A new method to predict venous complications in pediatric liver transplantation: Evaluation of splenic parameters by ultrasonography.

BACKGROUND: Venous complications after pediatric liver transplantation seriously affect the survival rate of patients and grafts. At present, the diagnostic indicators have not been unified. Venous complications may cause portal hypertension, which may lead to splenomegaly and splenic vein dilatation. Therefore, the changes in spleen may be closely related to the venous complications. The purpose of this study was to explore the relationship between ultrasonic splenic parameters and venous complications and to study whether these splenic parameters can be used for the diagnosis of venous complications. METHODS: We retrospectively included pediatric patients who underwent liver transplantation and collected ultrasonic spleen parameters before, and then 1-3 days, 1-3 weeks, 1-3 months, and 4-12 months after liver transplantation. We observed whether there were portal vein or hepatic vein complications within 1 year after liver transplantation. RESULTS: Among 109 pediatric patients after liver transplantation included in our study, 11 of them suffered from portal vein complications and nine hepatic vein complications. Spleen transverse diameter, spleen longitudinal diameter, spleen portal vein diameter, spleen index, spleen transverse diameter ratio, spleen longitudinal diameter ratio, and spleen index ratio were independent risk factors of venous complications. The accuracy of spleen transverse diameter (AUROC: 0.73), spleen index (AUROC: 0.70), spleen transverse diameter ratio (AUROC: 0.71), and spleen index ratio (AUROC: 0.72) in predicting venous complications were higher than other ones. CONCLUSIONS: Ultrasonic examination is a common follow-up method for pediatric patients after liver transplantation and the application of ultrasonic spleen parameters may be helpful to monitor venous complications.

Regulation of depressive-like behaviours by palmitoylation: Role of AKAP150 in the basolateral amygdala.

BACKGROUND AND PURPOSE: Protein palmitoylation is involved in learning and memory, and in emotional disorders. Yet, the underlying mechanisms in these processes remain unclear. Herein, we describe that A-kinase anchoring protein 150 (AKAP150) is essential and sufficient for depressive-like behaviours in mice via a palmitoylation-dependent mechanism. EXPERIMENTAL APPROACH: Depressive-like behaviours in mice were induced by chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Palmitoylated proteins in the basolateral amygdala (BLA) were assessed by an acyl-biotin exchange assay. Genetic and pharmacological approaches were used to investigate the role of the DHHC2-mediated AKAP150 palmitoylation signalling pathway in depressive-like behaviours. Electrophysiological recording, western blotting and co-immunoprecipitation were performed to define the mechanistic pathway. KEY RESULTS: Chronic stress successfully induced depressive-like behaviours in mice and enhanced AKAP150 palmitoylation in the BLA, and a palmitoylation inhibitor was enough to reverse these changes. Blocking the AKAP150-PKA interaction with the peptide Ht-31 abolished the CRS-induced AKAP150 palmitoylation signalling pathway. DHHC2 expression and palmitoylation levels were both increased after chronic stress. DHHC2 knockdown prevented CRS-induced depressive-like behaviours, as well as attenuating AKAP150 signalling and synaptic transmission in the BLA in CRS-treated mice. CONCLUSION AND IMPLICATIONS: These results delineate that DHHC2 modulates chronic stress-induced depressive-like behaviours and synaptic transmission in the BLA via the AKAP150 palmitoylation signalling pathway, and this pathway may be considered as a promising novel therapeutic target for major depressive disorder.

Regulation of anxiety-like behaviors by S-palmitoylation and S-nitrosylation in basolateral amygdala.

Protein posttranslational modification regulates synaptic protein stability, sorting and trafficking, and is involved in emotional disorders. Yet the molecular mechanisms regulating emotional disorders remain unelucidated. Here we report unknown roles of protein palmitoylation/nitrosylation crosstalk in regulating anxiety-like behaviors in rats. According to the percentages of open arm duration in the elevated plus maze test, the rats were divided into high-, intermediate- and low-anxiety groups. The palmitoylation and nitrosylation levels were detected by acyl-biotin exchange assay, and we found low palmitoylation and high nitrosylation levels in the basolateral amygdala (BLA) of high-anxiety rats. Furthermore, we observed that 2-bromopalmitate (2-BP), a palmitoylation inhibitor, induced anxiety-like behaviors, accompanied with decreased amplitude and frequency of mEPSCs and mIPSCs in the BLA. Additionally, we also found that inhibiting nNOS activity with 7-nitroindazole (7-NI) in the BLA caused anxiolytic effects and reduced the synaptic transmission. Interestingly, diazepam (DZP) rapidly elevated the protein palmitoylation level and attenuated the protein nitrosylation level in the BLA. Specifically, similar to DZP, the voluntary wheel running exerted DZP-like anxiolytic action, and induced high palmitoylation and low nitrosylation levels in the BLA. Lastly, blocking the protein palmitoylation with 2-BP induced an increase in protein nitrosylation level, and attenuating the nNOS activity by 7-NI elevated the protein palmitoylation level. Collectively, these results show a critical role of protein palmitoylation/nitrosylation crosstalk in orchestrating anxiety behavior in rats, and it may serve as a potential target for anxiolytic intervention.

Early transthoracic echocardiography and long-term mortality in moderate- to-severe acute respiratory distress syndrome: An analysis of the Medical Information Mart for Intensive Care database.

BACKGROUND: The clinical use of transthoracic echocardiography (TTE) in patients with acute respiratory distress syndrome (ARDS) in the intensive care unit (ICU) has dramatically increased, its impact on long-term prognosis in these patients has not been studied. This study aimed to explore the effect of early-TTE on long-term mortality in patients with moderate-to-severe ARDS in ICU. METHODS: A total of 2833 patients with moderate-to-severe ARDS who had or had not received early-TTE were obtained from the Medical Information Mart for Intensive Care (MIMIC-III) database after imputing missing values by a random forest model, patients were divided into early-TTE group and non-early-TTE group according to whether they received TTE examination in ICU. A variety of statistical methods were used to balance 41 covariates and increase the reliability of this study, including propensity score matching, inverse probability of treatment weight, covariate balancing propensity score, multivariable regression, and doubly robust estimation. Chi-Square test and t-tests were used to examine the differences between groups for categorical and continuous data, respectively. RESULTS: There was a significant improvement in 90-day mortality in the early-TTE group compared to non-early-TTE group (odds ratio = 0.79, 95% CI: 0.64-0.98, p-value = 0.036), revealing a beneficial effect of early-TTE. Net-input was significantly decreased in the early-TTE group on the third day of ICU admission and throughout the ICU stay, compared with non-early-TTE group (838.57 vs. 1181.89 mL, p-value = 0.014; 4542.54 vs. 8025.25 mL, p-value = 0.05). There was a significant difference in the reduction of serum lactate between the two groups, revealing the beneficial effect of early-TTE (0.59 vs. 0.83, p-value = 0.009). Furthermore, the reduction in the proportion of acute kidney injury demonstrated a correlation between early-TTE and kidney protection (33% vs. 40%, p-value < 0.001). CONCLUSIONS: Early application of TTE is beneficial to improve the long-term mortality of patients with moderate-to-severe ARDS.

Elucidation of common molecular diagnostic biomarkers between chronic periodontitis and Parkinson's disease via bioinformatics analyses.

BACKGROUND AND OBJECTIVES: Parkinson's disease (PD) and chronic periodontitis (CP) are both inflammatory diseases; a correlation between the two diseases has been reported, but the underlying mechanisms of this association have not been investigated. We investigated the common molecular mechanisms between PD and CP and the role of immune cells in the pathogenesis of them using bioinformatics analyses to elucidate the association between the two diseases. METHODS: We obtained gene expression data from the Gene Expression Omnibus (GEO) database: GSE10334, GSE16134, and GSE23586 for CP gingival samples and GSE20146 for PD brain samples. Subsequently, we conducted an enrichment analysis of the differentially expressed genes (DEGs) using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Moreover, all DEGs were analysed for protein-transcription factor interactions and protein-immune cell co-expression. We constructed protein-transcription factor, protein-protein interaction (PPI), and protein-immune cell co-expression networks using the Cytoscape software. Moreover, we identified the hub genes and investigated them for potential diagnostic value. RESULTS AND CONCLUSION: We identified 99 DEGs in the three CP datasets, 520 DEGs in the PD dataset and found five common DEGs in the CP and PD datasets, namely CXCR4, CXCL8, CD19, RPTN, and SLC16A9. These common DEGs identified in our study may have a potential impact on disease pathogenesis through the involvement of CXCR4-CXCL8-CD19 protein-complexes in dendritic cells. Therefore, CD19, LCP2, CXCR4, and LYN could be used as target molecules for the clinical diagnosis of both diseases.

An 8-gene predicting survival model of hepatocellular carcinoma (HCC) related to pyroptosis and cuproptosis.

BACKGROUND: The study aimed to establish a prognostic survival model with 8 pyroptosis-and-cuproptosis-related genes to examine the prognostic effect in patients of hepatocellular carcinoma (HCC). METHODS: We downloaded gene expression data and clinical information of HCC patients from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO). The clustering analysis and cox regression with LASSO were used for constructing an 8 PCmRNAs survival model. Using TCGA, ICGC and GEO cohort, the overall survival (OS) between high- and low- risk group was determined. We also evaluated independent prognostic indicators using univariate and multivariate analyses. The relatively bioinformatics analysis, including immune cell infiltration, function enrichment and drug sensitivity analyses, was performed as well. The gene expression of 8 PCmRNAs in vitro were validated in several HCC cell lines by qRT-PCR and Western blot. The relationship between GZMA and Fludarabine were further checked by CCK-8 assay. RESULTS: The survival prognostic model was constructed with ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA using data from TCGA cohort. The ICGC and GEO cohort were used for model validation. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. Risk scores had the highest predictable value for survival among Stage, Age, Gender and Grade. Most Immune cells and immune functions were decreased in high-risk group. Besides, function enrichment analyses showed that steroid metabolic process, hormone metabolic process, collagen - containing extracellular matrix, oxidoreductase activity and pyruvate metabolism were enriched. Potential drugs targeted different PCDEGs like Nelarabine, Dexamethasone and Fludarabine were found as well. ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NOD1 were upregulated while NLRP6 and GZMA were downregulated in most HCC cell lines. The potential therapy of Fludarabine was demonstrated when GZMA was low expressed in Huh7 cell line. CONCLUSION: We constructed a novel 8-gene (ATP7A, GLS, CDKN2A, BAK1, CHMP4B, NLRP6, NOD1 and GZMA) prognostic model and explored potential functional information and microenvironment of HCC, which might be worthy of clinical application. In addition, several potential chemotherapy drugs were screened and Fludarabine might be effective for HCC patients whose GZMA was low expressed.

Comparison of revascularization and conservative treatment for hemorrhagic moyamoya disease in East Asian Countries: a single-center case series and a systematic review with meta-analysis.

Objective: The optimal treatment approach for hemorrhagic moyamoya disease (HMMD) remains a topic of debate, particularly regarding the comparative efficacy of revascularization versus conservative treatment. Our study, which included a single-center case series and a systematic review with meta-analysis, aimed to determine whether surgical revascularization is associated with a significant reduction in postoperative rebleeding, ischemic events, and mortality compared to conservative treatment among East Asian HMMD patients. Methods: We conducted a systematic literature review by searching PubMed, Google Scholar, Wanfang Med Online (WMO), and the China National Knowledge Infrastructure (CNKI). The outcomes of surgical revascularization and conservative treatment, including rebleeding, ischemic events and mortality, were compared. The authors' institutional series of 24 patients were also included and reviewed in the analysis. Results: A total of 19 East Asian studies involving 1,571 patients as well as our institution's retrospective study of 24 patients were included in the study. In the adult patients-only studies, those who underwent revascularization had significantly lower rates of rebleeding, ischemic events, and mortality compared to those who received conservative treatment (13.1% (46/352) vs. 32.4% (82/253), P < 0.00001; 4.0% (5/124) vs. 14.9% (18/121), P = 0.007; and 3.3% (5/153) vs. 12.6% (12/95), P = 0.01, respectively). In the adult/pediatric patients' studies, similar statistical results of rebleeding, ischemic events, and mortality have been obtained (70/588 (11.9%) vs. 103/402 (25.6%), P = 0.003 or <0.0001 in a random or fixed-effects model, respectively; 14/296 (4.7%) vs. 26/183 (14.2%), P = 0.001; and 4.6% (15/328) vs. 18.7% (23/123), P = 0.0001, respectively). Conclusion: The current single-center case series and systematic review with meta-analysis of studies demonstrated that surgical revascularization, including direct, indirect, and a combination of both, significantly reduces rebleeding, ischemic events, and mortality in HMMD patients in the East Asia region. More well-designed studies are warranted to further confirm these findings.

Massive hemothorax secondary to internal jugular vein central venous catheter placement in a patient undergoing spinal surgery complicated by chest trauma: a case report.

BACKGROUND: Placement of a central venous catheter (CVC) is a common procedure for spinal surgery and is relatively safe under ultrasound guidance. CASE PRESENTATION: We report the case of a 56-year-old female who underwent ultrasound-guided placement of an internal jugular vein CVC for fluid replacement during spinal surgery for thoracic vertebral burst compression fracture and multiple rib fractures as a result of a high-altitude fall injury. Hemothorax developed intraoperatively. During a thoracotomy, the tip of the CVC was found within the chest cavity. The presence of chest trauma may impact on clinician's appreciation of the potential complications of internal jugular vein CVC placement. CONCLUSION: The present case demonstrates the need for clinical awareness of the potential complications of CVC placement in patients with chest trauma and the need for adequate training in this technique.

SNP-based high-density linkage map construction and QTL mapping of black spot disease resistance in Chinese sand pear.

Black spot disease (PBS) caused by Alternaria alternata is an economic disease of pear (Pyrus pyrifolia Nakai). Developing cultivars with durable PBS resistance traits is an important research objective for improving pear germplasm. The Deshengxiang is a popular pear variety in China and resistant to PBS. This study aimed to detect quantitative trait loci (QTL) associated with PBS resistance trait in pear and determine closely linked molecular markers by specific locus amplified fragment sequencing (SLAF-seq). F1 population resulting from a cross between "Deshengxiang" (female) and "Guiguan," a susceptible (male) variety, was developed and evaluated in 2016 and 2017. SLAF technology was used to discover SNPs in the F1 individuals and subsequently a high-density genetic linkage map for PBS resistance was constructed which contained 17,604 SNP markers. Based on the linkage map, the markers were distributed into 17 linkage groups, spanning 1548.48 cM, with a mean marker distance of 0.09 cM, representing the densest genetic map of the genus Pyrus. QTL analysis of PBS resistance identified a locus strongly related to PBS resistance at 77.68 ~ 112.99 cM on linkage group 15, which was further narrowed down to 93.79 ~ 112.99 cM. Two markers, Marker94293 and Marker94206, located at 97.47 and 102.93 cM, were closely associated with PBS resistance, with a Δ (SNP index) value of 0.46. Co-localization of QTL interval, bioinformatics analysis, and functional annotation revealed PBS putative candidate genes. Overall, the high-density pear linkage map is a suitable reference for mapping PBS resistance trait, QTL, and genes identified in this study contribute information that could be useful for PBS improvement in pear.

Reform and Practice of Ideological and Political Education of Core Courses of Biopharmaceutical Specialty———Taking The Course of Biotechnology Pharmacy as An Example / 中国生物化学与分子生物学报

As mentioned in this paper, the curriculum team of biotechnological pharmaceutics in Binzhou University reoriented the curriculum objective based on the educational policy: fostering virtue through education and consolidating fundamental spirit and soul. Additionally, the team drew on cutting-edge scientific and technological developments, social hotspots, national spirit, innovative thinking, dedication spirit and other elements, conducted in-depth study on the ideological and political elements of the subject and organically integrated them with the contents such as genetic engineering, cellular engineering, fermentation engineering, enzyme engineering, protein engineering, and established online and offline ideological and political database. Furthermore, with the aid of teaching apps like ‘Rain Classroom’, the teaching models include lecture, case-based teaching, group discussion, and blended teaching for the subject. In the meantime, the ideological and political educational requirements were integrated into the curriculum evaluation system. Taking the genetic engineering pharmaceutics as an example, reform and practice for the ideological and political education for the undergraduate subject, biotechnological pharmaceutics, was applied. This paper expatiated the teaching practice of the ideological and political education, and reviewed the outcomes of the curriculum reform over these years in an effort to formulate a set of all-round programs for the reform and practice of the ideological and political education that can be replicated and improved continuously. This paper aims not only in developing high-caliber biomedical talents with a strong sense of patriotism and social responsibility, but also in providing a reference for the teaching reform of related subjects.

Spatial and temporal expression patterns of Atoh1 during mice cerebellar development / 解剖学报

Objective To investigated the spatial and temporal expression of Atoh1 mRNA and protein level during the cerebellar development. Methods The frozen cerebellum sections of mice at different developmental stages were used to analyze the temporal and spatial expression patterns of Atoh1 mRNA by RNA scope technique, n= 3 for each group. Meanwhile, two reporter mice with different genetic modification method were utilized to analyze the spatial and temporal expression of Atoh1 at the protein level by immunofluorescence staining, n= 3 for each group. Results Atoh1 mRNA was highly expressed in the embryonic cerebellar rhombic lip (RL) and the external granule layer (EGL). At the protein level, staining result of Atoh1-3

Quality Evaluation of Temporomandibular Joint Images from 3 High-resolution Dynamic Sequences / 中国医学科学院学报

Objective To compare the image quality of three high-resolution dynamic MRI methods for evaluating the motion of temporomandibular joint disc and condyle. Methods Twenty-five patients with suspected temporomandibular joint disorders were examined by single-shot fast spin-echo (SSFSE),fast imaging employing steady-state acquisition (FIESTA),and spoiled gradient echo (SPGR) on the oblique sagittal position.Two radiologists performed subjective and objective evaluation on the images with double-blind method.The subjective evaluation included the signal intensity of mandibular condyle,articular disc,soft tissue around articular disc,and lateral pterygoid muscle,the contrast between articular disc and condyle,the contrast between articular disc and surrounding soft tissue,condylar motion,and disc movement.The objective evaluation indexes included image signal intensity,signal-to-noise ratio (SNR),and contrast-to-noise ratio (CNR).The subjective and objective indexes of the image quality were compared between the three sequences. Results The SSFSE sequence had lower signal intensity of articular disc and higher signal intensity of condyle and surrounding soft tissue than FIESTA and SPGR sequences (all P<0.001).The SPGR sequence showed higher signal intensity of lateral pterygoid muscle than the SSFSE and FIESTA sequences (P=0.017,P<0.001).Among the three sequences,SSFSE sequence showed the clearest articular disc structure (χ2=41.952,P<0.001),the strongest contrast between articular disc and condyle (χ2=35.379,P<0.001),the strongest contrast between articular disc and surrounding soft tissue (χ2=27.324,P<0.001),and the clearest movement of articular disc (χ2=44.655,P<0.001).SSFSE and FIESTA sequences showed higher proportion of disc displacement and reduction than SPGR sequence (all P<0.001).The CNR (χ2=21.400,P<0.001),SNR (χ2=34.880,P<0.001),and condyle signal intensity (F=337.151,P<0.001) demonstrated differences among SSFSE,FIESTA,and SPGR sequences.The CNR of SSFSE sequence was higher than that of FIESTA sequence (P<0.001),while it had no significant difference between SSFSE and SPGR sequences (P=0.472).In addition,the SSFSE sequence had higher SNR and signal intensity than FIESTA and SPGR sequences (all P<0.001). Conclusion The best image quality can be observed from SSFSE sequence where both the structure and movement of temporomandibular joint are well displayed.Therefore,SSFSE is preferred for the examination of temporomandibular joint movement.

Teaching reform and practice of 'Production Internship' course for biotechnology specialty from the perspective of training application-oriented talents / 生物工程学报

Production internship is an important teaching tache for undergraduate students to carry out engineering training by using professional skills, and it is a key starting point for fostering application-oriented talents in biotechnology. The Course Group of 'production internship of biotechnology majors' of Binzhou University is investigating application-oriented transformation for local regular colleges and universities, as well as fostering high-level application-oriented talents. By taking green fluorescent protein (GFP) polyclonal antibody as an example, the reform and practice on teaching content, teaching mode, assessment method, continuous improvement of curriculum were carried out. Moreover, the characteristics of the Yellow River Delta-Binzhou Biotechnology & Pharmaceutical Industrial Cluster were taken into account to intensify academic-enterprise cooperation. On one hand, this Course Group designed and rearranged the course contents, carried out essential training through online resources and platforms such as virtual simulation, and recorded, tracked and monitored the progress of production internship through practical testing and software platforms like 'Alumni State'. On the other hand, this Course Group established a practice-and application-oriented assessment method in the process of production internship and a dual evaluation model for continuous improvement. These reform and practices have promoted the training of application-oriented talents in biotechnology, and may serve as a reference for similar courses.

Research Progress on Gene Mutation and CHIP in Pathogenesis of MDS --Review / 中国实验血液学杂志

With the development of molecular biology techniques, the people's understanding of myelodysplastic syndromes (MDS) has greatly improved, a heterogeneous hematopoietic pre-malignant disorder of the stem cells. Gene mutations include RNA splicing, DNA methylation, chromosome modification, transcription factors, signal transduction kinases, RAS pathways, cohesion complexes, DNA repair, etc. Gene mutation is the determinant of diagnostic typing and therapeutic efficacy of MDS. The new concepts of CHIP and ICUS have aroused people's attention to the elderly patients with clonal hematopoiesis and non-clonal cytopenia but without MDS characteristics, who have the possibility of high-risk transformation to MDS and leukemia. In order to better understand the pathogenesis of MDS, the significance of gene mutations, CHIP and ICUS in the diagnosis and prognosis of MDS were reviewed in this paper.

Establishment and preliminary application of quantitative real-time PCR assay for the detection of SARS-CoV-2 subgenomic nucleocapsid RNA / 中华预防医学杂志

Objective: To establish a rapid and specific quantitative real-time PCR (qPCR) method for the detection of SARS-CoV-2 subgenomic nucleocapsid RNA (SgN) in patients with COVID-19 or environmental samples. Methods: The qPCR assay was established by designing specific primers and TaqMan probe based on the SARS-CoV-2 genomic sequence in Global Initiative of Sharing All Influenza Data (GISAID) database. The reaction conditions were optimized by using different annealing temperature, different primers and probe concentrations and the standard curve was established. Further, the specificity, sensitivity and repeatability were also assessed. The established SgN and genomic RNA (gRNA) qPCR assays were both applied to detect 21 environmental samples and 351 clinical samples containing 48 recovered patients. In the specimens with both positive gRNA and positive SgN, 25 specimens were inoculated on cells. Results: The primers and probes of SgN had good specificity for SARS-CoV-2. The minimum detection limit of the preliminarily established qPCR detection method for SgN was 1.5×102 copies/ml, with a coefficient of variation less than 1%. The positive rate of gRNA in 372 samples was 97.04% (361/372). The positive rates of SgN in positive environmental samples and positive clinical samples were 36.84% (7/19) and 49.42% (169/342), respectively. The positive rate and copy number of SgN in Wild strain were lower than those of SARS-CoV-2 Delta strain. Among the 25 SgN positive samples, 12 samples within 5 days of sampling time were all isolated with virus; 13 samples sampled for more than 12 days had no cytopathic effect. Conclusion: A qPCR method for the detection of SARS-CoV-2 SgN has been successfully established. The sensitivity, specificity and repeatability of this method are good.

Impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity and pulse pressure on all-cause mortality / 中华心血管病杂志

Objective: To evaluate the impact of individual and combined assessment of age- and sex-specific brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP) on all-cause mortality. Methods: This study is a prospective cohort study. Individuals participated in the Kailuan Study and completed baPWV measurements between 2010 and 2016 were included in this study. After stratifying by sex, 75th percentile baPWV and PP values for different age group were calculated at five years interval. BaPWV and PP values below the 75th percentile were defined as normal, and those above or equal to the 75th percentile were defined as increased. The participants were allocated to four groups according to their PP and baPWV status: normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group. The primary outcome was all-cause mortality during the follow-up period. Cox proportional hazards models were used to explore the impact of individual and combined assessment of baPWV and PP on all-cause mortality events. Results: A total of 39 339 participants were enrolled in this study, aged (49.3±12.8) years, of which 28 731 (73.03%) were males. There were 23 268, 6 025, 6 210 and 3 836 cases in the normal baPWV/PP group, high baPWV/normal PP group, normal baPWV/high PP group and high baPWV/PP group, respectively. The average follow-up duration was (4.98±2.53) years. During the follow-up period, all-cause mortality occurred in 998 individuals. Multivariate Cox regression analysis showed increased risk of all-cause mortality in the high baPWV/normal PP group (HR=1.27, 95%CI 1.07-1.50), and in the high baPWV/PP group (HR=1.33, 95%CI 1.08-1.65) compared to the normal baPWV/PP group. Increased pulse pressure alone had no impcat on all-cause death (HR=1.06, 95%CI 0.87-1.29). Conclusions: The risk of all-cause mortality significantly increases with increased age-and sex-specific baPWV and PP values. BaPWV may be a better predictor of all-cause mortality than PP in this cohort.

Optimization of the extraction process for Xuelian yishen formula by the combination of entropy weight method-analytic hierarchy process with Box-Behnken response surface methodology / 中国药房

OBJECTIVE To optimize the extraction process of Xuelian yishen formula. METHODS The contents of total flavone， echinacoside and acteoside， and extraction yield in Xuelian yishen formula were chosen as indexes， entropy weight method-analytic hierarchy process was adopted to determine the weight coefficient. Box-Behnken response surface methodology was used to optimize the extraction process of Xuelian yishen formula with extraction time， solid-liquid ratio and extraction times as factors， using comprehensive score of above indexes as index. RESULTS The optimal extraction process of Xuelian yishen formula was extraction time of 2 h， solid-liquid ratio of 1∶12， extracting for 3 times. Average comprehensive score of 3 validation tests was 96.40 points （RSD＝0.28%）， the deviation of which with predictive value was 0.98%. CONCLUSIONS The optimized extraction process is stable， feasible and reproducible， which can provide reference for the extraction process of Xuelian yishen formula.

Shenqi Dihuang Decoction inhibits high-glucose induced ferroptosis of renal tubular epithelial cells via Nrf2/HO-1/GPX4 pathway / 中国中药杂志

This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.

Animalexperiment on regulating effect of stored red blood cells transfusion on BMDMs in inflammatory conditions / 中国输血杂志

【Objective】 To discuss the regulating effect of stored red blood cells (RBCs) transfusion on BMDMs in inflammatory conditions, and the relationship between stored RBCs transfusion and inflammatory response induced by bacterial infection. 【Methods】 Forty C57BL/6 male mice of 6-8 weeks (18-22 g/mouse) were randomly divided into experimental group and control group. Each mouse was infected with 200 µL Pseudomonas aeruginosa injecting into the tail vein, and 400 µL fresh (storage >14 d) and stored RBCs (storage 0.05). F4/80 of experimental group and control group 2, 4 and 8 hours after RBCs infused were 1.83±0.11 vs 0.75±0.06, 0.46±0.06 vs 0.33±0.06 (P0.05), respectively. iNOS, TNF-α, MCP1 of M1 in liver of experimental group and control group 2, 4 and 8 hours after RBCs infused were respectively: iNOS 3.44±0.20 vs 2.46±0.08, 9.25±0.55 vs 2.67±0.12, 2.80±0.08 vs 2.39 ±0.01; TNF-α 1.69±0.22 vs 1.13±0.03, 1.44±0.24 vs 0.96±0.09, 1.31±0.05 vs 0.96±0.06; MCP1 4.96±0.08 vs 4.28±0.27, 4.63±0.04 vs 2.07±0.09, 2.28±0.19 vs 1.33±0.03 (P0.05). 【Conclusion】 Stored RBCs infusion can greatly promote the M1 polarization of BMDMs in liver.

Genotype-environment interaction on arterial stiffness: A pedigree-based study / 北京大学学报(医学版)

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.