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The matrix metalloproteinases family (MMPs) are proteins related to tumor formation and metastasis that have attracted the attention of scholars in recent years. Tumor cells can secrete MMPs during malignant transformation, and the expression of MMPs in different malignant tumors is diverse, and different members of MMPs do not have exactly the same biological properties. Matrix metalloproteinase-19 (MMP-19) is a new member of MMPs whose secretion increases rapidly during the malignant transformation of cells and is released into the extracellular space to participate in biological processes such as proliferation, adhesion, invasion, migration, and angiogenesis of tumor cells. In this paper, the progress of research on the biological properties of MMP-19 in tumors was reviewed to provide a theoretical basis for exploring the development of tumors, especially for studying the invasion and metastasis of tumor cells.
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Objective:To investigate the clinical efficacy of injectable polymyxin B combined with tigecycline in pneumonia caused by pan-drug resistant Klebsiella pneumonia (PDR-KP). Methods:The retrospective analysis utilized clinical data of 71 patients with PDR-KP admitted to the Neurointensive Care Unit of Beijing Chaoyang Integrative Medicine Emergency Medical Center between September 2018 and August 2021. All patients received injectable polymyxin B combined with tigecycline. The response rate, bacterial clearance rate, and safety of this therapeutic option were evaluated according to the clinical symptoms and biochemical parameters before treatment (baseline), 7 days after the treatment, and at the end of the treatment.Results:The treatment time of 71 patients ranged from 8 to 14 days, with an average of 11 days. The symptoms, signs, laboratory tests, and chest CT findings of most patients significantly improved after the treatment using polymyxin B combined with tigecycline. On the 7th day after the treatment, 37 patients were clinically effective, with a total effective rate of 52.1%(37/71); 41 patients obtained bacteriological clearance, with a bacterial clearance rate of 57.7%(41/71). At the end of treatment, 51 patients were clinically effective, with a total effective rate of 71.8%(51/71); 56 patients obtained bacteriological clearance, with a bacterial clearance rate of 78.9%(56/71). Compared with the results on the 7th day after the treatment, the total effective rate ( χ2=5.86, P=0.016) and bacterial clearance rate ( χ2=7.32, P=0.007) of patients at the end of treatment were significantly increased. Skin pigmentation occurred in 39.4%(28/71) of patients during the treatment. Conclusions:Polymyxin B combined with tigecycline can be tried as a treatment option for pneumonia caused by PDR-KP, but more reliable clinical evidence is still needed.
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Salivary gland cancer includes a group of heterogeneous malignant tumors. The latest WHO classification of head and neck tumors divides salivary gland cancer into 22 histopathological subtypes. The most common clinical subtypes include mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, acinar cell carcinoma and secretory carcinoma, etc. The histomorphology of the subtypes of salivary gland cancer overlaps, making diagnosis and differential diagnosis difficult. The main treatment for salivary gland cancer is tumor resection and postoperative radiotherapy as appropriate. Even in cases of local progression, recurrence and metastasis, the treatment options available are limited, mainly palliative treatment. Accurate determination of tumor receptor expression, genome and pathway changes is the key to changing the prognosis of patients with local progression or distant metastasis. In this paper, the known genetic mutations, amplifications and protein expression profiles of common salivary gland cancer histological subtypes was summarized, and the significance of the above-mentioned molecular genetic changes for disease diagnosis, future research and personalized targeted therapy was analyzed.
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Objective:To analyze the clinical characteristics and treatment of patients with serious interstitial lung diseases (SILD).Methods:The clinical data of 43 patients with SILD hospitalized in the respiratory intensive care unit of the Characteristic Medical Center of The Chinese People's Armed Police Force from January 2010 to December 2020 were retrospectively reviewed. According to the prognosis, the patients were divided into the death group and non-death group.Results:The included 43 patients include 31 cases of acute exacerbation of idiopathic interstitial pneumonia (AE-IIP), 18 cases of usual interstitial pneumonia (UIP) and 16 cases of nonspecific interstitial pneumonia (NSIP), in which 40% were aggravated due to co-infection and 33 patients were dead. The results showed that there was no significant difference between death and non-death patients in age, gender, smoking, hospitalization time, duration, clinical symptoms and signs, blood T lymphocyte subsets, co-infection, mechanical ventilation and glucocorticoid dose (all P>0.05), and there were significant differences in arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO 2/FiO 2) and arterial partial pressure of carbon dioxide (PaCO 2) (all P<0.05). The PaO 2/FiO 2 level in the dead patients was lower, who often accompanied by type Ⅱ respiratory failure. Conclusions:AE-IIP was more common in patients with SILD, and most of their chest images were consistent with UIP and NSIP. Pulmonary infection is a common cause of acute exacerbation of SILD, and type II respiratory failure in the progress of the disease is a sign of poor prognosis.
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Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation and aggressive arthritis. The basic pathological changes of RA include intra-articular hyperplasia synovitis and extra-articular vasculitis, symmetrical joint cavity effusion and stenosis, and the formation of pannus leading to the destruction of articular cartilage or joint accessory structures. In the course of RA, swelling and pain of the affected joints occur, causing joint deformities, joint stiffness, and joint dysfunction, and eventually disability. In recent years, significant progress has been made in the study of the relationship between nerve growth factor (NGF) and RA immunopathology. The results of existing studies have shown that the level of NGF in the synovial fluid of RA patients is elevated, suggesting that NGF plays an important role in immune inflammation-mediated pain behavior. In addition, nerve growth factor precursors (including proNGF and proBDNF, etc.) can promote cell apoptosis and inflammation. Among them, the levels of proBDNF and its receptors have significant changes in the blood of RA patients. Therefore, it can be inferred that proNGF and proBDNF may become new targets for RA treatment. According to the latest international domestic research results, in this paper the research progress of NGF and RA in immunopathology, immune inflammatory response, pain behavior, etc. were briefly introduced, and the potential application value of NGF in the treatment of RA was summarized.
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Objective To investigate the effects of umbilical cord mesenchymal stem cells (UCMSCs) on immune microenvironment and angiogenesis in patients with traumatic brain injury. Methods Cerebrospinal fluid (CSF) samples were divided into 4 groups, including normal group (n=6), traumatic brain injury group (n=6), traumatic brain injury+UCMSCs treatment group ( n=6 ) and craniocerebral trauma + conventional treatment group ( n=6 ) . The CSF samples were detected by liquid chromatography-mass spectrometry , and data were collected by data independent acquisition (DIA) technology. The differential proteins were screened by bioinformatics processing, and analyzed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results A total of 688 proteins were screened in CSF samples and reliably quantified. There were 38 differential proteins in the CSF of patients with traumatic brain injury after treatment with UCMSCs, including 20 up-regulated proteins and 18 down-regulated proteins. The results of GO analysis and KEGG analysis showed that the differential proteins were mainly immunoregulatory function-related proteins, angiogenesis-related proteins, and various connexins. Conclusions The main possible mechanism of UCMSCs in the treatment of traumatic brain injury is to regulate the stability of the immune microenvironment and to promote the regeneration and reconstruction of damaged brain tissue.
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Objective To compare the dosimetric characteristics of the methods of volumetric modulated arc therapy ( VMAT ) for craniospinal irradiation , and to compare their robustness to the field placement error . Methods Six patients receiving craniospinal irradiation were included. VMAT plans of each patient were optimized with overlap method and gradient-optimization method respectively using Pinnacle 9.8 VMAT treatment planning system. The length of the overlap region was set as 3 and 9 cm, respectively. Then the dose distributions under different VMAT programs were measured. Moreover, a 3 mm placement error was introduced, and the dose cold spot in the field junction region obtained by each plan was compared for robustness analysis. Results Under different overlapping lengths, the overlap method and the gradient optimization method both can optimize the VMAT plan that meeting the clinical requirements. In the field junction region, the dose distribution obtained by the overlap method was more uniform, and the difference in the uniformity index was statistically significant. When introducing a 3 mm placement error, the gradient optimization method obtained the most robust VMAT plan at 9 cm overlap length, and the overlap method could not obtained stabilized robust plan. Conclusions For the optimization of craniospinal irradiation VMAT plan, the commonly used overlap method can obtain a better dose distribution, but it can't improve robustness by increasing overlap length. However, using the gradient optimization method, the dose homogeneity in the field junction region is not good as the overlap method, but the plan robustness can be improved by increasing the overlap length.
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Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs ) on vascular endothelial growth factor ( VEGF ) and monocyte chemoattractant protein-1 ( MCP-1 ) of acute myocardial ischemia-reperfusion (AMI-R) injury in rats. Methods 24 Sprague-Dawley rats were randomly divided into sham group, AMI-R group and UCMSCs treatment groups on average. The rats were sacrificed on the 10th day after UCMSCs transplantation, and the myocardial tissues below the ligature were taken. The mRNA and protein expressions of MCP-1 of the tissue were detected by RT-PCR and Western Blot respectively, and the expression of VEGF protein was detected by immunohistochemistry. Results The relative expression levels of MCP-1 mRNA and the protein in UCMSCs group were significantly lower than those in sham group and AMI-R group (all P<0.05). The expression of VEGF protein in UCMSCs group was significantly higher than that in sham group and AMI-R group, the differences were statistically significant(all P<0.05). Conclusion UCMSCs transplantation can promote the angiogenesis and decrease the inflammation reaction in the treatment of acute myocardial ischemia-reperfusion injury.
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Objective To evaluate the influence of dosage,operation method,adverse reaction of endoscopic photodynamic therapy (EPDT) on its therapeutic efficacy in rabbit models of in-situ rectal cancer,so as to provide preclinical basis of photodynamic therapy for rectal cancer.Methods 20 rabbits with in-situ VX2 rectal cancer were randomly divided into control group,PDT low dose group,intermediate dose group,and high dose group.At 24 h before PDT,photosensitizer (hermimether) was intravenously injected into rabbits.630 nm semiconductor laser was used as light source.The growth of the tumor was observed by conventional endoscopy and endoscopic ultrasonography,and the survival time,general conditions and adverse reactions were recorded.The histopathological changes were observed by hematoxylin-eosin staining.Results At 7 d after PDT,the total response rates of low dose,intermediate dose and high dose group respectively were 40％ (slight),80％ (60％ remarkable and 20％ slight),100％ (20％ remarkable and 80％ slight).The average survival times of the three groups were 14 d,10 d and 5 d,respectively.The main adverse reactions were inflammation,intestinal obstruction,intestinal peristalsis loss and death.Conclusions The dosage of PDT is an important factor to influence the curative effect.The appropriate dose of PDT will have a better effect on the treatment of rectal cancer.A thorough study of these problems is helpful to the clinical application of PDT in the treatment of rectal cancer.
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Objective To explore the killing effect of dielectric barrier discharge (DBD) plasma on tumor cells and to analyze the DBD-induced apoptosis mechanism.Methods Thiazolyl blue tetrazolium bromide (MTT) assay method was used to detect the killing effect of low temperature plasma on the cytotoxicity of normal spleen leukocytes and acute promyelocytic leukemia cells (LT-12) at different doses.The changes of reactive oxygen species (ROS) level were measured after plasma treatment.The cell apoptosis rate was detected by Annexin V/PI double staining at different doses.The expression of apoptosis-related genes and proteins was detected by qRT-PCR and Western Blot.Results MTT results showed that the killing effect of plasma treatment was dose-dependent and time-dependent.The cell survival rate after 8 hours of treatment decreased from 98％ to 63％ with the dose increasing from 30 s to 240 s.The survival rate decreased from 78％ (2 h) to 39％ (24 h) after the treatment with a same dose (e.g.240 s).Annexin V/PI double staining results demonstrated that the plasma effect can induce apoptosis,and the apoptosis rate was not only positively correlated with the plasma dose,but also with the post-plasma time.The longer the post-plasma time,the higher was the apoptosis rate.The apoptotic rate of the 60 s dose treatment after 12 h was 48％ that increased to 55.3％ with the dose of 120 s.The production of reactive oxygen species (ROS) detected by flow cytometry also showed a time correlation of the plasma treatment.After the plasma treatment,the ROS level immediately increased to 1.24 times,and sharply increased to 5.39 times after 20 h post-plasma.The experimental results of qRT-PCR and Western blot showed that the expression of the genes and proteins of Caspase family and Bcl-2 family was very active at 8 to 12 h post-plasma treatment.Conclusions Low-temperature plasma can effectively kill tumor cells,and apoptosis is the main mechanism of death.The molecular mechanism of apoptosis of tumor cells induced by low temperature plasma was preliminary confirmed.
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Objective To prepare 5-aminolevulinic acid (ALA) and hematoporphyrin monomethyl ether (HMME) hydrogel suppositories and to evaluate their photosensitizer transfer efficiencies in rectal tumor tissue.Methods The BALB/c mice implanted SW837 rectal cancer cells subcutaneously were randomly divided into four groups:intrarectal suppository administration group,cutaneous administration group,intratumoral injection group and intravenous injection group.Fluorescence spectrophotometry was used to measure the concentration of protoporphyrin Ⅸ (PpⅨ) and HMME in rectal wall,skin and tumor tissue.The distribution of photosensitizer was determined by a fluorescence spectroscopy system.Results The concentration of PpⅨ in the ALA suppository administration group was 9.76 times (1 h) and 5.80 times (3 h) higher than that in the cutaneous administration group,and the differences were statistically significant (all P＜0.05).The maximal penetration depth of ALA in tumor tissue was about 3-6 mm at 2 h after the cutaneous administration.After the HMME suppository administration,the concentration of HMME in the rectal wall was very low.The maximal penetration depth of HMME in tumor tissue was less than 2 mm after the cutaneous administration.Conclusions ALA is more likely to penetrate mucosal barrier compared to skin tissue.The hydrogel suppository based rectal administration is expected to be a new administration method for the rectal cancer photodynamic therapy using ALA.
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Objective To investigate the effects of human umbilical cord mesenchymal stem cells (UC-MSCs) on vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) expression in acute myocardium infarction (AMI) rats. Methods The human UC-MSCs were cultured to the 4th generation for experiment. Sixty male Sprague-Dawley (SD) rats were randomly divided into sham group, AMI model group and UC-MSCs group, with 20 in each group. AMI animal model was produced by ligation of anterior descending coronary artery; in the sham group, the threading vein was gone below without ligation. In UC-MSCs group 2×106 UC-MSCs were infused through the caudal vein at 24 hours after successful model production. The animals were sacrificed after 7 days; the myocardial tissue and coronary artery below the ligation line were harvested. The mRNA and protein expressions of IL-6 in myocardium were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot. The positive expression of VEGF in coronary artery was observed by immunohistochemisty. Results Compared with the sham group, the mRNA and protein expressions of IL-6 in myocardium in AMI model group were increased significantly (gray value: 0.732±0.131 vs. 0.321±0.080, 0.678±0.191 vs. 0.286±0.061, both P < 0.05). Compared with the AMI model group, the mRNA and protein expressions of IL-6 in myocardium in UC-MSCs group were decreased significantly (gray value: 0.300±0.104 vs. 0.732±0.131, 0.312±0.101 vs. 0.678±0.191, both P < 0.05). Observation under light microscope, the VEGF positive cells in AMI model group was increased significantly compared with the sham group (cells/HP: 21.1±2.2 vs. 7.6±1.3, P < 0.05), the VEGF positive cells in UC-MSCs group were increased significantly compared with the AMI model group (cells/HP: 41.5±3.1 vs. 21.1±2.2, P < 0.05). Conclusion Human UC-MSCs could promote angiogenesis by the improvement of VEGF in coronary artery and inhibit the inflammation by the reduction of IL-6 in rats with AMI.
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Objective To evaluate the efficacy of the systemic photodynamic therapy (SPDT)for treating leukemia using a Brown Norway myeloid leukemia (BNML) rat model.Methods The BNML rat model was established by injecting green fluorescent protein (GFP)-LT12 cells into the tail vein.After GFP-LT12 injection,the early-SPDT group,mid-SPDT group and late-SPDT group were treated with SPDT at 5,10 and 15 days,the negative control group was fed as usually,and the Ara-c positive control group was treated with Ara-c at 7 days.The GFP-LT12 cells were traced by a fluorescence imaging system.The GFP-LT12 cells in the tissues and organs were detected by flow cytometry.The levels of IFN-γ,IL-1α,IL-1β,IL-2,IL-4,IL-6,IL-10 and TNF-α in serum were detected by milliplex rat cytokine 9 kits.Results Compared with the negative control group,the survival times of the rats in the earlySPDT group,mid-SPDT group and the late-SPDT group were prolonged (all P＜0.05).The ratios of GFP-LT12 cells in pulp and liver were decreased in the late-SPDT group.The levels of IL-1β,IL-10,TNF-α and IFN-γin serum of the late-SPDT group were decreased (all P＜0.05).Conclusion The SPDT is an effective method for the treatment of leukemia,and the anti-tumor immune effect may play a key role in this process.
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Objective To simulate the chemical microenvironment after traumatic brain injury (TBI) and to investigate the effect of this microenvironment on the survival and differentiation of neural stem cells (NSCs).Methods The brain tissue homogenate of TBI rat model was harvested to simulate the chemical microenvironment after TBI.The primary NSCs of rat model were isolated and extraction,and then identified the phenotype characteristics with immunofluorescence staining.The experiments were divided into control group,normal brain tissue extract group (BTE group) and traumatic brain injury tissue extract group (TBITE group).The cell growth and morphological changes of each group were observed dynamically.The expression of apoptosis related protein,which includes Bax,Bcl-2,caspase-3 and cleaved caspase-3,were detected by Western Blot 24 h after experiments.The proliferation of NSCs was detected by MTT assay and Western Blot after 3 days.The differentiation level of NSCs to neurons was detected by immunofluorescence staining after 7 days.Results The results of Western Blot showed that compared with the control group,there was no significant change of apoptosis in the BTE group,while the apoptosis in the BTE group was significantly increased,showed a increase of expression levels of Bax (F=18.06,P＜0.01) and Cleaved caspase-3 (F=23.86,P＜0.01),and a decrease of that of Bcl-2 (F=22.95,P＜0.01).The results of MTT assay showed that compared with the BTE group,the proliferation of NSCs in the TBITE group was decreased (F=41.99,P＜0.01).The immunofluorescence staining showed that compared with the control group,the neuronal differentiation rate was increased in the BTE group.Further,compared with the BTE group,the neuronal differentiation rate in the TBITE group was decreased (F=66.93,P＜0.01).Conclusion The injury microenvironment after TBI can significantly inhibit the survival and differentiation of NSCs,which provides a theoretical basis for clarifying the mechanism of endogenous nerve regeneration after TBI.
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Objective To study the effects of umbilical cord mesenchymal stem cells (UCMSCs) on the apoptosis of human breast cancer cell line MCF-7.Methods MCF-7 cells were co-cultured with different concentrations of UCMSCs.The apoptosis of MCF-7 cells was detected by in situ apoptosis and flow cytometry.Nude mouse subcutaneous tumor model was established by inoculating MCF-7 and MSCs cells subcutaneously on the right side of the back of a mouse.The MCF-7 cells were inoculated on the left side of the mouse as control.The tumor volume was measured every week to compare the difference between the two groups.On the 17th day after inoculation,the tumor tissue was harvested and the apoptosis of tumor cells was observed by a transmission electron microscopy.Results In situ apoptosis and flow cytometry showed that the early and late apoptosis rates of MCF-7 cells increased first and then decreased with the increase of UCMSCs concentration.The differences between the control and the MCF-7+UCMSCs group were statistically significant for early (F=39.80,P＜0.001) and late apoptosis rates (F=5.68,P＜0.01).The tumor volume of MCF-7+UCMSCs group was significantly lower than that of control group in 17 days after inoculation (F=9.81,P＜0.01).The representative apoptotic cells were observed by the transmission electron microscopyin the MCF-7 +UCMSCs group.Conclusion The UCMSCs with a certain concentration can effectively promote the apoptosis of MCF-7 cells.This study provides a certain experimental basis for the clinical treatment of breast cancer.
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Cell microencapsulation aims to wrap the living target cells by one or several materials with good biological compatibility and semipermeable membrane properties.Cell microencapsulation not only can achieve immune isolation and prevent the attacks by macromolecular immunes and immune cells,but also can allow the free access of metabolites,small molecule nutrients and bioactive substances to the microcapsule.With the continuous progress of interdisciplinary technologies,cell microencapsulation shows increasing application prospects of making up a variety of limitations of organ transplantation.Moreover,with the development and maturation of cell microencapsulation,it has shown a strong advantage in regenerative medicine,which will certainly promote the rapid development of artificial cells and artificial organs.In this paper,the preparation of cell microcapsules,the effects of the outer membrane of microcapsules on immunological macromolecules and cytokines,the immunogenicity of the outer membrane,and the representative applications of cell microencapsulation were summarized.
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Cell microencapsulation aims to wrap the living target cells by one or several materials with good biological compatibility and semipermeable membrane properties.Cell microencapsulation not only can achieve immune isolation and prevent the attacks by macromolecular immunes and immune cells,but also can allow the free access of metabolites,small molecule nutrients and bioactive substances to the microcapsule.With the continuous progress of interdisciplinary technologies,cell microencapsulation shows increasing application prospects of making up a variety of limitations of organ transplantation.Moreover,with the development and maturation of cell microencapsulation,it has shown a strong advantage in regenerative medicine,which will certainly promote the rapid development of artificial cells and artificial organs.In this paper,the preparation of cell microcapsules,the effects of the outer membrane of microcapsules on immunological macromolecules and cytokines,the immunogenicity of the outer membrane,and the representative applications of cell microencapsulation were summarized.
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Objective To investigate the value and efficacy of continuous renal replacement therapy(CRRT) for treatment of heat stroke patients complicated by multiple organ dysfunction syndrome(MODS). Methods The clinical data of 19 heat stroke patients complicated by MODS admitted into the hospital in a period from July 15,2010 to August 30,2010 and treated by CRRT were analyzed retrospectively. Continuous venovenous hemofiltation(CVVH) mode was used in all patients and the initial temperature of replacement fluid range was 28℃to 32℃persisting in 2.0 to 2.5 hours and afterward it maintained at 36℃. Prognosis and adverse effect were observed,the patients' body temperature,heart rate(HR),mean arterial pressure(MAP),acute physiology and chronic health evaluationⅡ(APACHEⅡ)scores,oxygenation index(PaO2/FiO2),the levels of serum urea nitrogen(BUN),serum creatinine(SCr), myoglobin(Mb),creatine kinase(CK),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and arterial lactate(Lac)were monitored before and after CRRT treatment. Results Fifteen patients were cured or improved,and 4 died. Compared with those before CRRT treatment,body temperature(℃),HR(bmp),MAP(mm Hg,1 mm Hg=0.133 kPa),APACHEⅡevaluation(score),PaO2/FiO2(mm Hg)were significantly improved(body temperature:36.8±0.2 vs. 41.6±0.3,HR:93.6±10.3 vs. 132.5±11.4,MAP:69.8±9.9 vs. 45.2±7.7,APACHEⅡ:12.3±3.9 vs. 29.6±4.6,PaO2/FiO2:213.6±95.4 vs. 126.5±87.4,all P<0.05);the levels of BUN(mmol/L),SCr(μmol/L), Mb(μg/L),CK(U/L),ALT(U/L),AST(U/L),Lac(mmol/L)were significantly reduced after the treatment(BUN:23.9±5.3 vs. 42.6±5.4,SCr:123±47 vs. 356±51,Mb:201±45 vs. 468±39,CK:217±32 vs. 843±41,ALT:79±36 vs. 894±88,AST:57±28 vs. 867±92,Lac:3.5±2.4 vs. 16.6±3.9,all P<0.05). In the process of the treatment,hemodynamics was stable,and no obvious side effects occurred. Conclusion CRRT treatment can exactly and safely reduce the core body temperature of patients with heat stroke,and it can also effectively eliminate metabolites of BUN,Cr,Mb,etc,ameliorate the inflammatory reaction and supporting the functions of liver,kidneys and other vital organs,thus the treatment is also safe and effective for such patients complicated by MODS.