Development of self-care scale for patients with lymphedema after breast cancer surgery and verification of its reliability and validity / 现代临床护理

Objective To develop a self-care scale for patients with lymphedema after breast cancer surgery and verify its reliability and validity.Methods Based on the model of knowledge,belief and practice,a questionnaire item pool was constructed after literature reviews and qualitative interviews.A questionnaire-based scale was drafted based on the established item pool by carrying out two rounds of consultation with 15 clinical nursing specialists,nursing administrators and nursing educators from 8 provinces or cities in China.Reliability and validity of the scale were tested using convenience sampling,involving 444 patients with breast cancer surgery related lymphedema from 7 general hospitals in Hubei and Henan provinces,China,between May and July 2023.Results The response rates for the two rounds of expert consultation were 93.75%and 93.33%,respectively.The authority coefficients of the two rounds were 0.86 and 0.89,respectively,and the coordination coefficients for the 2 rounds were 0.130 and 0.379,respectively.In the first round,the average importance rating was from 4.33 to 4.93 with the coefficient of variation from 0.05 to 0.19,and the full score ratio from 53.33%to 93.33%.In the second round,the average importance rating ranged from 2.86 to 4.93 with the coefficient of variation from 0.05 to 0.36,and the full score ratios from 7.14%to 92.86%.A total of 421 patients completed the survey.The overall Cronbach's α coefficient of the scale was 0.943,the overall split-half reliability was 0.824,the scale-level content validity index(S-CVI)was 0.912,and the item-level content validity index(I-CVI)of the total scale ranged from 0.857 to 1.000.The KMO value of exploratory factor analysis was 0.919,the Bartrett spherical test value was 4671.724(P<0.001),and the cumulative variance contribution rate was 64.155%.Confirmatory factor analysis showed a good model fit.After the reliability and validity tests,the scale was finalised and determined to consist of three dimensions with 33 items:knowledge(9 items),attitude(6 items)and behaviour(18 items).Conclusion The self-care scale for the patients with lymphedema after breast cancer surgery has demonstrated good reliability and validity,and makes it an effective assessment tool for the patients with lymphedema after breast cancer surgery.

Effects of icariin-astragaloside IV-puerarin mixture on cognitive function and ferroptosis amino acid metabolism pathway in APP/PS1 HAMP-/-mice / 中国病理生理杂志

AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seri-ously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P＜0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P＜0.05),the brain neurons were seriously damaged(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P＜0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P＜0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P＜0.05),the brain neuron damage was alleviated(P＜0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P＜0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.

Effect and mechanism of melatonin on the epithelial-mesenchymal transition of human peritoneal mesenchymal cells / 中国医科大学学报

Objective To investigate the effect and mechanism of melatonin on the epithelial-mesenchymal transition(EMT)of human peritoneal mesothelial cells.Methods A human peritoneal mesoepithelial cell line(HMrSV5)was cultured.Decorin(DCN)overex-pression and knockout plasmids were constructed.The cells were divided into the normal,TGF-β1,TGF-β1+melatonin,TGF-β1+mela-tonin+siDCN,TGF-β1+melatonin+siNC,and TGF-β1+DCN groups.The cell proliferation and survival rates were determined using Cell Counting Kit-8(CCK-8).The protein and mRNA expression levels of DCN,TGF-β1,Smad2,and E-cadherin were detected by Western blotting and real-time polymerase chain reaction(PCR),respectively.Results The CCK-8 assay showed that the cell survival rates were higher in the TGF-β1+melatonin,TGF-β1+melatonin+siDCN,and TGF-β1+DCN groups than the TGF-β1 group(P＜0.05).The cell sur-vival rate was higher for the TGF-β1+melatonin group than the TGF-β1+melatonin+siDCN group(P＜0.05).Western blotting and real-time PCR showed DCN and that E-cadherin were significantly down-regulated in the TGF-β1 group compared with the control group(P＜0.05).Compared with the TGF-β1 group,the TGF-β1+melatonin and TGF-β1+melatonin+siDCN groups showed up-regulated E-cadherin and DCN expression levels and down-regulated TGF-β1 and Smad2 expression levels(P＜0.05).Compared with the TGF-β1+melato-nin+siDCN group,the TGF-β1+melatonin+siDCN group showed up-regulated E-cadherin and DCN expression levels and down-regulated TGF-β1 and Smad2 expression levels(P＜0.05).Conclusion Melatonin can delay the EMT of human peritoneal mesoepithelial cells,and the DCNgene may be an important target to inhibit the EMT of these cells.

Clinical application of radiolabeled FAPIs in non-malignant lesions / 中华核医学与分子影像杂志

Fibroblast activation protein inhibitor (FAPI) has been the focus of nuclear medicine since its introduction. With the in-depth study of FAPI tracer, its clinical application in various non-malignant diseases has also been gradually reported. Many studies have confirmed its uptake in a variety of non-malignant diseases, which indicate that FAPI tracers have good application prospects. This article reviews the latest research status and clinical application of radiolabeled FAPIs in cardiovascular diseases, rheumatic immune diseases, immunoglobulin (Ig)G4-related diseases, renal fibrosis and other non-malignant diseases at home and abroad.

Correlation between serum uric acid level and body composition, exercise capacity and cardiopulmonary function in medical examination population / 中华健康管理学杂志

Objective:To investigate the correlation between blood uric acid level and body composition, exercise capacity, and cardiopulmonary function in medical examination population.Methods:In this cross-sectional study, 83 individuals who underwent physical examinations at Peking University Third Hospital from June 1, 2023, to October 1, 2023, and met the inclusion criteria were included. According to whether they had hyperuricemia (HUA), the participants were divided into HUA group (53 cases) and non-HUA group (30 cases). Body composition parameters, such as body mass index and visceral fat area, were measured with a body composition analyzer. Exercise capacity indicators, including grip strength, vertical jump, back strength, and sit-and-reach test, were measured using specific monitoring devices. Cardiopulmonary function was assessed using the stair index test. The clinical characteristics of the two groups were compared with t-tests or chi-square tests, and the correlation between uric acid levels and body composition, exercise capacity, and cardiopulmonary function was analyzed. Results:The HUA group had significantly higher skeletal muscle mass, body fat mass, body mass index, and visceral fat area when compared with the non-HUA group [(31.92±5.60) vs (26.11±6.19) kg, (23.66±9.33) vs (17.19±5.00) kg, (26.53±3.68) vs (23.27±3.59) kg/m2, 91.20 (74.25, 123.90) vs 68.25 (56.25, 90.48) cm 2, respectively] (all P<0.05). The grip strength, vertical jump, and back pull strength were all lower in the HUA group [32.70 (25.25, 40.30) vs 42.35 (35.95, 48.10) kg, 30.30 (24.10, 36.48) vs 40.55 (33.06, 45.10) kg, 24.20(20.60, 32.23) vs 29.90 (25.20, 35.50) cm, 65.60 (51.75, 78.00) vs 91.00 (67.25, 111.50) kg, respectivley] (all P<0.05). The increased step index was positively correlated with reduced risk of hyperuricemia ( OR=0.875, 95% CI: 0.793-0.966) ( P<0.05). Conclusions:Blood uric acid level is correlated with cardiopulmonary function in medical examination population. Individuals with better cardiopulmonary function have a lower risk of developing HUA. However, the relationship between blood uric acid level and body composition and exercise capacity is not clear.

Therapeutic effects of Qiliqiangxin capsule on heart failure in aging rats after acute myocardial infarction / 中华老年医学杂志

Objective:To investigate the impact of QiliQiangXin Capsules on ventricular remodeling and cardiac contraction and relaxation function in aging rats with heart failure following myocardial infarction.Methods:From August 2022 to August 2023, a total of 30 old rats were randomly assigned to three groups: sham-operated group, model group, and treatment group, with 10 rats in each group selected through a digital lottery method.The model and treatment groups were created by ligating the anterior descending branch of the left coronary artery.The rats in the treatment group received daily administration of Astragalosa hebecarpa Drabanemerosa Strong Heart Capsule(1.0 g/kg)via gavage after 4 weeks.After the 4-week drug administration period, echocardiography was performed to measure various parameters including left ventricular end-diastolic internal diameter(LVIDd), left ventricular end-systolic internal diameter(LVIDs), left ventricular ejection fraction(LVEF), left ventricular anterior wall myocardial thickness(LVAWd), mitral valve early diastolic peak flow velocity(E peak), and early diastolic velocity of mitral annulus(e peak)detected by tissue Doppler(TDI). The E/e value was calculated based on these measurements.Additionally, serum levels of B-type brain natriuretic peptide(BNP), matrix metalloproteinase 2(MMP-2), matrix metalloproteinase 9(MMP-9), and tumor necrosis factor(TNF-α)were measured using enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE)staining was employed to observe the morphological changes in myocardial tissue.Results:Compared to rats in the model group, rats in the treatment group exhibited lower left ventricular internal dimension at end-diastole(LVIDd)(9.1±0.6 mm vs.11.4±0.8 mm, P<0.01), lower left ventricular internal dimension at end-systole(LVIDs)(5.9±0.8 mm vs.8.7±0.9 mm, P<0.01), lower E/e ratio(13.4±2.0 vs.16.3±2.8, P<0.05), higher left ventricular ejection fraction(LVEF)(68.8±7.1% vs.52.0±8.4%, P<0.01), and elevated left ventricular anterior wall thickness at end-diastole(LVAWd)(1.5±0.2 mm vs.1.2±0.3 mm, P<0.05). In addition, compared to rats in the model group, the treatment group showed a decrease in brain natriuretic peptide(BNP)(0.26±0.04 μg/L vs.0.34±0.05 μg/L, P<0.01), decreased matrix metalloproteinase-2(MMP-2)(3697.0±857.7 μg/L vs.4719.5±703.5 μg/L, P<0.01), decreased matrix metalloproteinase-9(MMP-9)(87.3±13.8 μg/L vs.116.5±9.6 μg/L, P<0.01), decreased tumor necrosis factor-alpha(TNF-α)(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01), and lower TNF-α levels(165.3±36.9 μg/L vs.269.8±35.0 μg/L, P<0.01). Histological examination using hematoxylin and eosin(HE)staining revealed that the treatment group had less severe cardiac myocyte arrangement disorder and inflammatory reaction compared to the model group. Conclusions:Qiliqiangxin Capsules were found to effectively delay ventricular remodeling and improve myocardial contraction and relaxation function in aging rats with heart failure after acute myocardial infarction.

Clinical observation of letrozole combined with methylprednisolone in the treatment of infertile patients with polycystic ovary syndrome resistant to clomiphene / 中国药房

OBJECTIVE To explore the effects of letrozole combined with methylprednisolone on clinical outcomes， ovarian reserve function， serum sex hormones， and safety in infertile patients with polycystic ovary syndrome resistant to clomiphene. METHODS The clinical data of 78 infertile patients with polycystic ovary syndrome resistant to clomiphene in the Department of Gynecology of Qingdao Central Hospital from February 2021 to January 2022 was analyzed retrospectively， and all patients were divided into control group （42 cases） and observation group （36 cases） based on the treatment methods. The control group took letrozole 5 mg/d orally on the 5th to 9th day of the menstrual cycle. Vaginal ultrasound was used to monitor the development of the endometrium and follicles； estradiol valerate was used to correct endometrial thickness， and measures such as inducing ovulation with follicle-stimulating hormone were taken to promote pregnancy. On the basis of treatment in the control group， the observation group began taking methylprednisolone orally at a dose of 4 mg/d starting from the third day of natural menstruation or withdrawal bleeding. Both groups were treated for 6 menstrual cycles. The ovulation and pregnancy within one year， serum levels of sex hormones [estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， testosterone] and anti-Müllerian hormone （AMH）， ovulation indicators （follicle growth time， the number of ovulations， and the number of dominant follicles）， and the occurrence of adverse drug reactions were compared between the two groups. RESULTS After treatment， the biochemical pregnancy rate （72.22%） and clinical pregnancy rate （47.22%） of the observation group were significantly higher than those of control group （47.62%， 19.05%）； the serum levels of E2， LH， FSH， testosterone and AMH were significantly lower than the control group； the follicle growth time was significantly shorter than the control group； the number of ovulation and dominant follicles were significantly higher than the control group （P＜0.05）. There was no statistically significant difference in ovulation rate （94.44% vs. 83.33%） and total incidence of adverse drug reactions （8.33% vs. 9.52%） between the observation group and the control group （P＞0.05）. CONCLUSIONS Compared with letrozole alone， the combination of letrozole and methylprednisolone can significantly improve the pregnancy rate， the sex hormone levels and ovarian reserve function in infertile patients with polycystic ovary syndrome resistant to clomiphene， with high safety profiles.

Determination of Isobutyl Chloroformate Residue in Agatroban by Derivatization-Gas Chromatography-Mass Spectrometry / 分析化学

A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.

ox-LDL Promotes Bidirectional Regulation of Neuronal Apoptosis Through The PCSK9/LRP1 Signaling Pathway / 生物化学与生物物理进展

Obiective Alzheimer’s disease (AD) is a degenerative disease of the central nervous system (CNS) caused by a variety of risk factors. There are various pathological changes, but apoptosis of the neurological meridian cells is one of the most important pathological bases. Hyperlipidemia is a high-risk factor for the development of AD, which can lead to increased levels of oxidized low-density lipoprotein (ox-LDL) in brain tissues. PCSK9 is a protease closely related to lipid metabolism, but studies have shown that it may be related to the development of AD. LRP1 is abundantly expressed in neuronal cells, and it is an important transporter for the clearance of Aβ. There is now a large amount of literature confirming that PCSK9 can induce the degradation of LRP1. PI3K/AKT is an important signaling pathway in vivo, which plays an important role in apoptosis, and there is now a large amount of literature confirming that LRP1 activates the PI3K/AKT pathway, which has an anti-apoptotic effect. So can PCSK9 affect the PI3K/AKT pathway through LRP1 and thus regulate neuronal apoptosis? This deserves further investigation.The aim of this study was to explore the role of PCSK9 in mediating ox-LDL pro-apoptotic neuronal cell death and its mechanism, and then further elaborate the mechanism of hyperlipidemia leading to neurodegenerative diseases such as AD. MethodsFirstly, PC12 cells were treated with different concentrations of ox-LDL (0, 25, 50, 75 and 100 mg/L) for 24 h. Oil red O staining was used to detect lipid accumulation in PC12 cells, Hoechst33258 staining and flow cytometry to detect apoptosis in PC12 cells, ELISA to detect the content of Aβ secreted by PC12, Western blot to detect expression of SREBP2, PCSK9 and LRP1. Then PC12 cells were treated with 75 mg/L ox-LDL for different times (0, 6, 12, 24, 48 h), and Western blot were performed to detect the expression of SREBP2, PCSK9 and LRP1. Finally, after transfecting 100 nmol/L PCSK9 siRNA into PC12 cells for 48 h, PC12 cells were treated with 75 mg/L ox-LDL for 24 h, Hoechst33258 staining and flow cytometry to detect apoptosis rate of PC12 cells, and Western blot to detect PCSK9, LRP1, PI3K, AKT, P-PI3K , P-AKT, NF-κB, Bcl-2, Bax, Caspase-9 and Caspase-3 expression, and ELISA detected Aβ content secreted by PC12 cells. Resultsox-LDL increased lipid accumulation and promoted apoptosis and Aβ secretion in PC12 cells, as well as increasing the expression of SREBP2 and PCSK9 and decreasing the expression of LRP1 in PC12 cells. pCsk9 siRNA could be inhibited through the PI3K/AKT pathway and the NF-κB-Bcl-2/Bax-Caspase-9/3 pathway to inhibit ox-LDL-induced apoptosis in PC12 cells while increasing Aβ secretion in PC12 cells. Conclusionox-LDL plays a bidirectional regulatory role in ox-LDL-induced apoptosis of PC12 cells by inducing an increase in PCSK9 expression and a decrease in LRP1 expression in PC12 cells, which in turn affects different signaling pathways downstream.

Expression and distribution of brain⁃derived neurotrophic factor in different cerebrum regions of yak and cattle / 解剖学报

Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

Proposing an intelligent technique based on radial basis function neural network to forecast the energy spectrum of diagnostic X-ray imaging systems.

In digital subtraction angiography (digital subtraction total cerebral angiography), cardiac and macrovascular cardiography, anorectal radiology, fluoroscopy, and computed tomography (CT), a prior knowledge to X-ray energy spectrum is crucial for assessing the image quality and also calculating patient X-ray dosage. The present investigation's main objective is to propose an intelligent technique for faster calculating X-ray energy spectrum of medical imaging systems with different exposure settings of tube voltage, filter material, and thickness based on limited specific spectra. In this study, Monte Carlo N Particle (MCNP) simulation code was initially used to generate some limited X-ray spectra for tube voltages of 20, 30, 40, 50, 80, 100, 130, and 150 kV for two different filters of beryllium and aluminum with thicknesses of 0. 4, 0.8, 1.2, 1.6 and 2 mm. Tube voltage, type, and thickness of filter were used as the 3 inputs of 150 Radial Basis Function Neural Network (RBFNN) to forecast point by point of the X-ray spectrum. After training, the RBFNNs could forecast most of the X-ray spectra for tube voltages in the range of 20-150 kV and two various filters of aluminum and beryllium with thicknesses in the range of 0-2 mm.

Circulating circRNA expression profile and its potential role in late recurrence of paroxysmal atrial fibrillation post catheter ablation / 老年心脏病学杂志（英文版）

BACKGROUND@#Catheter-based pulmonary vein isolation (PVI) is an effective and well-established intervention for symptomatic paroxysmal atrial fibrillation (PAF). Nevertheless, late recurrences of atrial fibrillation (LRAF) occurring during 3 to 12 months are common, and the underlying mechanisms remain elusive. Circular RNAs (circRNAs) in atrial tissue have been linked to the pathophysiological mechanisms and progression of PAF in a few studies. However, their expression patterns in peripheral blood and regulatory function in LRAF are not clear.@*METHODS@#In the present study, the expression profile of circulating circRNAs in three paired nonvalvular PAF patients with or without LRAF was investigated by high-throughput sequencing and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and circRNA/miRNA regulatory network, were performed to predict the functions and potential regulatory roles of differentially expressed (DE) circRNAs.@*RESULTS@#A total of 12,834 circRNAs, comprising 5,491 down-regulated and 7,343 up-regulated circRNAs, were found to be DE in blood smaples from the two groups in peripheral blood between LRAF and non-recurrence control individuals. The most enriched GO categories in terms of molecular function, biological process, and cellular component features were catalytic activity, cellular metabolic process, and intracellular part, respectively. The KEGG enrichment study revealed that the most important metabolic process controlled by DE circRNAs is endocytosis. In the circRNA/microRNAs interaction network, four up-regulated circRNAs (hsa_circ_0002665, hsa_circ_0001953, hsa_circ_0003831, and hsa_circ_0040533) and one down-regulated circRNA (hsa_circ_0041103) were predicted to play potential regulatory roles in the pathogenesis of LRAF.@*CONCLUSIONS@#This investigation discovered the expression pattern of circulating circRNAs that is indicative of PAF late recurrence, which may serve as risk markers or therapeutic targets for LRAF after PVI.

Ethyl Lithospermate Reduces Lipopolysaccharide-Induced Inflammation through Inhibiting NF-κB and STAT3 Pathways in RAW 264.7 Cells and Zebrafish / 中国结合医学杂志

OBJECTIVE@#To explore the anti-inflammatory effects of ethyl lithospermate in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish, and its underlying mechanisms.@*METHODS@#3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations (12.5-100 µ mol/L) in RAW 264.7 cells. The cells were stimulated with LPS (100 ng/mL) for 12 h to establish an inflammation model in vitro, the production of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor α (TNF-α) were assessed by enzyme linked immunosorbent assay (ELISA). Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa B (NF-κB) p65, phospho-STAT3 (p-STAT3, Tyr705), inhibitor of NF-κB (IκB) α, and phospho-I κB α (p-IκB α, Ser32), and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705). Additionally, the yolk sacs of zebrafish (3 days post fertilization) were injected with 2 nL LPS (0.5 mg/mL) to induce an inflammation model in vivo. Survival analysis, hematoxylin-eosin (HE) staining, observation of neutrophil migration, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo.@*RESULTS@#The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100 µ mol/L. Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01), decreased IκBα degradation and phosphorylation (P<0.05) as well as the nuclear translocation of NF-κB p65 and p-STAT3 (Tyr705) in LPS-induced RAW 264.7 cells (P<0.01). Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish (P<0.05 or P<0.01). In addition, ethyl lithospermate also inhibited the mRNA expression levels of of IL-6, TNF-α, IκBα, STAT3, and NF-κB in LPS-stimulated zebrafish (P<0.01).@*CONCLUSION@#Ethyl lithospermate exerts anti-Inflammatory effected by inhibiting the NF-κB and STAT3 signal pathways in RAW 264.7 macrophages and zebrafish.

Clinical efficacy of demethylating drugs in treatment of patients with myelodysplastic syndromes / 白血病·淋巴瘤

Objective:To investigate the clinical efficacy and safety of demethylating drugs decitabine and azacitidine in treatment of myelodysplastic syndromes (MDS).Methods:The clinical data of 15 patients initially diagnosed with MDS in Fujian Provincial Hospital from May 2010 to May 2020 were retrospectively analyzed; 10 patients were treated with decitabine (10-30 mg·m -2·d -1, 3-5 d consecutively) and 5 patients were treated with azacitidine (75 mg·m -2·d -1 for 7 d consecutively). Gene mutation, risk stratification, efficacy and adverse reactions were observed. Results:Among 15 patients, 9 cases were males and 6 cases were females, with a median age of 64 years (51-84 years). The median follow-up time was 18 months (4-62 months). There were 3 cases in high-risk group, 10 cases in medium-risk group and 2 cases in low-risk group. SF3B1, TET2 and STAG2 mutations were more common in patients with low to moderate risk; DNMT3A, EZH2, U2AF1, RUNX1 and TP53 mutations were more common in patients with high-risk. All patients were evaluated for efficacy after 2-3 courses of treatment, and the total effective rate was 66.7% (10/15). Among them, 1 case (6.7%) achieved complete remission, 1 case (6.7%) achieved bone marrow complete remission (mCR), 2 cases (13.3%) achieved partial remission, and 6 cases (40%) achieved hematological improvement. During the treatment, 9 cases had grade 3-4 hematological toxicity and 6 cases had grade 3-4 infection. There was no grade 3-4 bleeding, nausea, vomiting and liver function damage. During the follow-up to May 2020, 9 patients survived and 6 patients died.Conclusions:Demethylating drugs decitabine and azacitidine have high rates of complete remission and partial remission and a low rate of adverse drug reactions in MDS patients.

Disease-modifying therapy for spinal muscular atrophy / 中华实用儿科临床杂志

Spinal muscular atrophy (SMA) was a severe inherited neuromuscular disease caused by the deficiency of the survival motor neuron (SMN) protein encoded by SMN1 gene with pathogenic variants.According to the age of onset and maximal achievement of motor function, SMA was classified into 4 subtypes.The most common and severe subtype was SMA type 1.During the natural course, most of patients with SMA type 1 die of respiratory failure within 2 years of age if not treated.Patients with other subtypes have progressive muscle weakness and atrophy at varying degrees.Before the emergence of disease-modifying therapy, a multidisciplinary management, including physical therapy, respiratory and nutritional support, has been the only approach to delay the disease progression and enhance the survival rate of SMA.However, motor milestone progress is unable to achieve by SMA patients, because the lack of SMN protein has not been solved.In the past 5 years, 3 drugs have been approved for the treatment of SMA.Clinical trials and a growing number of real-world study data have shown that medications of disease-modifying agents contribute to effectively improve motor function in SMA patients with different subtypes, and promote the motor milestone progress in some patients, which significantly reduce the mortality.However, treatment response of disease-modifying agents to SMA varies with the subtypes of SMA, individualized conditions and courses of disease.Therefore, it is particularly important to choose an optimal treatment to ensure the quality of life of patients.This review focuses on recent advances and emerging challenges in the treatment of SMA.

Detection of meningeal carcinomatosis by metagenomic next-generation sequencing and copy number variation analysis of cerebrospinal fluid / 中华神经科杂志

Objective:To evaluate the significance of copy number variation (CNV) and metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) in the diagnosis of meningeal carcinomatosis (MC).Methods:Ten patients with MC diagnosed in the Department of Neurology of Peking Union Medical College Hospital from March 2022 to June 2022 were consecutively enrolled in this study. The patients were diagnosed according to the criteria of the Chinese expert consensus on the diagnosis of MC by the Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology, and the diagnosis of MC was confirmed by CSF cytology. The control group included 10 patients who were diagnosed as autoimmune encephalitis or viral encephalitis. CSF mNGS and CNV analysis were performed simultaneously in all the patients.Results:Of the 10 patients with MC, 6 had lung adenocarcinoma, 4 had breast cancer. CSF mNGS and CNV analysis detected large CNV in 8 of 10 patients with MC, including 4 patients with breast cancer and 4 patients with lung cancer. The results of pathogenic microorganism analysis of CSF mNGS in all the patients were negative. Meanwhile, large CNV was not detected in the control group.Conclusions:CSF CNV can serve as a diagnostic marker for MC. The combination of mNGS and CNV analysis has demonstrated a high positive rate in the diagnosis of MC. The dual-omics analysis of pathogenic microorganisms and CNV has been proposed as a potential strategy to further expand the clinical utility of CSF mNGS in the realm of auxiliary diagnosis.

Effect of P-coumaric Acid on Apoptosis of Multiple Myeloma Cells Based on Oxidative Stress / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of p-coumaric acid on apoptosis of multiple myeloma cells and its related mechanism.@*METHODS@#Multiple myeloma cell line MM.1s cells were selected and treated with different concentrations of p-coumaric acid (0, 0.4, 0.8, 1.6, 3.2 mmol/L), and the inhibition rate and half inhibition concentration (IC50) were detected by CCK-8 method. Then MM.1s cells were treated with 1/2 IC50, IC50, 2 IC50 and transfected with ov-Nrf-2 and ov-Nrf-2+IC50. The apoptosis, ROS fluorescence intensity and mitochondrial membrane potential of MM.1s cells were detected by flow cytometry, and the relative expressions of cellular Nrf-2 and HO-1 protein were detected by Western blot.@*RESULTS@#P-coumaric acid inhibited the proliferation of MM.1s cells in a dose-dependent manner(r =0.997) with an IC50 value of 2.754 mmol/L. Compared with the control group, apoptosis and ROS fluorescence intensity of MM.1s cells were significantly increased in the 1/2 IC50 group, IC50 group, 2 IC50 group and ov-Nrf-2+IC50 group (P <0.01), the expressions of Nrf-2, HO-1 protein in the IC50 group and 2 IC50 group were significantly decreased (P <0.05). Compared with the IC50 group, the cells apoptosis and ROS fluorescence intensity were significantly decreased (P <0.01), and the expressions of Nrf-2 and HO-1 protein were significantly increased in the ov-Nrf-2+IC50 group (P <0.01).@*CONCLUSION@#P-coumaric acid can inhibit the proliferation of MM.1s cells and may target the Nrf-2/HO-1 signaling pathway to affect oxidative stress in MM cells thereby inducing their apoptosis.

Analysis of Organic Components and Their Migration Studies in Butyl Rubber Clousures of Cefmetazole Sodium for Injection by GC-MS/HPLC / 医药导报

Objective To investigate the organic components in cefmetazole sodium butyl rubber clousures for injection and their migration into drugs,and to evaluate the compatibility of pharmaceutical butyl rubber clousures with cefmetazole sodium.Methods The structures of volatile components in butyl rubber clousures of cefmetzole sodium for injection and those migrated into drugs were identified by GC/MS SCAN mode and National Institute of Standard and Technology(NIST)spectrum library.An HPLC method was established to quantitatively analyse the antioxidants and vulcanizing agents transferred from butyl rubber clousures into drugs.Results Organic compounds such as antioxidant BHT and silicone oil were identified by GC/MS.The HPLC was used to determine the peak area of antioxidant(168,264,330,1 076,1 010)and vulcanizing agent in the range of 0.5-100 μg·mL-1 with good linear relationship with the peak area.The average recoveries(low,medium,and high)of antioxidant and vulcanizing agents ranged from 90.0%to 110.0%,and the corresponding RSD were all less than 2%(n=9).It was found that the antioxidant BHT and silicone oil in cefmetazole sodium butyl rubber clousures for injection would migrate into the drug and affect the clarity of the solution.Conclusion GC-MS/HPLC method can be used as an effective method for quality control of packing materials(butyl rubber clousures)and drug compatibility studies,so as to ensure the safety of drug use by the public.

Health status of elderly residents in Beijing city: a survey and analysis based on the Health Criteria for Older Adults in China(2022) / 中华老年医学杂志

Objective:To evaluate and analyze the health status of elderly people from the physical, psychological and social aspects using the Health Criteria for Older Adults in China(2022), and to understand the impact of social demographic characteristics on the overall health status of the elderly.Methods:159 elderly people aged 60 years and over in the Lanyuan community of Malianwa Subdistrict, Haidian District, Beijing were selected by the stratified sampling method, with a mean age of(70.7±7.9)years, including 74 men and 85 women.The physical, psychological, social and overall health status of the elderly were comprehensively evaluated and analyzed from data collected through a self-designed questionnaire with face-to-face interviews at respondents' homes.Results:The percentage of participants in this community who were considered overall healthy was 30.2%(n=48). The proportions of those meeting the criteria for physical, mental and social health were 79.2%(n=126), 90.6%(n=144)and 32.1%(n=51), respectively.For participants of 3 age groups(60-69, n=89; 70-79, n=44; ≥80, n=26), differences in percentages of people who were considered not healthy, largely healthy and healthy, measured using the overall, physical, mental and social health criteria, were statistically significant( χ2=24.683, 57.096, 12.801, 11.802, all P<0.05), and results of the χ2test for trend showed that the frequency distribution of people with overall, physical, mental and social health decreased with age( χ2=16.878, 31.600, 9.626, 9.626, all P<0.05). Multivariate Logistic regression analysis showed that education level( OR=2.142, 95% CI: 1.053-4.538, P=0.035)was an influencing factor for overall health status of the elderly. Conclusions:The overall health status of community-dwelling elderly people in Beijing is relatively poor and deteriorates with age.Education level is a factor affecting their health status.Health assessment for the elderly should be strongly advocated, and targeted health education should be provided for the elderly in disease prevention and mental health care.

Effects of oxiracetam on neurological impairment and oxidative stress in lead-exposed rats / 中华行为医学与脑科学杂志

Objective:To investigate the effects of different doses of oxiracetam (ORC) on the neurological impairment and oxidative stress ability of lead(Pb)-exposed rats.Methods:Total 32 male SD rats with SPF grade were randomly divided into control group, the lead-exposed group, low-dose ORC intervention group and high-dose ORC intervention group according to the random number table method, with 8 rats in each group.The neurobehavioral indexes of rats were measured by gait score, tail flicking test, hindlimb support test and Morris water maze test.The lead content in hippocampal tissue was detected by spectrophotometry.The cell morphology of hippocampal tissue was observed by HE staining.Superoxide dismutase (superoxide dismutase, SOD) level in hippocampal tissues was detected by xanthine oxidase, and the level of malondialdehyde (MDA) in the hippocampus tissue was detected by the thiobarbiturate, and the level of glutathione peroxidase (GPx) in the hippocampus tissue was detected by chemical colorimetric.SPSS 24.0 software was used for statistical analysis, one-way ANOVA was used for multiple group comparisons and LSD- t test was used for further pairwise comparisons. Results:(1)After 8 weeks of lead exposure, there was no significant difference in body weight among the 4 groups( F=0.869, P=0.469). (2)Results of neurobehavioral indicators: there were statistically significant differences in gait scores, tail flick time, hind limb deployment distance, escape latency, and number of crossing platforms among the four groups of rats ( F=7.854, 13.630, 8.484, 23.485, 45.457, all P<0.05). The gait score, tail flick time, hind limb deployment distance, and escape latency of the lead-exposed group rats were higher than those of the control group (all P<0.05), while the number of crossing platforms was lower than that of the control group ( P<0.05). The gait score, tail flick time, hind limb deployment distance, and escape latency of the high-dose ORC intervention group were lower than those of the lead exposed group (all P<0.05), and the number of crossing platforms was higher than that of the lead exposed group ( P<0.05). (3)Lead content in hippocampal tissue: there was a statistically significant difference in lead content in the hippocampus of the four groups( F=309.013, P<0.001). The lead contents of lead exposed group ((1.21±0.10)μg/g), low-dose ORC intervention group ((1.03±0.10)μg/g) and high-dose ORC intervention group ((1.02±0.06)μg/g) were higher than that of the control group((0.02±0.00) μg/g) (all P<0.05), while the lead content in the low-dose ORC intervention group and high-dose ORC intervention group were both lower than that of the lead exposed group (both P<0.05). (4) HE staining showed that compared with the control group, the hippocampal tissue cells in the lead exposed group were arranged disordered, the tissue was loose, and the number of cells was reduced.Compared with the lead exposed group, the hippocampal histiocytes were closely arranged and regular, and the nuclei were fuller.(5)Oxidative stress levels in hippocampal tissue: there were significant differences in MDA, GPx content and SOD activity of hippocampal tissues in the four groups( F=69.879, 56.757, 11.644, all P<0.001). The levels of SOD ((2.03±0.18)U/mg, (3.42±0.26)U/mg), GPx((67.29±7.94)nmol/mg, (89.50±7.94)nmol/mg) in the hippocampus tissue of the lead exposed group were lower than those of the control group (all P<0.05), while the content of MDA was higher than that of the control group((43.73±3.74) nmol/mg, (16.42±1.60) nmol/mg)( P<0.05). The levels of SOD ((3.32±0.12) U/mg) and GPx ((84.11±6.26) nmol/mg) in the high-dose ORC intervention group were higher than those in the lead exposed group (both P<0.05), while the levels of MDA ((21.05±2.56) nmol/mg) was lower than that in the lead exposed group ( P<0.05). Conclusion:ORC can alleviate neurological damage in rats caused by lead exposure, which may be related to the up-regulation of antioxidant capacity of hippocampal tissues, thereby improving pathological damage.