OBJECTIVE To establish the drug use evaluation(DUE) standard of ticagrelor, and to provide a reference for the rational clinical application of ticagrelor. METHODS Based on the ticagrelor drug label, related guidelines and literature, combined with clinical expert consultation results, DUE standard from three levels (indications, medications and medication results) was established. A retrospective survey was conducted to evaluate the inpatients using ticagrelor from January 2021 to December 2021 in the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. RESULTS The DUE of ticagrelor was divided into three levels, including 3 first-level indexes, 14 second-level indexes and 60 third-level indexes. A total of 263 cases of using ticagrelor were included, of which the irrational rate was 72.62%. The irrational cases were mainly off-label use (60.08%), inappropriate drug conversion(14.83%) and unreasonable usage and dosage(5.70%), etc. CONCLUSION The established DUE standard of ticagrelor is scientific, practical and feasible, which can provide reference for clinical rational drug use and prescription evaluation.

Objective To study the probability distribution of Mosquito ovitrap Index(MOI)risk of dengue Aedes vector,so as to provide a new method for more scientific and accurate MOI risk assessment.Methods Cubic spline function,cumulative probability distribution and python language programming were used to fit and analyze the MOI surveillance data of Guangzhou from 2016 to 2019 years.Results The probability distribution table and distribution figure of MOI risk assessment in Guangzhou from January to December were developed.From January to December,the MOI critical values were 7.54～60.12 and 5.05～34.10 with a cumulative probability less than 0.01 or 0.05 respectively.The critical value was the lowest in January,followed by December and February.The highest was in June,followed by May and July.From January to December,the probabilities of MOI risk grade of transmission,outbreak and epidemic were 5.07%～66.60%,0.25%～36.19%and 0.00%～16.80%respectively.The lowest risk probability of transmission,outbreak and epidemic occurred in January,followed by February respectively.The highest risk probability values appeared in July,July and June,followed by June,June and May respectively.Conclusion The probability distribution of MOI risk in each month in Guangzhou had significant seasonal growth and decline laws and characteristics,which were worthy of attention in the monitoring,evaluation and control of dengue Aedes vector.It provided a new analysis method for MOI risk assessment fitting based on cubic spline functions and cumulative probability distribution.

Objective To investigate the value of the quantitative analysis of digital subtraction angiography(DSA)and dynamic contrast-enhanced CT in evaluating the efficacy of hepatic artery infusion chemotherapy(HAIC)for liver cancer.Methods Fifty patients who were clinically diagnosed with primary liver cancer and treated with HAIC at least 3 times were enrolled in the study.Based on the enhanced CT scans taken within 1 week before the 1st and 3rd HAIC,patients were divided into good response group(CR+PR)and poor response group(SD+PD)according to the modified response evaluation criteria in solid tumor.The hemodynamic parameters[time to peak(TP),peak density(PV),and slope of the rising edge of the time-density curve(SU)]of liver cancer on DSA before treatment and after two HAIC,as well as the changes in the CT values of liver cancer in each phase of CT enhancement were compared,and then sensitivity analysis was conducted.Significant indicators were further analyzed with Logistic regression and ROC curve to assess their efficacies in evaluating HAIC response in liver cancer.Results The differences in pre-treatment CT values and DSA indicators between two groups were trivial(P>0.05).All patients successfully completed HAIC twice.The enhanced CT taken 1 week before the 3rd HAIC showed reductions in the arterial-and venous-phase CT values in good response group(P<0.05),while no significant difference was found in the delayed-phase CT value(P>0.05).At the 3rd HAIC,DSA angiography demonstrated significant reductions in PV and SU,and a significant prolongation of TP in good response group(P<0.05);while there were no significant differences in various indicators in poor response group.Regression analysis showed that arterial-phase CT values and DSA angiography SU were significantly correlated with therapeutic efficacy.ROC curve results indicated that arterial-phase CT values and SU were effective indicators for evaluating therapeutic efficacy.Conclusion The SU from DSA angiography and the CT values from dynamic contrast-enhanced CT which can objectively reflect the changes in blood supply of liver cancer after HAIC and are associated with HAIC efficacy can serve as radiological evidence for evaluating HAIC response.

Objective To explore the differential expression of the key microfilament cytoskeleton-binding proteins in immature dendritic cells(imDCs)during antigen phagocytosis.Methods Monocytes(MOs)were isolated from peripheral blood of healthy individuals and cultured with recombinant human granulocyte-macrophage colony stimulating factor(rhGM-CSF)and recombinant human interleukin-4(rhIL-4)for 6 days to obtain imDCs.ImDCs were co-cultured with low molecular weight(40 kDa)and high molecular weight(150 kDa)dextrans for 1,3 and 6 hours,respectively.Flow cytometry was used to detect the percentage of imDCs phagocytosing dextran and the expression of immunophenotype molecules.The localization of filamentous actin(F-actin),PFN1,WASP,and α-actinin in cells were observed by immunofluorescence imaging.The differential expression of MCBPs at the mRNA and protein levels were respectively detected by q-PCR and Western blotting.Finally,the MCBPs with the highest component coefficients were identified based on the stepwise regression and principal component analysis method in systems biology algorithms.Results During the process of antigen phagocytosis,imDCs phagocytized low molecular weight antigens at a faster rate,with a phagocytic duration of approximately three hours.Their cell phenotypes and morphology gradually differentiated into mDCs,and F-actin remodeling was occurred significantly.The expression of MCBPs such as PFN1,CDM,WASP,CAPZB,Filamin A,α-actinin were downregulated,while the expression of WAVE1,Arp2/3 complex,and Fascin were upregulated.The mRNA expression of signaling protein Rac1 was upregulated,while the mRNA expressions of CDC42 and RhoA were downregulated.The immunofluorescence results showed that PFN1,WASP,and α-actinin were transposed during the antigen phagocytosis process of imDCs.The results of stepwise regression and principal component analysis showed that PFN1 had the highest component coefficient.Conclusions PFN1 may be a key MCBPs involved in the process of antigen phagocytosis of imDCs,which is of great significance for further understanding the relationship between changes in the cytoskeleton structure of imDCs and their immunological functions.

Background/Aims: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. Methods: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. Results: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. Conclusions The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

OBJECTIVES: This study aimed to analyze the bacteria in dental caries and establish an optimized dental-ca-ries diagnosis model based on 16S ribosomal RNA (rRNA) data of oral flora. METHODS: We searched the public databa-ses of microbiomes including NCBI, MG-RAST, EMBL-EBI, and QIITA and collected data involved in the relevant research on human oral microbiomes worldwide. The samples in the caries dataset (1 703) were compared with healthy ones (20 540) by using the microbial search engine (MSE) to obtain the microbiome novelty score (MNS) and construct a caries diagnosis model based on this index. Nonparametric multivariate ANOVA was used to analyze and compare the impact of different host factors on the oral flora MNS, and the model was optimized by controlling related factors. Finally, the effect of the model was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: 1) The oral microbiota distribution obviously differed among people with various oral-health statuses, and the species richness and species diversity index decreased. 2) ROC curve was used to evaluate the caries data set, and the area under ROC curve was AUC=0.67. 3) Among the five hosts' factors including caries status, country, age, decayed missing filled tooth (DMFT) indices, and sampling site displayed the strongest effect on MNS of samples (P=0.001). 4) The AUC of the model was 0.87, 0.74, 0.74, and 0.75 in high caries, medium caries, low caries samples in Chinese children, and mixed dental plaque samples after controlling host factors, respectively. CONCLUSIONS The model based on the analysis of 16S rRNA data of oral flora had good diagnostic efficiency.
Humans ; Child ; Bacteria/genetics* ; Dental Caries/microbiology* ; Dental Caries Susceptibility ; Microbiota/genetics* ; RNA, Ribosomal, 16S

Objective:To explore the effect of clinical conventional fractionated dose radiation on the expression levels of immunogenic cell death (ICD) related proteins in patients with nasopharyngeal carcinoma (NPC).Methods:A total of 38 newly-treated NPC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from November 2020 to December 2021 were enrolled, all of whom received induction chemotherapy and concurrent chemoradiotherapy, and another 20 healthy volunteers were selected as controls for a prospective study. The contents of ICD related proteins, namely calreticulin (CRT), high mobility group box 1 protein (HMGB-1) and heat shock protein 70 (HSP70) and the proportion of dendritic cell (DC) in the peripheral blood of patients were detected before treatment, after induction chemotherapy and after concurrent chemoradiotherapy, respectively. The correlation between the above indicators, general clinical data and short-term efficacy was analyzed by statistical methods such as t-test and analysis of variance (ANOVA). Results:The levels of HSP70 and HMGB-1 in peripheral blood of NPC patients before treatment were higher than those of healthy controls (both P<0.05). After concurrent chemoradiotherapy, the content of CRT was significantly higher than that before treatment ( P<0.05), whereas the difference before and after induction chemotherapy and the difference before and after concurrent chemoradiotherapy were not significantly correlated with the short-term efficacy of NPC patients. HSP70 level was significantly decreased after concurrent chemoradiotherapy ( P<0.001). There were no significant differences in the content of HMGB-1 after induction chemotherapy and concurrent chemoradiotherapy (both P>0.05). Conclusion:NPC patients receiving TPF regimen (docetaxel+cisplatin+fluorouracil) for induction chemotherapy and sequential cisplatin concurrent chemotherapy may induce ICD in NPC cells, and CRT has potential value in reflecting the clinical efficacy of NPC.

Objective To investigate the effect of preparation of shear-thinning CPC/LP nano-composite hydrogel for wound healing by supramolecular interaction of polydopamine(LP)and phy-cocyanin(CPC)based on nano-clayoxidation.Methods LP aggregates were formed by polymeriza-tion of dopamine monomers in weak alkaline oxygen-containing environment of nano-clay dispersion,and then mixed it with multifunctional CPC to form shear-thinning nanocomposite hydrogels by electro-static action and Schiff base.The microstructure,rheological properties,blood compatibility and wound healing effect of hydrogel were studied systematically.Results The gelation performance of CPC/LP nanocomposite hydrogel was related to LP content.When LP content was 3％and CPC con-tent was 0.5％,stable gel could be formed;rheological test results showed that the nanocomposite hydrogel had the properties of shear thinning and self-healing;the results of blood compatibility test showed that the hemolysis rate of the nanocomposite hydrogel was less than 5％,and it had good blood compatibility.In addition,the nanocomposite hydrogel could be injected into the injury site through a smaller needle to promote wound healing.Conclusion CPC/LP nanocomposite hydrogel exhibits excellent injectable properties and can effectively promote wound healing.

Objective To explore the possibility of β-lactoglobulin(BLG)as carrier of tamoxifen.Methods The binding mechanism of BLG and tamoxifen was studied by spectroscopic technique.Results Tamoxifen would lead to the fluorescence quenching of BLG,and its Kq value was much higher than the maximal Kq value of the dynamic quenching constant[(2.0 × 1010 mol/(L·s)].The quench-ing constant values were different under different pH values,and the values of thermodynamic parame-ters △H and △S were greater than 0.BLG can be combined with tamoxifen to form BLG-tamoxifen complex,and the endothermic process took hydrophobic force as the main force.Tamoxifen and BLG had different binding patterns under acidic and alkaline conditions,which mainly depended on the opening and closing state of the EF ring of BLG.Conclusion BLG has the ability to bind tamoxifen,which shows the potential value of BLG as a carrier of insoluble drugs.

Objective To investigate the effect of preparation of shear-thinning CPC/LP nano-composite hydrogel for wound healing by supramolecular interaction of polydopamine(LP)and phy-cocyanin(CPC)based on nano-clayoxidation.Methods LP aggregates were formed by polymeriza-tion of dopamine monomers in weak alkaline oxygen-containing environment of nano-clay dispersion,and then mixed it with multifunctional CPC to form shear-thinning nanocomposite hydrogels by electro-static action and Schiff base.The microstructure,rheological properties,blood compatibility and wound healing effect of hydrogel were studied systematically.Results The gelation performance of CPC/LP nanocomposite hydrogel was related to LP content.When LP content was 3％and CPC con-tent was 0.5％,stable gel could be formed;rheological test results showed that the nanocomposite hydrogel had the properties of shear thinning and self-healing;the results of blood compatibility test showed that the hemolysis rate of the nanocomposite hydrogel was less than 5％,and it had good blood compatibility.In addition,the nanocomposite hydrogel could be injected into the injury site through a smaller needle to promote wound healing.Conclusion CPC/LP nanocomposite hydrogel exhibits excellent injectable properties and can effectively promote wound healing.