ObjectivePhotoacoustic pump-probe imaging can effectively eliminate the interference of blood background signal in traditional photoacoustic imaging, and realize the imaging of weak phosphorescence molecules and their triplet lifetimes in deep tissues. However, background differential noise in photoacoustic pump-probe imaging often leads to large fitting results of phosphorescent molecule concentration and triplet lifetime. Therefore, this paper proposes a novel triplet lifetime fitting method for photoacoustic pump-probe imaging. By extracting the phase of the triplet differential signal and the background noise, the fitting bias caused by the background noise can be effectively corrected. MethodsThe advantages and feasibility of the proposed algorithm are verified by numerical simulation, phantom and in vivo experiments, respectively. ResultsIn the numerical simulation, under the condition of noise intensity being 10% of the signal amplitude, the new method can optimize the fitting deviation from 48.5% to about 5%, and has a higher exclusion coefficient (0.88>0.79), which greatly improves the fitting accuracy. The high specificity imaging ability of photoacoustic pump imaging for phosphorescent molecules has been demonstrated by phantom experiments. In vivo experiments have verified the feasibility of the new fitting method proposed in this paper for fitting phosphoometric lifetime to monitor oxygen partial pressure content during photodynamic therapy of tumors in nude mice. ConclusionThis work will play an important role in promoting the application of photoacoustic pump-probe imaging in biomedicine.

In this study, RAW264.7 cells were employed to investigate the effects of honey-processed Astragalus on their energy metabolism and polarization, and explore the scientific connotation of the enhanced efficacy of honey-processed Astragalus on invigorating spleen-stomach and replenishing Qi. The medicated sera were prepared by intragastric administration of rats with water extracts of crude and honey-processed Astragalus, and the composition changes of medicated sera of crude and honey-processed Astragalus were analyzed by using LC-MS technology. The cell survival rates were detected and the concentrations of medicated sera were screened through CCK-8 assay. The differences of cell phagocytic rates, ATP energy metabolism, and NO secretion between crude and honey-processed Astragalus were evaluated by using neutral red phagocytosis assay, ATP detection kit, and NO detection kit. The effects of crude and honey-processed Astragalus on TNF-α secretion of RAW264.7 cells were detected by employing ELISA kit. The effects of crude and honey-processed Astragalus on polarization of RAW264.7 cells were evaluated by utilizing flow cytometry. The differential metabolites related to glycolysis in cell lysates and culture media were screened by using LC-MS technology. The experiment was approved by the experimental animal ethics committee from Shanxi University of Chinese Medicine (No. AWE202407352). The results showed that the contents of betaine, amino acids, and ononin in the prepared medicated sera of rats treated by intragastric administration with water extracts of honey-processed Astragalus increased compared to those in crude one. The results of CCK-8 experiment showed that there were no cytotoxic effects on RAW264.7 cells in the medicated sera of crude and honey-processd Astragalus at different concentration. The phagocytic index and ATP yield both increased to varying degrees after administration of the medicated sera to cells. The secretion of NO in normal and inflammatory cells increased and decreased respectively, and the effect of honey-processed Astragalus was better than that of crude one. The results of ELISA kit showed that the medicated sera of both crude and honey-processed Astragalus could promote the secretion of TNF-α in a concentration-dependent manner, and the promoting effect of honey-processed Astragalus was stronger than that of crude one. The results of flow cytometry showed that the medicated sera of both crude and honey-processed Astragalus could promote M1-type polarization and inhibit M2-type polarization of RAW264.7 cells, and the effect of honey-processed Astragalus was better than that of crude one. Compared to crude Astragalus, the metabolites related to glycolysis in the cell lysates and culture media of the medicated sera of honey-processed Astragalus were generally on the rise, indicating that the effect on promoting glycolysis of honey-processed Astragalus was better than that of crude one. In summary, honey-processed Astragalus can promote the polarization and energy metabolism of RAW264.7 cells, and participate in positive immune regulation, which is correlated with its enhanced effect of invigorating spleen-stomach and replenishing Qi.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Piperazines are a class of new psychoactive substances with hallucinogenic effects that af-fect the central nervous system by affecting the level of monoamine neurotransmitters.Abuse of pipera-zines will produce stimulating and hallucinogenic effects,accompanied by headache,dizziness,anxiety,insomnia,vomiting,chest pain,tachycardia,hypertension and other adverse reactions,and may even cause cardiovascular diseases and multiple organ failure and lead to death,seriously affecting human physical and mental health and public safety.The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community.The study of its pharmacological toxi-cology and analytical methods has become a research hotspot in the field of forensic medicine.This paper reviews the in vivo processes,sample treatment and analytical methods of existing piperazines,in order to provide reference for forensic identification.

Objective:To compare and analyze the distribution characteristics of fluoride and arsenic in drinking water in coal-burning borne endemic fluorosis and arsenic poisoning areas and non-endemic areas of Guizhou Province, and to assess the health risk.Methods:From January 2018 to December 2019, drinking water samples were collected from all endemic and non-endemic townships in 37 coal-burning borne endemic fluorosis counties (cities and districts) and 4 coal-burning borne endemic arsenic poisoning counties (cities and districts) in Guizhou Province. Fluoride and arsenic levels in drinking water were determined in all the affected and non-affected townships. Among them, 3 800 water samples were collected from fluorosis areas, 1 445 water samples from non-endemic areas, and 117 water samples from arsenic poisoning areas and non-endemic areas, respectively. Based on Monte Carlo simulation, a health risk assessment model recommended by the US Environmental Protection Agency (EPA) was applied to quantitatively evaluate the health risks caused by fluoride and arsenic in drinking water in different regions through different pathways (drinking water intake or skin contact) to different populations (adult males, adult females and children).Results:According to the "Hygienic Standards for Drinking Water" (GB 5749-2022), the qualified rates of fluoride and arsenic levels in drinking water in the study area were 100%. The results of the health risk evaluation showed that in the same evaluation area (endemic area or non-endemic area), there were statistically significant differences in the average annual health risks caused by fluoride and arsenic exposure through drinking water among different populations through two different routes ( P < 0.001), with children's health risks > adult males > adult females ( P < 0.05). The average annual health risks of fluoride and arsenic in water samples from different water periods and source types were compared via the two exposure routes, and the differences were statistically significant ( P < 0.05). At high ( P95) and moderate ( P50) exposure levels, the average annual total health risks of fluoride in drinking water via the two exposure routes (drinking water intake and skin contact) for adult males, adult females, children and the general population in fluorosis areas were a -1: 2.50 × 10 -9 and 8.64 × 10 -10, 2.20 × 10 -9 and 7.61 × 10 -10, 3.00 × 10 -9 and 1.04 × 10 -9, 2.36 × 10 -9 and 8.15 × 10 -10, respectively, and a -1: 2.44 × 10 -9 and 6.92 × 10 -10, 2.15 × 10 -9 and 6.09 × 10 -10, 2.93 × 10 -9 and 8.32 × 10 -10, 2.30 × 10 -9 and 6.53 × 10 -10 in non-endemic areas, respectively; the average annual total health risks of adult males, adult females, children, and the general population caused by arsenic ingestion through drinking water and skin contact in arsenic poisoning areas were a -1: 9.10 × 10 -7 and 3.67 × 10 -7, 8.11 × 10 -7 and 3.22 × 10 -7, 1.13 × 10 -6 and 4.45 × 10 -7, 8.95 × 10 -7 and 3.47 × 10 -7, respectively, and a -1: 2.42 × 10 -6 and 5.61 × 10 -7, 2.11 × 10 -6 and 4.80 × 10 -7, 2.88 × 10 -6 and 6.55 × 10 -7, 2.21 × 10 -6 and 5.25 × 10 -7 in non-endemic areas, respectively; average annual total health risks of adult males, adult females, children and the general population were all in the safe range [fluoride in drinking water: negligible levels recommended by the Royal Society and the Dutch Ministry of Construction and Environment were 1.0 × 10 -7 a -1 and 1.0 × 10 -8 a -1, respectively; arsenic in drinking water: the maximum acceptable level recommended by the International Commission on Radiological Protection (ICRP) was 5.0 × 10 -5 a -1]. Conclusions:The fluoride and arsenic levels in the drinking water of coal-burning borne endemic fluorosis and arsenic poisoning areas and non-endemic areas in Guizhou Province meet the requirements of hygienic standards for drinking water; the overall health risks of fluoride and arsenic to people of different ages and genders ingested through drinking water and through skin contact are within an acceptable range.

Aim To design the pyrimidoindole deriva-tive N-butyl-9H-pyrimido[4,5-b]indole-2-carboxamide(BFPI)and synthesize it to investigate whether it in-hibits macrophage pyroptosis and foaming effects through the NLRP3/Caspase-1 pathway.Methods BFPI was synthesized using 2,4,6-triethoxycarbonyl-l,3,5-triazine and 2-aminoindole as starting materials and structurally characterized by 1H NMR,13C NMR,and ESI-MS.The in vitro cultured mouse monocyte macro-phage cell line RAW264.7 was divided into blank,model(PA)and therapeutic(BFPI)groups,and the cells in each group were treated with the corresponding culture medium for 24 h.The proliferative viability was detected by MTT assay,and the formation of intracel-lular lipid droplets was detected by oil red O staining,and NLRP3 was detected by Western-blot and RT-qPCR,caspase-1 and MCP-1 mRNA and protein ex-pression levels by Western blot and RT-qPCR.Results Compared with the blank group,the proliferation vi-ability of cells in the model group significantly de-creased and the formation of lipid droplets significantly increased;compared with the model group,the prolif-eration viability of cells in the treatment group signifi-cantly increased and the formation of lipid droplets sig-nificantly decreased,and the differences were statisti-cally significant(P＜0.01);compared with the blank group,the cellular NLRP3,caspase-1 and MCP-1 mR-NA and protein expression levels of cells in the model group significantly increased;compared with the model group,the expression levels of the above indexes of the cells in the treatment group significantly decreased,and the difference was statistically significant(P＜0.01).Conclusions BFPI contributes to delaying macrophage-derived foam cell formation during athero-genesis by inhibiting macrophage NLRP3,caspase-1,and MCP-1 expression and thereby promoting their pro-liferation and inhibiting lipid phagocytosis.

Objective:To investigate the laboratory detection methods for immune hemolytic transfusion reactions caused by anti-tigecycline antibody and the clinical diagnosis and treatment of one patient.Methods:The correlation between hemolysis-related laboratory indexes of the patient and the duration of medication was analyzed. Blood samples of the patient were tested using direct anti-human globulin test, free antibody test, and release test. Erythrocyte sensitization method and immune complexome analysis were used to detect the antibody against tigecycline in the serum of the patient. The properties and the titers of anti-tigecycline antibody were analyzed.Results:Anti-tigecycline antibody was found in the patient through the erythrocyte sensitization method and the immune complexome analysis, and the result of the direct anti-human globulin test was positive. The clinical symptoms and physical signs of the patient improved rapidly after withdrawal of tigecycline and blood transfusion. The patient was discharged after 14-day treatment with immunoglobulin and hormone.Conclusions:Tigecycline can cause hemolytic transfusion reactions. Serological tests are essential for the diagnosis of drug-induced hemolytic anemia. Withdrawal of medications and symptomatic treatment should be conduceted immediately when patients develop drug-related hemolytic anemia.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing