In this study, the reductive amination method was used to label IR783 on Astragalus polysaccharides(APS) for the first time, which was verified by ultraviolet-visible spectroscopy and infrared spectroscopy. Quantitative analysis methods of APS-IR783 in plasma and various tissue were established using a multifunctional microplate reader. The pharmacokinetics and tissue distribution of APS-IR783 in mice were investigated after a single intravenous injection of 30 mg·kg~(-1) APS-IR783, and pharmacokinetic parameters were calculated using DAS 2.0 software. The results showed that the APS used had a mass fraction of 93.69%, a relative molecular weight of 1.55×10~5, and a polydispersity index(PDI, M_w/M_n) of 1.73, close to a homogeneous polysaccharide. The IR783 labeling yield reached 86.50%, and the content of IR783 in APS-IR783 was 0.72%. After a single intravenous injection of 30 mg·kg~(-1), the pharmacokinetic parameters of APS in mouse plasma were as follows: T_(max) was(0.67±0.26) h; C_(max) was(1 599.29±159.30) mg·L~(-1); T_(1/2α) and T_(1/2β) were(2.29±3.06) h and(0.44±0.05) h, respectively; AUC_(0-t) was(23 398.91±2 907.03) mg·h·L~(-1); AUC_(0-∞) was(27 710.55±3 506.55) mg·h·L~(-1); MRT_(0-∞) was(34.38±12.59) h; CL was 0.001 L·h~(-1)·kg~(-1); V_z was(0.042±0.017) L·kg~(-1). The in vivo biodistribution study demonstrated that the in vivo exposure ratios of APS in different tissue were in the following order: spleen > liver > kidney > lung > heart > small intestine > muscle > large intestine > brain > stomach, where the top five tissue accounted for 87.54% of the total area under the curve(AUC). This study successfully labeled APS with a water-soluble near-infrared fluorescent probe of IR783 for the first time and revealed the pharmacokinetics and tissue distribution of APS in mice. The paper provides detailed in vivo behavior of APS after intravenous injection, which lays the foundation for the development and utilization of APS and related natural medicines.
Animals ; Mice ; Polysaccharides/chemistry* ; Tissue Distribution ; Astragalus Plant/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Fluorescent Dyes/pharmacokinetics* ; Female

OBJECTIVE: This study examines the sequential mediating roles of body pain and self-reported health in the association between sleep duration and self-reported life satisfaction among elderly Chinese adults. METHODS: Data from the fifth wave of the China Health and Retirement Longitudinal Survey (CHARLS) were used to analyse the relationships between sleep duration and body pain, self-reported health, and life satisfaction through logistic regression and Restricted Cubic Spline (RCS) analyses. The sequential mediation effects of body pain and self-reported health status were examined via chain mediation analysis. RESULTS: Logistic regression analysis showed that sleeping fewer than 6 hours or 6-7 hours was linked to higher risks of body pain, poor health, and dissatisfaction with life compared to sleeping 7-8 hours (all P < 0.05). Additionally, those sleeping more than 9 hours also had increased risks of poor health and dissatisfaction with life compared to those sleeping 7-8 hours (all P < 0.05). Chain mediation analysis showed that body pain and self-reported health status sequentially mediated 46.15% of the association between sleep duration and life satisfaction. CONCLUSION Body pain and self-reported health may shape the relationship between sleep duration and life satisfaction in elderly Chinese adults.
Humans ; Male ; Female ; Aged ; Personal Satisfaction ; Sleep ; Health Status ; Self Report ; China ; Middle Aged ; Longitudinal Studies ; Pain/psychology* ; Sleep Duration

Objective To assess the blood pressure control and its influencing factors among hypertensive patients in communities in different time periods by 24 h ambulatory blood pressure monitoring(24 h ABPM)and provide reference for optimizing the health management services for hypertension in communities. Methods A total of 765 hypertensive patients registered in the hypertension management project of national essential public health services in Sanxiang Town,Zhongshan City from October 2022 to September 2023 were identified as target subjects.The 24 h ABPM devices were distributed for blood pressure monitoring and a questionnaire survey was conducted to analyze the influencing factors of blood pressure control. Results Of all the participants,16.5% did not monitor blood pressure regularly,and 59.2% monitored blood pressure 1-2 times per week.The patients who were not on night shifts/staying up late had higher mean rates of achieving the target blood pressure and the circadian rhythm of blood pressure during 24 h,nighttime,and early morning than those who were on night shifts/staying up late(all P<0.05).The patients who never drank alcohol had higher rate of achieving the target blood pressure in early morning than those who drank alcohol(P=0.012).The average blood pressure during daytime,nighttime,and 24 h were different by sex(all P<0.05).The average blood pressure during nighttime was different by age and job types(all P<0.05).The average blood pressure during daytime,nighttime,and 24 h were different in patients with different body weight types(all P<0.05).The results of the multivariate logistic regression analysis showed that uncontrolled blood pressure during daytime was more likely to occur in male patients(OR=1.394,95%CI=1.045-1.858,P=0.024),and that during nighttime was more likely to be associated with male patients(OR=1.573,95%CI=1.088-2.275,P=0.016)and night shifts(OR=2.467,95%CI=1.198-5.077,P=0.014).It was difficult to achieve blood pressure control in early morning for the patients who drank alcohol for more than three times per week(OR=4.567,95%CI=1.629-12.807,P=0.004),woke up at night(OR=1.800,95%CI=1.125-2.878,P=0.014),and had night shifts(OR=1.579,95%CI=1.102-2.465,P=0.044).The patients on night shifts were more likely to have abnormal circadian rhythm of blood pressure(OR=1.753,95%CI:1.018-3.018,P=0.043). Conclusions The personal characteristics and lifestyle of hypertensive patients significantly affect the blood pressure control in different time periods(daytime,nighttime,and early morning)and the circadian rhythm of blood pressure.The family doctor team of community healthcare institutions can implement targeted and precise intervention measures for hypertensive patients according to the influencing factors of blood pressure control in different time periods,so as to achieve better management effects.
Humans ; Blood Pressure Monitoring, Ambulatory ; Hypertension/physiopathology* ; Male ; Female ; Middle Aged ; Circadian Rhythm ; Blood Pressure ; Surveys and Questionnaires ; Adult ; Aged ; Time Factors

Objective:To explore the clinical features and genetic basis for a fetus featuring Rhizomelic skeletal dysplasia.Methods:A fetus diagnosed at the Reproductive and Genetic Center of Suzhou Municipal Hospital in November 2020 was selected as the study subject. Whole exome sequencing (WES) was carried out for the fetus and its parents. Candidate variants were verified by Sanger sequencing. Peripheral blood smears of both parents were also examined.Results:The fetus was found to have a small chest and short limbs, which had suggested skeletal dysplasia. Genetic testing revealed that the fetus has harbored compound heterozygous variants of the LBR gene, including a paternally derived c. 1687+ 1G>A and a maternally derived c. 1757G>A (p.Arg586His). The blood smear of the father showed Pelger-Huёt anomaly with hyposegmentation of neutrophil nuclei, while the neutrophils of the mother appeared to be normal. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), the c. 1757G>A (p.Arg586His) variant was classified as likely pathogenic (PM3_Strong+ PM2_Supporting+ PP3), and so was the c. 1687+ 1G>A variant (PVS1-Moderate+ PM3+ PM2-Supporting+ PP4). Conclusion:The compound heterozygous variants of the LBR gene probably underlay the pathogenesis of skeletal dysplasia in this fetus.

Objective:To explore the clinical characteristics and genetic basis for a fetus with Joubert syndrome.Methods:A pregnant woman who had visited Suzhou Municipal Hospital on February 26, 2021 was selected as the study subject. The fetus and her parents were subjected to whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. cDNA analysis of her father and RNA sequencing of her sister were also carried out.Results:The fetus was found to harbor compound heterozygous variants of the TCTN1 gene, namely c. 624G>A and c. 96dupA (p.Glu33Argfs*49), which were inherited from her father and mother, respectively. Her sister also carried the paternal c. 624G>A variant, and mRNA transcripts with the c. 624G>A variant of the TCTN1 gene were not detected by cDNA analysis of her father and RNA sequencing of her sister. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 624G>A and c. 96dupA variants were both classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The compound heterozygous variants of the TCTN1 gene probably underlay the pathogenesis in this fetus. Above finding has also expanded the mutational spectrum of the TCTN1 gene.

Objective Dexmedetomidine(Dex)is a highly selective α2 adrenoceptor agonist that reduces blood pressure and heart rate.However,its ability to provide stable hemodynamics and a clinically significant reduction in blood loss in spine surgery is still a matter of debate.This study aimed to investigate the effects of Dex on intraoperative hemodynamics and blood loss in patients undergoing spine surgery. Methods The Web of Science,MEDLINE,EMBASE,and the Cochrane Library were searched up to February 2023 for randomized controlled trials(RCTs)including patients undergoing spine surgeries under general anaesthesia and comparing Dex and saline.A fixed-or random-effect model was used depending on heterogeneity. Results Twenty-one RCTs,including 1388 patients,were identified.Dex added the overall risk of intraoperative hypotension(odds ratio[OR]:2.11;95％confidence interval[CI]:1.24-3.58;P=0.006)and bradycardia(OR:2.48;95％CI:1.57-3.93;P=0.0001).The use of a loading dose of Dex led to significantly increased risks of intraoperative hypotension(OR:2.00;95％CI:1.06-3.79;P=0.03)and bradycardia(OR:2.28;95％CI:1.42-3.66;P=0.0007).For patients receiving total intravenous anesthesia,there was an increased risk of hypotension(OR:2.90;95％CI:1.24-6.82;P=0.01)and bradycardia(OR:2.66;95％CI:1.53-4.61;P=0.0005).For patients in the inhalation anesthesia group,only an increased risk of bradycardia(OR:4.95;95％CI:1.41-17.37;P=0.01)was observed.No significant increase in the risk of hypotension and bradycardia was found in the combined intravenous-inhalation anesthesia group.The incidence of severe hypotension(OR:2.57;95％CI:1.05-6.32;P=0.04),but not mild hypotension,was increased.Both mild(OR:2.55;95％CI:1.06-6.15;P=0.04)and severe(OR:2.45;95％CI:1.43-4.20;P=0.001)bradycardia were associated with a higher risk.The overall analyses did not reveal significant reduction in intraoperative blood loss.However,a significant decrease in blood loss was observed in total inhalation anesthesia subgroup(mean difference[MD]:-82.97;95％CI:-109.04--56.90;P＜0.001). Conclusions Dex increases the risks of intraoperative hypotension and bradycardia in major spine surgery.The administration of a loading dose of Dex and the utilization of various anesthesia maintenance methods may potentially impact hemodynamic stability and intraoperative blood loss.

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Objective To analyze the literature on artificial intelligence in forensic research from 2012 to 2022 in the Web of Science Core Collection Database,to explore research hotspots and developmen-tal trends.Methods A total of 736 articles on artificial intelligence in forensic medicine in the Web of Science Core Collection Database from 2012 to 2022 were visualized and analyzed through the litera-ture measuring tool CiteSpace.The authors,institution,country(region),title,journal,keywords,cited references and other information of relevant literatures were analyzed.Results A total of 736 articles published in 220 journals by 355 authors from 289 institutions in 69 countries(regions)were identi-fied,with the number of articles published showing an increasing trend year by year.Among them,the United States had the highest number of publications and China ranked the second.Academy of Forensic Science had the highest number of publications among the institutions.Forensic Science Inter-national,Journal of Forensic Sciences,International Journal of Legal Medicine ranked high in publica-tion and citation frequency.Through the analysis of keywords,it was found that the research hotspots of artificial intelligence in the forensic field mainly focused on the use of artificial intelligence technol-ogy for sex and age estimation,cause of death analysis,postmortem interval estimation,individual identification and so on.Conclusion It is necessary to pay attention to international and institutional cooperation and to strengthen the cross-disciplinary research.Exploring the combination of advanced ar-tificial intelligence technologies with forensic research will be a hotspot and direction for future re-search.

Objective To explore the roles of iron overload in pro-atherogenic activation of foam cells.Methods RAW264.7 and MOVAS cells were stimulated by oxLDL,ferrimine citrate and deferoxamine respectively.Prussian Blue and Oil Red O staining were used to detect iron deposition and foam cell.CCK-8 test,DHE probe,ELISA,RT-qPCR were performed to detect the cell death rate,reactive oxygen species(ROS)generation,lipid peroxidation molecules[glutathione peroxidase(GSH),glutathione peroxidase 4(GPX4),malondialdehyde(MDA)content]and the mRNA level of ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCG1),inductible nitris oxide synthase(iNOS),arginase-1(Arg-1),α-smooth muscle actin(α-SMA),smooth muscle 22 alpha(SM22a),osteopontin(OPN),Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α).Results Iron overload could reduced reverse cholesterol transporters(ABCA1 and ABCG1),promote foam cells generation,increased cell death rate,induced the expression of lipid peroxidation molecules(GSH,GPX4,MDA),and promoted pro-inflammatory M1 marker of macrophage and synthetic marker expression of vascular smooth muscle cell(VSMC)and inflammatory cytokines(IL-1β,TNF-α).Conclusion Iron overload promotes the generation of foam cells derived from macrophages and smooth muscle cells and transform them into pro-atherosclerotic phenotype,aggravates cell lipid peroxidation and inflammatory reaction,which contributes to the progress of atherosclerosis.