Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective:To analyze the value of the modified 5-factor frailty index in assessing postoperative complications and mortality in elderly hip fracture patients.Methods:In this retrospective study, clinical data were collected of hip fracture patients aged 60 years and above surgically treated at Beijing Luhe Hospital affiliated to Capital Medical University between January 2015 and December 2019.Patients' group assignment was based on whether the modified frailty index score was ≤1 or ≥2, and a post-surgery follow-up was conducted for survival at 30 days, 1 year, 2 years, and 4 years, which was analyzed by the Kaplan-Meier method.Multivariate Cox regression analysis was used to identify factors affecting death in elderly patients.Results:A total of 1 208 patients were included, with 890 in the group with the index score ≤1 and 318 in the group with the index score ≥2.There was no difference in mortality at 30 days(1.6% or 14/890 vs.1.9% or 6/318, P=0.707), 1-year(11.3% or 99/874 vs.11.6% or 36/310, P=0.917), 2-years(19.7% or 168/852 vs.24.3% or 73/300, P=0.099)and 4-years(44.0% or 238/541 vs.51.5% or 106/206, P=0.071). The incidence of postoperative complications in the group with the score ≥2 was higher(14.8% or 47/318 vs.9.7% or 86/890, P=0.012), including the incidence of stroke(6.3% or 20/318 vs.1.8% or 16/890, P<0.001)and the incidence of postoperative pneumonia(6.0% or 19/318 vs.3.1% or 28/890, P=0.029), and the differences were statistically significant.Multivariate Cox regression analysis showed that age, being female, the Charlson comorbidity index score and low hemoglobin at admission were risk factors for 1-year, 2-year and 4-year mortality post-surgery(all P<0.05), while the modified frailty index score had no correlation with postoperative mortality. Conclusions:A modified frailty index ≥2 is predictive of increased risk of postoperative pneumonia and stroke in patients with hip fractures, but is not correlated with the risk of postoperative mortality.

Objective To study the influence of implant depth and scanning rod lengths on the accuracy of digital impression for single-tooth implant restoration of the mandibular posterior teeth.Methods Five standard dental cast models with missing right mandibular first molar(46)were prepared with the subgingival implant depths of 0,1,3,5 and 7 mm.ITI RC and ITI RC H11 scanning rods were connected to the replacement body and placed into the seating tract for scanning.The reference data were obtained using a 3D dental scanner,and the experimental data were obtained by 10 scans of each model using a digitized intraoral scanner.Geomagic Wrap 2021 was used to analyze the model data to test the trueness and precision of the models.Results The trueness did not differ significantly among the groups(P>0.05).The implant depth of 1 mm achieved the highest impression precision(66.81±2.45 μm),and the depth of 0 mm resulted in a significantly lower precision(95.60±3.04 μm)than the depth of 1 and 3 mm.Starting from the subgingival depth of 1 mm,the precision of the scan decreased progressively with the increase of the implant depth.At the subgingival implant depth of 5 or 7 mm,the use of an extended rod significantly improved the scan precision.Conclusion For single-tooth implant restoration of the mandibular posterior teeth,the implant depth can substantially affect the accuracy of digital impression,which decreases as the implant depth increases.For a deep implant,the use of a longer scanning rod can improve the scanning accuracy.

Objective To study the influence of implant depth and scanning rod lengths on the accuracy of digital impression for single-tooth implant restoration of the mandibular posterior teeth.Methods Five standard dental cast models with missing right mandibular first molar(46)were prepared with the subgingival implant depths of 0,1,3,5 and 7 mm.ITI RC and ITI RC H11 scanning rods were connected to the replacement body and placed into the seating tract for scanning.The reference data were obtained using a 3D dental scanner,and the experimental data were obtained by 10 scans of each model using a digitized intraoral scanner.Geomagic Wrap 2021 was used to analyze the model data to test the trueness and precision of the models.Results The trueness did not differ significantly among the groups(P>0.05).The implant depth of 1 mm achieved the highest impression precision(66.81±2.45 μm),and the depth of 0 mm resulted in a significantly lower precision(95.60±3.04 μm)than the depth of 1 and 3 mm.Starting from the subgingival depth of 1 mm,the precision of the scan decreased progressively with the increase of the implant depth.At the subgingival implant depth of 5 or 7 mm,the use of an extended rod significantly improved the scan precision.Conclusion For single-tooth implant restoration of the mandibular posterior teeth,the implant depth can substantially affect the accuracy of digital impression,which decreases as the implant depth increases.For a deep implant,the use of a longer scanning rod can improve the scanning accuracy.

Mastitis is one of the most widespread infectious diseases that adversely affects the profitability of the dairy industry worldwide. Accurate diagnosis and identification of pathogens early to cull infected animals and minimize the spread of infection in herds is critical for improving treatment effects and dairy farm welfare. The major pathogens causing mastitis and pathogenesis are assessed first. The most recent and advanced strategies for detecting mastitis, including genomics and proteomics approaches, are then evaluated .Finally, the advantages and disadvantages of each technique, potential research directions, and future perspectives are reported. This review provides a theoretical basis to help veterinarians select the most sensitive, specific, and cost-effective approach for detecting bovine mastitis early.

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

Periodontitis imparting the increased risk of atherosclerotic cardiovascular diseases is partially due to the immune subversion of the oral pathogen, particularly the Porphyromonas gingivalis (P. gingivalis), by inducing apoptosis. However, it remains obscure whether accumulated apoptotic cells in P. gingivalis-accelerated plaque formation are associated with impaired macrophage clearance. Here, we show that smooth muscle cells (SMCs) have a greater susceptibility to P. gingivalis-induced apoptosis than endothelial cells through TLR2 pathway activation. Meanwhile, large amounts of miR-143/145 in P.gingivalis-infected SMCs are extracellularly released and captured by macrophages. Then, these miR-143/145 are translocated into the nucleus to promote Siglec-G transcription, which represses macrophage efferocytosis. By constructing three genetic mouse models, we further confirm the in vivo roles of TLR2 and miR-143/145 in P. gingivalis-accelerated atherosclerosis. Therapeutically, we develop P.gingivalis-pretreated macrophage membranes to coat metronidazole and anti-Siglec-G antibodies for treating atherosclerosis and periodontitis simultaneously. Our findings extend the knowledge of the mechanism and therapeutic strategy in oral pathogen-associated systemic diseases.
Animals ; Mice ; Endothelial Cells ; Toll-Like Receptor 2 ; Macrophages ; Apoptosis ; Atherosclerosis ; Myocytes, Smooth Muscle ; MicroRNAs

Objective:To develop the discrimination experience questionnaire for HIV/acquired immunodeficiency syndrome(AIDS) patients and test the reliability and validity of the questionnaire.Methods:Based on the literature review and semi-structured interviews to clarify the operational definition of discrimination for HIV/AIDS and develop the item pool. The questionnaire was developed though 2 rounds Delphi consultation and a pilot test. A total of 410 HIV/AIDS patients in Shanghai Public Health Clinical Center of Fudan University from June to December 2020 were selected to investigate the questionnaire, item analysis was used to screen items. SPSS 22.0 software was used for reliability test and exploratory factor analysis, the AMOS 21.0 software was used for confirmatory factor analysis to test the reliability and validity of the questionnaire.Results:The questionnaire consisted 2 dimensions(external discrimination and internal discrimination) and 10 items. Exploratory factor analysis showed that two common factors were extracted from the frequency of discrimination and the degree of negative psychological impact of discrimination experience on patients, and the cumulative variance contribution rates were 48.367% and 55.403%, respectively. The confirmatory factor analysis on the frequency of discrimination showed that Chi square degree of freedom ratio ( χ2/ df) was 2.831, P<0.05, root mean square of approximation error (RMSEA) was 0.093, goodness of fit index (GFI) was 0.928, comparative fit index (CFI) was 0.925, incremental fit index (IFI) was 0.926; the confirmatory factor analysis on the negative psychological impact of discrimination experience on patients showed that χ2/ df was 1.740, P<0.05; RMSEA was 0.076, GFI was 0.925, CFI was 0.936, IFI was 0.938. The content validity of the questionnaire was 0.9. The Cronbach α coefficientof questionnaire was 0.811, and the test-retest coefficient was 0.862 ( P<0.01). Conclusions:The discrimination experience questionnaire for HIV/AIDS patients has good reliability and validity, and it can be used to measure the discrimination for HIV/AIDS patients.

Background: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC 0–24h /MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid E max (Hill) equation. The dose was calculated based on the AUC 0–24h /MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 µg/mL, 811.99 ± 54.70 μg·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 µg/mL, 735.85 ± 26.20 μg·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 µg/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC 0–24h /MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. suis infections.

Endothelial cell injury is a major contributor to cardiovascular diseases.The 2,3,5,4’-Tetrahydroxystilbene-2-O-β-D-Glucoside (TSG) contributes to alleviate human umbilical vein endothelial cells (HUVECs) injury through mechanisms still know a little. This study aims to clarify the TSG effects on gene expression (mRNA and microRNA) related to oxidative stress and endoplasmic reticulum stress induced by H2O2 in HUVECs. We found that TSG significantly reduced the death rate of cells and increased intracellular superoxide dismutase activity. At qRT-PCR, experimental data showed that TSG significantly counteracted the expressions of miR-9-5p, miR-16, miR-21, miR-29b, miR-145-5p, and miR-204-5p. Besides, TSG prevented the expression of ATF6 and CHOP increasing. In contrast, TSG promoted the expression of E2F1. In conclusion, our results point to the obvious protective effect of TSG on HUVECs injury induced by H2O2, and the mechanism may through miR16/ATF6/ E2F1 signaling pathway.