AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

OBJECTIVE: To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes. METHODS: The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score. RESULTS: A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect. CONCLUSION Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.
Humans ; Cell Cycle ; Multiple Myeloma/genetics* ; Prognosis ; Risk Factors

Objective: To understand the incidence of chronic obstructive pulmonary disease (COPD) in the Suzhou cohort, and explore the risk factors for the development of COPD in Suzhou, and provide a scientific basis for COPD prevention. Methods: This study was based on the China Kadoorie Biobank project in Wuzhong District, Suzhou. After excluding individuals with airflow obstruction and self-reported chronic bronchitis, emphysema, or pulmonary heart disease at baseline, 45 484 individuals were finally included in the analysis. Cox proportional risk models were used to analyze risk factors of COPD and calculate hazard ratios and 95% confidence interval (CI) in the Suzhou cohort. The effect modifications of smoking on the association between other risk factors and COPD were evaluated. Results: Complete follow-up was available through December 31, 2017. Participants were followed up for a median of 11.12 years, and 524 individuals were diagnosed with COPD during the follow-up period; the incidence was 105.54 per 100 000 person-years. Multivariate Cox proportional risk regression models showed that age (HR=3.78, 95%CI:3.32-4.30), former smoking (HR=2.00, 95%CI:1.24-3.22), current smoking (<10 cigarettes/day, HR=2.14, 95%CI:1.36-3.35;≥10 cigarettes/day, HR=2.69, 95%CI:1.60-4.54), history of respiratory disease (HR=2.08, 95%CI:1.33-3.26), daily sleep duration ≥10 hours (HR=1.41, 95%CI:1.02-1.95) were associated with increased risk of COPD. However, education level of primary school and above (primary or junior high school, HR=0.65, 95%CI:0.52-0.81; high school and above, HR=0.54, 95%CI:0.33-0.87), consuming fresh fruit daily (HR=0.59, 95%CI:0.42-0.83) and consuming spicy food weekly (HR=0.71, 95%CI:0.53-0.94) were associated with reduced risk of COPD. Conclusions: The incidence of COPD is low in Suzhou. Older age, smoking, history of respiratory disease, and long sleep duration were risk factors for the development of COPD in the Suzhou cohort.
Humans ; Incidence ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Risk Factors ; Smoking/epidemiology* ; Tobacco Smoking

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve^® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve^® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve^® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve^® system.
Aged ; Aged, 80 and over ; Aortic Valve ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Prospective Studies ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome

SARS-CoV-2 has infected more than 600 million people worldwide and caused more than 6 million deaths. The emerging novel variants have made the epidemic rebound in many places. Meteorological factors can affect the epidemic spread by changing virus activity, transmission dynamic parameters and host susceptibility. This paper systematically analyzed the currently available laboratory and epidemiological studies on the association between the meteorological factors and COVID-19 incidence, in order to provide scientific evidence for future epidemic control and prevention, as well as developing early warning system.
Humans ; SARS-CoV-2 ; COVID-19 ; Meteorological Concepts ; Laboratories ; Epidemiologic Studies

Phyllanthus emblica is a kind of traditional medicine and medicinal and edible plant, with rich variety resources and high development value. It is a key poverty alleviation variety in China at present. As P. emblica processing industry is rising gradually in recent years, in order to fully develop and utilize its industrial resources, this paper systematically introduces current comprehensive development and utilization of P. emblica, discusses the problems in P. emblica processing industry, and puts forward comprehensive development and utilization strategies and industrial models in terms of cultivation, breeding, grading, quality evaluation and waste recycling, so as to provide a certain reference for promoting the high-quality development of P. emblica industry in China.
China ; Medicine ; Medicine, Traditional ; Phyllanthus emblica ; Plant Breeding ; Plant Extracts

OBJECTIVE: To analyze and predict the effect of coronavirus infection on hematopoietic system and potential intervention drugs, and explore their significance for coronavirus disease 2019 (COVID-19). METHODS: The gene expression omnibus (GEO) database was used to screen the whole genome expression data related with coronavirus infection. The R language package was used for differential expression analysis and KEGG/GO enrichment analysis. The core genes were screened by PPI network analysis using STRING online analysis website. Then the self-developed apparent precision therapy prediction platform (EpiMed) was used to analyze diseases, drugs and related target genes. RESULTS: A database in accordance with the criteria was found, which was derived from SARS coronavirus. A total of 3606 differential genes were screened, including 2148 expression up-regulated genes and 1458 expression down-regulated genes. GO enrichment mainly related with viral infection, hematopoietic regulation, cell chemotaxis, platelet granule content secretion, immune activation, acute inflammation, etc. KEGG enrichment mainly related with hematopoietic function, coagulation cascade reaction, acute inflammation, immune reaction, etc. Ten core genes such as PTPRC, ICAM1, TIMP1, CXCR5, IL-1B, MYC, CR2, FSTL1, SOX1 and COL3A1 were screened by protein interaction network analysis. Ten drugs with potential intervention effects, including glucocorticoid, TNF-α inhibitor, salvia miltiorrhiza, sirolimus, licorice, red peony, famciclovir, cyclosporine A, houttuynia cordata, fluvastatin, etc. were screened by EpiMed plotform. CONCLUSION SARS coronavirus infection can affect the hematopoietic system by changing the expression of a series of genes. The potential intervention drugs screened on these grounds are of useful reference significance for the basic and clinical research of COVID-19.
COVID-19 ; Computational Biology ; Follistatin-Related Proteins ; Hematopoietic System ; Humans ; Pharmaceutical Preparations ; SARS-CoV-2

Paired box transcription factors (paired box, PAX) and their homologues found in a large number of vertebrates and invertebrates play a key role in many stages of embryonic development. The gene family gets its name because of its conserved paired domain, in addition to its octapeptide and homologous domain. According to the composition of the domain and sequence homology, the gene family is mainly divided into four subfamilies: PAX1 / 9 (PAX1, PAX9), PAX2 / 5 / 8 (PAX2, PAX5, PAX8), PAX3 / 7 (PAX3, PAX7), PAX4 / 6 (PAX4, PAX6). Each subfamily has different characteristic structures, such as PD-OP of PAX1 / 9 subfamily, PD-OP-PTHD of PAX2 / 5 / 8 subfamily, PD-OP-PTHD of PAX3 / 7 subfamily and PD and PTHD of PAX4 / 6 subfamily. Among them, the three members of the PAX family, PAX2 PAX4 and PAX6, play an important role in multiple stages of pancreatic development and differentiation, and also play a key role in regulating the synthesis and secretion of islet hormone. Understanding the original and differentiated roles of these transcription factors in pancreas will help finding potential treatment for diabetes. Furthermore, PAX1 / 9 families may serve as potential biomarkers for evaluation of tumor development and progression, such as the methylation levels of PAX1 and expression of PAX9 in tumor. PAX3 / 7 was transcription factors involved in the development of skeletal muscle. This paper reviewed the special and temporal expression of PAX genes in a wide variety of tumor and the function and structural abnormalities PAX gene were summarized in this paper.