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 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.

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.

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

Objective: To preliminary, explore the effect of small intestinal epithelial dendritic cells on the occurrence and development of nonalcoholic fatty liver disease in mice. Methods: Thirty-two (half male and half female) 4-week-old C57BL/6 mice were randomly divided into two groups. The mice were fed with normal diet (SD group) and high-fat diet (HFD group). Eight mice (half male and half female) were randomly killed from each group over the 14 and 20-weeks feeding period to observe their body weight, liver and small-intestine wet weight. Alanine aminotransferase, aspartate aminotransferase, blood glucose, high-density lipoprotein, low-density lipoprotein, total cholesterol and triglyceride were determined by eyeball blood samples. Pathological diagnosis and alcoholic fatty liver disease activity score were collected. The number of mice small intestinal dendritic cells was observed under a microscope. Statistical analysis was performed to compare two groups of independent samples with homogeneity test of variance, t test, and covariance analysis. Results: The body weight, liver wet weight, serum alanine aminotransferase and aspartate aminotransferase of mice in HFD group were significantly higher than those of control group at 20 weeks (P < 0.05), and the serum high density lipoprotein of mice in HFD group was significantly higher than that of SD group at 14 weeks (P < 0.05). At 14th weeks, the liver tissue of mice in HFD group had early pathological manifestations of hepatitis (fatty degeneration, punctate necrosis and balloon-like degeneration). Of which 87.5% (7/8) of them were diagnosed as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while only a few mice in SD group had early pathological manifestations of hepatitis. At 20th weeks, all mice in HFD group were diagnosed with non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while none of the mice in SD group was diagnosed with non-alcoholic fatty liver disease. At both time points, the percentage of small intestinal dendritic cells in HFD group was significantly higher than that in SD group (14 weeks: 4.181 ± 4.314 vs. 15.099 ± 10.349; 20 weeks: 9.615 ± 8.267 vs. 32.839 ± 24.475, both P < 0.05). Statistical analysis combined with the alcoholic fatty liver disease activity score showed that there was no linear correlation between the two groups (regression coefficient was 20.196%). Conclusion The number and different staging of small intestinal dendritic cells in mice is associated with the occurrence and development of NAFLD.

Objective To investigate the characteristics of the microbiota of colonic lavage fluid from patients with diarrhoea-predominant irritable bowel syndrome (D-IBS).Methods From August 2014 to March 2015,at the Department of Gastroenterology Shanxi Provincial People's Hospital,39 patients with D-IBS were enrolled and during the same period 39 patients with self-reported symptoms such as occasional abdominal discomfort or abdominal pain but were excluded from the diagnosis of irritable bowel syndrome (IBS) were selected as control group.The colonic mucosal tissues and colonic lavage fluid of two groups of patients were collected.DNA was extracted from tissues and colonic fluid.Ten dominant bacteria,including Bacteriodes prevotella,Bacteroidetes,Clostridium,Bifidobacterium,Dialister pneumosintes,Enteropathogenic Escherichia coli,Faecalibacterium prausnitzii,Firmicutes,Lactobacillus and Salmonella,were analyzed by real-time fluorescence quantitative polymerase chain reacticn (RT-PCR).T test and Spearman correlation analysis were performed for statistical analysis.Results The numbers of Bacteriodes prevotella in colonic lavage fluid and the descending colon mucosal tissues of patients in D-IBS group were 3.096 ± 1.462 and 4.278 ± 0.290,respectively,which were lower than those of control group (4.842 ± 1.032 and 5.341 ± 0.433,respectively),and the differences were statistically significant (t =6.093 and 12.657,both P ＜ 0.01).Correspondingly,the numbers of Bacteroidetes were 3.259 ± 0.607 and 3.698 ± 0.554,respectively,which were lower than those of control group (4.085 ± 0.504 and 4.339 ± 0.263,respectively),and the differences were statistically significant (t =6.538 and 6.528,both P ＜ 0.01).The numbers of Clostridium were 5.254 ± 0.522 and 4.471 ± 0.690,which were lower than those of control group (5.949 ± 0.505 and 4.950 ± 0.604,respectively),and the differences were statistically significant (t =5.976,P ＜ 0.0l;t =3.262,P =0.002).The number of Faecalibacterium prausnitzii from colonic lavage fluid of patients in D-IBS group was 2.238 ± 1.845,which was lower than that of control group (3.222 ± 1.450),and the difference was statistically significant (t =2.619,P =0.011).The Firmicutes (r =0.678,P =0.012),Lactobacillus (r =0.358,P =0.034),Bifidobacterium (r =0.418,P =0.042) and Faecalibacterium prausnitzii (r =0.568,P =0.022) from colonic mucosal tissues were all positively correlated with those from colonic lavage fluid.However,Salmonella (r =-0.638,P =0.012) and Enteropathogenic Escherichia coli (r =-0.343,P =0.025) were negatively correlated with those from mucosal tissues.Conclusions An imbalance of the microbiota in colonic lavage fluid is found in D-IBS patients.The numbers of Bacteriodes prevotella,Bacteroidetes,Clostridium and Faecalibacterium prausnitzii significantly decrease.