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Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.
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The ICR(Institute of Cancer Research)mouse infection model was constructed to study the pathogenicity of Sal-monella Telelkebir serotype,and the pathogenic identification of mouse isolates was carried out.Observe the bacterial excretion cycle,evaluate the pathogenicity of Salmonella serotype to mice,and calculate the LD50 by the changes in clinical characteris-tics,histopathology and tissue bacterial load of infected mice;by flight mass spectrometry,biochemical identification,serotype identification,molecular typing and other experiments,compared with human isolates;virulence gene analysis was carried out by PCR experiment and whole genome sequencing.The LD50 of Salmonella Telelkebir is 2.67 × 108 CFU/mL;curling and fluffing may occur 0.5 h after infection;autopsy of dead mice showed that the small intestine was severely congested,with more bubbles and fluid accumulation,cecal necrosis,liver apical degeneration and necrosis,necrotic foci on the surface of the kidney and spleen atrophy;the bacterial load of spleen,kidney,lung,liver and jejunum in mice reached its peak at 3 days after infection,while that of heart at 6 days;the bacterial excretion time of the high-dose group exceeded 100 days;The level of CD3 in tissues increased with increasing dose,with inflammatory cell infiltration,myocardial capillary dilation and hyperemia,large area of vacuoles,degeneration and necrosis of hepatocytes,obvious enlargement of splenic sinus,blurred zoning,thickening of glomerular basement membrane,partial exfoliation of ciliated epithelium,atrophy and exfoliation of jejunal villi;PCR and whole genome sequencing revealed Salmonella-related virulence genes such as cdtB,plt A and pltB.This study was the first to successfully establish the ICR mouse model of Salmonella Telelkebir,demonstrating that this serotype of Salmonella has some pathogenicity.
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Objective@#To investigate the breakfast consumption of middle school students and to analyze its relationship with physical fitness, so as to provide reference for improving physical fitness of middle school students.@*Methods@#A total of 2 732 middle school students from Shangrao City were selected in September 2021 by random cluster stratified sampling. The breakfast consumption behaviors of middle school students were investigated by questionnaire, and the general information, family information and other lifestyle behaviors were collected. The physical fitness test includes grip strength, standing long jump, 1 minute sit up, sit forward bend, 50 m run and 20 m shuttle run test (20 m SRT) to evaluate the strength, flexibility, speed and endurance of middle school students. χ 2 tests were used to compare the correlation between different demographic characteristics, breakfast behavior and physical fitness,and Logistic regression analysis was used to infer the correlation strength between breakfast behavior and physical fitness.@*Results@#The detection rate of physical fitness failure among middle school students was 21.5%. There were statistically significant differences between breakfast frequency and grip strength and 20 m SRT( χ 2=8.27, 13.90, P < 0.05 ). Logistic regression analysis results showed that 20 m SRT was positively correlated with breakfast frequency (sometimes eat breakfast, OR =1.51, skip or occasionally eat breakfast OR =2.08, P <0.05).@*Conclusion@#The low frequency of breakfast consumption of middle school students is associated with low performance on 20 m SRT. Schools and families should pay attention to the breakfast consumption of middle school students to ensure adequate daily nutrition intake.
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Background/Aims@#A high-quality sample allows for next-generation sequencing and the administration of more tailored precision medicine treatments. We aimed to evaluate whether heparinized wet suction can obtain higher quality samples than the standard dry-suction method during endoscopic ultrasound (EUS)-guided biopsy of pancreatic masses. @*Methods@#A prospective randomized crossover study was conducted. Patients with a solid pancreatic mass were randomly allocated to receive either heparinized wet suction first or dry suction first. For each method, two needle passes were made, followed by a switch to the other method for a total of four needle punctures. The primary outcome was the aggregated white tissue length. Histological blood contamination, diagnostic performance and adverse events were analyzed as secondary outcomes. In addition, the correlation between white tissue length and the extracted DNA amount was analyzed. @*Results@#A total of 50 patients were enrolled, and 200 specimens were acquired (100 with heparinized wet suction and 100 with dry suction), with one minor bleeding event. The heparinized wet suction approach yielded specimens with longer aggregated white tissue length (11.07 mm vs 7.96 mm, p=0.001) and less blood contamination (p=0.008). A trend towards decreasing tissue quality was observed for the 2nd pass of the dry-suction method, leading to decreased diagnostic sensitivity and accuracy, although the accumulated diagnostic performance was comparable between the two suction methods. The amount of extracted DNA correlated positively to the white tissue length (p=0.001, Spearman ̕s ρ=0.568). @*Conclusions@#Heparinized wet suction for EUS tissue acquisition of solid pancreatic masses can yield longer, bloodless, DNA-rich tissue without increasing the incidence of adverse events (ClinicalTrials.gov. identifier NCT04707560).
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OBJECTIVE@#To clarify the epidemiological characteristics and spatial distribution patterns of human norovirus outbreaks in China, identify high-risk areas, and provide guidance for epidemic prevention and control.@*METHODS@#This study analyzed 964 human norovirus outbreaks involving 50,548 cases in 26 provinces reported from 2012 to 2018. Epidemiological analysis and spatiotemporal scanning analysis were conducted to analyze the distribution of norovirus outbreaks in China.@*RESULTS@#The outbreaks showed typical seasonality, with more outbreaks in winter and fewer in summer, and the total number of infected cases increased over time. Schools, especially middle schools and primary schools, are the most common settings of norovirus outbreaks, with the major transmission route being life contact. More outbreaks occurred in southeast coastal areas in China and showed significant spatial aggregation. The highly clustered areas of norovirus outbreaks have expanded northeast over time.@*CONCLUSION@#By identifying the epidemiological characteristics and high-risk areas of norovirus outbreaks, this study provides important scientific support for the development of preventive and control measures for norovirus outbreaks, which is conducive to the administrative management of high-risk settings and reduction of disease burden in susceptible areas.
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Humanos , Gastroenteritis/epidemiología , Norovirus , Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , China/epidemiología , GenotipoRESUMEN
This research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.
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Ratas , Animales , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/tratamiento farmacológico , Metabolómica/métodos , Microbioma Gastrointestinal , AminoácidosRESUMEN
Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M(Q1, Q3)] of 0.40 (0.22-0.8) ng·g-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M(Q1, Q3)] of 0.13 (0.09, 0.17) ng·g-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values<0.05). The consumption [M(Q1, Q3)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant-1·day-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all Pvalues<0.05). The prevalence [M(Q1, Q3)] of codeine, methadone, ketamine and morphine were 0.0056% (0.0034%, 0.0092%), 0.0148% (0.009%, 0.0267%)、0.0333% (0.0210%, 0.0710%) and 0.0072% (0.0038%, 0.0117%), respectively. The estimated number of drug users [M(Q1, Q3)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925). Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
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Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.
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Humanos , Fisura del Paladar/genética , Labio Leporino/genética , Estudio de Asociación del Genoma Completo , Predisposición Genética a la Enfermedad , Factores de Riesgo , Polimorfismo de Nucleótido SimpleRESUMEN
Objective To investigate the effects and mechnism of abnormal stress promoting macrophage mobility inhibitory factor(MIF),cyclooxygenase 2(COX2)and prostaglandin E2(PGE2)in the progression of temporomandibular joint osteoarthritis(TMJOA).Methods From January 2020 to December 2021,TMJOA and temporomandibular joint internal derangement(TMJID)patients(30 cases in each group,we divided the TMJOA into group TMJ Ⅰ,Ⅱ,Ⅲ according to the stage)who were admitted to TMJOA special clinic of the First Affiliated Hospital of Xinjiang Medical University and accompanied by abnormal occlusion were collected.The pain score of the occlusal state of the patients was evaluated by visual analogue scale.The expression levels of MIF,COX2 and PGE2 in synovial fluid were detected by ELISA.We used the unilateral anterior crossbite for TMJOA(UAC)rats model(the grouped into:UAC-4 weeks,UAC-8 weeks and UAC-12 weeks group),and control group at the same time(grouped into:Ctrl-4 weeks,Ctrl-8 weeks and Ctrl-12 weeks group),each group had 6 rats.The expression levels of MIF,COX2 and PGE2 in serum and synovial fluid of rats were detected by ELISA.The expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2 in temporomandibular joint of rats were detected by Western blotting.The fluid flow shear stress(FFSS)model of fibroblast-like synovial cells(FLSs)was established,and the mRNA and protein expression levels of above indexes were detected by RT-PCR and Western blotting.Results Visual analogue scale evaluation showed that the pain score of TMJOA Ⅰ and Ⅱ group was significantly higher than that of TMJID(P<0.001).ELISA results showed that the expression levels of MIF,COX2 and PGE2 in synovial fluid in TMJOA group were higher than those in TMJID group(P<0.05),and the expression levels were the highest in TMJOA Ⅱ group.Compared with control group,the expressions of MIF,COX2 and PGE2 in serum and synovial fluid at UAC-4 weeks,8 weeks and 12 weeks were slightly higher,and significantly higher at UAC-8 weeks in rat TMJOA model(P<0.05).In addition,the expression trend of protein levels in temporomandibular joint tissues was similar,which showed higher expression levels of IL-1β,IL-18,MIF,COX2 and PTGER2(P<0.05).In the cell model where FFSS interfered with FLSs,with the increase of FFSS,cell with deformation,incomplete cell membrane and reduced number.Compared with control group,the expression levels of IL-1β,IL-18,MIF,COX2 and PGE2(PTGER2)of FLSs were increased in 1,3,5 and 10 dyn/cm2 intervention groups(P<0.05).Conclusion MIF,COX2 and PGE2 were highly expressed in temporomandibular joint synovial fluid of TMJOA patients with malocclusion.And these three factors were also highly expressed in serum and synovial fluid of UAC rats.The abnormal fluid shear stress promotes the secretion of MIF,COX2 and PGE2 by FLSs to participate in joint microenvironment inflammation and accelerate disease progression.
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Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1(HMGB1)through exosomes and its regulatory pathway.Methods We used wild-type(WT)and ASC-/-mice for this study.We randomly selected five mice per group from each strain and fed them either a normal diet(ND)or a high-fat diet(HFD)for eight weeks.The control group consisted of WT mice fed with the normal diet;the HFD group were WT mice with the HFD;the microflora disturbance(MD)group were ASC-/-mice fed with the normal diet;the high-lipid microflora disturbance(HLMD)group were ASC-/-mice with HFD.We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1.We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR.The AML12 cells were treated with palmitic acid(PA)and lipopolysaccharide(LPS)for 24 h to build an in vitro model.We also detected HMGB1/CD63 levels using Western blotting.To understand the regulatory mechanism of exosome release,we employed siRNA intervention.Results The secretion of exosomes increased significantly in HFD group compared with control group[(3.5±0.2)ng/ml vs.(1.1±0.3)ng/ml,P<0.05],HLMD group compared with those in MD group[(3.2±0.2)ng/ml vs.(1.9±0.4)ng/ml,P<0.05].Using immunofluorescence detection,we observed increased co-localization of exosome markers(ALP or VPS16)with HMGB1 in HFD group compared with control group.We also observed this in AML12 cells treated with PA and LPS compared with blank control.The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group(41.5±10.2 vs.1.3±0.3,P<0.05),HLMD group was significantly higher than that in MD group(48.6±7.2 vs.1.5±0.5,P<0.05).TLR4 expression was higher in HFD group compared with control group(13.8±6.2 vs.2.8±0.9,P<0.05),HLMD group compared with MD group(22.6±4.1 vs.2.5±1.5,P<0.05).In intestinal mucosal cells,the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group(0.6±0.2 vs.0.4±0.1,P<0.05),and HLMD group compared with MD group(0.9±0.2 vs.0.5±0.1,P<0.05).In vitro,the HMGB1 of exosomes was increased in endotoxin group(5.1±0.8)and high lipid endotoxin group(5.5±0.7)compared with control group(3.8±0.6,P<0.05).On the other hand,the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group(3.7±0.6 vs.3.8±0.6,P>0.05).Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells,and regulated by Toll-like receptor 4(TLR4)under a high-fat diet and intestinal flora disorder,which may be one of the contributing factors in promoting the development of steatohepatitis.
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With the rapid development of artificial intelligence and deep learning,virtual reality(VR)and augmented reality(AR)technologies have been widely used in the medical field with their unique advantages.Despite the rapid advances of techniques in colorectal surgery,the risk of colorectal surgery remained high due to the complexity of colorectal anatomy,and the burden of postoperative symptoms remained high.VR and AR technologies can help overcome some of these challenges.The application of VR and AR in colorectal surgery was reviewed,including education and training,surgical assistance,patient education,symptom management,etc.,in order to provide references for clinical application of VR and AR in colorectal surgery.
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AIM To study the secondary metabolites from symbiotic fungi Talaromyces amestolkiae of Syngnathus acus Linnaeus.METHODS The methanol extract from Talaromyces amestolkiae fermentation was isolated and purified by silica gel,Sephadex LH-20,TLC and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Ten compounds were isolated and identified as 2,4-bis(1,1-dimethylethyl)benzeneethanol(1),aspergillumarins A(2),peniciisocoumarins H(3),2-(2-hydroxypropyl)-5-methyl-7-hydroxychromone(4),6-demethylvermistatin(5),penicimarin B(6),penicimarin C(7),8-hydroxy-6-methoxy-3-methylisocoumarin(8),polygonolide(9),ganoderpurine(10).CONCLUSION Compound 1 is a new natural product.Compounds 3-5,8-10 are isolated from this fungi for the first time.
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Objective: To estimate the consumption level of four drugs in Beijing using wastewater-based epidemiology (WBE). Methods: The primary sludge from one large wastewater treatment plants (WWTPs) was collected in Beijing from July 2020 to February 2021. The concentrations of codeine, methadone, ketamine and morphine in the sludge were detected through solid-phase extraction-liquid chromatography-tandem mass spectrometry. The consumption, prevalence and number of users of four drugs were estimated by using the WBE approach. Results: Among 416 sludge samples, codeine had the highest detection rate (82.93%, n=345) with a concentration [M (Q1, Q3)] of 0.40 (0.22-0.8) ng·g-1, and morphine had the lowest detection rate (28.37%,n=118) with a concentration [M (Q1, Q3)] of 0.13 (0.09, 0.17) ng·g-1. There was no significant difference in the consumption of the four drugs on working days and weekends (all P values>0.05). Drug consumption was significantly higher in winter than that in summer and autumn (all P values <0.05). The consumption [M (Q1, Q3)] of codeine, methadone, ketamine and morphine in winter was 24.9 (15.58, 38.6), 9.39 (4.57, 26.72), 9.84 (5.18, 19.45) and 5.67 (3.57, 13.77) μg·inhabitant-1·day-1, respectively. For these drugs, there was an upward trend in the average drug consumption during summer, autumn and winter (the Z values of the trend test were 3.23, 3.16, 2.19, and 3.32, respectively and all P values<0.05). The prevalence [M (Q1, Q3)] of codeine, methadone, ketamine and morphine were 0.0056% (0.003 4%, 0.009 2%), 0.0148% (0.009 6%, 0.026 7%),0.0333% (0.0210%, 0.0710%) and 0.0072% (0.003 8%, 0.011 7%), respectively. The estimated number of drug users [M (Q1, Q3)] was 918 (549, 1 511), 2 429 (1 578, 4 383), 5 451 (3 444, 11 642) and 1 173 (626, 1 925),respectively. Conclusion: Codeine, methadone, ketamine and morphine have been detected in the sludge of WWTPs in Beijing, and the consumption level of these drugs varies in different seasons.
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Humanos , Beijing , Monitoreo Epidemiológico Basado en Aguas Residuales , Aguas del Alcantarillado/análisis , Aguas Residuales , Ketamina/análisis , Codeína/análisis , Metadona/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
The Ministry of Education and other four departments jointly issued the Notice on the Construction of high-level schools of public Health, proposing that "it will take ten years to build a number of high-level schools of public health, and form a high-quality education development system to adapt to the construction of modern public health system". At present, the construction of high-level public health schools in various universities in China is in full swing. The high-level School of Public Health and the CDC have played an important role in constructing the national public health system and the human health community. The high-level public health schools are of strategic significance and important value to the development of the CDC. The review presents reflections and insights on the role of high-level public health schools in the development of the CDC and the challenges they might face.
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Humanos , Estados Unidos , Escuelas de Salud Pública , Instituciones Académicas , Universidades , Salud PúblicaRESUMEN
Objective To evaluate the economics of azacitidine versus decitabine in the treatment of myelodysplastic syndrome(MDS)from the perspective of health system in China,and provide references for clinical drug selection.Methods A Markov model was constructed based on the data of a multi-center retrospective cohort study(NCT01409070),with a model simulation time limit of 10 years and the cycle period of 28 days.The quality-adjusted life years(QALYs)was used as health output index and incremental cost-utility ratio(ICUR)was calculated to evaluate the economics of azacitidine versus decitabine in the treatment of MDS.One-way sensitivity analysis and probabilistic sensitivity analysis were adopted to examine the robustness of the model simulation results.Results The results of basic analysis showed that compared with decitabine group,the total cost of azacitidine group reduced by 281 185.46 yuan and the utility increased by 0.17 QALYs.Azacitidine therapeutic regimen was the absolute dominance plan.One-way sensitivity analysis showed that progression-free survival state utility value,discount rate and decitabine cost had greater influence on the results.The results of probabilistic sensitivity analysis suggested that azacinidine therapy was always economical within the willingness to pay threshold range of 3 times Chinese per capita gross domestic product in 2021.Conclusion From the perspective of health system in China,azacitidine has more cost-utility advantages than decitabine in the treatment of MDS.
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OBJECTIVE@#To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects.@*METHODS@#Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles.@*RESULTS@#A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness.@*CONCLUSION@#The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
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Humanos , Masculino , Persona de Mediana Edad , Femenino , Índice Tobillo Braquial , Estudios de Cohortes , Interacción Gen-Ambiente , Rigidez Vascular/genética , Linaje , Análisis de la Onda del Pulso/métodos , GenotipoRESUMEN
OBJECTIVE@#To explore the association between the use of metformin and the risk of ischemic stroke in patients with type 2 diabetes.@*METHODS@#A prospective cohort study was designed from the Fangshan family cohort in Beijing. According to metformin use at baseline, 2 625 patients with type 2 diabetes in Fangshan, Beijing were divided into metformin group or non-metformin group and the incidence of ischemic stroke between the different groups during follow-up was estimated and compared by Cox proportional hazard regression model. The participants with metformin were first compared with all the parti-cipants who did not use metformin, and then were further compared with those who did not use hypoglycemic agents and those who used other hypoglycemic agents.@*RESULTS@#The patients with type 2 diabetes were with an average age of (59.5±8.7) years, and 41.9% of them were male. The median follow-up time was 4.5 years. A total of 84 patients developed ischemic stroke during follow-up, with a crude incidence of 6.4 (95%CI: 5.0-7.7) per 1 000 person-years. Among all the participants, 1 149 (43.8%) took metformin, 1 476 (56.2%) were metformin non-users, including 593 (22.6%) used other hypoglycemic agents, and 883 (33.6%) did not use any hypoglycemic agents. Compared with metformin non-users, the Hazard ratio (HR) for ischemic stroke in metformin users was 0.58 (95%CI: 0.36-0.93; P = 0.024). Compared with other hypoglycemic agents, HR was 0.48 (95%CI: 0.28-0.84; P < 0.01); Compared with the group without hypoglycemic agents, HR was 0.65 (95%CI: 0.37-1.13; P=0.13). The association between metformin and ischemic stroke was statistically significant in the patients ≥ 60 years old compared with all the metformin non-users and those who used other hypoglycemic agents (HR: 0.48, 95%CI: 0.25-0.92; P < 0.05). Metformin use was associated with a lower incidence of ischemic stroke in the patients with good glycemic control (0.32, 95%CI: 0.13-0.77; P < 0.05). In the patients with poor glycemic control, and the association was not statistically significant (HR: 0.97, 95%CI: 0.53-1.79; P>0.05). There was an interaction between glycemic control and metformin use on incidence of ischemic stroke (Pinteraction < 0.05). The results of the sensitivity analysis were consistent with the results in the main analysis.@*CONCLUSION@#Among patients with type 2 diabetic in rural areas of northern China, metformin use was associated with lower incidence of ischemic stroke, especially in patients older than 60 years. There was an interaction between glycemic control and metformin use in the incidence of ischemic stroke.
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Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Metformina/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios de Cohortes , Accidente Cerebrovascular Isquémico/complicaciones , Estudios Prospectivos , Hipoglucemiantes/efectos adversos , Accidente Cerebrovascular/prevención & control , Estudios RetrospectivosRESUMEN
To investigate the crucial role of particle size in the biological effects of nanoparticles, a series of mesoporous silica nanoparticles (MSNs) were prepared with particle size gradients (50, 100, 150, 200 nm) with the traditional Stober method and adjusting the type and ratio of the silica source. The correlation between toxicity and size-caused biological effects were then further examined both in vitro and in vivo. The results indicated that the prepared MSNs had a uniform size, good dispersal, and ordered mesoporous structure. Hemolytic toxicity was found to be independent of particle size. At the cellular level, MSNs with smaller particle sizes were more readily internalized by cells, which initiated to more intense oxidative stress, therefor inducing higher cytotoxicity, and apoptosis rate. In vivo studies demonstrated that MSNs primarily accumulated in the liver and kidneys of mice. Pharmacokinetic analysis revealed that larger MSNs were eliminated more efficiently by the urinary system than smaller MSNs. The mice's body weight monitoring, blood tests, and pathological sections of major organs indicated good biocompatibility for MSNs of different sizes. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Zhejiang Chinese Medical University. Overall, this study prepared MSNs with a particle size gradient to investigate the correlation between toxicity and particle size using macrophages and endothelial cells. The study also examined the biosafety of MSNs with different particle sizes in vivo and in vitro, which could help to improve the safety design strategy of MSNs for drug delivery systems.
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Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.
Asunto(s)
Recién Nacido , Humanos , Femenino , Embarazo , Síndrome de Sjögren/tratamiento farmacológico , Mujeres Embarazadas , Hidroxicloroquina/uso terapéutico , Estudios Retrospectivos , Glucocorticoides , Nacimiento Prematuro/epidemiología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Resultado del Embarazo , gammaglobulinasRESUMEN
Aim To explore a potential new target for the prevention and treatment of diabetic cardiomyopathy ( DCM) in mice. Methods The myocardial proteomics of normal and diabetic mice was studied. The GEO database GSE161931 dataset was analyzed using R language with P < 0.05 and I log