Ras-related C3 botulinum toxin substrate 1(RAC1)is a crucial member of the Ras GTPase super-family,exerting an overriding role in cell behaviors such as motility,proliferation and adhesion,and is involved in regu-lating vascular permeability and cellular barrier function.Recently,the significance of RAC1 in the etiology and progres-sion of various pulmonary disorders has garnered increasing attention,which sheds light on lung disease study.In this re-view,we introduce the characteristics of RAC1 systematically and recapitulate its effects and molecular mechanisms in the context of lung tumors,chronic obstructive pulmonary disease,lung injury and pulmonary arterial hypertension,hoping to provide new insights for future pulmonary disease treatment.

The banana Fusarium wilt (BFW) caused by Fusarium oxysporum f. sp. cubense tropical race4 (FocTR4) is difficult to control worldwide, which causes a huge economic losse to banana industry. The purpose of this study was to screen Trichoderma strains with antagonistic activity against FocTR4, to isolate and purify the active compound from the fermentation broth, so as to provide important biocontrol strains and active compound resources. In this work, Trichoderma strains were isolated and screened from the rhizosphere soil of crops, and the strains capable of efficiently inhibiting FocTR4 were screened by plate confrontation, and further confirmed by testing inhibition for the conidial germination and mycelial growth of FocTR4. The phylogenetic tree clarified the taxonomic status of the biocontrol strains. Moreover, the active components in the fermentation broth of the strains were separated and purified by column chromatography, the structure of the most active component was analyzed by nuclear magnetic resonance spectroscopy (NMR), the BFW control effect was tested by pot experiments. We obtained a strain JSHA-CD-1003 with antagonistic activity against FocTR4, and the inhibition rate from plate confrontation was 60.6%. The fermentation broth of JSHA-CD-1003 completely inhibited the germination of FocTR4 conidia within 24 hours. The inhibition rate of FocTR4 hyphae growth was 52.6% within 7 d. A phylogenetic tree was constructed based on the ITS and tef1-α gene tandem sequences, and JSHA-CD-1003 was identified as Trichoderma brevicompactum. Purification and NMR identification showed that the single active compound was trichodermin, and the minimum inhibitory concentration (MIC) was 25 μg/mL. Pot experiments showed that the fermentation broth of strain JSHA-CD-1003 was effective against BFW. The control rate of leaf yellowing was 47.4%, and the rate of bulb browning was 52.0%. Therefore, JSHA-CD-1003 effectively inhibited FocTR4 conidial germination and mycelium growth through producing trichodermin, and showed biocontrol effect on banana wilt caused by FocTR4, thus is a potential biocontrol strain.
Fusarium ; Musa ; Phylogeny ; Trichodermin ; Hypocreales

Lymphoma is a common hematological malignant tumor which poses a great threat to human health. Chemotherapy, molecular targeted therapy, and hematopoietic stem cell transplantation constitute the main treatment methods for lymphoma, however, there are still some patients with lymphoma suffer from drug resistance, relapse and refractory. Ferroptosis is a newly discovered mode of programmed cell death, which is related to iron-dependent lipid peroxidation damage. Targeting ferroptosis provides a novel landscape for inhibiting the growth of lymphoma. We reviewed the mechanism of ferroptosis from the initial signals, intermediate events, effect stages, defense mechanisms and summarized the research progress of ferroptosis in lymphoma, providing novel therapeutic targets in the treatment of lymphoma.

OBJECTIVE: To investigate the therapeutic mechanism of resveratrol (RES) for Alzheimer's disease (AD) in light of network pharmacology. METHODS: We searched PubChem, BATMAN-TCM, Genecards, AD, TTD, String 11.0, AlzData, SwissTargetPrediction, Metascape and other databases for the therapeutic targets of RES and human AD-related targets. The intersection was determined using Venny 2.1 to obtain the therapeutic targets of RES for AD. The protein-protein interaction (PPI) network was constructed, the gene ontology (GO) was enriched and the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG pathway) were analyzed. Cytoscape 3.7.1 software was used to construct a target-signaling pathway network of RES in the treatment of AD. Molecular docking verification was carried out on SwissDock (http://www.swissdock.ch/docking). We examined a 293Tau cell model of AD for changes in protein levels of pS396, pS199, Tau5, CDK5, glycogen synthase kinase 3β (GSK3β) and p-GSK3β in response to RES treatment using Western blotting. RESULTS: We obtained 182 targets of RES, 525 targets related to AD, and 36 targets of RES for AD treatment, among which 34.6% of the targets were protein-modifying enzymes, 27.7% were metabolite invertase, 13.8% were gene-specific transcriptional regulators, and 10.3% were transporters. The core key targets of RES in the treatment of AD included INS, APP, ESR1, MMP9, IGF1R, CACNA1C, MAPT (microtubule- associated protein Tau), MMP2, TGFB1 and GSK3B. Enrichment analysis of GO biological process suggested that the biological function of RES in AD treatment mainly involved the response to β-amyloid protein, positive regulation of transferase activity, the transmembrane receptor protein tyrosine kinase signaling pathway, regulation of behavior, learning or memory, aging, and transmembrane transport. KEGG pathway enrichment analysis showed that the most significantly enriched signaling pathways were AD pathway, PI3K-AKT signaling pathway, cGMP-PKG signaling pathway, and MAPK signaling pathway. Molecular docking results showed that RES had strong binding with ESR1, GSK3B, MMP9, IGF1R, APP and INS. In the cell model of AD, treatment with 50 μmol/L RES for 12 h significantly reduced the levels of pS396 and pS199 by regulating CDK5 and GSK3β activity ( CONCLUSIONS RES produces therapeutic effects on AD by acting on multiple targets and affecting multiple signaling pathways and improves AD-associated pathologies
Alzheimer Disease/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases ; Resveratrol/pharmacology*

Objective:To investigate and understand the general situation and quality of life of migrant workers with pneumoconiosis, and analyze the influencing factors, so as to provide scientific basis for effective countermeasures to improve the quality of life of migrant workers with pneumoconiosis.Methods:In June 2019, 79 cases of migrant workers' pneumoconiosis diagnosed by Shandong Occupational Disease Hospital from March 2017 to August 2018 were selected as the study object by cluster random sampling method. Questionnaires and on-site visits were used to investigate the quality of life and its influencing factors. The questionnaire was administered by self-designed questionnaire and WHO quality of life questionnaire.Results:The farmer's pneumoconiosis patients are generally lower in culture. High school or above is only 6.33% (5/79) . Their economic income is low. The monthly income of less than 1000 RMB is 49.37% (39/79) . The disease was heavy and pneumoconiosis was 58.23% (46/79) . Pneumoconiosis patients without systematic treatment accounted for 69.62% (55/79) . Only 11.39% of rural workers with pneumoconiosis can timely increase or decrease clothing and wear masks to avoid respiratory irritation. Pneumoconiosis patients who smoked accounted for 77.22% (61/79) . The quality of life of the pneumoconiosis patients in the physiological, psychological, social and environmental fields were (10.40±2.31) , (11.40±2.82) , (11.46±3.03) and (8.38±3.37) respectively. The influencing factors of quality of life were pneumoconiosis stage, education level, economic income and smoking ( P< 0.05) . Conclusion:The quality of life of migrant workers with pneumoconiosis is generally low. The main factors that affect the quality of life of patients are disease severity (pneumoconiosis stage) , education level, economic income and smoking.

Objective:To investigate and understand the general situation and quality of life of migrant workers with pneumoconiosis, and analyze the influencing factors, so as to provide scientific basis for effective countermeasures to improve the quality of life of migrant workers with pneumoconiosis.Methods:In June 2019, 79 cases of migrant workers' pneumoconiosis diagnosed by Shandong Occupational Disease Hospital from March 2017 to August 2018 were selected as the study object by cluster random sampling method. Questionnaires and on-site visits were used to investigate the quality of life and its influencing factors. The questionnaire was administered by self-designed questionnaire and WHO quality of life questionnaire.Results:The farmer's pneumoconiosis patients are generally lower in culture. High school or above is only 6.33% (5/79) . Their economic income is low. The monthly income of less than 1000 RMB is 49.37% (39/79) . The disease was heavy and pneumoconiosis was 58.23% (46/79) . Pneumoconiosis patients without systematic treatment accounted for 69.62% (55/79) . Only 11.39% of rural workers with pneumoconiosis can timely increase or decrease clothing and wear masks to avoid respiratory irritation. Pneumoconiosis patients who smoked accounted for 77.22% (61/79) . The quality of life of the pneumoconiosis patients in the physiological, psychological, social and environmental fields were (10.40±2.31) , (11.40±2.82) , (11.46±3.03) and (8.38±3.37) respectively. The influencing factors of quality of life were pneumoconiosis stage, education level, economic income and smoking ( P< 0.05) . Conclusion:The quality of life of migrant workers with pneumoconiosis is generally low. The main factors that affect the quality of life of patients are disease severity (pneumoconiosis stage) , education level, economic income and smoking.

Objective: To investigate the safety and long-term efficacy of a new treatment, echocardiography-guided transthoracic laser ablation of the animal interventricular septum (IVS), for obstructive hypertrophic cardiomyopathy (HOCM). Methods: Ten healthy sheep were randomly divided into two groups: experimental group: sheath puncture with laser ablation (energy: 3 W, 1000 J), sham control group: sheath puncture only without laser ablation. Echocardiography and electrocardiogram (ECG) were recorded before operation, immediately after operation, and 1, 3 and 6-month after the operation. Left ventricular systolic and diastolic function, longitudinal strain, difference of time to peak between the ablation segment and the surrounding segments were analyzed. Blood samples were collected before and one hour after the operation to examine the serological results. Results: Immediately and 6 months after the operation, all animals survived with normal cardiac function. No severe complications such as cardiac tamponade or bundle branch block occurred. The Troponin I level was significantly elevated immediately after the operation(P<0.05). The thickness of the ablated IVS was significantly reduced 6 months after the operation compared with before the operation[(3.23±1.21)mm vs (8.53±0.44)mm, P<0.05]. M-mode echocardiography showed that the amplitude of movement of the ablated region of the experimental group 6 months after the operation was significantly decreased compared with the control group(P<0.05). Three dimensional strain analysis showed that for the experimental group, the longitudinal strain of the ablation segment was significantly reduced and the difference of time to peak was significantly delayed, compared with the control group(P<0.05). Conclusions Echocardiography-guided transthoracic laser ablation of IVS is a safe, effective, and minimally invasive method. It is capable to reduce the volume of IVS without influencing the cardiac function, which makes it a potential alternative for HOCM treatment.

Objective To evaluate the clinical efficacy and safety of 595-nm pulsed dye laser with topical timolol maleate 0.5％ solution for the treatment of superficial infantile hemangioma (IH).Methods Complete clinical data were collected from 156 infants with superficial IH,who received treatment with 595-nm pulsed dye laser combined with topical timolol maleate 0.5％ solution in the Department of Dermatology of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from July 2015 to July 2016,and analyzed retrospectively.Of the 156 patients,44 were males,and 112 were females,with an average age of 3.8 ± 0.7 months (range,24 days-1 year).These patients were treated with 595-nm pulsed dye laser every 5 weeks and topical application of timolol maleate solution twice a day.Each treatment with timolol maleate solution lasted 30 minutes.When the hemangioma regressed generally,the treatment with laser and timolol maleate solution was stopped.At weeks 5,10,15 and 30,the visual analogue scale (VAS) was used to evaluate the efficacy,and adverse reactions were recorded.These patients were followed up till 6 months after the end of treatment.The relationships of area and thickness of hemangioma with treatment duration,treatment sessions and VAS scores were analyzed.Results After 5-30 weeks of treatment,hemangiomas regressed to different extents,and the cure rate was 93.59％ (146/156).At weeks 5,10,15 and 30,the VAS scores were 3.12 ± 0.23,4.45 ± 0.52,5.45 ± 0.71 and 7.59 ± 1.64 respectively.Repeated-measures analysis of variance showed that the VAS scores all significantly increased over time (F =189.35,P ＜ 0.05) in the 3 groups with different initial thickness of hemangiomas (＜ 1 mm,1-3 mm,and ＞ 3 mm),and significantly differed among the above 3 groups at different time points (F =215.56,P ＜ 0.05),and the group with the initial thickness of hemangiomas ＜ 1 mm showed the highest VAS scores.The total treatment duration was significantly shorter in the group with the initial thickness of hemangiomas ＜ 1 mm (2.71 ± 0.58 months) than in those with the initial thickness of hemangiomas 1-3 mm (8.22 ± 0.67 months,P ＜ 0.05) and ＞ 3 mm (11.03 ± 0.72 months,P ＜ 0.05).The VAS scores also significantly differed among the 3 groups with different initial area of hemangiomas (＜ 3 cm2,3-9 cm2 and ＞ 9 cm2),and significantly increased over time in these groups;Kruskal-Wallis H test showed that there was a significant difference in the treatment sessions among the above 3 groups (H =10.45,P ＜ 0.01),and the group with the initial area of hemangiomas ＜ 3 cm2 showed the least treatment session.The adverse reactions were mild,and no adverse cardiovascular or respiratory events were observed.Conclusion The 595-nm pulsed dye laser combined with topical timolol maleate 0.5％ solution is effective and safe for the treatment of superficial IH.

OBJECTIVETo explore the distribution and antibiotic resistance of pathogens in lesions of diabetic foot osteomyelitis (DFO) and analyze the risk factors causing osteomyelitis.

METHODSA total of 372 patients with diabetic foot infections hospitalized between January 2011 and December 2014, including 203 with osteomyelitis (OM group) and 169 without osteomyelitis (non-OM group), were examined for the distribution and antibiotic resistance profile of the pathogens in the wounds. Logistic regression analysis was used to analyze the risk factors causing osteomyelitis.

RESULTSGram-negative bacteria were the predominant pathogens (53.7%) in the infected wounds in OM group, whereas Gram-positive bacteria were the most frequently found (56.7%) in non-OM group (P=0.001). Among the Gram-positive bacteria, Staphylococcus was the dominating flora (35.1%). The resistance rate to oxacillin and cefoxitin of the isolated bacteria in OM group (64.9% and 68.5%, respectively) was significantly higher than that in non-OM group (29.2% and 32.6%, respectively; P<0.05). Among the gram-negative bacteria, Enterobacteriaceae was the dominating flora (62.4%), with a higher resistance rate to Cefepime and Aztreonam in OM group (30.1% and 38.6%, respectively) than in non-OM group (15.1% and 22.2%, respectively; P<0.05). Logistic regression analysis indicated that the infection by multi-drug resistant bacteria and an wounds area >4 cm(2) were the risk factors for osteomyelitis in patients with diabetic foot infections (P<0.05).

CONCLUSIONIn addition to an empirical anti-infection therapy, clinicians should choose specific antibiotics against Gram-negative bacteria according to the microbial spectrum and antibiotic resistance of pathogens in patients with DFO; patients with diabetic foot infections by multi-drug resistant bacteria and those with a wound area exceeding 4 cm(2) are exposed to an increased risk of osteomyelitis.

Anti-Bacterial Agents ; Cephalosporins ; Diabetic Foot ; microbiology ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; classification ; isolation & purification ; Gram-Positive Bacteria ; classification ; isolation & purification ; Humans ; Osteomyelitis ; microbiology ; Risk Factors ; Wound Infection ; microbiology

Objective To explore the distribution and antibiotic resistance of pathogens in lesions of diabetic foot osteomyelitis (DFO) and analyze the risk factors causing osteomyelitis. Methods A total of 372 patients with diabetic foot infections hospitalized between January 2011 and December 2014, including 203 with osteomyelitis (OM group) and 169 without osteomyelitis (non-OM group), were examined for the distribution and antibiotic resistance profile of the pathogens in the wounds. Logistic regression analysis was used to analyze the risk factors causing osteomyelitis. Results Gram-negative bacteria were the predominant pathogens (53.7%) in the infected wounds in OM group, whereas Gram-positive bacteria were the most frequently found (56.7%) in non-OM group (P=0.001). Among the Gram-positive bacteria, Staphylococcus was the dominating flora (35.1%). The resistance rate to oxacillin and cefoxitin of the isolated bacteria in OM group (64.9%and 68.5%, respectively) was significantly higher than that in non-OM group (29.2%and 32.6%, respectively;P<0.05). Among the gram-negative bacteria, Enterobacteriaceae was the dominating flora (62.4%), with a higher resistance rate to Cefepime and Aztreonam in OM group (30.1% and 38.6%, respectively) than in non-OM group (15.1% and 22.2%, respectively; P<0.05). Logistic regression analysis indicated that the infection by multi-drug resistant bacteria and an wounds area >4 cm2 were the risk factors for osteomyelitis in patients with diabetic foot infections (P<0.05). Conclusions In addition to an empirical anti-infection therapy, clinicians should choose specific antibiotics against Gram-negative bacteria according to the microbial spectrum and antibiotic resistance of pathogens in patients with DFO; patients with diabetic foot infections by multi-drug resistant bacteria and those with a wound area exceeding 4 cm2 are exposed to an increased risk of osteomyelitis.