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AIMS: This study was carried out with the purpose of investigating the association between serum lactadherin, monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF[alpha]) and carotid-femoral pulse wave velocity (PWV) in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 105 subjects including 27 T2DM patients without vascular complications (DM), 28 T2DM patients with vascular complications (DC), 25 elderly healthy volunteers (older) and 25 younger healthy volunteers (younger) were recruited into the study. Carotid-femoral PWV was measured using an automatic device. Serum lactadherin, MCP-1 and TNF[alpha] were determined by enzyme linked immunosorbent assay. RESULTS: PWV and lactadherin, MCP-1 and TNF[alpha] were significantly higher in DM and DC groups than those of older and younger groups. PWV and lactadherin were higher in older group than those of younger group. Moreover, lactadherin was significantly correlated with MCP-1, TNF[alpha], PWV, HbA1c and 2h postprandial blood glucose (P2hBG) (P<0.05). In multivariate regression analysis, the independent determinants of lactadherin were HbA1c, P2hBG and age (P<0.05). CONCLUSIONS: These findings underscore that lactadherin is correlated with poor blood glucose control and diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension., Methods: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups., Results: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period., Conclusions: Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470)., Competing Interests: Conflict of Interest All authors declare that they have no competing interests., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence., Methods: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed., Results: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group ( P >0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage ( n =62, 42.5%) and the early stage ( n =46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene ( HR =4.177, 95% CI : 2.086-8.364, P <0.001) and minimal residual disease≥0.01% on day 46 ( HR =2.013, 95% CI : 1.163-3.483, P =0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol., Conclusions: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Objective: To investigate the clinicopathological, immunophenotypic and molecular genetic characteristics, and differential diagnosis of NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) in the gastrointestinal tract. Methods: Two NTRK-RSCNs diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China and one case diagnosed at Zhengzhou Central Hospital, Zhengzhou, China from 2019 to 2022 were collected. The clinical data, histopathology, immunophenotypes and prognosis were analyzed. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect NTRK gene rearrangements, while relevant literature was also reviewed and discussed. Results: Two patients were male and one was female, with the age of 17, 47 and 62 years, respectively. The tumors were located in the duodenum, ascending colon and descending colon, respectively. The tumors were protuberant masses with gray and rubbery sections. Their maximum diameter was 2.5, 5.0 and 10.0 cm, respectively. Histologically, the tumors invaded mucosa, intrinsic muscle and serosal adipose tissue. Tumor cells consisted of spindle or oval shaped cells with monotonous morphology and arranged in bundles or stripes pattern. Spindle cells were mildly to moderately atypical, with slightly eosinophilic cytoplasm and inconspicuous nucleoli. Necrosis and mitotic figures were observed in one high-grade tumor. All tumors expressed CD34, S-100 and pan-TRK in varying degrees. FISH analysis showed that NTRK1 gene was break-apart in 1 case and NTRK2 gene break-apart in 2 cases. NGS technologies showed LMNA::NTRK1 fusion in one case, STRN::NTRK2 fusion in another case. All patients recovered well after the surgery without recurrence at the end of the follow-up. Conclusions: NTRK-RSCN is rarely diagnosed in the gastrointestinal tract and has significant variations in morphology. It overlaps with various other mesenchymal tumors which should be considered as differential diagnoses. Be familiar with the features of histological morphology in combination with immunophenotype and molecular genetic characteristics can not only help diagnose NTRK-RSCNs, but provide therapeutic targets for clinical treatment.

Background: Compound Taxus capsule, as an antineoplastic Chinese patent drug, has been increasingly applied as an adjunctive treatment for the management of non-small-cell lung cancer (NSCLC) and some other malignancies, but research about its antitumor activity and radiosensitization effect on hepatocellular carcinoma (HCC) cells is very rare., Purpose: To investigate the antitumor activity and radiosensitization effect of Compound Taxus on HCC cells and to preliminarily explore the possible molecule mechanisms involved., Methods: Cell viability, cell cycle distribution, apoptosis, DNA damage repair and protein expression levels were detected by CCK-8 assay, flow cytometry, immunofluorescence staining, western blotting analysis and immunohistochemical staining, respectively. The migration and invasion activities and vasculogenic mimicry (VM) formation and angiogenesis were evaluated by tube formation and VM formation assay. Radiation survival curves were obtained from the colony formation assay in human HCC cell lines, Smmc7721 and Bel7402 cells, pretreated with or without Compound Taxus before receiving X-ray irradiation. A Bel7402 tumor-bearing mouse model was established and the radiosensitization effect of Compound Taxus in vivo was evaluated by analyzing tumor volume and tumor weight in different groups receiving different treatments., Results: Compound Taxus decreased viability, induced G2/M arrest, promoted apoptosis, suppressed migration and invasion, and inhibited VM formation and angiogenesis in Smmc7721 and Bel7402 cells. Furthermore, Compound Taxus inhibited irradiation-induced DNA damage repair, enhanced the radiosensitivity of Smmc7721 and Bel7402 cells and improved the anti-tumor therapeutic efficacy of irradiation in Bel7402 tumor-bearing mice. Radiotherapy in combination with Compound Taxus showed the best tumor inhibition compared to that of Compound Taxus alone or irradiation alone. In addition, Compound Taxus significantly down-regulated NF-κB p65, p-NF-κB p65 and Bcl-2, and up-regulated Bax in vitro and in vivo, yet NF-κB p65 overexpression reversed the proapoptotic effect of Taxus on HCC cells, indicating that the NF-κB signaling pathway might be an important signal mediator in the Compound-Taxus-modulated biological responses., Conclusion: Our findings suggest that Compound Taxus shows marked antitumor activity and significant radiosensitization effect on HCC cells, making it possible for Compound Taxus to become a promising auxiliary modality for HCC management and a potential radiosensitizer of HCC in the future., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients., Purpose: To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values., Study Type: Retrospective cohort., Population: Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM)., Field Strength/sequence: 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences., Assessment: Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months., Statistical Tests: Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%)., Results: ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM., Conclusions: T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM., Evidence Level: 3 TECHNICAL EFFICACY: 5., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background: Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications., Purpose: Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models., Materials and Methods: 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test., Results: A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001)., Conclusion: The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Shi, Liu, Gao, Zhao, Zhang, Yang, Li, Wang, Du, Li, Bo, Zhuang, Fan, Sun and Xu.)

Aging is associated with gradual changes in liver structure, altered metabolites and other physiological/pathological functions in hepatic cells. However, its characterized phenotypes based on altered metabolites and the underlying biological mechanism are unclear. Advancements in high-throughput omics technology provide new opportunities to understand the pathological process of aging. Here, in our present study, both metabolomics and phosphoproteomics were applied to identify the altered metabolites and phosphorylated proteins in liver of young (the WTY group) and naturally aged (the WTA group) mice, to find novel biomarkers and pathways, and uncover the biological mechanism. Analysis showed that the body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the WTA group. The grips decreased with age, while the triglyceride (TG) and cholesterol (TC) did not change significantly. The increase of fibrosis, accumulation of inflammatory cells, hepatocytes degeneration, the deposition of lipid droplets and glycogen, the damaged mitochondria, and deduction of endoplasmic reticulum were observed in the aging liver under optical and electron microscopes. In addition, a network of metabolites and phosphorylated proteomes of the aging liver was established. Metabolomics detected 970 metabolites in the positive ion mode and 778 metabolites in the negative ion mode. A total of 150 pathways were pooled. Phosphoproteomics identified 2618 proteins which contained 16621 phosphosites. A total of 164 pathways were detected. 65 common pathways were detected in two omics. Phosphorylated protein heat shock protein HSP 90-alpha (HSP90A) and v-raf murine viral oncogene homolog B1(BRAF), related to cancer pathway, were significantly upregulated in aged mice liver. Western blot verified that protein expression of MEK and ERK, downstream of BRAF pathway were elevated in the liver of aging mice. However, the protein expression of BRAF was not a significant difference. Overall, these findings revealed a close link between aging and cancer and contributed to our understanding of the multi-omics changes in natural aging., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality., Methods: We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated., Results: The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission., Conclusions: Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients., (© 2023 JGC All rights reserved; www.jgc301.com.)

Background: To analyze the clinical effect of debranching thoracic endovascular aortic repair combined with ascending aortic banding., Methods: The clinical data of patients who underwent a debranching thoracic endovascular aortic repair combined with ascending aortic banding at Anzhen Hospital (Beijing, China) between January 2019 and December 2021 were reviewed to evaluate the occurrence and outcomes of postoperative complications., Results: A total of 30 patients underwent a debranching thoracic endovascular aortic repair combined with ascending aortic banding. There were 28 male patients (93.3%) with an average age of 59.9 ± 11.8 years. Twenty-five patients underwent simultaneous surgery and five patients had staged surgery. Postoperatively, two patients developed complete paraplegia (6.7%), three patients developed incomplete paraplegia (10%), two patients developed cerebral infarction (6.7%), and one patient developed femoral artery thromboembolism (3.3%). No patient died during the perioperative period, and one patient (3.3%) died during the follow-up period. None of the patients underwent retrograde type A aortic dissection during the perioperative and postoperative follow-up periods., Conclusions: Banding the ascending aorta with a vascular graft to restrict its movement and to serve as the proximal anchoring area of the stent graft can reduce the risk of retrograde type A aortic dissection.

AMP-activated protein kinase alpha 2 (AMPKα2) regulates energy metabolism, protein synthesis, and glucolipid metabolism myocardial cells. Ketone bodies produced by fatty acid β-oxidation, especially β-hydroxybutyrate, are fatty energy-supplying substances for the heart, brain, and other organs during fasting and long-term exercise. They also regulate metabolic signaling for multiple cellular functions. Lysine β-hydroxybutyrylation (Kbhb) is a β-hydroxybutyrate-mediated protein posttranslational modification. Histone Kbhb has been identified in yeast, mouse, and human cells. However, whether AMPK regulates protein Kbhb is yet unclear. Hence, the present study explored the changes in proteomics and Kbhb modification omics in the hearts of AMPKα2 knockout mice using a comprehensive quantitative proteomic analysis. Based on mass spectrometry (LC-MS/MS) analysis, the number of 1181 Kbhb modified sites in 455 proteins were quantified between AMPKα2 knockout mice and wildtype mice; 244 Kbhb sites in 142 proteins decreased or increased after AMPKα2 knockout (fold change >1.5 or <1/1.5, p < 0.05). The regulation of Kbhb sites in 26 key enzymes of fatty acid degradation and tricarboxylic acid cycle was noted in AMPKα2 knockout mouse cardiomyocytes. These findings, for the first time, identified proteomic features and Kbhb modification of cardiomyocytes after AMPKα2 knockout, suggesting that AMPKα2 regulates energy metabolism by modifying protein Kbhb., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Minimal research has been performed regarding total arch replacement through partial upper sternotomy in patients with acute type A aortic dissection who are obese, and the safety and feasibility of this procedure need to be further investigated. The present study investigated the potential clinical advantages of using a partial upper sternotomy versus a conventional full sternotomy for total arch replacement in patients who were obese., Methods: This was a retrospective study. From January 2017 to January 2020, a total of 65 acute type A aortic dissection patients who were obese underwent total arch replacement with triple-branched stent graft. Among them, 35 patients underwent traditional full sternotomy, and 30 patients underwent partial upper sternotomy. The perioperative clinical data and postoperative follow-up results of the two groups were collected, and the feasibility and clinical effect of partial upper sternotomy in total arch replacement were summarized., Results: The in-hospital mortality rates of the two groups were similar. The total operative time, cardiopulmonary bypass, aortic cross-clamp, cerebral perfusion, and deep hypothermic circulatory arrest times were also similar in both groups. The thoracic drainage and postoperative red blood cell transfusion volumes in the partial upper sternotomy group were significantly lower than those in the full sternotomy group. Mechanical ventilation time was shorter in the partial upper sternotomy group than that in the full sternotomy group. Additionally, the incidences of pulmonary infection, hypoxemia, and sternal diaphoresis were lower in the partial upper sternotomy group than those in the full sternotomy group., Conclusion: This study showed that total arch replacement surgery through a partial upper sternotomy in patients with acute type A aortic dissection who are obese is safe, effective, and superior to full sternotomy in terms of blood loss, postoperative blood transfusion, and respiratory complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xie, He, Wu, Qiu, Jiang, Gao and Chen.)

Diabetic cardiovascular complication is a common systemic disease with high morbidity and mortality worldwide. We hypothesise that exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs-exos) can rescue these disorders and alleviate vascular remodeling in diabetes. Morphological, non-targeted metabolomics and 4D label-free proteomics techniques were used to analyze the aortas of db/m mice as normal control group (NCA), saline treated db/db mice (DMA), and hUCMSCs-exos treated db/db mice (DMTA), and to clarify the molecular mechanism of the protection of hUCMSCs-exos in vascular remodeling from a new point of view. The results showed that 74 metabolites were changed significantly in diabetic aortas, of which 15 were almost restored by hUCMSCs-exos. In proteomics, 30 potential targets such as Stromal cell-derived factor 2-like protein 1, Leukemia inhibitory factor receptor, Peroxisomal membrane protein and E3 ubiquitin-protein ligase MYCBP2 were detected. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based analysis showed that Central carbon metabolism in cancer and Galactose metabolism pathway were up-regulated to near normal by hUCMSCs-exos in metabolomics, with janus associated kinase-signal transducer and activator of transcription (JAK-STAT) pathway displayed in proteomics. According to bioinformatics and integrated analysis, these targeted molecules of hUCMSCs-exos to attenuate the vascular remodeling were mainly associated with regulation of energy metabolism, oxidative stress, inflammation, and cellular communications. This study provided a reference for the therapy of diabetes-induced cardiovascular complications., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To determine the optimal timing of thoracic endovascular aortic repair (TEVAR) for patients with uncomplicated type B dissections who have a smoking history., Methods: Data from 308 consecutive patients with uncomplicated type B dissections, who have a smoking history and onset-to-TEVAR time within 90 days, were analyzed. The patients were divided into two groups: Acute and subacute phases. Univariate and multivariate regression analyses were performed. Smooth curve fitting and threshold analysis were performed to characterize the relationship between the onset-to-TEVAR time and follow-up deaths., Results: There were no significant differences between the two groups. Smooth curve fitting and threshold effect analysis showed that if early TEVAR was performed within 9.4 days from onset, there was better long-term survival and there was no significant difference after 9.4 days., Conclusion: By studying the relationship between onset-to-TEVAR time and all-cause mortality, we found that early TEVAR may have a lower all-cause mortality rate during follow-up in uncomplicated type B dissection patients who have a smoking history and within 90 days from onset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gao, Li, Zhang, Zhang and Xu.)

In recent years, great progress has been made in the treatment of Stanford type B aortic dissection, especially endovascular repair technology has become the main treatment. However, it is only used to repair the primary tear, the residual tears and false lumen are often left at the distal end, which causes adverse events such as distal aortic dilatation or even rupture. At present, there are many studies on the influencing factors of aortic remodeling, which provide some references for the prognosis of patients.The aorta carries the transportation of blood flow, and various factors affecting hemodynamics also affect the remodeling of aorta. Some researchers reported several factors related to negative remodeling and added auxiliary techniques, and achieved gratifying results. However, because of the different conditions of each patient, the specific treatment method is still unclear, the factors affecting the aortic remodeling effect also have not been thoroughly studied. Clarifying the influencing factors of negative remodeling is helpful to screen high-risk patients, optimize the treatment plan and improve the prognosis.

The root Rhynchosia volubilis was widely used for contraception in folk medicine, although its molecular mechanism on antifertility has not yet been revealed. In human sperm, it was reported that the cation channel of sperm, an indispensable cation channel for the fertilization process, could be regulated by various steroid-like compounds in plants. Interestingly, these nonphysiological ligands would also disturb the activation of the cation channel of sperm induced by progesterone. Therefore, this study aimed to explore whether the compounds in R. volubilis affect the physiological regulation of the cation channel of sperm. The bioguided isolation of the whole herb of R. volubilis has resulted in the novel discovery of five new prenylated isoflavonoids, rhynchones A - E (1:  - 5: ), a new natural product, 5'- O -methylphaseolinisoflavan (6: ) ( 1 H and 13 C NMR data, Supporting Information), together with twelve known compounds (7:  - 18: ). Their structures were established by extensive spectroscopic analyses and drawing a comparison with literature data, while their absolute configurations were determined by electronic circular dichroism calculations. The experiments of intracellular Ca 2+ signals and patch clamping recordings showed that rhynchone A (1: ) significantly reduced cation channel of sperm activation by competing with progesterone. In conclusion, our findings indicat that rhynchone A might act as a contraceptive compound by impairing the activation of the cation channel of sperm and thus prevent fertilization., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Hirschsprung's disease (HSCR) is an intestinal disease caused by defects in neural crest cell migration, proliferation, differentiation, and survival. Many reports have proposed that miRNA dysregulation is related to the occurrence of HSCR. However, the roles and mechanisms of miRNAs have not been thoroughly studied. The levels of miR‑92a and KLF4 were examined using qRT‑PCR and immunohistochemistry, respectively. Cell viability, migration and apoptosis were evaluated by MTT, Transwell and flow cytometry assays, respectively. A dual‑luciferase reporter assay was employed to verify the binding relationship between miR‑92a and KLF4. Levels of PI3K/AKT signals were further determined by western blot assay. Herein, elevated expression of miR‑92a and reduced expression of KLF4 were found in HSCR tissues, and their expression patterns were negatively correlated. Overexpression of miR‑92a inhibited cell viability and migration but enhanced cell apoptosis. However, overexpression of KLF4 had the opposite effects. Mechanistically, KLF4 was a target of miR‑92a and it negatively affected biological functions by activating PI3K/AKT signaling. These results proved that miR‑92a inhibited the proliferation and metastasis of nerve cells by regulating the KLF4/PI3K/AKT axis.

Ethnopharmacological Relevance: Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai"., Aim of the Study: This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments., Materials and Methods: First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylin & eosin (H&E) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration., Results: Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P < 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment., Conclusion: HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Anti-complementary activity-guided fractionation led to the isolation of a new abietane diterpene ( 1 ) and twenty-five known compounds ( 2-26 ) from the twigs and leaves of Juniperus tibetica . All the compounds were isolated from J. tibetica for the first time. The structure of 1 was assigned by spectroscopic data and X-ray crystallography analysis. Five lignans ( 2 , 3 , 7 , 9 and 10 ), two flavones ( 19 and 22 ), and one coumarin ( 23 ) exhibited anti-complementary activity with CH 50 values ranging from 0.3 to 3.69 mM.

Objectives: To study the clinical features and prognosis of children with acute leukemias of ambiguous lineage (ALAL) under different diagnostic criteria., Methods: A retrospective analysis was performed on the medical data of 39 children with ALAL who were diagnosed and treated from December 2015 to December 2019. Among the 39 children, 34 received treatment. According to the diagnostic criteria for ALAL by World Health Organization and European Group for the Immunological Characterization of Leukemias, the 39 children were divided into two groups: ALAL group ( n =28) and myeloid expression group ( n =11). The clinical features, treatment, and prognosis were compared between the two groups., Results: The 34 children receiving treatment had a 3-year event-free survival (EFS) rate of 75%±9% and an overall survival rate of 88%±6%. The children treated with acute myeloid leukemia (AML) protocol had a 3-year EFS rate of 33%±27%, those treated with acute lymphoblastic leukemia (ALL) protocol had a 3-year EFS rate of 78%±10%, and those who had no remission after induction with AML protocol and then received ALL protocol had a 3-year EFS rate of 100%±0% ( P <0.05). The children with negative minimal residual disease (MRD) after induction therapy had a significantly higher 3-year EFS rate than those with positive MRD (96%±4% vs 38%±28%, P <0.05). Positive ETV6-RUNX1 was observed in the myeloid expression group, and positive BCR-ABL1 , positive MLL-r , and hyperleukocytosis (white blood cell count ≥50×10 9 /L) were observed in the ALAL group. There was no significant difference in the 3-year EFS rate between the myeloid expression and ALAL groups (100%±0% vs 66%±11%, P> 0.05)., Conclusions: ALL protocol has a better clinical effect than AML protocol in children with ALAL, and positive MRD after induction therapy suggests poor prognosis. Hyperleukocytosis and adverse genetic changes are not observed in children with myeloid expression, and such children tend to have a good prognosis, suggesting that we should be cautious to take it as ALAL in diagnosis and treatment.

Hepatoblastoma is the most common malignant hepatic tumour type with hypervascularity in early childhood. In recent decades, emerging evidence has proven that long non‑coding RNAs (lncRNAs) serve an important oncogenic role in the pathogenesis of hepatoblastoma. However, the underlying mechanism of lncRNA taurine upregulated 1 (TUG1) in the angiogenesis of hepatoblastoma remains unknown. The expression patterns of TUG1 and microRNA (miR)‑204‑5p were detected in hepatoblastoma tissues and cell lines via reverse transcription‑quantitative PCR and were analysed using a Pearson's correlation test. A tube formation assay was performed using human umbilical vein endothelial cells to assess the vasculogenic activity of treated HuH‑6 cells. ELISA was used to detect the level of the secretory proangiogenic factor VEGFA in the culture media of HuH‑6 cells. A dual luciferase reporter assay was performed to validate the binding relationships of TUG1/miR‑204‑5p and miR‑204‑5p/Janus kinase 2 (JAK2). Moreover, western blotting was conducted to measure the protein expression levels of VEGFA, phosphorylated (p)‑JAK2, JAK2, p‑STAT3 and STAT3. It was identified that TUG1 was upregulated, while miR‑204‑5p was downregulated in hepatoblastoma tissues and cells. TUG1 knockdown inhibited angiogenesis induced by hepatoblastoma cells. Furthermore, miR‑204‑5p was identified as a target of TUG1. The results demonstrated that TUG1 attenuated the inhibitory effect of miR‑204‑5p on the JAK2/STAT3 pathway and promoted angiogenesis in hepatoblastoma cells. In summary, TUG1 was upregulated in hepatoblastoma and suppressed miR‑204‑5p, thereby activating the downstream signalling pathway of JAK2/STAT3 to facilitate angiogenesis. The present findings will provide novel targets for the treatment of hepatoblastoma.

Mitogen-activated protein kinases (MPKs) play essential roles in guard cell signaling, but whether MPK cascades participate in guard cell ethylene signaling and interact with hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), and ethylene-signaling components remain unclear. Here, we report that ethylene activated MPK3 and MPK6 in the leaves of wild-type Arabidopsis thaliana as well as ethylene insensitive2 (ein2), ein3, nitrate reductase1 (nia1), and nia2 mutants, but this effect was impaired in ethylene response1 (etr1), nicotinamide adenine dinucleotide phosphate oxidase AtrbohF, mpk kinase1 (mkk1), and mkk3 mutants. By contrast, the constitutive triple response1 (ctr1) mutant had constitutively active MPK3 and MPK6. Yeast two-hybrid, bimolecular fluorescence complementation, and pull-down assays indicated that MPK3 and MPK6 physically interacted with MKK1, MKK3, and the C-terminal region of EIN2 (EIN2 CEND). mkk1, mkk3, mpk3, and mpk6 mutants had typical levels of ethylene-induced H 2 O 2 generation but impaired ethylene-induced EIN2 CEND cleavage and nuclear translocation, EIN3 protein accumulation, NO production in guard cells, and stomatal closure. These results show that the MKK1/3-MPK3/6 cascade mediates ethylene-induced stomatal closure by functioning downstream of ETR1, CTR1, and H 2 O 2 to interact with EIN2, thereby promoting EIN3 accumulation and EIN3-dependent NO production in guard cells., (© 2021 Institute of Botany, Chinese Academy of Sciences.)

Diabetic cardiomyopathy (DCM) causes heart failure and increases the mortality in diabetic patients. Myocardial apoptosis and fibrosis are the main features of DCM and aging. The aim is to study the underlying mechanism of D-pinitol (DP) on myocardial apoptosis and fibrosis in an elderly diabetic mouse model. The diabetic model was established by SAMP-8 mice that were injected with streptozotocin daily for five consecutive days. The mice were administrated of DP (150 mg kg -1  day -1 ) by gavage for 10 weeks. The common metabolic disorder indices, cardiac dysfunction, oxidative stress, myocardial apoptosis and fibrosis, and PI3K/Akt/mTOR pathway were investigated. Our findings suggested that DP has a protective effect on DCM, which may be related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP may be a novel clinical application in fighting against DCM. PRACTICAL APPLICATIONS: D-pinitol (DP) was found in large quantities in soybean and legume foods. DP has a variety of functions, including hypoglycemic, anti-oxidation, anti-inflammatory, cardioprotective, and anti-tumor activity. We used the streptozotocin-induced SAMP8 mice as the diabetic model and treated with DP. We found that DP can improve cardiac dysfunction and inhibits the oxidative stress, myocardial apoptosis and fibrosis. DP has a significant effect on diabetic cardiomyopathy (DCM). The molecular mechanisms are related to regulating oxidative stress, and PI3K/Akt/mTOR pathway involving cardiac fibrosis and apoptosis. DP can prevent and/or delay the onset of DCM., (© 2021 Wiley Periodicals LLC.)

Low-dimensional hybrid organic-inorganic perovskites (HOIPs) possess more localized electronic states and narrower conduction and valence bands to promote self-trapping of excitons and stronger exciton emission; therefore, they are widely used as building blocks for various applications in the fields of optoelectronics, photovoltaics, light-emitting diodes, luminescence, fluorescence, and so forth. Despite the past decades of intensive study, the discovered low-dimensional chiral HOIPs are rare as of the 1D chiral HOIP single crystals reported in 2003, as well as the low-dimensional chiral HOIP ferroelectrics are particularly scarce since the first chiral two-dimensional (2D) and/or one-dimensional (1D) HOIP ferroelectrics reported. Herein, two new low-dimensional HOIPs with the same conformational formula [R-MPA] 2 CdCl 4 (R-MPA + = ( R )-(-)-1-methyl-3-phenylpropylamine) were successfully synthetized by means of regulating the stoichiometric proportion of R-MPA and CdCl 2 in two ways of 1:1 ( 1 ) and 2:1 ( 2 ). By combining single-crystal X-ray diffraction, circular dichroism (CD) spectroscopy, differential scanning calorimetry, temperature-dependent dielectric constant, temperature-dependent second-harmonic generation (SHG) effect, polarization-dependent SHG response, and P - E hysteresis loop, we reveal that 1 is a 1D nonchiral molecular ferroelectric and 2 is the first zero-dimensional (0D) chiral ferroelectric with distinct CD signals; meanwhile, 2 exhibits increased properties of high- T c , large dielectric constant, SHG isotropy, and ferroelectricity than that of 1 . These results not only shed light on the high tunability of the low-dimensional HOIP ferroelectrics but also open up an avenue to explore multifunctional chiral ferroelectrics.

The aim of this paper was to discuss the effect of swertiamarin, gentiopicrin and sweroside on rheumatoid arthritis fibroblast-like synoviocytes(RA-FLSs) and B-cell lymphoma-2(Bcl-2) and their mechanisms. ZINC database and RCSB PDB database were retrieved for 3 D chemical structures of swertiamarin, gentiopicrin and sweroside and 3 D target protein structures. AutoDock Mgltools 1.5.6, AutoDockVina 1.1.2 and pyMOL 2.2.0 were applied for molecular docking to analyze the relationship between Bcl-2(1 GJH) target protein and important ingredients. The cell apoptosis of RA-FLSs was tested by Annexin V-FITC. The Bcl-2 protein expression of RA-FLSs treated with different ingredients was tested by Western blot. The Bcl-2 mRNA expression of RA-FLSs treated with different ingredients was tested by RT-PCR. Swertiamarin, gentiopicrin and sweroside were docked well with Bcl-2(1 GJH). The binding energy of swertiamarin was-6.9 kcal·mol~(-1), the binding energy of gentiopicrin was-6.7 kcal·mol~(-1) and the binding energy of sweroside was-6.4 kcal·mol~(-1). Compared with the blank group, the Bcl-2 protein expression of each group were reduced, while that of the gentiopicrin group was the highest(P&lt;0.01). Compared with the blank group, the Bcl-2 mRNA expression of each groups were reduced. Gentiopicrin can reduce the Bcl-2 protein expression and the Bcl-2 mRNA expression, so as to promote the RA-FLSs apoptosis.

Few studies have described chimeric antigen receptor-modified T cell (CAR-T) therapy for central nervous system (CNS) B-cell acute lymphocytic leukemia (B-ALL) patients due to life-threatening CAR-T-related encephalopathy (CRES) safety issues. In this study, CAR-Ts targeting CD19 with short hairpin RNA (shRNA)-IL-6 gene silencing technology (ssCART-19s) were prepared. We conducted a phase 1 clinical trial (ClinicalTrials.gov number, NCT03064269). Three patients with relapsed CNS B-ALL were enrolled, conditioned with the fludarabine and cyclophosphamide for lymphocyte depletion and infused with ssCART-19s for three consecutive days. Clinical symptoms and laboratory examinations were monitored. After ssCART-19 treatment, three patients' symptoms resolved almost entirely. Brain leukemic infiltration reduced significantly based on magnetic resonance imaging (MRI), and there were no leukemic blasts in cerebrospinal fluid (CSF), which was confirmed by cytological and molecular examinations. Additionally, increases in the levels of cytokines and immune cells were observed in the CSF of all patients. Only grade 1 cytokine release syndrome (CRS) manifesting as fever was noted in patients. In conclusion, CAR-Ts with shRNA-IL-6 gene knockdown migrated into the CNS, eradicated leukemic cells and elevated cytokines in CSF with mild, acceptable side effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Hepatic damage has been recognized as one of the major complications in diabetes mellitus. Our previous studies have verified that grape seed procyanidin B2 (GSPB2) played a protective effect on hepatic damage of diabetes. We used isobaric tag for relative and absolute quantitation proteomics here to identify the alterant mitochondrial protein profile in diabetic liver and to seek the protective targets of GSPB2. Proteomics found that 171 proteins were upregulated or downregulated in the liver mitochondria of diabetic group compared to the control group. Of these proteins, 61 were normalized after GSPB2 treatment. These back-regulated proteins are involved in the process of fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, oxidative stress, and apoptosis. Some differentially expressed proteins were confirmed by western blotting. Our study might help to better understand the mechanism of mitochondrial dysfunction in diabetic liver damage, and provide novel targets for estimating the protective effects of GSPB2. PRACTICAL APPLICATIONS: Grape seed procyanidin B2 (GSPB2), a polyphenolic component found in red wine and grapes, has beneficial effects such as antioxidative stress, antiapoptosis, and cardiovascular protection. We used proteomics here to identify the differentially expressed mitochondrial proteins in diabetic liver after GSPB2 treatment and to seek the protective targets of GSPB2. We found that the differentially expressed proteins were involved in carbon metabolism, oxidative phosphorylation, fatty acid metabolism, citrate cycle, oxidative stress, and apoptosis. These proteins may play a key role in diabetic hepatic damage as functional proteins. Targeting these proteins including apply of GSPB2 could potentially lead to an effective treatment in the diabetic hepatic disease., (© 2020 Wiley Periodicals LLC.)

Objective: To investigate the short-term and long-term curative efficacy of low-intensity traditional chemotherapy regimen for elderly patients with acute myeloid leukemia (AML, non-M 3 ) and related adverse reactions, in order to explore whether low-intensity traditional chemotherapy regimen still has application value in the treatment of elderly AML patients today., Methods: The clinical characteristics, treatment response and prognosis of 67 elderly patients with AML (non-M 3 ) admitted to our hospital from June 2008 to December 2018 were retrospectively analyzed. All patients received low-intensity conventional chemotherapy (i.e. lower standard dose, and without new drugs listed in China since the 21st century), including DA, HA, CAG, etc. The CR rate, median survival time and 5-year cumulative survival rate of patients were evaluated, and the related indexes were compared with the data reported in domestic and foreign literatures at the same time., Results: The CR rate was 55.2% (37/67), the median survival time was 13.7 months, and the 5-year cumulative survival rate was (24.4±6.3)% in patients received low-intensity tradional chemotherapeutic regimens. The CR rates of high-risk group and non-high-risk group were 38.7% (12/31) and 69.4% (25/36), respectively; the median survival time of high-risk group and non-high-risk group was 8.9 months and 25.2 months respectively; the 5-year cumulative survival rate of high-risk group was (10.2±6.6)% and that of non-high-risk group was (36.0± 9.4)%. Compared with the data reported in the literature at the same time, the data obtained from the low-intensity traditional chemotherapy regimen for the elderly AML did not have an obvious disadvantage, morever had relatively short bone marrow suppression time, low induction early mortality rate and low incidence of severe infection., Conclusion: At present, the low-intensity traditional chemotherapy regimen still has good curative effect and survival advantages for elderly AML patients, especially for non-high-risk patients. The adverse reactions are controllable, and the physical and economic conditions of the vast majority of patients can bear the treatment regimen.

Inflammatory cytokines were involved in pathological conditions of osteoporosis (OP). However, the specific OP-associated inflammatory cytokines are still awaiting to be detected by using a systemic method. Herein, we adopted an extreme sampling scheme and examined inflammatory cytokines between subjects with low and high bone mineral density (BMD) through protein microarray. First, 8 candidate cytokines including B lymphocyte chemoattractant (BLC), osteopontin (OPN) and insulin-like growth factor-binding protein 4 (IGFBP4) were identified in the discovery extreme sampling subgroup. Then, the different expressions for BLC, OPN and IGFBP4 were validated and replicated in two independent extreme sampling subgroups. Further functional experiments showed that the cytokine BLC was involved in bone metabolism by inhibiting bone formation and promoting bone resorption. Together, this study further revealed that inflammatory cytokines were closely related with OP, and that they highlighted critical roles of BLC in the pathogenesis of OP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Stanford type A aortic dissection (STAAD) is a critical cardiovascular disease, and surgical procedure is the first-choice treatment. The classical surgical procedure still leads to a high mortality rate and neurological complications. In this study, we introduce a new modified Sun's procedure and investigate the association between the branch-first technique and the postoperative outcomes of patients with STAAD., Methods: A total of 108 consecutive patients with STAAD who underwent arch replacement and stent elephant trunk procedure at Beijing Anzhen Hospital between July, 2017 and November, 2018 were included in the analysis. The patients were divided into two groups: the branch-first group and the classic group. The branch-first group and the classic group comprised 24 patients (22.2%) and 84 patients (77.8%), respectively., Results: Patients in the branch-first group had a significantly shorter cardiopulmonary bypass (CPB) duration (172.4±29.9 vs. 194.9±47.4 min; P=0.035), Intensive care unit (ICU) stay [17.0 (14.6-38.2) vs. 42.1 (19.7-87.2) hours; P<0.001], and mechanical ventilation time [15.5 (11.9-40.0) vs. 19.0 (17.0-45.6) hours; P=0.018] than patients in the classic group. The branch-first was associated with a reduction in postoperative neurological complications in all models., Conclusions: The benefits of the branch-first technique, including lower CPB duration, better bilateral cerebral perfusion, and higher nasopharyngeal temperature during hypothermic arrest, contributed to a shortened recovery time for patients after surgery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3791). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe -/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe -/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.

Background: The preferred treatment for uncomplicated type B dissection (thoracic endovascular aortic repair [TEVAR] or medical) is still under debate. Since 2001, our center has performed TEVAR for uncomplicated type B dissection. Based on our data, 5- and 10-year survival rates among patients with uncomplicated type B dissection after TEVAR were 96.5% and 83.0%, respectively. We, therefore, believe that TEVAR is preferable for uncomplicated type B dissections. This study analyzed the impact of a pre-operative smoking history on long-term survival after TEVAR in patients with uncomplicated type B dissections., Methods: From May 2001 to December 2013, data from 751 patients with type B dissections were collected and analyzed. Patients were divided into two groups (337 smoking patients and 414 non-smoking patients). The Kaplan-Meier method and log-rank test were used to compare survival curves of the two groups. Multivariable analyses using the Cox proportional hazards model were used to estimate the effects of smoking on survival rates., Results: The 5- and 10-year survival rates of non-smokers were 97.6% (95% confidence interval [CI], 96.0%-99.2%) and 87.0% (95% CI, 81.6%-92.7%), respectively, and 94.9% (95% CI, 92.2%-97.7%) and 73.8% (95% CI, 62.3%-87.5%) for smokers, respectively (Log-rank test, P = 0.006). Multivariable analyses showed that smoking increased the risk of death during follow-up, 2.1-fold when compared to non-smokers (P = 0.039)., Conclusion: A pre-operative smoking history increases long-term mortality rates after TEVAR in patients with uncomplicated type B dissections.

The current study aimed to evaluate the expression and role of miR-212 in the progression of pituitary adenoma (PA), thereby providing a theoretical basis and potential therapy methods for PA patients. Our data showed that miR-212 levels were significantly reduced in PA tissues than normal pituitary tissues. However, no significant difference was identified in the serum of PA patients and healthy control. In addition, the expression of miR-212 in invasive PA was significantly lower than that in noninvasive and normal pituitary tissues. Moreover, the level of miR-212 was decreased with the increase of tumor invasion. Meanwhile, the expression of miR-212 in giant adenomas was significantly lower than that in macroadenomas and microadenomas. Furthermore, inhibition of miR-212 significantly enhanced the proliferation and invasive capacity of GH3 cells. Dual luciferase reporter assay and western blot analysis confirmed that c-Met was a target gene of miR-212. More importantly, upregulation of c-Met significantly prompted PA cell proliferation mainly as a result of the enhanced level of phosphorylation of AKT. This effect could be abolished when c-Met was silenced in GH3 cells. In summary, reduced miR-212 expression in PA contributed to abnormal cancer cell proliferation and invasion mainly by targeting c-Met., (© 2019 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Objective: In the present study, we investigated the associations between D-dimer levels at admission and early adverse events in patients with acute type A aortic dissection undergoing arch replacement and the frozen elephant trunk (FET)., Methods: We retrospectively analyzed data of patients with acute type A aortic dissection undergoing aortic arch surgery and FET from July 2017 to December 2018 at Beijing Anzhen Hospital. D-dimer levels were evaluated within 24 h of admission. Multivariate Cox regression analysis was used to determine independent predictors of early postoperative adverse events., Results: A total of 347 patients were included in the study. The average age of the patients was 48.07 ± 10.56 years, with male predominance (79.25%). The incidence of 90-day postoperative adverse events was 18.7%, consisting of 14.7% mortality and 4.0% permanent neurological dysfunction (PND). The median D-dimer level was 1.95 ug/ml (interquartile range, 0.77-3.16 ug/ml). Multivariable Cox regression analysis revealed that D-dimer level was independently associated with 90-day postoperative adverse events after adjustment for confounding factors (hazard ratio = 1.19 per 10 ug/ml increase in D-dimer, 95% confidence interval: 1.01-1.41; P = 0.039). Kaplan-Meier analysis revealed that the highest tertile (median 6.27 ug/ml) had more 90-day postoperative adverse events compared with the median and lowest tertiles ( P = 0.0014). Sub-analysis found that the association remained unchanged., Conclusion: Increased D-dimer levels at admission were associated with 90-day postoperative adverse events in patients with acute type A aortic dissection undergoing arch replacement and FET. These results may help clinicians optimize the risk evaluation and perioperative clinical management to reduce early adverse events., Key Question: Explore the relationship between D-dimer and early outcomes in patients with aortic dissection with arch replacement., Key Findings: Increased D-dimer at admission was associated with adverse events in patients with aortic dissection with arch surgery., Take-Home Message: The high-risk patients deserve close medical monitoring., (Copyright © 2020 Tong, Zheng, Zhang, Zhu, Gao, Zhang, Jin and Xu.)

The progression of diabetic cardiomyopathy is related to cardiomyocyte dysfunction and apoptosis. Our previous studies showed that asporin (ASPN) was significantly increased in the myocardium of db/db mice through proteomics, and grape seed procyanidin B2 (GSPB2) significantly inhibited the expression of ASPN in the heart of db/db mice. We report here that ASPN played a critical role in glycated low-density lipoproteins (gly-LDL) induced-cardiomyocyte apoptosis. We found that gly-LDL upregulated ASPN expression. ASPN increased H9C2 cardiomyocyte apoptosis with down-regulation of Bcl-2, upregulation of transforming growth factor-β1, Bax, collagen III, fibronectin, and phosphorylation of smad2 and smad3. However, GSPB2 treatment reversed ASPN-induced impairments in H9C2 cardiomyocytes. These results provide evidence for the cardioprotective action of GSPB2 against ASPN injury, and thus suggest a new target for fighting against diabetic cardiomyopathy., (© 2019 International Federation for Cell Biology.)

Background: In the design and development of small-caliber artificial blood vessels, endothelialization is a key issue, but it is not well understood at present. Some studies have used vascular endothelial growth factor (VEGF) sustained-release methods to promote endothelial cell proliferation. However, this method is not ideal. This study has used drugs to induce endothelial cells to produce VEGF. This method in turn functions to promote cell proliferation and promote the endothelialization of artificial blood vessels. This study aimed to investigate the effect of the antiplatelet drug tirofiban on endothelial cell proliferation in vitro., Methods: In this study, human umbilical vein endothelial cells (HUVECs) were used to determine the effect of tirofiban-stimulated cell proliferation. Analysis of cell proliferation, assayed by the Cell Counting Kit-8 assay, showed that the number of cells was increasingly higher than in the absence of tirofiban. It was also observed that heparin enhanced the tirofiban effect. The cell VEGF expression at different time points after tirofiban addition was detected by western blot analysis., Results: The absorbance values of the experimental (1 μg/mL tirofiban) and the control groups (0 tirofiban) were 1.74 (SD, 0.03) and 1.51 (SD, 0.07) (P < .001), respectively, after 4 days of culture under the same conditions. The amount of VEGF produced by HUVECs gradually increased after treatment with tirofiban, reached a peak at 2 hours, and was 1.3-fold greater than the control group (P = .034). Compared with the tirofiban-only group, the absorbance value of the tirofiban and 10 μg/mL of heparin group was significantly increased (P < .001)., Conclusions: Tirofiban promoted the proliferation of HUVECs by promoting the synthesis of VEGF in HUVECs. Heparin enhanced tirofiban activity in promoting HUVEC proliferation., (Copyright © 2019. Published by Elsevier Inc.)

Objective: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB., Methods: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively., Results: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression., Conclusion: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy., (© 2020 S. Karger AG, Basel.)

Objectives: To study the perioperative outcomes and long-term survival rates in patients undergoing thoracic endovascular aortic repair (TEVAR) for uncomplicated type B dissection., Methods: A total of 751 patients with uncomplicated type B dissection who underwent TEVAR at our centre between May 2001 and December 2013 were retrospectively reviewed. The mean age of all patients (619 males and 132 females) was 52.8 ± 10.9 years. The follow-up period ranged from 1 to 170 months (median 70 months)., Results: Five patients died during the perioperative period (mortality rate 0.7%). Four patients (0.5%) developed retrograde type A dissection. Two patients (0.3%) developed paraplegia and 1 patient developed incomplete paralysis (0.1%). There were no postoperative cerebral infarctions. The 5- and 10-year survival rates were 96.5% [95% confidence interval (CI) 95.0-98.0%] and 83.0% (95% CI 77.9-88.4%), respectively. The 5- and 10-year reintervention rates were 4.6% (95% CI 3.0-6.2%) and 7.9% (95% CI 5.3-10.5%), respectively., Conclusions: Although the application of TEVAR for patients with uncomplicated dissection is still under debate, many patients who have undergone TEVAR have benefitted substantially from the treatment. Our data showed that TEVAR had low mortality and complication rates both in the short- and long-term follow-up periods. TEVAR may be considered as a first choice for patients with uncomplicated type B dissection., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: The aortic arch replacement and cardiopulmonary bypass (CPB) are both associated with the early mortality after cardiothoracic surgery. This study aimed to investigate the relationship between CPB time and 90-day post-operative mortality in patients undergoing aortic arch surgery using the frozen elephant trunk (FET) technique with selective ante-grade cerebral perfusion (SACP)., Methods: We retrospectively reviewed data of 377 adult patients undergoing aortic arch surgery via FET with SACP from July 1, 2017 to December 31, 2018 at Beijing Anzhen Hospital. The baseline characteristics, intra-operative data, and post-operative data were collected. Univariate and multivariate Cox regression analyses were used to determine independent predictors of 90-day post-operative mortality., Results: The 90-day post-operative mortality was 13.53%. The 78.51% of patients were men. There were 318 (84.35%) type A aortic dissections and 28 (7.43%) aortic aneurysms. Among those, 264 (70.03%) were emergency operations. Median CPB time was 202.0 (176.0, 227.0) min. Multivariate Cox regression analysis revealed that CPB time was independently associated with 90-day post-operative mortality after adjusting confounding factors (hazard ratio: 1.21/10 min increase in CPB time, 95% confidence interval: 1.15-1.27, P < 0.001). Kaplan-Meier analysis based on CPB time tertiles revealed that the top tertile (median 236.0 min) was associated with reduced survival rate compared with middle and bottom tertiles (P < 0.001). Each sub-group analysis based on the complexity of the underlying disease process showed similar associations between CPB time and 90-day post-operative mortality., Conclusions: CPB time remains a significant factor in determining 90-day post-operative mortality in patients undergoing aortic arch surgery using FET with SACP. Surgeons should be aware of the relationship between CPB time and 90-day post-operative mortality during operative procedures and avoid extended CPB time as far as possible.

Objective: The aim of this study was to analyze the mediating effect of body dissatisfaction in correlation between obesity and dietary behavior changes for weight loss (DBCWL)., Methods: A total of 680 primary and middle school students were included in this study. Their body height, weight, and waistline were effectively measured, and they were also evaluated to assess their body dissatisfaction, perception of dietary behaviors, and DBCWL. The correlation among these factors was analyzed using mediating effect models., Results: The prevalence of overweight/obesity and abdominal obesity was significantly higher in males than in females (P < 0.05). Overweight/obesity, abdominal obesity, and body dissatisfaction significantly increased the risk for DBCWL (OR = 2.57, 2.77, and 1.95, respectively). Overweight/obesity and abdominal obesity significantly increased the risk for body dissatisfaction (OR = 6.00 and 4.70, respectively). Significant mediating effects of body dissatisfaction were observed in correlation between overweight/obesity and DBCWL and between abdominal obesity and DBCWL (OR = 2.20 and 1.92, respectively; P < 0.05), and the proportions of mediating effects among the total effects were 48.89% and 46.60%, respectively., Conclusion: Body dissatisfaction might play an important mediating effect in association between DBCWL and obesity, which indicates that guiding children to correctly recognize their body might be more conducive than promoting obese children toward weight loss through dietary behavior changes., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Background: Reserpine is currently used by millions of Chinese hypertensive patients, in spite of the continued concern of its depressogenic effect, even when used in low dose. This study aimed to investigate the association between low-dose reserpine use and depression in older Chinese hypertensive patient., Methods: In this cross-sectional, case-control study, we recruited patient aged 60 years or over who had regularly taken one or two tables of "compound reserpine and triamterene tablets (CRTTs)" for more than one year (reserpine user) from 26 community health centers located in 10 provinces in China. For each patient who took CRTTs, we selected an age (within five years) and sex matched hypertensive patient who had never taken any drugs containing reserpine (non-reserpine user) as control. Depressive symptoms were evaluated using a Chinese depression scale adapted from the Zung Self-Rating Depression Scale. Demographic, clinical data and laboratory examination results within six months were collected., Results: From August 2018 to December 2018, 787 reserpine user and 787 non-reserpine user were recruited. The mean age of all study subjects was 70.3 years, with about equal numbers of males and females. The mean depression score was 40.4 in reserpine users and 40.6 in non-reserpine users ( P = 0.7). The majority of study subject had a depression score < 53 (87.6% in reserpine users and 88.2% in non-reserpine users, respectively). There were no significant differences in the prevalence of mild, moderate or severe depression in reserpine users and non-reserpine users., Conclusions: There is no association between low-dose reserpine use and depression in older hypertensive patient. The role of reserpine in the treatment and control of hypertension should be reconsidered; and further studies, especially randomized, controlled clinical trials to compare efficacy and safety of reserpine and other widely recommended anti-hypertensive agents are needed.

Background: Liver function is routinely assessed in clinical practice as liver function tests provide sensitive indicators of hepatocellular injury. However, the prognostic value of enzymes that indicate hepatic injury has never been systematically investigated in lymphoma, including diffuse large B-cell lymphoma (DLBCL)., Methods: This study examined the prognostic value of baseline aspartic transaminase (AST) in DLBCL patients. The association between AST and clinical features was analyzed in 179 DLBCL patients treated from 2006 to 2016. All enrolled patients were treated with R-CHOP or R-CHOP-like chemotherapy. Log-rank test, univariable analysis, and subgroup analysis were performed to evaluate the impact of AST on survival., Results: AST 33.3 U/L was considered to be the optimal threshold value for predicting prognosis. A higher AST level was associated with advanced stage (P = 0.001), poorer performance status (P = 0.014), elevated lactate dehydrogenase level (P <  0.0001), presence of B symptoms (P = 0.001), high-risk International Prognostic Index (IPI, IPI 3-5) (P = 0.002), non-germinal center B-cell subtypes (P = 0.038), hepatitis B virus surface antigen positivity (P = 0.045) and more extra nodal involvement (ENI, ENI ≥ 2) (P = 0.027). Patients with a higher AST level had a shorter overall survival (OS) (2-year OS rate, 53.6% vs. 83.6%, P <  0.001). Subgroup analysis indicated that higher AST levels have poorer prognostic values in patients without B symptoms and LDH positive groups., Conclusion: A pretreatment AST level is associated with OS in DLBCL patients treated with R-CHOP or similar chemotherapy regimens. A high pretreatment AST level might be a reliable prognostic factor for predicting a dismal outcome in DLBCL patients. Serum AST levels may be investigated for use as an easily determinable, inexpensive biomarker for risk assessment in patients with DLBCL.