice were randomly divided into 9 groups according to their body weight，control group， Lysimachiae Herba water extract group， Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba water extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 30% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 60% ethanol extract group， Tripterygii Radix et Rhizoma combined with Lysimachiae Herba 95% ethanol extract group and Tripterygii Radix et Rhizoma combined with Lysimachiae Herba ethyl acetate extract group. The dosage of Tripterygii Radix et Rhizoma and Lysimachiae Herba were 2，1 g·kg^-1 based on crude drugs， respectively. The control group was given an equal volume of solvent， and each group was given by gavage for 14 consecutive days. The blood and liver tissues were taken 24 hours after the last administration. The enzyme linked immunosorbent assay （ELISA） was used to detect serum biochemical indexes and liver lipid peroxidation/antioxidant indexes in mice. Meanwhile， principal component analysis was used to evaluate the attenuating effect and the mechanism of Lysimachiae Herba extract on toxicity of Tripterygii Radix et Rhizoma. Result:Compared with control group， Tripterygii Radix et Rhizoma caused the levels of alanine aminotransferase（ALT），aspartic acid amino transferase（AST），alkaline phosphatase（ALP） in serum of mice， and the levels of malondialdehyde （MDA） in liver， and comprehensive score of toxicity （Z value） produced by the above four indexes increased significantly （P<0.01）. The levels of total superoxide dismutase （T-SOD），glutathione-peroxidase （GPX），glutathione-S transferase （GST） decreased significantly （P<0.01） in liver. Compared with Tripterygii Radix et Rhizoma group， after intervention with extracts of two solvents （water， 30% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP and liver MDA were significantly decreased （P<0.05， P<0.01）， while the levels of liver T-SOD， GPX and GST were significantly increased （P<0.01）. After intervention with extracts of two solvents （60% ethanol， 95% ethanol） of Lysimachiae Herba， the levels of serum ALT， AST， ALP were significantly decreased （P<0.01）， and liver GPX levels were significantly increased （P<0.01）. After the intervention with ethyl acetate extract of Lysimachiae Herba， only the level of serum AST was significantly decreased （P<0.05） and the level of GPX was significantly increased （P<0.05）. After the intervention with extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol， ethyl acetate） of Lysimachiae Herba， it can significantly reduce the comprehensive score of toxicity （P<0.01）. The overall decline rates of toxicity were 127.5%， 113.4%， 98.1%， 56.3% and 31.0% respectively. Among them， the toxicity reduction rate of the extracts with water as a solvent was 14.1%， 29.4%， 71.2%， 96.5% higher than those of other solvent extracts with ethanol. Conclusion:The extracts of different solvents （water， 30% ethanol， 60% ethanol， 95% ethanol and ethyl acetate） of Lysimachiae Herba can reverse the toxicity induced by Tripterygii Radix et Rhizoma in varying degrees. Among them， water and 30% ethanol are the best solvents for detoxification， especially water as the extraction solvent， and with the increase of ethanol content or fat solubility of extraction solvent， the detoxification shows a downward trend.

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q₁-Q₄), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q₁ group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q₂ group(41-<51 mmHg) (n=8 196); Q₃ group (51-<61 mmHg) (n= 8 270); Q₄ group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.