Objective To investigate the protective effect and mechanism of liraglutide on the paraquat (PQ)⁃ induced Parkinson's disease (PD) mouse model. Methods Totally 24 Kunming mice were randomly divided into control group, PQ group and PQ +liraglutide group, 8 mice in each group. PD model was established by intraperitoneal injection of PQ (10 mg/kg) for 5 consecutive days, and liraglutide (50 nmol/kg) was injected intraperitoneally for 7 consecutive days. The free⁃standing and locomotor activity of mice were measured by behavioral method. Immunofluorescence was used to observe the number of tyrosine hydroxylase (TH) and ionized calcium binding adaptor molecule 1 (Iba1) immunoreactive cells. Western blotting was used to detect the expression of protein TH, glial fibrillary acidic protein (GFAP), mitofusin⁃2 (Mfn2) and dynamin⁃related protein 1 (Drp1). Results The numbers of free⁃standing and locomotor activity numbers decreased significantly (P<0.01, P < 0.05) in PQ group compared with the control group, and the number of TH immunoreactive cells and TH protein expression in substantia nigra decreased significantly (P<0.01, P<0.01) compared with the control group, while the number of Iba1 immunoreactive cells and GFAP protein expression increased significantly (P<0.01, P<0.01) compared with the control group; the expression of Drp1 protein in PQ group was significantly higher than that in control group (P<0.05), while the Mfn2 protein expression decreased significantly (P<0.05) compared with the control group. After treatment with liraglutide, the number of TH positive cells in PQ + liraglutide group was significantly lower than that in control group (P<0.05); the numbers of free⁃standing and locomotor activity increased significantly (P<0.05, P<0.05) in PQ + liraglutide group compared with the PQ group, and the number of TH positive cells and expression of TH protein in PQ + liraglutide group were significantly higher than that in PQ group (P<0.01, P< 0.01); while the number of Iba1 positive cells and GFAP protein expression decreased significantly (P<0.01, P<0.05) compared with the PQ group; the Drp1 protein expression decreased significantly (P<0.01) compared with the PQ group, while the expression of Mfn2 protein in PQ + liraglutide group was significantly higher than that in PQ group (P<0.01). Conclusion Liraglutide has neuroprotective effect by reducing neuroinflammation in substantia nigra, regulating mitochondrial fusion and fission.

Objective To investigate the effects of inhibiting KDM2A gene on the proliferation,invasion and migration of liver cancer cells and its possible regulatory mechanism.Methods Forty pairs of HCC tissues and their adjacent normal counterparts were collected from 2014 to 2017 in Tongji Hospital,Tongji Medical College Affiliated to Huazhong University of Science and Technology.Human liver cancer cell lines HepG2,Huh7,HCCLM3,MHCC-97H and normal liver cells LO2 were cultured in vitro.The mRNA and protein expression levels of KDM2A in HCC tissues and cells were detected by qRT-PCR and Western blotting.Huh7 cells were taken and set up as follows:(1)si-NC group(transfected with si-NC)and si-KDM2A group(transfected with si-KDM2A);(2)mimic-NC group(transfected with mimic-NC),miRNA-29a-3p mimic group(transfected with miRNA-29a-3p mimic),inhibitor-NC group(transfected with inhibitor-NC)and miRNA-29a-3p inhibitor group(transfected with miRNA-29a-3p inhibitor).The mRNA and protein expression levels of KDM2A were detected by qRT-PCR and Western blotting.The invasion and migration of cells were detected by Transwell,the proliferation of cells was detected by CCK-8 methods.The online databases TargetScan,miRDIP,miRWalk,Starbase and miRDB were used to predict the binding sites of KDM2A and miR-29a-3p.The KDM2A 3'-UTR(WT)or KDM2A 3'-UTR(MUT)report plasmid was co-transfected with NC-miRNA or miR-29a-3p mimics respectively for 48 h in 293T cells,and the luciferase activity was detected by the luciferase reporter gene detection system.Results Compared with adjacent normal counterparts,the relative mRNA and protein expression levels of KDM2A in HCC tissues increased significantly(P＜0.05).Compared with LO2,the relative mRNA and protein expression levels of KDM2A in HepG2,Huh7,HCCLM3 and MHCC-97H increased significantly(P＜0.05).Compared with si-NC group,the proliferation,invasion and migration of Huh7 cells in si-KDM2A group decreased significantly(P＜0.05 or P＜0.01).The analysis results of TargetScan,miRDIP,miRWalk,Starbase and miRDB showed that there were binding sites between KDM2A and miR-29a-3p.The results of the dual luciferase reporter assay showed that miR-29a-3p mimic significantly reduced KDM2A-MUT luciferase activity(P＜0.01).After overexpression of miRNA-29a-3p,the relative mRNA and protein expression levels of KDM2A were decreased(P＜0.01),the proliferation,invasion and migration abilities were decreased(P＜0.05)in Huh7 cells.After inhibiting the expression of miRNA-29a-3p,the relative mRNA and protein expression levels of KDM2A were increased(P＜0.05),the proliferation,invasion and migration abilities were enhanced(P＜0.05)in Huh7 cells.Conclusion Inhibiting the expression of KDM2A can reduce the proliferation and migration ability of Huh7 cells.miR-29a-3p may be the upstream regulator of KDM2A and participate in the occurrence and development of hepatocellular carcinoma.

ATG8-binding proteins play a key role in autophagy, selective autophagy or non-autophagy process by interacting between ATG8 and the ATG8-interacting motif (AIM) or the ubiquitin-interacting motif (UIM). There is great progress of ATG8-binding proteins in yeast and mammalian studies. However, the plant domain is still lagging behind. Therefore, the structure characteristics of plant ATG8 binding protein were firstly outlined. Unlike the single copy of ATG8 gene in yeast, many homologous genes have been identified in plant. The LIR/ AIM-docking site (LDS) of ATG8 protein contains W and L pockets and is responsible for binding to AIM. The ATG8 protein binds to UIM-containing proteins via UIM-docking site (UDS) instead of LDS. UDS is in the opposite position to LDS, so the ATG8 can bind both AIM and UIM proteins. Secondly, the structure and function of ATG8-binding proteins, especially the selective autophagy receptors, were systematically described. The protein NBR1 and Joka2, as proteaphagy receptors, guide ubiquitination protein aggregates to autophagosome for degradation by binding to AIM and ATG8 in Arabidopsis and tobacco, respectively. AtNBR1 also promotes plant immunity by binding the capsid protein of cauliflower mosaic virus and silencing suppressor HCpro of turnip mosaic virus, mediating pathogen autophagy. AtNBR1 still degrades chloroplast by microautophagy under photoinjure or chlorophagy during ibiotic stress. And the protein ORM mediates the degradation of plant immune receptor flagellin sensing 2 (FLS2) through AIM binding to ATG8. Interestingly, ATI1 and ATI2 participate in both chlorophagy and ERphagy. Otherwise, ER membrane protein AtSec62, soluble protein AtC53, and ubiquitin-fold modifier1-specific ligase 1 (UFL1) can be directly bound to ATG8 as ER autophagy receptors. As pexophagy receptor, AtPEX6 and AtPEX10 bind to ATG8 via AIM and participate in pexophagy. RPN10, as a 26S proteasome subunit, whose C-terminal UIM1 and UIM2 bind ubiquitin and ATG8, respectively, mediates the selective autophagy degradation of 26S proteasome inactivation when fully ubiquitinated. Plant-specific mitochondrial localization proteins FCS-like zinc finger (FLZ) and friendly (FMT) may also be mitophagy receptors. CLC2 binds to ATG8 via the AIM-LDS docking site and is recruited to autophagy degradation on the Golgi membrane. The tryptophan-rich sensory protein (TSPO) in Arabidopsis was involved in clearing free heme, porphyrin and plasma membrane intrinsic protein 2;7 (PIP2;7) through the combination of AIM and ATG8. The conformation of GSNOR1 changes during anoxia, exposing the interaction between AIM and ATG8, leading to selective degradation of GSNOR1. At last, the ATG8 binding proteins involved in autophagosome closure, transport and synthetic synthesis was summarized. For example, plant-specific FYVE domain protein required for endosomal sorting 1 (FREE1) is involved in the closure of autophagosomes during nutrient deficiency. Therefore, according to the recent research advances, the structure and function of plant ATG8-binding proteins were systematically summarized in this paper, in order to provide new ideas for the study of plant selective autophagy and autophagy.

Objective:To understand the characteristics and differences of diarrhea-related symptoms caused by different pathogens, and the clinical features of various pathogens causing diarrhea.Methods:Etiology surveillance program was conducted among 20 provinces of China from 2010 to 2016. The acute diarrhea outpatients were collected from clinics or hospitals. A questionnaire was used to survey demographics and clinical features. VFeces samples were taken for laboratory detection of 22 common diarrhea pathogens, to detect and analyze the clinical symptom pattern characteristics of the patient’s.Results:A total of 38 950 outpatients were enrolled from 20 provinces of China. The positive rates of Rotavirus and Norovirus were the highest among the five diarrhea-causing viruses (Rotavirus: 18.29%, Norovirus: 13.06%). In the isolation and culture of 17 diarrhea-causing bacterial, Escherichia coli showed the highest positive rates (6.25%). The clinical features of bacterial diarrhea and viral diarrhea were mainly reflected in the results of fecal traits and routine examination, but pathogenic Vibrio infection was similar to viral diarrhea. Conclusion:Infectious diarrhea presents different characteristics due to various symptoms which can provide a basis for clinical diagnosis.

OBJECTIVE: To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients. METHODS: The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ［75 mg/(m RESULTS: Median follow-up time of all the patients was 15 months. The CR rate and MRD CONCLUSION The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; Cytarabine/therapeutic use* ; Daunorubicin ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Remission Induction ; Retrospective Studies

OBJECTIVETo establish Surface-enhanced Raman Spectroscopy (SERS) can be used as a rapid and reliable method to distinguish virulent strain and mild strain of L. pneumophila.

METHODSMortality data were collected from company departments through administrative documents, death certificates, etc. Trend analyses of cancer mortality were performed on the basis of 925 cancer deaths between 2001 and 2010.

RESULTSOur results indicated that the peaks of high virulence strains reached ⋝4000. This criterion was verified by subsequent cell experiments. In addition, we also conducted SERS rapid identification on the virulence of several collected clinical strains and obtained accurate results.

CONCLUSIONThe present study indicates that the established SERS protocol can be used as a rapid and reliable method to distinguish virulent and mildly virulent strains of L. pneumophila, which can be further used in clinical samples.

Cell Line ; Citric Acid ; chemistry ; Gold ; chemistry ; Humans ; Legionella ; isolation & purification ; pathogenicity ; Nanoparticles ; chemistry ; Spectrum Analysis, Raman ; methods ; Time Factors ; Tiopronin ; chemistry ; Virulence

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.
Adult ; Humans ; Male ; United States ; Erectile Dysfunction/etiology* ; Nutrition Surveys ; Metals, Heavy ; Risk Assessment

Recently, the hepatotoxicity issue regarding to Psoraleae Fructus (PF) has attracted remarkable concerns, which highlights the urgent need to explore the toxicity attenuation method for PF. In this study, we proposed an alcohol soaking and water rinsing method for pre-processing PF based on the record in the classics - "Lei Gong Pao Zhi Lun", aiming to attenuate the potential hepatotoxicity of PF. The optimal pre-processing methods and parameters were investigated by U*12(10⁸) uniform design coupled with 3D-cultured human-derived liver organoids model and high-content imaging. The results showed that there were significant variations among the hepatotoxicity intensities of different pre-processed PF products. Four factors, including the concentration of alcohol, the ratio of material and alcohol in alcohol soaking, the time of alcohol soaking and the times of water rinsing, were found as independent significant factors (all P<0.01). The optimal pre-process parameters were further predicted and verified as follows: the alcohol concentration is 80%, the times of alcohol soaking is 3, the ratio of alcohol and material of alcohol soaking is 3, the time for alcohol soaking is 30 h, the ratio of water and material of water rinsing is 2, the times of water rinsing is 3, the time water rinsing is 12 h and the time of steaming is 5 h. This research demonstrated that the alcohol soaking and water rinsing method can effectively reduce the potential hepatotoxicity of PF. This method provides a reference for reducing the risk of PF liver injury from the perspective of Chinese medicinal materials pre-processing.

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Leukemia, Promyelocytic, Acute/therapy* ; Prognosis ; Myelodysplastic Syndromes/drug therapy* ; Neoplasms, Second Primary/drug therapy* ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances. Methods: Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology. Results: Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( < 0.05 or < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% . 17.8% and 10.0%, < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups. Conclusions The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.
Animals ; Biomechanical Phenomena ; Blast Injuries ; etiology ; pathology ; Disease Models, Animal ; Explosions ; Lung Injury ; etiology ; pathology ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley