RESUMO
The spread of pathological α-synuclein (α-syn) is a crucial event in the progression of Parkinson's disease (PD). Cell surface receptors such as lymphocyte activation gene 3 (LAG3) and amyloid precursor-like protein 1 (APLP1) can preferentially bind α-syn in the amyloid over monomeric state to initiate cell-to-cell transmission. However, the molecular mechanism underlying this selective binding is unknown. Here, we perform an array of biophysical experiments and reveal that LAG3 D1 and APLP1 E1 domains commonly use an alkaline surface to bind the acidic C terminus, especially residues 118 to 140, of α-syn. The formation of amyloid fibrils not only can disrupt the intramolecular interactions between the C terminus and the amyloid-forming core of α-syn but can also condense the C terminus on fibril surface, which remarkably increase the binding affinity of α-syn to the receptors. Based on this mechanism, we find that phosphorylation at serine 129 (pS129), a hallmark modification of pathological α-syn, can further enhance the interaction between α-syn fibrils and the receptors. This finding is further confirmed by the higher efficiency of pS129 fibrils in cellular internalization, seeding, and inducing PD-like α-syn pathology in transgenic mice. Our work illuminates the mechanistic understanding on the spread of pathological α-syn and provides structural information for therapeutic targeting on the interaction of α-syn fibrils and receptors as a potential treatment for PD.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Amiloide/metabolismo , Antígenos CD/metabolismo , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , Animais , Linhagem Celular Tumoral , Endocitose , Humanos , Camundongos , Degeneração Neural/patologia , Neurônios/metabolismo , Fosforilação , Fosfosserina/metabolismo , Ligação Proteica , Eletricidade Estática , alfa-Sinucleína/química , alfa-Sinucleína/toxicidade , Proteína do Gene 3 de Ativação de LinfócitosRESUMO
The BAX protein is a pro-apoptotic member of the Bcl-2 family, which triggers apoptosis by causing permeabilization of the mitochondrial outer membrane. However, the activation mechanism of BAX is far from being understood. Although a few small-molecule BAX activators have been reported in the literature, their crystal structures in complex with BAX have not been resolved. So far, their binding modes were modeled at most by simple molecular docking efforts. Lack of an in-depth understanding of the activation mechanism of BAX hinders the development of more effective BAX activators. In this work, we employed cosolvent molecular dynamics simulation to detect the potential binding sites on the surface of BAX and performed a long-time molecular dynamics simulation (50 µs in total) to derive the possible binding modes of three BAX activators (i.e., BAM7, BTC-8, and BTSA1) reported in the literature. Our results indicate that the trigger, S184, and vMIA sites are the three major binding sites on the full-length BAX structure. Moreover, the canonical hydrophobic groove is clearly detected on the α9-truncated BAX structure, which is consistent with the outcomes of relevant experimental studies. Interestingly, it is observed that solvent probes bind to the trigger bottom pocket more stably than the PPI trigger site. Each activator was subjected to unbiased molecular dynamics simulations started at the three major binding sites in five parallel jobs. Our MD results indicate that all three activators tend to stay at the trigger site with favorable MM-GB/SA binding energies. BAM7 and BTSA1 can enter the trigger bottom pocket and thereby enhance the movement of the α1-α2 loop, which may be a key factor at the early stage of BAX activation. Our molecular modeling results may provide useful guidance for designing smart biological experiments to further explore BAX activation and directing structure-based efforts toward discovering more effective BAX activators.
Assuntos
Membranas Mitocondriais , Simulação de Dinâmica Molecular , Proteína X Associada a bcl-2/metabolismo , Simulação de Acoplamento Molecular , Membranas Mitocondriais/metabolismo , Sítios de Ligação , ApoptoseRESUMO
In recent years, protein-ligand interaction scoring functions derived through machine-learning are repeatedly reported to outperform conventional scoring functions. However, several published studies have questioned that the superior performance of machine-learning scoring functions is dependent on the overlap between the training set and the test set. In order to examine the true power of machine-learning algorithms in scoring function formulation, we have conducted a systematic study of six off-the-shelf machine-learning algorithms, including Bayesian Ridge Regression (BRR), Decision Tree (DT), K-Nearest Neighbors (KNN), Multilayer Perceptron (MLP), Linear Support Vector Regression (L-SVR), and Random Forest (RF). Model scoring functions were derived with these machine-learning algorithms on various training sets selected from over 3700 protein-ligand complexes in the PDBbind refined set (version 2016). All resulting scoring functions were then applied to the CASF-2016 test set to validate their scoring power. In our first series of trial, the size of the training set was fixed; while the overall similarity between the training set and the test set was varied systematically. In our second series of trial, the overall similarity between the training set and the test set was fixed, while the size of the training set was varied. Our results indicate that the performance of those machine-learning models are more or less dependent on the contents or the size of the training set, where the RF model demonstrates the best learning capability. In contrast, the performance of three conventional scoring functions (i.e., ChemScore, ASP, and X-Score) is basically insensitive to the use of different training sets. Therefore, one has to consider not only "hard overlap" but also "soft overlap" between the training set and the test set in order to evaluate machine-learning scoring functions. In this spirit, we have complied data sets based on the PDBbind refined set by removing redundant samples under several similarity thresholds. Scoring functions developers are encouraged to employ them as standard training sets if they want to evaluate their new models on the CASF-2016 benchmark.
Assuntos
Aprendizado de Máquina , Proteínas , Algoritmos , Teorema de Bayes , Ligantes , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: This study aimed to investigate the association between enhanced recovery after surgery (ERAS) nursing program and stoma-related complications (SRCs) and prognosis in patients with low rectal cancer (LRC) undergoing abdominoperineal resection with sigmoidostomy. METHODS: LRC patients who underwent elective abdominoperineal resection with sigmoidostomy between May 2016 and May 2019 were retrospectively enrolled. The occurrence of early major or minor SRCs (within postoperative 30 days) was set as the primary end-point. Clinicopathological variables and laboratory tests were compared between patients with or without SRCs. The univariate and multivariate logistic regression analyses were performed to investigate risk factors for SRCs. Hospitalization satisfaction-related and prognosis-related variables were compared between LRC patients with or without ERAS nursing program. RESULTS: A total of 288 patients were enrolled and the incidence of SRCs was 26.7% (77/288). ERAS nursing program was the only independent risk factor for SRCs in LRC patients (OR 2.04, 95%CI 1.31-3.12, P = 0.016) by the multivariate logistic regression analysis. Moreover, ERAS nursing program was associated with higher hospitalization satisfaction rate, faster bowel function recovery, better psychological status, and higher quality of life. CONCLUSIONS: ERAS nursing program was a protective factor for SRCs and associated with improved prognosis in LRC patients undergoing elective abdominoperineal resection with sigmoidostomy.
Assuntos
Recuperação Pós-Cirúrgica Melhorada , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Protectomia , Avaliação de Programas e Projetos de Saúde , Fatores de Proteção , Estudos Retrospectivos , Sigmoidoscopia , Estomas Cirúrgicos , Resultado do TratamentoRESUMO
The host-guest properties of [15]paracyclophane ([15]PCPs) are engendered by π-metalation, which exhibits fantastic regioselectivity toward a macrocyclic molecule. The synthesis and characterization of mono-, di-, and trimetalated [15]PCPs are discussed in this article, and the anion binding behavior of 3Ru-[15]PCP-II6+, one of the trimetalated [15]PCPs, driven by anion-π interactions, is comprehensively demonstrated in both solution and the solid state. The anion binding properties of 3Ru-[15]PCP-II6+ in solution are investigated by 1H NMR titrations, showing selectivity toward ReO4- in both organic and aqueous solutions. The binding mode is unexpected; the anionic guest stacks over the host rather than threads it. This selectivity for ReO4- is also supported by water-nitromethane extraction experiments, which demonstrate that its partition from water into the organic phase by 3Ru-[15]PCP-II·6OTf is maintained to some extent in the presence of excess Cl-, SO42-, H2PO4-, NO3-, and ClO4-.
RESUMO
In structure-based drug design, scoring functions are often employed to evaluate protein-ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benchmark developed by us provides an answer to this demand. CASF is designed as a "scoring benchmark", where the scoring process is decoupled from the docking process to depict the performance of scoring function more precisely. Here, we describe the latest update of this benchmark, i.e., CASF-2016. Each scoring function is still evaluated by four metrics, including "scoring power", "ranking power", "docking power", and "screening power". Nevertheless, the evaluation methods have been improved considerably in several aspects. A new test set is compiled, which consists of 285 protein-ligand complexes with high-quality crystal structures and reliable binding constants. A panel of 25 scoring functions are tested on CASF-2016 as a demonstration. Our results reveal that the performance of current scoring functions is more promising in terms of docking power than scoring, ranking, and screening power. Scoring power is somewhat correlated with ranking power, so are docking power and screening power. The results obtained on CASF-2016 may provide valuable guidance for the end users to make smart choices among available scoring functions. Moreover, CASF is created as an open-access benchmark so that other researchers can utilize it to test a wider range of scoring functions. The complete CASF-2016 benchmark will be released on the PDBbind-CN web server ( http://www.pdbbind-cn.org/casf.asp/ ) once this article is published.
Assuntos
Quimioinformática/métodos , Desenho de Fármacos , LigantesRESUMO
Addressing the challenge of accurately monitoring polycyclic aromatic hydrocarbons (PAHs) in aquatic systems, this study employed diffusive gradients in thin-films (DGT) technique to achieve methods detection limits as low as 0.02 ng L-1 to 0.05 ng L-1 through in situ preconcentration and determination of time-integrated concentrations. The efficacy of the developed DGT samplers was validated under diverse environmental conditions, demonstrating independence from factors such as pH (5.03-9.01), dissolved organic matter (0-20 mg L-1), and ionic strength (0.0001-0.6 M). Notably, the introduction of a novel theoretical approach to calculate diffusion coefficients based on solvent-accessible volume tailored for PAHs significantly enhanced the method's applicability, particularly for organic pollutants with low solubility. Field deployments in coastal zones validated the DGT method against traditional grab sampling, with findings advocating a 4 to 7-day optimal deployment duration for balancing sensitivity and mitigating lag time effects. These results provide a sophisticated, efficient solution to the persistent challenge of monitoring hydrophobic organic pollutants in aquatic environments, broadening the scope and applicability of DGT in environmental science and providing a robust tool for researchers.
RESUMO
Objective: This study aimed to investigate the effect of nursing intervention based on the G-Caprini scale on the incidence of venous thromboembolism (VTE) after gynecological surgery and patients' satisfaction rate for nursing care. Methods: Ninety-eight patients who attended Taizhou People's Hospital and underwent gynecological surgery between January 2021 and December 2021 were selected as subjects and divided into two groups according to a random number table, with 49 cases in each group. The control group was given conventional nursing care, and the experimental group received nursing intervention based on the G-Caprini scale. The rate of postoperative lower-limb deep-vein thrombosis in the two groups was compared, and the incidence of VTE and the level of nursing satisfaction in the two groups were statistically analyzed. Results: The incidence of postoperative VTE in each risk class of the G-Caprini scale was lower in the experimental group than in the control group, and the difference was statistically significant (P < 0.01). In the experimental group, 47 patients were very satisfied with the nursing care, 1 was satisfied, and 1 was dissatisfied, which meant the nursing satisfaction rate in the experimental group was 97.96 (48/49). In the control group, 40 patients were very satisfied with the nursing care, 2 were satisfied, 1 was basically satisfied, and 6 were dissatisfied; thus, the satisfaction rate for nursing care in the control group was 87.75%. The difference between the two groups was statistically significant (χ 2 = 19.657, p < 0.05). Conclusion: Nursing interventions based on the G-Caprini rating scale were significantly effective in preventing VTE in patients after gynecological surgery and resulted in higher levels of patient satisfaction in terms of nursing care.
RESUMO
Beclin 1 is an essential autophagy gene and a haploinsufficient tumor suppressor. Beclin 1 is the scaffolding member of the Class III phosphatidylinositol-3-kinase complex (PI3KC3) and recruits two positive regulators Atg14L and UVRAG through its coiled-coil domain to upregulate PI3KC3 activity. Our previous work has shown that hydrocarbon-stapled peptides targeted to the Beclin 1 coiled-coil domain reduced Beclin 1 homodimerization and promoted the Beclin 1-Atg14L/UVRAG interaction. These peptides also induced autophagy and enhanced the endolysosomal degradation of cell surface receptors like EGFR. Here, we present the optimization of these Beclin 1-targeting peptides by staple scanning and sequence permutation. Placing the hydrocarbon staple closer to the Beclin 1-peptide interface enhanced their binding affinity by â¼10- to 30-fold. Optimized peptides showed potent antiproliferative efficacy in cancer cells that overexpressed EGFR and HER2 by inducing necrotic cell death but not apoptosis. Our Beclin 1-targeting stapled peptides may serve as effective therapeutic candidates for EGFR- or HER2-driven cancer.
Assuntos
Antineoplásicos/farmacologia , Proteína Beclina-1/metabolismo , Proliferação de Células/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Antineoplásicos/química , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Receptores ErbB/metabolismo , Células HEK293 , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Necrose/induzido quimicamente , Peptídeos/química , Conformação Proteica , Proteólise , Receptor ErbB-2/metabolismoRESUMO
Human heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) serves as a key regulating protein in RNA metabolism. Malfunction of hnRNPA1 in nucleo-cytoplasmic transport or dynamic phase separation leads to abnormal amyloid aggregation and neurodegeneration. The low complexity (LC) domain of hnRNPA1 drives both dynamic phase separation and amyloid aggregation. Here, we use cryo-electron microscopy to determine the amyloid fibril structure formed by hnRNPA1 LC domain. Remarkably, the structure reveals that the nuclear localization sequence of hnRNPA1 (termed PY-NLS), which is initially known to mediate the nucleo-cytoplamic transport of hnRNPA1 through binding with karyopherin-ß2 (Kapß2), represents the major component of the fibril core. The residues that contribute to the binding of PY-NLS with Kapß2 also exert key molecular interactions to stabilize the fibril structure. Notably, hnRNPA1 mutations found in familial amyotrophic lateral sclerosis (ALS) and multisystem proteinopathoy (MSP) are all involved in the fibril core and contribute to fibril stability. Our work illuminates structural understandings of the pathological amyloid aggregation of hnRNPA1 and the amyloid disaggregase activity of Kapß2, and highlights the multiple roles of PY-NLS in hnRNPA1 homeostasis.
Assuntos
Amiloide/metabolismo , Núcleo Celular/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/química , Ribonucleoproteína Nuclear Heterogênea A1/genética , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Transporte Ativo do Núcleo Celular , Esclerose Lateral Amiotrófica , Microscopia Crioeletrônica , Células HEK293 , Humanos , Carioferinas/metabolismo , Modelos Moleculares , Mutação , Conformação Proteica , Domínios ProteicosRESUMO
Congenital long QT syndrome (LQTS) is a cardiac electrophysiological disorder due to genetic mutations. Patients with LQTS, if untreated, have a high incidence of ventricular tachycardia and cardiac arrest. Adrenergic activities are believed to play a major role in triggering the onset of cardiac events. The current mainstay of therapy for LQTS is oral beta-blockers, which improves clinical symptoms and reduces the incidence of sudden cardiac death in approximately 70% of the patients. Left cardiac sympathetic denervation (LCSD) is an alternative therapy for patients who are resistant to beta-blockers. Its clinical use, however, has been hindered by the complexity of the procedure and complications after the surgery. Video-assisted thoracoscopic sympathectomy has been used to treat patients with palmar and axillary hyperhidrosis. We suggest that the use of the microinvasice thoracoscopic technique may greatly simplify the LSCD procedure, making it the first-line therapy for LQTS.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Coração/inervação , Síndrome do QT Longo/congênito , Síndrome do QT Longo/cirurgia , Microcirurgia/métodos , Simpatectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Ensaios Clínicos como Assunto , Medicina Baseada em Evidências , Humanos , Resultado do TratamentoRESUMO
Previous studies have shown that an increase in coronary flow or shear force enhances the oxygen consumption and contractility of myocardium (the "Gregg effect"). Recent studies have indicated that an increase in coronary shear force also affects atrioventricular conduction and ventricular repolarization. The mechanisms of "Gregg effect" and the shear force-induced alterations in cardiac electrophysiology are unclear. It has been proposed that the distension of the coronary arteries and the stretch of the surrounding myocytes may play a key role but this is not supported by the latest studies. Intracoronary perfusion increases coronary endothelial synthesis of nitric oxide and prostacyclin. Emerging evidence has indicated that both nitric oxide and prostacyclin prolong the action potential duration or effective refractory period in the in vitro and in vivo animal heart. We therefore hypothesized that shear force-induced alterations in cardiac function and electrophysiology are largely attributed to the enhanced endothelial release of nitric oxide and prostacyclin.
Assuntos
Circulação Coronária/fisiologia , Endotélio Vascular/fisiologia , Sistema de Condução Cardíaco/fisiologia , Mecanotransdução Celular/fisiologia , Modelos Cardiovasculares , Óxido Nítrico/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Resistência ao Cisalhamento , Estresse MecânicoRESUMO
Patients with rheumatoid arthritis (RA) have an increased prevalence of coronary heart disease and a high cardiovascular mortality rate. The causes of increased coronary heart disease in RA patients are poorly understood. Conventional cardiovascular risk factors, such as inactivity, overweight or dyslipidemia may play a role, but they do not seem to be wholly responsible for the increased cardiovascular risk. RA is associated with a high incidence of inflammation and vascular endothelial injuries. Endothelial dysfunction is one of the key steps in the pathogenesis of atherosclerosis in non-RA patients. Therefore, we hypothesized that inflammation-induced vascular endothelial injuries may be responsible for the increased risk of coronary heart disease and high rates of cardiovascular mortality in patients with RA.
Assuntos
Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Doença das Coronárias/epidemiologia , Doença das Coronárias/imunologia , Endotélio Vascular/imunologia , Vasculite/epidemiologia , Vasculite/imunologia , Causalidade , Ensaios Clínicos como Assunto , Comorbidade , Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/imunologia , Endotélio Vascular/lesões , Humanos , Modelos Cardiovasculares , Modelos Imunológicos , Medição de Risco/métodos , Fatores de RiscoRESUMO
Assessment of the spatial dispersion of ventricular refractory periods has become an important part of electrophysiological study in both experimental and clinical settings, because inhomogeneity of ventricular refractoriness is associated with an increased risk of life-threatening ventricular arrhythmias. Previous animal studies in dog and sheep have demonstrated that local ventricular fibrillation (VF) intervals measured from the heart surface correlate well with the ventricular effective refractory periods measured from the same ventricular sites. We hypothesise that local VF intervals may also predict the ventricular refractory periods in human hearts, hence, can be used to assess the spatial dispersion of refractoriness and to predict the risk of ventricular arrhythmias.
Assuntos
Eletrocardiografia/métodos , Sistema de Condução Cardíaco/fisiopatologia , Ventrículos do Coração/inervação , Ventrículos do Coração/fisiopatologia , Período Refratário Eletrofisiológico , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/fisiopatologia , Animais , Mapeamento Potencial de Superfície Corporal/métodos , Ensaios Clínicos como Assunto , Frequência Cardíaca , Humanos , Modelos Cardiovasculares , Modelos Neurológicos , Estatística como AssuntoRESUMO
AIM: To investigate risk factor management in diabetic patients undergoing coronary angiography. METHODS: Hemoglobin (Hgb) A1c, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), blood pressure (BP), and body mass index (BMI) were cardiovascular risk factors analyzed in 284 consecutive type 2 diabetic patients who underwent coronary angiography. RESULTS: Coronary artery disease (CAD) was identified in 233 (82.0%) diabetic patients. The mean HgbA1c fraction for all patients at hospital admission was 9.7+/-1.4%. The mean concentration of LDL-C, HDL-C, and triglycerides was 2.82+/-0.9, 0.92+/-0.28, and 2.56+/-0.81 mmol/L, respectively. One hundred and twenty-two (43.0%) patients had LDL-C <2.6 mmol/L, 70 (24.7%) patients had a blood pressure of less than 130/85 mm Hg, and 158 (55.7%) had BMI <30 kg/m(2). Only 26 (9.1%) patients had optimal control of the above cardiac risk factors. The average LDL-C, triglycerides, and blood pressure in patients with severe coronary artery disease were higher than those in patients with moderate to mild coronary artery disease (p<0.01; unpaired t-test). CONCLUSIONS: Cardiovascular risk factors were poorly controlled in type 2 diabetic patients. The average LDL-C, triglycerides, and blood pressure in patients with severe coronary artery disease were higher than those in patients with moderate to mild coronary artery disease.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Idoso , Doenças Cardiovasculares/epidemiologia , Angiografia Coronária , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the epidemiologic features of disseminated histoplasmosis (PDH) in Hubei province. METHODS: Bone marrow smears of 12 patients diagnosed as Kala-azer in Hubei province including 4 patients in Jingsan, 2 patients in Shashi and each 1 in Yichang, Jinmen, Zhongxiang, Luotian, Xianning and Guanghua respectively were re-examed under microscope. Peripheral blood and bone marrow smears of several patients were detected. After inoculated the bone marrow, peripheral blood, liver and spleen tissue of patients in MLI, the single colony was trans-inoculated in BHIB, SDA and CMA and incubated at 25 degrees C and 35 degrees C. Bone marrow, peripheral blood and bacterial fluid of yeast-phase Histoplasma capsulatum (H.cap) were injected into the abdominal cavity of Kunming mice and nude mice. When symptoms and signs developed, the spleen tissue was separated, then observed under microscope and cultured. Mycelium-phase and Yeast-phase H.cap were inoculated in urase and gelatin medium, then incubated at 25 degrees C and 35 degrees C. Histoplasmin was injected subcutaneously into patients, and then followed for 48 - 72 hours. Amphotericin B was selected to treat the PDH patients. RESULTS: Moriform cell cluster and sausage-shaped cell were not observed in mononuclear-macrophages in the bone marrow smears from 12 patients. Leishman-Donovan body was found only in one patient. There wasn't kinetoplast in the cellular plasm of spores in 11 patients and no transeptae was found. The reaction of H.cap to urease was positive and H.cap did not liquefy the gelatin. It appeared to be mycelium-phase at 25 degrees C but no penicillus and catenulate conidia was found. The characteristic denticle macroconidia was observed but produced red coloring matter. It also appeared to be yeast-phase at 35 degrees C. Yeast-phase spores were observed under microscope. No sausage-shaped spore and transeptae were identified. H.cap could be acquired in the spleen tissue in Kunming mice and nude mice. Bacterium forms, characteristics under microscope and biochemical reaction of mycelium-phase and yeast-phase H.cap were different from some other kinds of dimorphic fungi such as Penicillium marneffei and Histoplasm duboisii etc. CONCLUSION: There were scattered epidemics of PDH in Hubei province. The detection rate of PDH was higher in the southeast area then in the northwest area. The golden standards of clinic diagnosis were mycological culture and inoculation to animals. Amphotericin B was necommended as the first choice for treatment.