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Background: Fibroblast-derived exosomes can regulate the electrical remodeling of cardiomyocytes, and the intermediate-conductance calcium-activated potassium channel (KCa3.1) is important in atrial electrical remodeling. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the regulation of cardiac electrophysiology by exosomes linked to KCa3.1. Methods: Atrial myocytes (AMs) and atrial fibroblasts were isolated from Sprague-Dawley suckling rats and cultured individually. The cellular atrial fibrillation (AF) model was established via electrical stimulation (1.0 v/cm, 10 Hz), and fibroblast-derived exosomes were isolated via ultracentrifugation. Exosomes were co-cultured with AMs to investigate their influences on KCa3.1 and the underlying mechanisms. Nanoparticle tracking analysis and transmission electron microscopy were used to measure exosome particle sizes and concentrations. Whole-cell patch clamp was applied to record the current density of KCa3.1 and action potential duration (APD). The expression of miR-21-5p was detected by reverse-transcription polymerase chain reaction (RT-PCR). Western blotting or immunofluorescence was used to measure the expression of exosomal markers, Akt phosphorylation, and KCa3.1. Results: Rapid pacing promoted the secretion of exosomes from atrial fibroblasts and miR-21-5p expression in atrial fibroblasts and exosomes. KCa3.1 protein expression and current density significantly increased, and APD50 and APD90 were sharply shortened after rapid pacing in AMs. TRAM-34 (KCa3.1 blocker) extended APD and reduced susceptibility to AF. KCa3.1 and P-AKT expressions were amplified after co-culturing AMs with exosomes secreted by atrial fibroblasts. In contrast, the increase in KCa3.1 expression was reversed after the cells were co-cultured with exosomes secreted by atrial fibroblasts that were transfected with miR-21-5p inhibitors or after the use of LY294002, a PI3K/Akt pathway inhibitor. Conclusions: Rapid pacing promoted the secretion of exosomes from fibroblasts, and miR-21-5p was upregulated in exosomes. Moreover, the miR-21-5p-enriched exosomes upregulated KCa3.1 expression in AMs via the PI3K/Akt pathway.
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Based on China's health-related policy documents,combining the development history of health concepts and quality management theories,the evolution of China's view of healthcare service quality is sorted out.Moreover,based on the objectives of payment reform and the possible impact on healthcare service quality,the focus of healthcare service quality evaluation in the context of health insurance payment reform is elaborated.It aims to explore the focus of medical service quality evaluation at the present stage,and to provide a reference for better utilization of the evaluation results to improve the quality of medical services.
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Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (INa.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC50) values of Mel on transient sodium current (INa.T) and specific INa.L opener 2 nmol·L-1 sea anemone toxins II (ATX II) increased INa.L were 686.615 and 7.37 μmol·L-1, respectively. Mel did not affect L-type calcium current (ICa.L), transient outward current (Ito), and AP. In addition, 16 μmol·L-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking INa.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).
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The problems during medical consumables selection were analyzed with a fishbone diagram.The selection process was optimized based on PDCA cycle,and a standardized selection plan for medical consumables was formulated by combining the practical experience of hospital management,and the practicability and feasibility of the selection plan was verified.References were provided for medical institutions to select cost-effective medical consumables.
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With the development of modern surgery, the field of hernia and abdominal wall surgery is undergoing a transformative change, and new techniques, new concepts, and recent progress are being updated, which have motivated the high-quality development of the discipline. In the past two decades, the development of hernia and abdominal wall surgery in China has been recognized by international peers. Many young surgeons have gradually become the main force in the treatment of hernia and leaders in surgical technique. The innovation and development of discipline will never terminate; young surgeons as the main force should seriously think about how to improve their professional qualities. Young surgeons are interested in the innovation of surgical techniques and need to push for a traditional operation on the one hand and an innovative operation on the other. Updates to concepts and acquisition of new materials are more important, which can provide a solid foundation for technological innovation. Young surgeons should start with the basics and classics. Understanding the history and development of new techniques, new concepts and recent progress, and grasping indications of clinical application, is the important part of growing up for young surgeons, which can make surgical treatment more standardized, benefit patients, and promote the progress of Chinese specialized medical education.
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Humanos , Pared Abdominal/cirugía , Hernia , Cirujanos , Herniorrafia/métodos , China , Mallas QuirúrgicasRESUMEN
Objective To investigate the effect of different coating methods on production quality of complex and flexible silicone vascular replicas. Methods Based on models of anterior communicating artery aneurysms, several patient-specific models were made by using spray-coating method and brush-spin-coating method respectively, and two methods for making the same vascular structure were quantitatively compared in terms of thickness growth, circumferential uniformity and light transmittance. Results Brush-spin-coating method was better than spray-coating method in the thickness control and coating uniformity for fabrication of vessels with large curvature, variable diameter and straight tube, and the model had preferably light transmittance and surface smoothness. The relative deviation of thickness by brush-spin-coating method was decreased by 8. 9% , 10. 8% and 16. 9% respectively compared with spray-coating method. Conclusions At present stage, the brush-spin coating method has the advantage of thickness uniformity and light transmittance over the spray-coating method in making silicone phantoms, and it has promising application prospects in fluid mechanics field of in vitro experiment on large vessels.
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Resistance to radiotherapy is frequently observed in the clinic and leads to poor prognosis of non-small cell lung cancer (NSCLC). How to overcome resistance to radiotherapy is a challenge in the treatment of NSCLC. In this study, PPDPF was found to be upregulated in NSCLC tissues and cell lines, and its expression negatively correlated with the overall survival of patients with NSCLC. PPDPF promoted the growth, colony formation and invasion of lung cancer cells. Moreover, knockout of PPDPF inhibited tumorigenesis in the KL (KrasG12D; LKB1f/f) mouse model of lung cancer. Additionally, overexpression of PPDPF led to radioresistance in lung cancer cells, and knockdown of PPDPF sensitized lung cancer cells to radiotherapy. Mechanistically, PPDPF interacted with BABAM2 (an antiapoptotic protein) and blocked its ubiquitination by MDM2, thus stabilizing BABAM2 and promoting the radioresistance of lung cancer cells. Our present study suggested PPDPF as a therapeutic target in NSCLC.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Animales , Carcinogénesis , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo , Humanos , Ratones , Ratones Desnudos , Pronóstico , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE@#To explore the contribution of ferroptosis to myocardial injury in mouse models of sepsis and the role lipocalin-2 (Lcn2) in ferroptosis.@*METHODS@#Adult male C57BL/6 mice were randomized equally into sham-operated group, cecal ligation and puncture (CLP)-induced sepsis group, and CLP + Fer-1 group where the mice received intraperitoneal injection of 5 mg/mL Fer-1 (5 mg/kg) 1 h before CLP. The left ventricular functions (including LVEF%, LVFS%, LVIDd and LVIDs) of the mice were assessed by echocardiography at 24 h after CLP. Myocardial injury in the mice was observed with HE staining, and the changes of myocardial ultrastructure and mitochondria were observed using transmission electron microscopy (TEM). Serum TNF-α level was measured with ELISA, and the changes of myocardial iron content were detected using tissue iron kit. The protein expressions of myocardial Lcn2, glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) were determined with Western blotting.@*RESULTS@#The septic mice showed significantly decreased LVEF%, LVFS% and LVIDd and increased LVIDs at 24 h after CLP (P < 0.05), and these changes were significantly improved by Fer-1 treatment. Sepsis caused obvious myocardial pathologies and changes in myocardial ultrastructure and mitochondria, which were significantly improved by Fer-1 treatment. Fer-1 treatment also significantly ameliorated sepsis-induced elevations of serum TNF-α level, myocardial tissue iron content, and Lcn2 protein expression and the reduction of GPX4 and FSP1 protein expression levels (P < 0.05).@*CONCLUSION@#GPX4- and FSP1-mediated ferroptosis are involved in myocardial injury in mice with CLP-induced sepsis, and inhibition of ferroptosis can attenuate septic myocardial injury, in which Lcn2 may play a role.
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Animales , Masculino , Ratones , Ferroptosis , Lesiones Cardíacas , Lipocalina 2 , Ratones Endogámicos C57BL , Sepsis/metabolismoRESUMEN
Objective:We aimed to build a novel model with metastasis-related genes (MTGs) signature for predicting progression-free interval (PFI) of papillary thyroid carcinoma (PTC) .Methods:We integrated PTC datasets with the MTGs to identify differentially expressed MTGs (DE-MTGs), then we established a novel MTGs based signature and validated it in external datasets and cell lines. Finally, we established a signature and clinical parameters-based nomogram for predicting the PFI of PTC.Results:We identified 155 DE-MTGs related to PFI in PTC. The functional enrichment analysis showed that the DE-MTGs were associated with essential oncogenic processes. Consequently, we established and optimized a novel 10-gene signature. The novel signature had a C-index of 0.76 and the relevant nomogram had a C-index of 0.80. Also, it was closely related to pivotal clinical characters of multiple datasets and invasiveness of PTC cell lines. And the signature was an independent prognostic factor in PTC. Finally, we built a nomogram including the signature and relevant clinical factors. The efficacy was satisfying in predicting PTC’s PFI.Conclusions:The MTG signature and nomogram were closely associated with PTC prognosis and may help clinicians improve the individualized prediction of PFI.
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【Objective】 To investigate the mechanisms of chelerythrine on the treatment of breast cancer based on network pharmacology and molecular docking. 【Methods】 The targets corresponding to chelerythrine and breast cancer were obtained from Mala Cards and Swiss Target Prediction databases. Chelerythrine-related and breast cancer-related targets were found and then combined to get an intersection, which represented potential anti-breast cancer targets of chelerythrine. A protein-protein interaction (PPI) network was constructed from the STRING database and key genes were screened using the topological analysis. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of targets were conducted using metascape database. The relationship between the expressions of key target genes and the survival curve was analyzed using the Kaplan-Meier Plotter database. Molecular docking analysis was performed by AutoDock Vina to verify whether chelerythrine has a definite affinity with key targets. 【Results】 A total of 37 potential targets were obtained in chelerythrine against breast cancer. The result of the topology analysis included 8 key targets. The GO enrichment analysis included 317 GO items. The KEGG pathway analysis included 80 pathways, which were closely related to the PI3K/AKT signaling pathway, the ErbB signaling pathway, VEGF signaling pathway, and others. The results of the survival curve analysis showed that the expression levels of CHEK1, PIK3CA, mTOR and PTGS2 genes were related to the survival time of breast cancer patients. The results of molecular docking proved that the combined activity of chelerythrine with key targets was excellent. 【Conclusion】 Chelerythrine may play an anti-breast cancer role via the PI3K/AKT signaling pathway and has the potential to be developed into a clinical drug for breast cancer.
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Objective:To synthesize a 68Ga-labeled oxalyldiaminopropionic acid (ODAP)-urea based prostate specific membrane antigen (PSMA) targeting probe, and evaluate its properties in vitro and in vivo. Methods:Ligand P151 was synthesized by solid-phase synthesis and its Ki value was determined. The ligand P151 was added into the mixture of 68GaCl 3 and NaOAc solution and was reacted at 95 ℃ for 10 min. The labeling yield and in vitro stability of 68Ga-P151 were determined by high performance liquid chromatography (HPLC). The lipid-water partition coefficient (log P) and cell binding ability were determined. The biodistribution of 68Ga-P151 in normal KM mice was determined. MicroPET imaging of 68Ga-P151 was carried out in prostate cancer 22Rv1 tumor-bearing mice and compared with 68Ga-PSMA 617. Independent sample t test was used to analyze the data. Results:P151 was successfully synthesized with the Ki of 0.58 nmol/L, the labeling yield more than 95% and the radiochemical purity more than 95%. After placement in saline or human serum albumin (HSA) solution at 37 ℃ for 2 h, the radiochemical purity of 68Ga-P151 was still more than 95%, indicating a good stability in vitro. The lipid-water partition coefficient (log P) of 68Ga-P151 was -2.65±0.17, indicating a good hydrophilicity. 68Ga-P151 specifically bound to PSMA in prostate cancer LNCaP cells with the uptake value of (0.83±0.04) percentage injection activity (%IA)/10 5 cells. Biodistribution of normal mice showed that 68Ga-P151 was mainly excreted through kidneys and other organs showed low uptake. MicroPET imaging of tumor-bearing mice showed the maximum standardized uptake value (SUV max: 0.79±0.23 vs 0.54±0.05; t=2.12), tumor/kidney ratio (2.04±0.65 vs 1.88±0.33; t=0.44) and tumor/muscle ratio (12.83±5.18 vs 6.95±1.63; t=2.17) between 68Ga-P151 and 68Ga-PSMA 617 were not significantly different (all P>0.05). Conclusions:68Ga-P151 can be prepared simply and labeled in high yield and show improved pharmacokinetic properties in vivo. The imaging of 68Ga-P151 on PSMA positive tumor is comparable to that of 68Ga-PSMA 617, making it a potential radiopharmaceutical for the diagnosis of prostate cancer.
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Objective To screen the secretory factor-related, mechanoresponsive microRNAs (miRNA) of osteocytes. Methods Cyclic mechanical tensile strain (ε=2.5,f=0.5 Hz) was applied to osteocytes and osteoblasts cultured in vitro respectively, and the differentially expressed miRNAs only in the osteocytes were screened out by using miRNA chip. Through bioinformatics technology, in these differentially expressed miRNAs, the target genes of secretory factors including insulin-like growth factor-1(IGF-1), nitric oxide synthesase (NOS), fibroblast growth factor 23 (FGF23) and sclerostin (SOST) were further screened out. Then the selected miRNAs were compared with the biochip detected, differentially expressed miRNAs in femur bone of the mice which were trained on treadmill, and four of these miRNAs were randomly selected for quantitative PCR verification. Results For the 77 differentially expressed miRNAs only in the mechanically strained osteocytes in vitro, 22 miRNAs whose target genes were the 4 secreted factors (IGF-1, NOS, FGF23 and SOST), were screened out. Moreover, a total of 11 miRNAs in the 22 miRNAs were differentially expressed in femur bone of the treadmill trained mice with the same trend as those in osteocytes in vitro, and the randomly selected miR-361-3p, miR-3082-5p, miR-6348 and miR-706 were confirmed to be differentially expressed with the same trend in femur bone and osteocytes. Conclusions These mechanoresponsive miRNAs differentially expressed only in osteocytes, such as miR-361-3p, miR-3082-5p, miR-6348 and miR-706, probably influence osteoblastic differentiation or bone metabolism through regulating the secretory factors.
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Bone tissue plays an important role in maintaining physical activity and health. The study of the biological functions of bone tissue cells and their application in tissue engineering is of great significance for clinical prevention and treatment of orthopedic-related diseases. Tea polyphenols are the main components of tea, with natural antioxidant, scavenging free radical activity and anti-inflammatory effects. Research results indicated that tea polyphenols can promote the bone remodeling process mainly by enhancing the formation of osteoblasts and reducing the occurrence of osteoclasts. In addition, tea polyphenols can also be used as surface modification molecules of artificial bone materials and are widely used in the field of bone tissue engineering. In this paper, the regulatory effects of tea polyphenols in bone tissue cells and its application in tissue engineering were reviewed, and related research contents were summarized and prospected, in order to provide reference and theoretical basis for subsequent research work.
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In recent years, drug-resistant bacteria have developed into a global problem. Common clinically resistant bacteria and their natural antibiotic synergists are the objects of research in this paper. Through consulting the relevant literature at home and abroad, the combination of various natural products and antibiotics commonly used in clinic to reduce the various bacterial drug resistance and the mechanism of action are summarized and analyzed. The related studies on the common drug-resistant bacteria in clinical practice and the natural antibiotic synergists to reduce their resistance were summarized in this paper. The results show that natural products can be used as antibiotic synergists due to their structural complexity and novelty, which provides new ideas and methods for clinical treatment of drug-resistant bacterial infections.
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Objective To investigate the clinical value of biological mesh in repairing abdominal wall defect after tumor resection.Methods 15 patients with abdominal wall defect left over by radial resection of abdominal wall tumor were treated with primary biological mesh herniorrhaphy from Sep 2015 to Sep 2017 at the Department of Hernia and Abdominal Wall Surgery of Beijing Chaoyang Hospital.Results The operation was successful in all 15 patients.The operation time was 95 (65-145)main.The hospital stay was 17 (9-22) d.The patients were followed up for 18 (17-32) months.postoperative seroma occurred in 8 cases,postoperative fever occurred in 1 case.One case died of multiple systemic metastases of advanced gastric cancer.All the other patients were followed up without complaining about local pain,foreign body sensation,intestinal obstruction,intestinal fistula.Conclusions Biological mesh is safe and feasible for the treatment of abdominal wall defect after tumor resection.
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Objective@#To investigate the clinical value of biological mesh in repairing abdominal wall defect after tumor resection.@*Methods@#15 patients with abdominal wall defect left over by radial resection of abdominal wall tumor were treated with primary biological mesh herniorrhaphy from Sep 2015 to Sep 2017 at the Department of Hernia and Abdominal Wall Surgery of Beijing Chaoyang Hospital.@*Results@#The operation was successful in all 15 patients. The operation time was 95(65-145)min. The hospital stay was 17(9-22)d. The patients were followed up for 18(17-32) months. postoperative seroma occurred in 8 cases, postoperative fever occurred in 1 case. One case died of multiple systemic metastases of advanced gastric cancer. All the other patients were followed up without complaining about local pain, foreign body sensation, intestinal obstruction, intestinal fistula.@*Conclusions@#Biological mesh is safe and feasible for the treatment of abdominal wall defect after tumor resection.
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Objective: To compare the chemical components in raw products and characteristic processed products with porcine cardiac blood of Salviae Miltiorrhizae Radix et Rhizoma from Menghe medical school.Method: The ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was performed on an ACQUITY UPLC® C18 column (2.1 mm×100 mm,1.7 μm),mobile phase was 0.1% formic acid aqueous solution (A)-0.1% formic acid acetonitrile solution (B) for gradient elution (0-1 min,8% B,1-1.5 min,8%-20% B,1.5-4 min,20% B,4-5 min,20%-60% B,5-9 min,60%-70% B,9-10 min,70%-95% B,10-13 min,95% B).The column temperature was 40℃ and the flow rate was 0.3 mL·min-1.Q-TOF/MS with electrospray ionization (ESI) and scanning range of m/z 50-1 200 were applied for analysis under positive and negative ion mode,respectively.All ionic peaks were assigned by comparison of reference substances,mass spectra data,database matching and literature reference,changes of chemical components in Salviae Miltiorrhizae Radix et Rhizoma were investigated by comparing number and area of ionic peaks before and after processing.Result: A total of 59 components were identified from raw products and characteristic processed products,and peak areas of 25 components showed obvious change.However,there were no new compound was found in characteristic processed products.After being processed with porcine cardiac blood,the contents of water-soluble ingredients (protocatechuic aldehyde,salvianolic acid C,F,G),fat-soluble ingredients (tanshinaldehyde,tanshindiol A,tanshinone Ⅰ) and amino acid (L-phenylalanine) in Salviae Miltiorrhizae Radix et Rhizoma were significantly increased.Conclusion: Changes of contents of chemical components in raw products and processed products of Salviae Miltiorrhizae Radix et Rhizoma are remarkable,part of water-soluble ingredients,fat-soluble ingredients and amino acids have quantitative change,which may be related to promoting treatment of Salviae Miltiorrhizae Radix et Rhizoma on cerebral ischemia after being processed with porcine cardiac blood.
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Objective To fulfill standardized and precision management of medical consumables purchasing. Methods Medical consumables purchasing was executed based on the e-commerce platform in the drug exchange facility, the access process was standardized for medical consumables, and the monitoring and supervision were implemented for price inquiry, purchasing ways, introduction flow of new products, qualification inspecting of suppliers and etc. Results The improved medical consumables purchasing flow based on drug exchange mode contributed to decreasing purchasing cost, avoiding bidding risks as well as precision management. Conclusion The purchasing based on drug exchange is of great value for hospital medical consumables purchasing management.
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The porcine cardiac blood processed Salvia miltiorrhiza (PCB Danshen) is the characteristic processing of Menghe medical school and has been inherited for hundreds of years, commonly used in the treatment of brain ischemia-induced agitation, palpitation and phlegm confusing heart. Ancient and modern physicians believe that porcine cardiac blood is a guiding for heart nourishing drugs, which could enhance the effects of Salvia miltiorrhiza by nourishing and soothing the nerves. However, the material basis and processing mechanism of PCB Danshen are still unclear. This paper investigated the historical evolution and modern research of PCB Danshen, including the clinical application, the intention of clinic processing, the processing technology and recent research of PCB Danshen. In addition, the major problems and significance in research and development of PCB Danshen were further thought and prospected, hoping to provide basic data for material basis and processing mechanism of PCB Danshen, and provide effective support for inheriting and carrying forward the characteristic processing technology of Menghe medical school.
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Objective To investigate the clinical significance of serum procalcitonin(PCT)and B-type natri-uretic peptide(BNP)before and after fluid resuscitation in patients with septic shock.Methods A total of 62 patients with septic shock were selected from January to December in 2015.The patients with arterial blood gas,24 hours of cumulative resuscitation fluid and the time of resuscitation were monitored and recorded.PCT and BNP levels were detected.Results The resuscitation fluid was(7 899.31 ± 1 337.64)mL and the time of resuscitation was(19.07 ± 5.64)h in the treatment of body fluid resuscitation in 62 patients.There were sig-nificant differences in pH,Na+,Cl-,PCT and BNP values before and after treatment,the differences were sta-tistical significant(P<0.05).There was a negative correlation between serum PCT and 24% cumulative ser-um(r= -0.956,P<0.05).Conclusion The levels of serum BNP and PCT in patients with septic shock were closely related to the disease,and can be used to monitor the therapeutic efficacy in patients with septic shock.