Objective To investigate the impact of red blood cell suspension infusion across various perioperative periods on patients with valvular heart disease. Methods The patients with valvular heart disease admitted to Tianjin Chest Hospital from 2018 to 2020 were selected. Based on the timing of perioperative red cell suspension infusion, patients were categorized into three groups: a group 1 receiving intraoperative red cell suspension infusion, a group 2 receiving red cell suspension infusion within 24 hours after entering the ICU, and a group 3 receiving red cell suspension infusion at both time points. The laboratory results, perioperative blood component infusion volume, and other relevant parameters were retrospectively analyzed. After propensity score matching, the differences in different variables among the three groups were compared. Results After propensity score matching, 102 patients were enrolled, including 52 males and 50 females, with an average age of (61.74±10.58) years. There were 34 patients in each group. The preoperative hemoglobin (Hb) value of the group 2 was significantly higher than that of the group 1 and the group 3, and the amount of red cell suspension and autoblood transfusion was the lowest (P<0.05). Group 1 had the highest postoperative Hb, as well as the highest Hb and hematocrit (HCT) levels within 24 hours post-surgery (P<0.05). The group 1 had the lowest plasma, platelet and cryoprecipitate infusion volumes, and the shortest cardiopulmonary bypass time, aortic occlusion time, postoperative ICU stay and hospital stay, and the least blood loss and total drainage volume (P<0.05). The difference between postoperative and preoperative Hb (△Hb1) was highest in group 1 (P<0.05). Conclusion For patients with valvular heart disease, intraoperative-only infusion of red blood cell suspension is associated with a better prognosis at discharge and during follow-up.

The iridoid glycosides from Veronica anagallis-aquatica L. alleviate heart failure by modulating the gut microbiota and influencing the production of two metabolites with potential antihypertrophic effects, HVA and 2OH-VA.Image 1.

Constructing an efficient and easy-to-operate multigene expression system is currently a crucial part of plant genetic engineering. In this study, a fragment carrying three independent gene expression cassettes and the expression unit of the gene-silencing suppressor protein(RNA silencing suppressor 19 kDa protein, P19) simultaneously was designed and constructed. This fragment was cloned into the commonly used plant expression vector pCAMBIA300, and the plasmid pC1300-TP2-P19 was obtained. Each gene expression cassette consists of different promoters, fusion tags, and terminators. The target gene can be flexibly inserted into the corresponding site through enzymatic digestion and ligation or recombination and fused with different protein tags, which provides great convenience for subsequent detection. The enhanced green fluorescent protein(eGFP) reporter gene was individually constructed into each expression cassette to verify the feasibility of this vector system. The results of tobacco transient expression and laser-confocal microscopy showed that each expression cassette presented independent and normal expression. Meanwhile, the three key enzyme genes in the betanin synthesis pathway, BvCYP76AD, BvDODA1, and DbDOPA5GT, were constructed into the three expression cassettes. The results of tobacco transient expression phenotype, protein immunoblotting(Western blot), and chemical detection of product demonstrated that the three exogenous genes were highly expressed, and the target compound betanin was successfully produced. The above results indicated that the constructed multigene expression system for plants in this study was efficient and reliable and can achieve the co-transformation of multiple plant genes. It can provide a reliable vector platform for the analysis of plant natural product synthesis pathways, functional verification, and plant metabolic engineering.
Nicotiana/metabolism* ; Genetic Vectors/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Genetic Engineering/methods* ; Green Fluorescent Proteins/metabolism* ; Gene Expression

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective To analyze the target,signal pathway and potential mechanism of Banxia Baizhu Tianma Decoction in the treatment of epilepsy based on network pharmacology,and to verify it by molecular docking technology and animal experiments.Methods The active ingredients and drug targets of Banxia Baizhu Tianma Decoction were screened by BATMAN and other databases.The targets of epilepsy-related diseases were obtained by GeneCards and other databases,and the intersection targets were taken.Constructing'drug-ingredient-target-disease'network and PPI network to screen the core targets.The core active ingredients were screened according to GO,KEGG functional enrichment analysis and'pathway-target-active ingredient'network.Molecular docking was used to verify the core targets and core active ingredients.In the animal experiment,the rat model of epilepsy was induced by lithium chloride-pilocarpine,and 40 Wistar rats were divided into normal control group,model control group,carbamazepine group and Banxia Baizhu Tianma Decoction group.The seizures were observed by behavior.Nissl staining was used to observe neuronal damage in hippocampus.Immunohistochemistry was used to detect the expression of BAX,BCL-2 and Caspase-3 protein.Results A total of 1072 targets of Banxia Baizhu Tianma Decoction were screened,1046 disease targets of epilepsy were screened,and 220 intersection targets of Banxia Baizhu Tianma Decoction in the treatment of epilepsy were screened.The core targets AKT1,ALB,ACTB,INS and TNF of PPI network were obtained.KEGG pathway mainly involves TNF signaling pathway,IL-17 signaling pathway,cAMP signaling pathway,pathways of neurodegeneration-multiple diseases,serotonergic synapse and Dopaminergic synapse.The core active ingredients with the highest correlation in the'pathway-target-active component'network were Betulin,Ephedrine,Ergotamine and Thymol.Results of molecular docking indicated that the core target had satisfactory affinity with those active ingredients.Animal experiments showed that Banxia Baizhu Tianma Decoction could effectively reduce epileptic seizures in rats,improve hippocampal neuronal damage in rats,significantly reduce the percentage of neuronal apoptosis,significantly down-regulate the expression of pro-apoptotic proteins BAX and Caspase-3,and up-regulate the expression of anti-apoptotic protein BCL-2.Conclusion Banxia Baizhu Tianma Decoction has the characteristics of multi-component,multi-target and multi-pathway in the treatment of epilepsy.Inhibiting neuronal apoptosis and reducing hippocampal neuronal damage may be one of the important mechanisms for its treatment of epilepsy.

Objective:We aimed to analyze the spatio-temporal trend of breast cancer incidence and mortality in Shandong Province from 2012 to 2023 and predict the development trend from 2024 to 2030.Methods:Data on the incidence and mortality of breast cancer in Shandong Province from 2012 to 2023 were obtained from the Shandong Cancer Registry. The incidence, age-specific incidence, mortality, and age-specific mortality in different years, as well as in urban and rural areas, were calculated, and the rates were standardized based on the age composition of the Chinese standard population in 2000. The average annual percent change (AAPC) rate was calculated using Joinpoint 4.8.0.1 software. The global and local spatial autocorrelation analysis were performed using GeoDa 1.12 software. The Bayesian age-period-cohort model was used to predict the trend of breast cancer incidence and mortality from 2024 to 2030.Results:From 2012 to 2023, the breast cancer age-standardized incidence rate (ASIR) showed an increasing trend. The ASIR increased from 30.48/100 000 in 2012 to 39.94/100 000 in 2023 (AAPC=2.59%, P<0.001). The ASIR of urban and rural females also showed an upward trend. Additionally, the ASIR in rural areas (AAPC=3.33%, P<0.001) increased more than that in urban areas (AAPC=1.83%, P=0.002). The incidence peak of breast cancer mainly concentrated in population aged 45-64 years, and with the increase of years, the incidence peak gradually moved forward. The age-standardized mortality rate (ASMR) showed a downward trend. The ASMR decreased from 6.89/100 000 in 2012 to 4.93/100 000 in 2023 (AAPC=-3.12%, P<0.001). The ASMR of urban and rural females also showed a downward trend (urban: AAPC=-3.56%, P=0.007; rural: AAPC=-2.72%, P<0.001). The spatial analysis showed that from 2015 to 2023, the clustering areas of breast cancer incidence and mortality in Shandong had changed significantly. In 2015, the "High-high clusters" of ASIR mainly included Wendeng District in Weihai City, Dongying District, Kenli District, Lijin County, Guangrao County in Dongying City, Tianqiao District, Shizhong District in Jinan City; In 2023, the "High-high clusters" mainly included Jiaxiang County, Liangshan County, Jinxiang County, Wenshang County, Rencheng District in Jining City, Hedong District in Linyi City, Guangrao County in Dongying City. In 2015, the "High-high clusters" of ASMR only included Wenshang County in Jining City. In 2023, the "High-high clusters" mainly included Laizhou County in Yantai City, Junan County and Yishui County in Linyi City, Gaotang County in Liaocheng City, Dongping County and Ningyang County in Taian City. The Bayesian age-period-cohort model predicted that the ASIR trend of breast cancer in Shandong tended to be smooth (AAPC=0.33%, P=0.001). However, the ASMR remained decreasing (AAPC=-4.68%, P<0.001). Conclusions:The breast cancer incidence in Shandong showed an increasing trend, and it is expected to be smooth by 2030. However, the mortality showed a continuous downward trend. The incidence peak was mainly in the population aged 45-64 years, with obvious regional differences. Targeted prevention and control measures should be taken for high-risk groups and areas in Shandong Province.

Objective:To understand spatial aggregation of lung cancer mortality and its changing trends over the past fifty years in different counties and districts of Shandong Province from 1970 to 2021.Methods:The mortality data of lung cancer were obtained from the death registration system of Shandong province and three retrospective surveys of death cause. The mortality rate and age-standardized mortality rate were used to describe the changing trend of lung cancer in different years, and the contribution value of population factors and non-population factors in lung cancer mortality change was calculated by the mortality differential decomposition method. GeoDa 1.20 and ArcGIS 10.8 software were used for spatial autocorrelation analysis and visualization map display.Results:The crude mortality rate of lung cancer in Shandong Province showed a significant upward trend from 1970 to 2021, rising from 7.22 per 100 000 in 1970-1974 to 62.73 per 100 000 in 2020-2021, with an increase of 7.69 times. Meanwhile, the standardized mortality rate of lung cancer exhibited a trend of increasing first and then decreasing. The differential analysis of lung cancer mortality in different years revealed that changes in crude mortality rates were the result of the combined effects of demographic and non-demographic factors. The proportion of population factors (aging population) leading to an increase in lung cancer mortality rate rose from 2.12% in 1990-1992 to 40.20% in 2020-2021. From a spatial distribution perspective, there were significant regional differences in lung cancer mortality rates among counties (cities, districts) in Shandong Province across different eras. Compared to the period of 1970-1974, the lung cancer mortality rates in all counties and districts in 2020-2021 showed a considerable increase, and there were noticeable changes in the areas of high-high and low-low clustering of lung cancer mortality rates across different eras.Conclusion:There have been significant temporal and spatial changes in the mortality rate of lung cancer in Shandong Province from 1970 to 2021. The crude mortality rate has shown an upward trend, while the standardized mortality rate increases first and then decreases. The concentration of lung cancer mortality rates in counties and districts has also undergone significant changes.

Objective:To describe the distribution characteristics and trends of mortality and spatial aggregation of esophageal cancer in Shandong Province from 1970 to 2021.Methods:The mortality data of esophageal cancer were obtained from the death registration system of Shandong Province and three national all-cause mortality retrospective surveys. The crude mortality rate (CMR) and age-standardized mortality rate (ASMR, the Segi′s world standard population) were used to describe the mortality of esophageal cancer. Mortality differential decomposition was applied to quantify the contributions of demographic and non-demographic factors. The death levels of esophageal cancer in different counties (cities and districts) in Shandong Province from 1970 to 1974 and 2020 to 2021 were visualized by the ArcGIS 10.8 software, and global and local autocorrelation analyses were conducted by using the GeoDa 1.12 software.Results:The CMR of esophageal cancer in Shandong Province increased first and then decreased from 1970 to 2021. The CMR of esophageal cancer decreased from 17.59/100 000 in the period of 1970—1974 to 14.32/100 000 in the period of 2020—2021. The ASMR of esophageal cancer decreased from 20.04/100 000 in the period of 1970—1974 to 6.53/100 000 in the period of 2020—2021. Compared with the period of 1970—1974, both demographic and non-demographic factors contributed to the increase in esophageal cancer mortality rate from 1990 to 1992. However, demographic factors continued to contribute to the increase in esophageal cancer mortality rate from 2004 to 2005, 2011 to 2013, and 2020 to 2021, while non-demographic factors contributed to the continuous decrease in esophageal cancer mortality rate. The global autocorrelation analysis results showed that the Moran′s I index of ASMR of esophageal cancer in each county (city, district) of Shandong Province from 1970 to 1974 and from 2020 to 2021 were 0.67 and 0.57, respectively. Local autocorrelation analysis showed that there were 19 and 13 areas of high-high clustering of esophageal cancer in the periods of 1970—1974 and 2020—2021, respectively, with 12 overlapping counties (cities, districts). Conclusion:From 1970 to 2021, the CMR of esophageal cancer increases first and then decreases, while the ASMR of esophageal cancer gradually decreases in Shandong Province. The distribution of esophageal cancer mortality has significant spatial aggregation and changes over time.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.