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Microbial necromass carbon (MNC) is an important stable organic C component. However, the variation of MNC and its potential relationship with humus components in composting remains uncertain. During a 45-day chicken manure composting study with and without biochar, MNC ranged from 24.9 to 77.9 g/kg and increased significantly by 80.9 % to 133 %. MNC constituted 5.77 % to 21.3 % of total organic C, with bacterial/fungal necromass C ratio ranging from 0.82 to 1.78. The MNC/humus C ratio ranged from 0.15 to 0.55, and humic acid C showed significant positive associations with bacterial necromass C (R2 = 0.72) and fungal necromass C (R2 = 0.51). Biochar addition reduced electrical conductivity and moisture content, increased pH, and induced microbial phosphorus limitation, thereby enhancing MNC content by 29.2 % and promoting humification. Our study is the first to elucidate the relationship between microbial necromass and humus substances, providing fundamental data for advancing the microbial carbon pump theory in composting.
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Protein aggregation caused by the disruption of proteostasis will lead to cellular cytotoxicity and even cell death, which is implicated in multiple neurodegenerative diseases. The elimination of aggregated proteins is mediated by selective macroautophagy receptors, which is termed aggrephagy. However, the identity and redundancy of aggrephagy receptors in recognizing substrates remain largely unexplored. Here, we find that CCDC50, a highly expressed autophagy receptor in brain, is recruited to proteotoxic stresses-induced polyubiquitinated protein aggregates and ectopically expressed aggregation-prone proteins. CCDC50 recognizes and further clears these cytotoxic aggregates through autophagy. The ectopic expression of CCDC50 increases the tolerance to stress-induced proteotoxicity and hence improved cell survival in neuron cells, whereas CCDC50 deficiency caused accumulation of lipid deposits and polyubiquitinated protein conjugates in the brain of one-year-old mice. Our study illustrates how aggrephagy receptor CCDC50 combats proteotoxic stress for the benefit of neuronal cell survival, thus suggesting a protective role in neurotoxic proteinopathy.Abbreviations: AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; ATG5: autophagy related 5; BODIPY: boron-dipyrromethene; CASP3: caspase 3; CCDC50: coiled-coil domain containing 50; CCT2: chaperonin containing TCP1 subunit 2; CHX: cycloheximide; CQ: chloroquine; CRISPR: clustered regulatory interspaced short palindromic repeat; Cas9: CRISPR-associated system 9; DAPI: 4',6-diamidino-2-phenylindole; FK2: Anti-ubiquitinylated proteins antibody, clone FK2; FUS: FUS RNA binding protein; GFP: green fluorescent protein; HD: Huntington disease; HTT: huntingtin; KEGG: Kyoto Encyclopedia of Genes and Genomes; LDS: LIR-docking site; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPT/tau: microtubule associated protein tau; MIU: motif interacting with ubiquitin; NBR1: NBR1, autophagy cargo receptor; OPTN: optineurin; PD: Parkinson disease; PI: propidium iodide; ROS: reactive oxygen species; SOD1: superoxide dismutase 1; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 binding protein 1; Ub: ubiquitin; UDS: UIM-docking site; UIM: ubiquitin interacting motif; UPS: ubiquitin-proteasome system.
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The maintenance of lysosome homeostasis is crucial for cell growth. Lysosome-dependent degradation and metabolism sustain tumor cell survival. Here, we demonstrate that CCDC50 serves as a lysophagy receptor, promoting tumor progression and invasion by controlling lysosomal integrity and renewal. CCDC50 monitors lysosomal damage, recognizes galectin-3 and K63-linked polyubiquitination on damaged lysosomes, and specifically targets them for autophagy-dependent degradation. CCDC50 deficiency causes the accumulation of ruptured lysosomes, impaired autophagic flux, and superfluous reactive oxygen species, consequently leading to cell death and tumor suppression. CCDC50 expression is associated with malignancy, progression to metastasis, and poor overall survival in human melanoma. Targeting CCDC50 suppresses tumor growth and lung metastasis, and enhances the effect of BRAFV600E inhibition. Thus, we demonstrate critical roles of CCDC50-mediated clearance of damaged lysosomes in supporting tumor growth, hereby identifying a potential therapeutic target of melanoma.
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The assembly of the NLRP3 inflammasome can be initiated by a wide range of stimuli including exogenous infection as well as endogenous damage. Therefore, the tight regulation of the NLRP3 inflammasome is crucial for the host to resist microbial invasion and maintain homeostasis. Our recent work has identified a negative regulator of NLRP3-mediated inflammation, namely CCDC50 (coiled-coil domain containing protein 50). CCDC50 can be induced by NLRP3 agonists and then functions as a macroautophagy/autophagy cargo receptor to recognize K63-polyubiquitinated NLRP3 and deliver it to MAP1LC3/LC3-conjugated phagophores for degradation. CCDC50 inhibits the polymerization of NLRP3 and the recruitment of PYCARD/ASC, consequently suppressing the assembly of inflammasomes. ccdc50-knockout mice are more susceptible to dextran-sulfate (DSS)-induced colitis and exhibit more severe gut inflammation with elevated NLRP3 inflammasome activity, suggesting a protective role of CCDC50 in the pathology and progression of inflammatory bowel disease (IBD). Our finding reveals a function of autophagy-related proteins in the regulation of NLRP3-mediated inflammation, thus demonstrating the intricate crosstalk between autophagy and inflammation.
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Colite , Inflamassomos , Peptídeos e Proteínas de Sinalização Intracelular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Camundongos , Autofagia , Colite/induzido quimicamente , Colite/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
The performance of garden waste on spent mushroom substrate (SMS) and chicken manure (CM) co-composting efficiency and humification is unclear. Therefore, this study investigated the impact of garden waste addition on SMS-CM co-composting physicochemical properties, humification process, and the spectral characteristics of dissolved organic matter (DOM). The results showed that garden waste improved the physicochemical properties of SMS-CM co-compost, the thermophilic period was advanced 2 days, the seed germination index increased by 30.2%, and the total organic carbon and total nitrogen content increased by 8.80% and 15.0%, respectively. In addition, garden waste increased humic substances (HS) and humic acid (HA) contents by 10.62% and 34.52%, respectively; the HI, PHA and DP increased by 31.53%, 43.19% and 55.53%, respectively; and the SUVA254 and SUVA280 of DOM also increased by 6.39% and 4.39%, respectively. In particular, HA content and DOM humification increase rapidly in the first 10 days. The increase of HA accounted for 52% of the total increase during composting. Fourier-transform infrared and two-dimensional correlation analysis further confirmed that garden waste could facilitate the degradation of organic molecules, including amino acids, polysaccharides, carboxyl groups, phenols, and alcohol, and contributed to the preferential utilization of carboxyl groups and polysaccharides and thus enhanced humification.
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Agaricales , Compostagem , Animais , Solo , Matéria Orgânica Dissolvida , Esterco , Galinhas , Jardins , Substâncias HúmicasRESUMO
Based on the measured water quality data of Huangyuan County, Huzhu Tu Autonomous County, and Minhe Hui Tu Autonomous County in Hehuang Valley of Qinghai province in the normal and wet seasons, the effects of land use and land cover patterns on regional seasonal water quality were analyzed using remote sensing technology and mathematical statistics. The results showed that:â the concentrations of total nitrogen and total phosphorus in the surface water of Hehuang Valley were high. Water pollution areas (Class â £ and â ¤) were mainly concentrated in the lower reaches of the river and the junction of tributaries. â¡ The explanation rate of land use to water quality in the normal season was higher than that in the wet season. The optimal scale was the 200 m buffer scale in the normal season, and farmland and towns were the main influencing factors. The optimal scale in the wet season was the 5 km buffer scale, and the main influencing factor was the forest. ⢠In the normal season, the proportion of farmland was positively correlated with the concentration of total nitrogen and permanganate index but negatively correlated with the concentration of total phosphorus. The proportion of town area was positively correlated with the water quality index. The proportion of grassland area in the wet season was positively correlated with the permanganate index. The proportion of forestland area was negatively correlated with water quality index in both periods. Farmland, grassland, and town areas were the "source" landscape of pollutants, but farmland also played a role in intercepting pollutants to a certain extent. Forest land was the "sink" landscape of pollutants. ⣠The pattern of forestland in the 200 m buffer zone in the normal season had a high explanatory rate for water quality, and the largest patch index (LPI) and patch density (PD) were the main factors. The study showed that it is an important measure to purify the surface water quality of Hehuang Valley by rationally planning the proportion of residential land and cultivated land and improving the coverage rate and aggregation degree of forestland around the riparian zone.
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Poluentes Ambientais , Poluentes Químicos da Água , China , Monitoramento Ambiental/métodos , Nitrogênio/análise , Fósforo/análise , Rios , Poluentes Químicos da Água/análise , Qualidade da ÁguaRESUMO
Microglia-induced neuroinflammation plays a critical role in neurological diseases. At present, RIPK2 is considered to participate in inflammatory and autoimmune cellular pathways and diseases. RIPK2 is found to be a pivotal therapeutic target in neurologic disorders related to inflammation. In our research, we discovered the protective function of tunicatachalcone (TC) against neuroinflammation. TC is a natural chalcone compound derived from Pongamia pinnata, a medicinal plant. The results revealed that TC (5-20 µM) ameliorated the activation of BV-2 microglia induced by lipopolysaccharide (LPS) in a dose-dependent way, which was proved by the reduced production of inflammation-related mediators. By using SPR-LC-MS/MS analysis, we revealed the potent inhibitory function of TC against neuroinflammation mediated by microglia via targeting RIPK2. A strong binding between TC and RIPK2 was further demonstrated based on the results of SPR, MST and molecular modeling. Through applying mRNA transcriptomics and bioinformatics analysis, it was demonstrated that TC could mediate RIPK2-dependent gene transcription to exert the neuroprotective effect. In summary, our research presented that RIPK2 was a possible therapeutic target of TC.
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Produtos Biológicos , Microglia , Produtos Biológicos/farmacologia , Cromatografia Líquida , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Doenças Neuroinflamatórias , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/metabolismo , Proteína Serina-Treonina Quinase 2 de Interação com Receptor/farmacologia , Espectrometria de Massas em TandemRESUMO
Glioblastoma (GBM) is among the most aggressive human cancers. Although oncolytic virus (OV) therapy has been proposed as a potential approach to treat GBM, it frequently fails because GBM cells are usually nonpermissive to OV. Here, we describe a dual-step drug screen for identifying chemical enhancers of OV in GBM. From a high-throughput screen of 1416 FDA-approved drugs, an inhibitor of CDK4/6 was identified as the top enhancer, selectively increasing potency of two OV strains, VSVΔ51 and Zika virus. Mechanistically, CDK4/6 inhibition promoted autophagic degradation of MAVS, resulting in impaired antiviral responses and enhanced tumor-selective replication of VSVΔ51 in vitro and in vivo. CDK4/6 inhibition cooperated with VSVΔ51 to induce severe DNA damage stress and amplify oncolysis. In GBM xenograft models, combined treatment with CDK4/6 inhibitor and VSVΔ51 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. Further investigation revealed that CDK4/6 inhibitor and VSVΔ51 synergistically induced immunogenic cell death and boosted antitumor immunity. Together, this study features a promising approach of treating aggressive GBM through the combination of CDK4/6 inhibitor with OV. SIGNIFICANCE: This study proposes inhibition of cyclin-dependent kinases as a clinically translatable combinatorial strategy to enhance the efficacy of oncolytic virotherapy in GBM.
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Neoplasias Encefálicas , Glioblastoma , Terapia Viral Oncolítica , Vírus Oncolíticos , Infecção por Zika virus , Zika virus , Animais , Antivirais , Neoplasias Encefálicas/metabolismo , Morte Celular , Linhagem Celular Tumoral , Quinase 4 Dependente de Ciclina , Quinases Ciclina-Dependentes , Glioblastoma/patologia , Humanos , Camundongos , Terapia Viral Oncolítica/métodos , Linfócitos T/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Infecção por Zika virus/tratamento farmacológicoRESUMO
The iminoboryl o-carboranes (Me3Si)-Cb-B≡N-R (Cb = B10C2H10, 3a, R = SiMe3; 3b, R = tBu) have been successfully synthesized by tetrahydrofuran (THF)-promoted isomerization from the corresponding o-carborane-fused aminoboriranes Cb{BN(SiMe3)R} (2). The synthetic protocol of the previously reported borirane 2a was optimized. The borirane Cb{BN(SiMe3)tBu} (2b) and the iminoboranes 3a and 3b were fully characterized by NMR, IR, and single-crystal X-ray diffraction analyses. The borirane 2a isomerizes more readily than 2b. The kinetics study revealed a bimolecular mechanism between borirane and THF, which is in good agreement with the computationally proposed reaction pathway. The title compounds are thermally robust, but compound 3a dimerized in the presence of a catalytic amount of tBuNC to give the cyclodimer 4. Quick equilibrium between 4 and the isonitrile adduct 4·tBuNC was observed in solution.
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The NLRP3-directed inflammasome complex is crucial for the host to resist microbial infection and monitor cellular damage. However, the hyperactivation of NLRP3 inflammasome is implicated in pathogenesis of inflammatory diseases, including inflammatory bowel disease (IBD). Autophagy and autophagy-related genes are closely linked to NLRP3-mediated inflammation in these inflammatory disorders. Here, we report that CCDC50, a novel autophagy cargo receptor, negatively regulates NLRP3 inflammasome assembly and suppresses the cleavage of pro-caspase-1 and interleukin 1ß (IL-1ß) release by delivering NLRP3 for autophagic degradation. Transcriptome analysis showed that knockdown of CCDC50 results in upregulation of signaling pathways associated with autoinflammatory diseases. CCDC50 deficiency leads to enhanced proinflammatory cytokine response triggered by a wide range of endogenous and exogenous NLRP3 stimuli. Ccdc50-deficient mice are more susceptible to dextran sulfate (DSS)-induced colitis and exhibit more severe gut inflammation with elevated NLRP3 inflammasome activity. These results illustrate the physiological significance of CCDC50 in the pathogenicity of inflammatory diseases, suggesting protective roles of CCDC50 in keeping gut inflammation under control.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Autofagia , Sulfato de Dextrana/toxicidade , Inflamassomos/genética , Inflamação , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genéticaRESUMO
DNA sensing and timely activation of interferon (IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells. However, overactivation of immune responses may lead to tissue damage and autoimmune diseases; therefore, these processes must be intricately regulated. STING is the key adaptor protein, which is activated by cyclic GMP-AMP, the second messenger derived from cGAS-mediated DNA sensing. Here, we report that CCDC50, a newly identified autophagy receptor, tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for degradation. Knockout of CCDC50 significantly increases herpes simplex virus 1 (HSV-1)- or DNA ligand-induced production of type I IFN and proinflammatory cytokines. Ccdc50-deficient mice show increased production of IFN, decreased viral replication, reduced cell infiltration, and improved survival rates compared with their wild-type littermates when challenged with HSV-1. Remarkably, the expression of CCDC50 is downregulated in systemic lupus erythematosus (SLE), a chronic autoimmune disease. CCDC50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE patients. CCDC50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE serum. Thus, our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation.
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Doenças Autoimunes , Interferon Tipo I , Viroses , Animais , Autofagia , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Interferons , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Camundongos , Camundongos KnockoutRESUMO
Nuclear factor κB (NF-κB)-mediated signaling pathway plays a crucial role in the regulation of inflammatory process, innate and adaptive immune responses. The hyperactivation of inflammatory response causes host cell death, tissue damage, and autoinflammatory disorders, such as sepsis and inflammatory bowel disease. However, how these processes are precisely controlled is still poorly understood. In this study, we demonstrated that ankyrin repeat and suppressor of cytokine signaling box containing 1 (ASB1) is involved in the positive regulation of inflammatory responses by enhancing the stability of TAB2 and its downstream signaling pathways, including NF-κB and mitogen-activated protein kinase pathways. Mechanistically, unlike other members of the ASB family that induce ubiquitination-mediated degradation of their target proteins, ASB1 associates with TAB2 to inhibit K48-linked polyubiquitination and thereby promote the stability of TAB2 upon stimulation of cytokines and lipopolysaccharide (LPS), which indicates that ASB1 plays a noncanonical role to further stabilize the target protein rather than induce its degradation. The deficiency of Asb1 protects mice from Salmonella typhimurium- or LPS-induced septic shock and increases the survival of mice. Moreover, Asb1-deficient mice exhibited less severe colitis and intestinal inflammation induced by dextran sodium sulfate. Given the crucial role of ASB proteins in inflammatory signaling pathways, our study offers insights into the immune regulation in pathogen infection and inflammatory disorders with therapeutic implications.
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Colite/imunologia , NF-kappa B/imunologia , Processamento de Proteína Pós-Traducional , Infecções por Salmonella/imunologia , Choque Séptico/imunologia , Proteínas Supressoras da Sinalização de Citocina/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Colite/induzido quimicamente , Colite/genética , Colite/mortalidade , Sulfato de Dextrana , Genes Reporter , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos , Luciferases/genética , Luciferases/imunologia , MAP Quinase Quinase Quinases/genética , MAP Quinase Quinase Quinases/imunologia , Camundongos , Camundongos Knockout , NF-kappa B/genética , Ligação Proteica , Infecções por Salmonella/genética , Infecções por Salmonella/microbiologia , Infecções por Salmonella/mortalidade , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Choque Séptico/induzido quimicamente , Choque Séptico/genética , Choque Séptico/mortalidade , Transdução de Sinais , Proteínas Supressoras da Sinalização de Citocina/genética , Análise de Sobrevida , UbiquitinaçãoRESUMO
Autophagy is a conserved process that delivers cytosolic substances to the lysosome for degradation, but its direct role in the regulation of antiviral innate immunity remains poorly understood. Here, through high-throughput screening, we discovered that CCDC50 functions as a previously unknown autophagy receptor that negatively regulates the type I interferon (IFN) signaling pathway initiated by RIG-I-like receptors (RLRs), the sensors for RNA viruses. The expression of CCDC50 is enhanced by viral infection, and CCDC50 specifically recognizes K63-polyubiquitinated RLRs, thus delivering the activated RIG-I/MDA5 for autophagic degradation. The association of CCDC50 with phagophore membrane protein LC3 is confirmed by crystal structure analysis. In contrast to other known autophagic cargo receptors that associate with either the LIR-docking site (LDS) or the UIM-docking site (UDS) of LC3, CCDC50 can bind to both LDS and UDS, representing a new type of cargo receptor. In mouse models with RNA virus infection, CCDC50 deficiency reduces the autophagic degradation of RIG-I/MDA5 and promotes type I IFN responses, resulting in enhanced viral resistance and improved survival rates. These results reveal a new link between autophagy and antiviral innate immune responses and provide additional insights into the regulatory mechanisms of RLR-mediated antiviral signaling.
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Proteína DEAD-box 58/metabolismo , Helicase IFIH1 Induzida por Interferon/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Vírus de RNA/fisiologia , Receptores Imunológicos/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , Humanos , Interferon Tipo I/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/metabolismo , NF-kappa B/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , UbiquitinaçãoRESUMO
Innate immunity is the first-line defense against antiviral or antimicrobial infection. RIG-I and MDA5, which mediate the recognition of pathogen-derived nucleic acids, are essential for production of type I interferons (IFN). Here, we identified mitochondrion depolarization inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibited the response and antiviral activity of type I IFN during viral infection. Furthermore, we found that the PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin mediated mitophagy, thus negatively regulating the activation of RIG-I and MDA5. Parkin directly interacted with and catalyzed the K48-linked polyubiquitination and subsequent degradation of RIG-I and MDA5. Thus, we demonstrate that Parkin limits RLR-triggered innate immunity activation, suggesting Parkin as a potential therapeutic target for the control of viral infection.
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Proteína DEAD-box 58/metabolismo , Imunidade Inata , Helicase IFIH1 Induzida por Interferon/metabolismo , Mitocôndrias/imunologia , Receptores Imunológicos/metabolismo , Vírus Sendai/imunologia , Ubiquitina-Proteína Ligases/metabolismo , Vesiculovirus/imunologia , Células A549 , Animais , Chlorocebus aethiops , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Hidrazonas/farmacologia , Imunidade Inata/efeitos dos fármacos , Interferon Tipo I/metabolismo , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/virologia , Mitofagia , Proteínas Quinases/metabolismo , Células RAW 264.7 , Vírus Sendai/genética , Vírus Sendai/patogenicidade , Células THP-1 , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Desacopladores/farmacologia , Células Vero , Vesiculovirus/genética , Vesiculovirus/patogenicidadeRESUMO
OBJECTIVE: To study the therapeutic effects and its mechanism of combination of hemofiltration (HF) and peritoneal dialysis (PD) in the treatment of severe acute pancreatitis (SAP). METHODS: Forty patients with SAP were divided at random into the HF + PD group (therapeutic group, 25 patients) and the non-HF + PD group (contrast group, 15 patients). Both groups were treated by the conventional mode of therapy. The release time of abdominal pain and distention, CT scores, APACHE II scores, the time of hospital stay, cost of treatment in hospital, operative rate and rate of complications and recovered rate of the two groups were compared. Simultaneously, the concentration of serum and fluid filtrated pro-inflammatory cytokines TNF, IL-6 and IL-8 were also determined pro and post the therapy. RESULTS: The time needed for the disappearance of abdominal pain and the amelioration of abdominal distension, CT scores, APACHE II scores, the average hospital stay and hospital cost of the therapeutic group were significantly decreased compared with those of the contrast group. The cytokines detected at the end of 1d, 2d after HF + PD were decreased significantly compared with those observed in pro HF + PD and the contrast group. CONCLUSIONS: The above results show that the cytokines overproduced during the development of SAP can be removed effectively from the circulation and the fluid filtrated by means of HF + PD. The continual deterioration of the local focus and systemtic presentation could be prevented effectively too, and the earlier the treatment of HF + PD, the better the prognosis.