Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

Objective:To explore the key factors affecting health-related quality of life in children with brain tumors following initial diagnosis and to analyze its impact on survival and prognosis.Methods:Seventy-eight pediatric brain tumor patients who participated in a prospective cohort study between June 1st，2016 and June 30th，2021 were included for health-related quality of life assessment and long-term follow-up（median follow-up duration：52 months）.Results:The male-to-female ratio among the 78 children was 1.1：1，with a median age of 7.0（4.0，10.0）years. The scores of the Pediatric Quality of Life Inventory? 4.0 Generic Core Scales（PedsQL? 4.0）were（67.40±18.26）for parent proxy reports and（67.87±20.40）for child self-reports. Cronbach's α coefficients ranged from 0.790 to 0.927，with the intraclass correlation coefficient（ICC）was 0.673. According to the PedsQL? 4.0，impaired quality of life was observed in 50.0% of children by parent proxy report and 52.8% by child self-report，primarily affecting physical and role functioning. In addition，70% of caregivers reported impaired quality of life，with worry being the most prominent issue. Key factors affecting children's quality of life included radiotherapy，tumor stage，annual family income，and parents' marital status，while caregivers' quality of life was influenced by radiotherapy and the child's IgA levels（all P<0.05）. Children with decreased total scores，impaired physical functioning，or impaired emotional functioning on the PedsQL? 4.0 parent proxy report exhibited an increased risk of mortality（all P<0.05）. In multivariate Cox regression analysis，independent prognostic factors included a decrease in the total score on the PedsQL? 4.0 parent proxy report（ HR=6.702，95% CI：1.442-31.151， P<0.05），presence of hydrocephalus（ HR=33.602，95% CI：4.354-259.333， P<0.05），tumor recurrence（ HR=16.846，95% CI：3.158-89.852， P<0.05），and absence of hydrocephalus shunt surgery（ HR=13.428，95% CI：1.761-102.394， P<0.05）. Conclusion:The quality of life of newly diagnosed children with brain tumors is lower than that of healthy children，and quality of life is an important prognostic factor. Quality of life assessment should be an integral component of a comprehensive management program for children with brain tumors.

Objective:To explore the clinical manifestations and genetic basis for a rare case of Generalized arterial calcification of infancy (GACI).Methods:A 44-day-old female infant who was treated at Baoding Hospital of Beijing Children′s Hospital Affiliated to Capital Medical University on August 26, 2022 was selected as the study subject. Clinical data of the child was collected, and Trio-whole exome sequencing (Trio-WES), whole genome copy number variation sequencing (CNV-seq) and minigene splicing assay were carried out to analyze the pathogenicity of the variants.Results:The child had presented with fever and high inflammatory indicators, for which treatment with various antibiotics was ineffective. Ultrasound had revealed extensive arterial calcification and arterial wall thickening. The child was suspected for GACI with arteritis related to the primary disease. Her fever was relieved by treatment with glucocorticoid and biological agents. Trio-WES revealed that she has harbored compound heterozygous variants of the ABCC6 gene, namely c. 4404-1G>A and c. 4041+ 5G>T, for which the latter was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variants were classified as likely pathogenic (PVS1+ PM2_Supporting) and variant of unknown significance (PM2_Supporting+ PM3+ PP3), respectively. The result of CNV-seq was negative. And the minigene splicing assay has further verified that both variants can result in alternative splicing. Conclusion:For pyrexia with unknown causes and refractory to conventional treatment, it is necessary to recommend early genetic testing to avoid missed diagnosis of GACI.

Objective:To explore the effect of nursing intervention based on information-knowledge-attitude-practice model (IKAP) in preventing radiodermatitis in tumor radiotherapy patients.Methods:This was a quasi-experimental study. A total of 72 patients who received radiotherapy in the Department of Oncology, the Second Hospital of Shanxi Medical University from August to October 2022 were selected and divided into the experimental group and the control group with 36 patients in each group by randomized digits table method. The control group received routine nursing, while the experimental group received nursing based on the IKAP. The self-management efficacy, radiodermatitis, self-perceived burden and quality of life of patients in the two groups were evaluated one day before and at the end of radiotherapy.Results:Thirty-five patients from each group completed the study. There were 11 males and 24 females in the control group, aged (58.09 ± 7.33) years old. There were 13 males and 22 females in the experimental group, aged (58.06 ± 7.28) years old.There was no statistically significant difference in self-management efficacy, self-perceived burden, and quality of life scores between the two groups of patients before intervention (all P>0.05). After intervention, the self-management efficacy,self-perceived burden, and quality of life scores of the experimental group were (106.89 ± 3.78), (18.69 ± 2.21), and (8.09 ± 1.27) points, respectively, the control group was (80.69 ± 5.76), (29.97 ± 2.48), and (15.91 ± 2.37) points, respectively. The differences between the two groups were statistically significant ( t=2.50, 1.12, 7.24, all P<0.01). The incidence of radiodermatitis above grade 2 in the experimental group was 31.4%(12/35), which was lower than 60.0%(21/35) in the control group, the difference was statistically significant ( χ2=4.64, P<0.01). Conclusions:Nursing intervention based on IKAP can improve the self-management efficacy, reduce the self-perceived burden and the incidence of radiodermatitis, and further improve the quality of life of tumor radiotherapy patients.

Objective:To search, screen and summarize the best evidence of screening and management of patients with post-stroke fatigue, and to provide basis for early identification of clinical staff.Methods:According to the "6S" pyramid model, the system searches for relevant evidence on post stroke fatigue screening and management from UpToDate, BMJ Best Practice, International Guidelines Collaboration Network, New Zealand Guidelines Collaboration Group, Ontario Registered Nurses Association website, Scottish Interhospital Guidelines Network, Joanna Briggs Institute Evidence Based Health Care Center database, and Yimaitong, National Stroke Foundation, Stroke Association, National Stroke Center, Cochrane Library, PubMed, Embase, CINAHL, CNKI, WanFang Datebase, VIP and CBM from January 2013 to March 2023 regarding screening and management of post stroke fatigue patients. Researchers screen literature, evaluate quality, and summarize evidence.Results:Fifteen articles were selected, including 1 clinical decision, 3 guidelines, 3 expert consensus, 2 evidence summary, 5 systematic review and 1 randomized controlled trial. A total of 22 best evidence items were summarized from seven aspects of screening assessment, risk factors, psychosocial intervention, activity and rest, health education, complementary therapy, and follow-up.Conclusions:The study summarized the best evidence for the screening and management of patients with post-stroke fatigue, so as to provide a more scientific and systematic approach to the management of post-stroke fatigue and provide a reference for improving the long-term quality of life of stroke patients.

Objective:To evaluate association of peripheral blood brain-derived neurotrophic factor (BDNF) with Alzheimer's disease (AD) .Methods:Databases including Pubmed, Cochrane library, Web of science, Embase, China National Knowledge Infrastructure, CBM disc, VIP-CSTJ and Wanfang Data were used to collect case-control studies related to the concentration of BDNF in peripheral blood of dementia patients with Alzheimer's type(DAT) and mild cognitive impairment(MCI). After extracting data and appraising the quality of the included studies, meta-analysis were conducted using Review Manager 5.3 and CMA 3.0.Results:A total of 51 articles were included in the analysis, with a total subjects of 7 182, including 2 673 subjects in DAT group, 1 506 subjects in MCI group, and 3 003 subjects in control group.The Meta-analysis showed that the levels of peripheral blood BDNF in patients with DAT were significantly lower than normal control group(SMD=-0.71, 95% CI : -0.99--0.43, P<0.001) ( n=5 111), and there were no statistical differences in peripheral blood BDNF levels between MCI group and control group and between DAT group and MCI group.The subgroup analysis showed that the level of serum BDNF in patients with DAT (SMD=-0.85, 95% CI: -1.15--0.55, P<0.001)( n=4 425) and MCI(SMD=-0.38, 95% CI: -0.62--0.14, P=0.002)( n=2 476) was significantly lower than that in normal control group, and the level of serum BDNF (SMD=-0.76, 95% CI: -1.37--0.16), P=0.01)( n=1 630) in patients with DAT was lower than that in MCI; However, there were no statistical difference among DAT, MCI and control groups in the level of plasma BDNF( P>0.05). Conclusion:The patients with DAT and mild cognitive impairment have lower level of serum BDNF, which suggesting that serum BDNF level may be a potential biomarker for early diagnosis of AD.

OBJECTIVE To analyze the influential factors for potentially inappropriate medication （PIM） in elderly cancer patients. METHODS The data of elderly cancer patients hospitalized in a hospital from January to December 2021 were collected. According to the Beers standard of the American Geriatrics Society in 2019 （hereinafter referred to as the “2019 version of Beers standard”） and Criteria for Potentially Inappropriate Drug Use in Chinese Elderly （2017 version） （hereinafter referred to as the “Chinese PIM standard”）， the PIM status of elderly cancer patients was retrospectively analyzed. Multivariate Logistic regression analysis was used to identify influential factors for PIM. RESULTS A total of 293 patients were included in the study. According to the 2019 version of Beers standard， 211 patients （72.01%） had PIM， of which 204 （69.62%） had PIM related to drugs， 6 （2.05%） had PIM related to diseases or symptoms， 46 （15.70%） had PIM that should be used with caution， 32 （10.92%） had PIM with drug-drug interaction that should be avoided， and 11 （3.75%） had PIM based on renal function； the top 5 drugs in the list of incidence were proton pump inhibitors， metoclopramide， the first-generation antihistamines as promethazine， analgesics as ibuprofen and megestrol. According to the Chinese PIM standard， there were 132 patients （45.05%） with PIM， of which 119 （40.61%） had PIM related to drugs， involving 25 drugs （included 7 high-risk drugs and 18 low-risk drugs）， and 24 （8.19%） with PIM in disease status； top 4 drugs in the list of incidence were promethazine， megestrol， ibuprofen and cimetidine. Multivariate Logistic regression analysis showed that compared with patients with hospital stay≤10 days， patients with hospital 20054） stay between 11 and 30 days had a higher risk of PIM [odds ratio （OR）＝8.836 8， 95% confidence interval （CI） （3.217 8， 31.940 9）， P＝0.000 1]； compared with the patients with the 65895198。E-mail：fjman@cmpt.ac.cn number of clinical disease diagnosed≤5， patients with the number of clinical disease diagnosed≥11 had a higher risk of PIM [OR＝10.930 1， 95%CI （3.000 9， 70.922 9）， P＝0.001 8]； compared with surgical treatment， patients receiving antineoplastic drugs had a higher risk of PIM [OR＝2.209 5， 95%CI （1.180 2， 4.176 9）， P＝0.013 6]. CONCLUSIONS Elderly cancer patients have multiple diseases， complicated medication， and a high incidence of PIM. The length of hospital stay （11-30 d）， the number of clinical disease diagnosed （≥11） and anti-tumor drugs are main influential factors for PIM in patients.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.