Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

Osteoporotic fractures represent the most severe complications of osteoporosis,characterized by insidious onset,high mortality and disability rates,and a steadily increasing incidence,imposing a significant socioeconomic burden.Western medicine has advantages in diagnosis and surgical interventions,while traditional Chinese medicine excels in holistic manage-ment and the restoration of bodily equilibrium.The integration of both traditional Chinese medicine(TCM)and western medicine emerges as an effective therapeutic strategy for osteoporotic fractures.In order to propagate the concept of integrated diagnosis and treatment,foster the advancement of integrated medical techniques for osteoporotic fractures,and establish standardized and nor-mative protocols for disease prevention,diagnosis,and treatment,a consensus expert group,led by Geriatric Branch of Chinese Geriatrics Society,the Young Osteoporosis Group of Orthopedics Branch of Chinese Medical Association,Osteoporosis Group of Orthopedics Branch of Chinese Physician Association,and Osteoporosis Professional Committee of the Shanghai Society of Inte-grated Traditional Chinese and Western Medicine,was established.This group engaged in deliberations and formulated the"Ex-pert Consensus on Integrated Traditional Chinese and Western Medicine Diagnosis and Treatment of Osteoporotic Fractures"elu-cidating the concept of integrated medicine and offering recommendations in the domains of prevention,diagnosis,and treatment,with the aspiration of ameliorating the prognosis of osteoporotic fractures and enhancing the quality of life for these patients.

Aim To study the effects of Taohong Siwu Tang(TSD)on serum lipid metabolites in rats with abnormal uterine bleeding(AUB),and to analyze the mechanism of action of TSD in improving lipid metabo-lism disorders in AUB.Methods The rat model of AUB was replicated by the method of incomplete abor-tion with drugs,and the lipid metabolites of serum were detected by applying UPLC-Q-Exactive Orbitrap/MS technology,and combined with the principal com-ponent analysis and orthogonal partial least squares-discriminant analysis to screen for differential lipids,the changes of lipids in serum before and after the in-tervention of TSD were clarified.Results A total of 11 differential lipids were screened,mainly phosphati-dyl inositol,phosphatidic acid,phosphatidyl ethanola-mine,phosphatidyl serine,sterol lipids,ceramide,acrylolipids and fatty acids.The screened differential lipids all tended to regress to normal after the adminis-tration of TSD intervention.Conclusion Improvement of AUB by TSD may be related to lipid metabolism such as phosphatidic acid,phosphatidyl inositol,phos-phatidyl ethanolamine,phosphatidyl serine,and ce-ramide.

Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

OBJECTIVE: This study aimed to develop an artificial neural network (ANN) model combined with dietary retinol intake from different sources to predict the risk of non-alcoholic fatty liver disease (NAFLD) in American adults. METHODS: Data from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) 2007-2014 were analyzed. Eligible subjects ( n = 6,613) were randomly divided into a training set ( n ₁ = 4,609) and a validation set ( n ₂ = 2,004) at a ratio of 7:3. The training set was used to identify predictors of NAFLD risk using logistic regression analysis. An ANN was established to predict the NAFLD risk using a training set. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of the model using the training and validation sets. RESULTS: Our study found that the odds ratios ( ORs) and 95% confidence intervals ( CIs) of NAFLD for the highest quartile of plant-derived dietary retinol intake (i.e., provitamin A carotenoids, such as β-carotene) ( OR = 0.75, 95% CI: 0.57 to 0.99) were inversely associated with NAFLD risk, compared to the lowest quartile of intake, after adjusting for potential confounders. The areas under the ROC curves were 0.874 and 0.883 for the training and validation sets, respectively. NAFLD occurs when its incidence probability is greater than 0.388. CONCLUSION The ANN model combined with plant-derived dietary retinol intake showed a significant effect on NAFLD. This could be applied to predict NAFLD risk in the American adult population when government departments formulate future health plans.
Adult ; Humans ; Vitamin A ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Nutrition Surveys ; Diet ; Neural Networks, Computer

Objective:To explore the predictive value of deep learning (DL)-based coronary artery calcification score (CACS) for obstructive coronary artery disease (CAD) and noncalcified plaque/mixed plaque in type 2 diabetes mellitus (T2DM).Methods:Forty hundred and twenty-four consecutive T2DM patients who accepted CACS scan and coronary CT angiography (CCTA) from December 2012 to December 2019 were included retrospectively, with clinical risk factors and plaque features collected. Plaque composition was classified as calcified, non-calcified or mixed plaque. Obstructive CAD was defined as maximum diameter stenosis≥50%. CACS was calculated with a fully automated method based on DL. Univariate and multivariate logistic regressions were applied to select statistically significant factors and the odds ratios(ORs) were measured. Receiver operating characteristic (ROC) curve was evaluated to assess the predictive performance.Results:Increased CACS was associated with a significantly higher odds of obstructive CAD in CCTA (adjusted ORs were 2.22, 6.18 and 16.98 for CACS=1-99, 100-299, 300-999 vs. CACS=0, and P values were 0.009,<0.001,<0.001 respectively). The area under ROC curve (AUC) of CACS to predict obstructive CAD was 0.764. Compared with 0, increased CACS was associated with increased risk of non-calcified/mixed plaque (adjusted ORs were 2.75, 4.76, 5.29 for CACS=1-99, 100-299, 300-999 respectively and P values were 0.001,<0.001,<0.001 respectively). The AUC of CACS to predict non-calcified/mixed plaque was 0.688. It took 1.17 min to perform automated measurement of CACS based on DL in total, which was significantly less than manual measurement of 1.73 min ( P<0.001). Conclusion:DL-based CACS can predict obstructive CAD and non-calcified plaque/mixed plaque in T2DM, which is economical and efficient, and has important value for clinical diagnosis and treatment.

OBJECTIVE: To analyze the RHD genotype of a blood donor with Del phenotype in Yunnan. METHODS: Rh serological phenotype was identified. RHD gene was detected by PCR-SSP typing, and its 10 exons were sequenced. Exon 9 was amplified for sequencing and analysis. RHD zygosity was detected. RESULTS: The Rh phenotype of this specimen was CcD^elee. Genomic DNA exhibited a 1 003 bp deletion spanning from intron 8, across exon 9 into intron 9. The deletion breakpoints occurred between two 7-bp short tandem repeat sequences. There was no variation in the sequences of the remaining exons. The Rh hybridization box test showed that there was one RHD negative allele. CONCLUSION This specimen is Del type caused by deletion of RHD exon 9.
Humans ; Blood Donors ; Rh-Hr Blood-Group System/genetics* ; China ; Phenotype ; Exons ; Genotype ; Alleles

Objective:To explore the effect of long noncoding RNA(lncRNA)THAP7-AS1 on the glycolysis of gastric cancer(GC)cells by regulating methyltransferase-like 3(METTL3)mediated N6-methyladenosine(m6A)modification. Methods:Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the expression levels of THAP7-AS1 and METTL3 in GC tissues and their relationship with the overall survival of GC patients.Real-time fluorescence quantitative PCR and Western blotting were used to analyze the expression of THAP7-AS1,METTL3 mRNA,glucose transporter 1(GLUT1)mRNA,and METTL3 protein in GC tissues and paracancerous tissues samples collected from 80 GC patients in Department of Oncology,The Third Affiliated Hospital of Zunyi Medical University(the First People's Hospital of Zunyi),and the relationship between THAP7-AS1 levels and the clinicopathological characteristics of GC patients was analyzed.Real-time fluorescence quantitative PCR and Western blotting were used to verify the expression of THAP7-AS1,METTL3 mRNA,GLUT1 mRNA,and METTL3 protein in GES-1,BGC-823 and SGC-7901 cells.Lentiviral infection was used to knock-down THAP7-AS1 or overexpress METTL3 BGC-823 and SGC-7901 cells,and real-time fluorescence quantitative PCR and Western blotting were used to examine effect of different treatment on the expression of THAP7-AS1,METTL3 mRNA,GLUT1 mRNA,and METTL3 protein;colorimetry assay was used to detect the m6A modification level in the total RNA;methylated RNA immunoprecipitation(MeRIP)-quantitative PCR(qPCR)was used to detect the GLUT1 m6A modification level;glycolysis stress test kits were used to detect the extracellular acidification rate(ECAR),glucose uptake and lactate production of treated GC cells;Western blotting was used to examine the expression levels of METTL3,GLUT1,M2 type pyruvate kinase(PKM2)and lactic dehydrogenase(LDHA)proteins in treated GC cells;EdU staining,wound healing assay and Transwell invasion assay were used to evaluate the proliferation,migration and invasion of treated GC cells.Finally,a mouse model of subcutaneously transplanted GC tumor was established using nude mice,and the effect of knocking-down THAP7-AS1 was assessed by measuring the tumor volume and weight,as well as the expression levels of METTL3 and GLUT1 proteins in transplanted GC tumor tissues. Results:Analysis of the GEPIA database showed that the expression levels of THAP7-AS1 and METTL3 was higher in GC tissue than those in normal gastric tissues,and the expression levels of THAP7-AS1 and METTL3 are negatively correlated with overall survival of GC patients(P＜0.05).Compared with the paracancerous tissues(or normal gastric epithelial cells),the expression levels of THAP7-AS1,METTL3 mRNA,GLUT1 mRNA and METTL3 protein was significantly increased in GC tissues(or GC cells),and the higher the expression of THAP7-AS1,the higher the TNM stage,the lower the degree of tumor differentiation,and the easier the occurrence of microvascular infiltration and lymph node metastasis(P＜0.05).Knocking-down of THAP7-AS1 down-regulated the expression levels of METTL3 mRNA,GLUT1 mRNA and METTL3 protein,the m6A modification levels in total RNA and GLUT1,the ECAR levels,the glucose uptake,the lactate production,EdU positive rate,scratch healing rate,the number of invaded cells,and the expression levels of glycolysis-related proteins(METTL3,GLUT1,PKM2 and LDHA)in GC cells(P＜0.05).Overexpression of METTL3 could partially reverse these effects of THAP7-AS1 knock-down(P＜0.05).In vivo experiments showed that THAP7-AS1 knock-down can obviously inhibit the growth of transplanted GC tumors(P＜0.05). Conclusion:lncRNA THAP7-AS1 can promote the glycolysis which further promotes the proliferation,migration and invasion of GC cells by regulating METTL3 mediated m6A modification.

Abstract OBJECTIVE To conduct visual analysis of the annual differentiated performance data of clinical pharmacists by using R language to find out the shortcomings and promote the progress of clinical pharmacists and department development. METHODS The weight scores of clinical pharmacists’ performance assessment in 2021 were collected, and R language was used to draw rectangular tree diagram, violin case diagram and Sankey diagram for data visualization analysis. RESULTS The basic work of clinical pharmacy department accounted for the largest weight, followed by clinical affairs, pharmaceutical quality control affairs and pioneering affairs in the middle of the weight, while teaching, scientific research weight was insufficient. There were also great differences in the weight of clinical pharmacists. Among the 8 clinical pharmacists, 3 focused on basic, 3 on all-round development, 1 on clinical, and the work weight of 1 needed to be comprehensively improved. CONCLUSION R language visualization can be used to analyze the weight composition of clinical pharmacy department, which is convenient to formulate the direction of department rectification and promote the improvement of clinical pharmacists team level.

Objective:To investigate the difference in the peri-coronary fat attenuation index (FAI) between using coronary calcium score (CCS) images and coronary CT angiography (CCTA) images, and to explore the feasibility and befitting threshold of FAI measured on CCS images.Methods:The clinical and imaging data of patients who underwent CCTA examination from August 2019 to August 2020 were retrospectively analyzed in the First Affiliated Hospital of Soochow University. According to the inclusion and exclusion criteria, there were 122 cases in non-calcified plaque group (144 coronary arteries) and 97 cases in none-plaque group (186 coronary arteries). The coronary arteries were delineated both on CCS and CCTA images with Perivascular Fat Analysis Tool; the regions of interest of peri-coronary adipose tissue were generated automatically after setting the threshold of fat tissue. Then the FAI value was calculated. The thresholds were set in four levels (-190--30, -185--25, -180--20 and -175--15 HU) for CCS images and one level (-190--30 HU) for CCTA images. The intra-class correlation coefficient (ICC) was used to evaluate the consistency of the measurements of FAI values on CCS and CCTA images between the two physicians. Paired t test was used to compare the differences of FAI values between CCS and CCTA images, and Pearson correlation coefficient was used to evaluate the correlation between CCS-FAI and CCTA-FAI. Results:(1) FAI values measured on CCS and CCTA images by 2 physicians showed good consistency; (2) At the threshold of -185--25 HU, there was no significant difference in FAI values between the CCS and CCTA images for non-calcified plaque group [(-84.15±5.99)HU vs. (-83.83±5.98)HU, t=0.79, P=0.429], as well as for the none-plaque group [(-83.41±5.75)HU vs.(-83.84±6.25)HU, t=-1.08, P=0.280]; (3) There were significant differences on FAI values between the CCS images and CCTA images at the threshold of -190--30、-180--20 and -175--15 HU (all P<0.05); (4) There were moderate correlations on FAI values between the CCS images and CCTA images under different thresholds both in non-calcified plaque group and none-plaque group. Conclusion:It is feasible to measure FAI on CCS images, and the befitting threshold is -185--25 HU.