Staphylococcus aureus is a Gram-positive bacterium with strong pathogenicity. With the widespread use of antibiotics， its multi-drug resistance has gradually increased. Among them， methicillin-resistant S. aureus （MRSA） is one of the main pathogens of hospital and community infections. Antimicrobial peptides are short-chain peptides with good antibacterial effects and low drug resistance， which have been widely studied in recent years. This study summarizes the mechanism of action of antimicrobial peptides and related study on antimicrobial peptides against MRSA from different sources. It is found that the mechanisms of action of antimicrobial peptides include targeting bacterial cell membranes， bacterial cells， and bacterial cell walls， etc. Besides isolating antimicrobial peptides with anti-MRSA activity from animals， plants， and microorganisms， antimicrobial peptides can also be obtained through synthetic methods. Among them， GHa-derived peptides from animal sources， Ib-AMP4 from plant sources， Ph-SA from microbial sources， the synthetic peptide LLKLLLKLL-NH2， and so on， due to their effective antibacterial activity， rapid bactericidal speed， and low toxicity， are promising candidates for anti-MRSA drugs.

ObjectiveTo explore the understanding degree of medical students, researchers, and medical statistics teachers on P value in statistics and its related factors, so as to provide references for the improvement of medical statistics teaching. MethodsConvenience sampling method was used to distribute 175 questionnaires through the online platform questionnaire star (Wenjuanxing). Based on case study, the questionnaire was designed with 6 true-or-false questions about P values. Accuracy rate of understanding on P value by medical students, researchers and professional teachers was evaluated through questionnaire survey. Descriptive analysis and multivariate logistic regression analysis were used to explore the related factors affecting the understanding of P value. ResultsA total of 170 questionnaires were collected, with 50 from the medical students, 98 from the researchers, and 22 from the professional teachers, respectively. The results indicated that the professional teachers had the highest accuracy rate (89.5%), whereas the medical students had a relatively low accuracy rate (31.6%). Multivariate logistic regression analysis revealed that individuals with a doctoral degree, compared to those with a bachelor’s degree or below, had a higher accuracy rate (OR=2.10, 95%CI: 1.18‒3.76, P=0.012). Additionally, researchers who had received training in medical statistics (OR=4.20, 95%CI: 2.23‒7.93, P<0.001) or medical research design courses (OR=2.40, 95%CI:1.33‒4.33, P=0.004) exhibited higher accuracy rates. ConclusionMedical students and researchers generally have misunderstandings about P values. It is recommended to improve the understanding about P values, such as strengthening medical statistics teaching at the academic education levels, setting up medical research design courses, increasing student-led discussions, and intensifying continuing education and science popularization activities.

Humans ; Animals ; Culicidae ; Flavivirus ; Cell Line ; Spiramycin

The COVID-19 pandemic has resulted in excess deaths worldwide. Conventional antiviral medicines have been used to relieve the symptoms, with limited therapeutic effect. In contrast, Lianhua Qingwen Capsule is reported to exert remarkable anti-COVID-19 effect. The current review aims to: 1) uncover the main pharmacological actions of Lianhua Qingwen Capsule for managing COVID-19; 2) verify the bioactive ingredients and pharmacological actions of Lianhua Qingwen Capsule by network analysis; 3) investigate the compatibility effect of major botanical drug pairs in Lianhua Qingwen Capsule; and 4) clarify the clinical evidence and safety of the combined therapy of Lianhua Qingwen Capsule and conventional drugs. Numerous bioactive ingredients in Lianhu Qingwen, such as quercetin, naringenin, β-sitosterol, luteolin, and stigmasterol, were identified to target host cytokines, and to regulate the immune defence in response to COVID-19. Genes including androgen receptor (AR), myeloperoxidase (MPO), epidermal growth factor receptor (EGFR), insulin (INS), and aryl hydrocarbon receptor (AHR) were found to be significantly involved in the pharmacological actions of Lianhua Qingwen Capsule against COVID-19. Four botanical drug pairs in Lianhua Qingwen Capsule were shown to have synergistic effect for the treatment of COVID-19. Clinical studies demonstrated the medicinal effect of the combined use of Lianhua Qingwen Capsule and conventional drugs against COVID-19. In conclusion, the four main pharmacological mechanisms of Lianhua Qingwen Capsule for managing COVID-19 are revealed. Therapeutic effect has been noted against COVID-19 in Lianhua Qingwen Capsule.
Humans ; COVID-19 ; Pandemics ; Drugs, Chinese Herbal/therapeutic use* ; Antiviral Agents/therapeutic use* ; COVID-19 Drug Treatment

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.
Transcription Factors ; Polygonatum ; Phylogeny ; Transcriptome ; Gene Expression Regulation ; Arabidopsis

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective To investigate the modification effect of atmospheric temperature on outpatient visits caused by O₃ in Linzhi City. Methods The daily outpatient data, the daily O₃ concentration and daily meteorological data (including daily average temperature, average relative humidity, etc.) in Linzhi City from 2018 to 2019 were collected. The distributed lag non-liner-model (DLNM) was used to quantitatively evaluate the impact of O₃ in different temperature layers on the risk of outpatient visits. Results At low temperature layers, the cumulative relative risk (CRR) of total outpatient visits and non-injury outpatient visits increased by 53.8%（4.2% -126.9%) and 59.1%（5.8% -139.2%）for every 10 μg/m³ increase of O₃ concentration, respectively. The subgroup analysis showed that for every 10 μg/m³ increase of O₃ concentration at low temperature, the CRR of patients with circulatory diseases, men, women, and people being <14 years old and 14-65 years old increased by 152.1% (15.1% - 451.9%), 58.3% (2.1%-145.5%), 49.2% (3.0% -116.1%), 39.6% (2.5% - 90.3%), and 61% (0.8%-157.1%), respectively. Conclusion The average temperature may have a modifying effect on the outpatient visits caused by O₃ in Linzhi City. In general, the cumulative risk increases as the temperature decreases.

Objective To compare the effects of Autoregressive Integrated Moving Average model-X (ARIMAX) and multivariate Long Short Term Memory Network (multivariate LSTM) in the prediction of daily total death toll in Yancheng City. Methods Based on total death toll data, meteorological data and air quality data from January 1^st, 2014 to June 30^th,2017 in Yancheng City, Jiangsu province, ARIMAX model and multivariate LSTM model were established to predict the daily total death toll from July 1^st,2017 to July 14^th,2017. RMSE, MAE and MAPE were used as evaluation indexes to compare the prediction effects of these two models. Results RMSE, MAE and MAPE of ARIMAX model and multivariate LSTM model were 20.742、15.094、9.921 and 47.182、35.863、19.633, respectively. Conclusion ARIMAX model is better than multivariate LSTM model to predict the daily death toll in Yancheng city.

This paper summarizes the development trend and characteristics of public opinion on health protection and disinfection strategies in the COVID-19 epidemic. The experience and deficiency of the strategies are discussed from the perspective of public opinion, and suggestions on how health protection and disinfection can help prevent and control infectious diseases are also put forward: to strengthen health protection and disinfection in key places and units; to evaluate health protection and disinfection effects as well as the transmission mechanism of virus in the environment; to establish a professional health protection and disinfection emergency science popularization mechanism and information release channel; to speed up the formulation and revision of health protection and disinfection standards related to the epidemic.