BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

【Objective】 To analyze the independent influencing factors of repeated extracorporeal shock wave lithotripsy (ESWL) in the treatment of upper urinary calculi (UUC), based on which a nomogram model was established to predict the efficacy. 【Methods】 Clinical and imaging data of 203 patients receiving repeated ESWL during Jan.2020 and Dec.2022 were collected, including 117 cases in the successful group and 86 cases in the unsuccessful group.The patients’ age and sex, stone volume (SV), surface area (SA), skin-to-site distance (SSD), maximum CT value, mean stone density (MSD), and stone heterogeneity index (SHI) were compared between the two groups.The independent predictors were analyzed with logistic regression and the meaningful variables (P<0.05) were used to establish a nomogram.The efficacy of the model was evaluated using receiver operating characteristic (ROC) curve and decreasing curve analysis (DCA).Internal validation was also performed. 【Results】 Stepwise regression showed that SV, SSD, MSD and SHI were independent influencing factors (P<0.05).The area under the ROC curve (AUC), optimal threshold, sensitivity and specificity were 0.793 (95%CI: 0.674-0.911), 0.619, 77.1% and 74.0%, respectively.The DCA curve was above two extreme curves.Hosmer-Lemeshow test and calibration curve showed that the nomogram had a good fitting degree (χ²=5.526, P=0.489), and the correction C-index was 0.746. 【Conclusion】 SV, SSD, MSD and SHI are independent predictors of the efficacy of repeated ESWL in the treatment of UUC.The nomogram established based on the above indicators has good predictive efficiency and clinical applicability.

OBJECTIVE：To provide refere nce f or the quality control and evaluation of rice-wine processed Coptidis Rhizoma decoction piece. METHODS ：Taking 17 batches of rice-wine processed Coptidis Rhizoma decoction piece from different manufacturers as samples ，HPLC method was adopted to determine the contents of 4 kinds of alkaloids as epiberberine ，coptisine， palmatine and berberine. The compound weights of epiberberine ，berberine，palmatine and berberine were calculated by the subjective and objective combination weighting method （AHP combined with variation coefficient ）. Then the quality evaluation method was used to evaluate the quality of decoction pieces combined with the appearance of decoction pieces and the contents of 4 alkaloids. The percent mass constant was calculated and the grade of rice-wine processed Coptidis Rhizoma decoction piece was classified. RESULTS ：According to the results of content determination of 4 kinds of alkaloids ，among 17 batches of samples ，a total of 13 batches of samples met the requirements of 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. Mass constants of 13 batches of qualified samples were 10.03-26.96，and the percent mass constants were 37.20％-100％. If the percent mass constant ≥ 80％ of the sample was listed as the first-class product ，the sample with the percent mass constant between 50％-＜80％ was classified as the second-class product ，and the rest was listed as the third-class product ，therefore the quality constant of first-class product was ≥21.57，that of second-class product was 13.48-＜21.57，and that of third-class product was ＜13.48. According to the grading standard ，3 batches of 13 batches of qualified samples are classified as first-class products ，6 batches are classified as second-class products ，4 batches are classified as third-class products. CONCLUSIONS ：The established subjective and objective combination weighting method and quality constant method can more scientifically and reasonably classify rice-wine processed Coptidis Rhizoma decoction piece.

OBJECTIVE： To provide reference for optimizing the treatment of children with infective endocarditis. METHODS： Clinical pharmacists provide whole process pharmaceutical care for a child with congenital heart disease and infective endocarditis admitted to our hospital in April 2017.  According to the individual situation of child， when therapy efficacy was poor， medication suggestions were put forward by timely referring to the guide and literature as well as combined with pharmacists’ work experience. RESULTS： After treatment with vancomycin at normal dose of 38 mg/（kg·d）， the vancomycin blood concentration （1.3 μg/mL） was low， and the treatment effect was poor. Clinical pharmacist made two suggestions to adjust the dose of vancomycin. The first dose was 45 mg/（kg·d）， the second dose was 60 mg/（kg·d）； pediatrician adopt clinical pharmacist recommendations completely. After treatment， the child’s body temperature was normal； vancomycin blood trough concentration increased to 5.8-6.5 μg/mL， and the disease was controlled. CONCLUSIONS： During vancomycin treatment of infective endocarditis in children， clinical pharmacists should provide pharmaceutical care throughout the course and pay close attention to the blood trough concentration of vancomycin in order to ensure the rational use of drugs in children.

Objective To investigate effects of Levosimendan on hemodynamics in heart failure patients with low cardiac output. Methods A total of 27 heart failure patients with low cardiac output were recruited in the surgical intensive care unit (SICU)of Beijing Hospital from July 2009 to May 2016. All patients were treated with continuous intravenous infusion of Levosimendan 12.5 mg within 24 h at a rate of 0.1~0.2 μg· kg -1·min-1. Hemodynamic variables were monitored by pulse-indicated continuous cardiac output(PICCO)at baseline ,24 h ,4 d and 7 d after infusion. Results There were no significant differences in systolic blood pressure(SBP) ,diastolic blood pressure(DBP) ,heart rate(HR)and global end diastolic volume index (GEDI)as comparing baseline with 24 h ,4 d and 7 d after infusion of levosimendan. The significant differences were found in central venous pressure (CVP) ,systemic vessel resistance index (SVRI) , extravascular lung water index (EVLWI ) among baseline versus 24 h ,4 d and 7 d after infusion of levosimendan[(8.34± 2.87)mmHg vs.(6.35± 2.31),(6.81± 2.03),(5.92± 2.23)mmHgforCVP ,(2 682.0 ± 388.9)dyn·s-1·cm -5·m-2vs. (2 170.0 ± 410.9) ,(2 062.0 ± 340.6 ) ,(1 960.0 ± 380.2 )dyn ·s-1·cm-5·m-2for SVRI ,(8.90 ± 2.45)ml/kg vs. (6.60 ± 2.66) ,(5.92 ± 2.88) ,(5.46 ± 2.52) ml/kg for EVLWI ,P=0.001 ,0.003 or＜0.01 ,respectively].As compared with hemodynamic variables at baseline ,brain natriuretic peptide levels were decreased ,and cardiac index ,cardiac function index and stroke volume index were increased at 24 h ,4 d and 7 d after infusion of Levosimendan (P＜0.01 ,0.05 or 0.01 , respectively ). Conclusions A single-dose intravenous infusion of Levosimendan can increase cardiac output and decrease systemic vascular resistance in heart failure patients with low cardiac output ,which maintain quite a long time.

Objective To prospectively investigate the effects of high-flow nasal oxygen on hypoxemic patients after surgery.Methods A total of 108 postoperation hypoxemic patients (150 mmHg ≤ PaO2/FiO2 ＜300 mmHg, PaCO2 ≤50 mmHg) in Beijing Hospital Surgical Intensive Critical Unit was in cluded and assigned randomly to two groups from June 2016 to April 2017.Fifty four patients (study group) who received high-flow nasal oxygen therapy were compared with 54 patients (control group) who received noninvasive ventilation therapy.The data of reintubation and mortality in 28 days after extubation were collected and analyzed.Results No significant differences were found for reintubation rate (11.1％ vs 13.0％,P =0.767) and mortality (5.6％ vs 7.4％, P =0.696) in 28 days after extubation between two groups.In subgroup analysis, no significant differences were found for different hypoxima level (250 mmHg ≤ PaO2/FiO2 ＜ 300 mmHg,200 mmHg ≤ PaO2/FiO2 ＜ 250 mmHg and 150 mmHg≤ PaO2/FiO2 ＜ 200 mmHg) between two groups, for reintubation rate (0 vs 3.7％,P =0.296;20％ vs 14.3％,P =0.684;30％ vs 30.8％,P =0.968, respectively) and mortality (0 vs 3.7％,P =0.296;6.7％ vs 7.1％,P =0.960;20％ vs 15.4％,P =0.772, respectively).Face skin breakdown were significantly more common in control group (1 1.1％ vs 0,P =0.012).Conclusions High-flow nasal oxygen therapy was not inferior to noninvasive ventilation for mild and moderate hypoxemic patients after surgery.High-flow nasal oxygen therapy is safe and effective for these patients.

ObjectiveTo verify the reliability of the mouse model of cerebral cortical microinfarct induced by two-photon microscopy and to explore its pathological changes.MethodsSeventeen male C57BL/6J mice were randomly divided into a microinfarct group (n=11) or a sham operation group (n=6).A thinned cranial window of 3 mm diameter was performed over the cerebral cortex with a high-speed micro-drill until the small blood vessels were clearly observed under a dissecting microscope.Then, a permanent single cortical penetrating arteriole occlusion was induced with a gradually enhanced ultrashort laser irradiation through the thinned cranial window with two-photon microscopy.At 7 days after modeling, the cerebral microinfarct volume was measured with HE staining, and the neuron loss, activation of glial cells and deposition of 3-nitrotyrosine were assessed using immunohistochemistry.ResultsThe target vessels of cerebral cortex in 8 (72.7%) mice were occluded and the microinfarcts formed in the microinfarct group, and the average microinfarct volume was 317.23±20.29 μm3.There were remarkable neuron loss and microglia infiltration in the infarcted core, a large number of reactive astrocytes surrounding the infarcted lesion, and massive deposition of 3-nitrotyrosine in the peri-infarct area.No infarcts were observed in the sham operation group.The deposition of 3-nitrotyrosine in the sham operation group was significantly less than that in the microinfarct group (8.00±1.48 vs.98.38±9.10;t=23.962, P<0.001).Conclusions The mouse model of cerebral cortical microinfarct induced by two-photon microscopy is reliable, and its histopathologic changes are consistent with the pathologic features of cerebral microinfarct.

Objective To evaluate the effect of mouse nerve growth factor on fracture healing.Methods Cochrane library, Pubmed, EMbase, CNKI,VIP,Wanfang Data and CBM were searched for the randomized controlled trials(RCTs)of mouse nerve growth factor on fracture healing from the date of establishment of the databases to May 2014.Three independent rese archers evaluated the included studies using GRADE,according to recommend classification method of GRADE system by three researchers,crtical evaluated and data extracted of the quality of the included studies,which conform to the quality standard of RCT was analyzed by Meta analysis.The extracted data were analyzed by RevMan 5.0 and GRAED proiler.Results A total 5 trials were discovered and all of these were in Chinese.Compared with conventional treatment was improved a lot[MD =-8.74,95%CI( -9.79,-7.68),P<0.0001].However, adverse drug reaction in patients with mouse nerve growth factor were increased[OR =14.66,95%CI(1.89, 113.99),P=0.01].The both outcomes were low quality in the GRADE system.Conclusion Mouse nerve growth factor can improve fracture healing and the side effects will also increase.

Objective To systematically review articles about therapeutic drug monitoring of vancomycin in Chinese adults, so as to provide a reference of vancomycin trough concentrations for clinical evidence-based medicine.Methods Literature concerning vancomycin therapeutic drug monitoring were electronically retrieved in, CBM, Wanfang data, CNKI and Vip.Furthermore, the articles written in English by Chinese author in PubMed, EMbase were included.All the data were searched from inception of the database or network to Aug.2014.Two reviews independently screened literature according to the inclusion and exclusion criteria, and assessed the quality of literature using the Combieg and NOS.Analyzing the types of studies, the number of therapeutic monitoring of vancomycin, trough serum concentration, clinical outcome and renal function.Results A total of 35 studies including 32 cross-sectional studies and 3 cohort studies were included, all studies were observational studies.3099 patients with 5206 blood concentrations monitoring results were eligible for final analyses in all 32 cross-sectional studies.The rates of trough serum concentration in 5-15 mg/L was 53.6%.Compared with the trough concentrations between 5 and 15 mg/L, clinical cure rate was no significant difference in the trough concentrations of over 15μg/mL.However, the incidence rate was significantly reduced in renal toxicity in 5-15 mg/L trough serum concentration.Conclusions For adults, trough serum concentration of vancomycin should adopt the 5-15 mg/L in China.However, considering lack of high-level evidence, so it needs to be studied further.

Objective To investigate the expression of matrixmetalloprotein -9(MMP-9)and E-cad-herin in triple negative breast cancer ( TNBC) and its relationship with the clinicopathologic features of TNBC .To analyze the function of MMP -9 and E-cadherin in TNBC .Methods Immunohistochemical method was used to detect the expression of MMP -9 and E-cadherin in 127 cases of TNBC.Results The MMP-9 positive rate was 53.54%and E-cadherin positive grade was 32.28%in TNBC.Expression of MMP-9 was correlated with tumor size(P=0.007),histological grade(P=0.006),TNM stage(P=0.003),lymph node metastasis(P=0.000)and lymph duct invasive(P=0.000).Expression of E-cadherin was correlated with lymph node metasta-sis(P=0.016)and lymph duct invasive(P=0.015).However,they were not correlated with other factors .Con-clusion The expression of MMP -9 and E -cadherin was correlated with invasion and metastasis in TNBC , which could be an important research topic in the future studies .