Image_1_Investigation and analysis of carbapenem-resistant gram-negative bacterial infection rates across hospitals in Shandong Province in China.tif

BackgroundThe increasing incidence of carbapenem-resistant bacterial infections has become a serious public health threat. This study aimed to investigate and analyze the current regional differences in carbapenem-resistant gram-negative bacteria (CRGN) in a major Province of China, and provide suggestions for preventing hospital infections.MethodsA questionnaire survey was used to obtain the current data on CRGN from 36 hospitals in Shandong Province, China, from 2019 to 2020. The association between the detection rates and discovery rates of CRGN and the use of antibacterial drugs was analyzed using Spearman's correlation coefficient. In addition, we compared the detection rates of CRGN and antibacterial drugs using hospitals categorized according to different levels and economic areas using the Kruskal-Wallis test.ResultsThe average detection rates of CRGN across the 36 hospitals varied from 1.91% to 66.04%. The discovery rate of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) remained below 5‰, and that of carbapenem-resistant Pseudomonas aeruginosa (CRPA) was below 10‰. Except for CRAB, the correlations between the detection rate and antimicrobial drug use intensity and carbapenem drug use percentage were 0.11–0.29 and 0.31–0.47, respectively. Carbapenem drug use was higher in the provincial hospital group than in the prefecture-level hospitals (P ConclusionsThe detection and discovery rates of CRE were low, and those of CRAB were high in Shandong Province. Larger hospitals have higher carbapenem drug use. These results can be used as a reference for preventing CRGN infections in developing countries and provide a basis for regional carbapenem resistance prevention and control strategies.</p

Treatments for cesarean scar pregnancy: 11-year experience at a medical center

Cesarean scar pregnancy (CSP) is a long-term complication after cesarean section that can cause severe maternal morbidity and mortality. Although a variety of treatments have been described, there is no consensus as to the optimal management approach. Many grading systems for CSP have been proposed, among which the classification made by the consensus of Chinese experts in 2016 was shown to provide improved treatment guidance for clinical practice. The purpose of the present study was to analyze the success rate of different treatments for each type of CSP as classified according to the Chinese Expert’s Consensus (2016), and to develop a management strategy for CSP. A retrospective study was performed among patients diagnosed with CSP at Shandong Provincial Hospital between January 2009 and December 2019. We reviewed clinical characteristics, treatment methods, and subsequent outcomes; and analyzed these endpoints using the statistical software package SPSS 22.0 (SPSS, Inc., Chicago, IL). For type I CSP, systemic methotrexate (MTX) administration exhibited a success rate of 79.2% for type Ia and 14.3% for type Ib. Local and systemic MTX administration success rates were 88.9% for type Ia and 66.7% for type Ib. Dilation and curettage (D&C), curettage after uterine artery embolization (UAE + C), and hysteroscopic curettage (H + C) were 100% successful. For type II, UAE + C, H + C, and laparoscopy combined with hysteroscopic curettage (L + H+C) were 100% successful. D&C had a success rate of 97.0% for type IIa and 88.9% for type IIb. The success rate of systemic MTX administration was 52.0% for type IIa and 62.5% for type IIb. Both UAE + C and L + H+C had 100% success rates for type IIIa CSPs, while for type IIIb, the success rate was 87.9% for UAE + C vs. 96.6% for L + H+C. For type I CSPs, D&C was quick, easy, and safe; for type II, H + C was more suitable. For type III and some type II patients who wished to undergo simultaneous repair of the cesarean defect, L + H+C was the optimal method. UAE can be used as a complementary option instead of a prophylactic measure, and when difficulties with endoscopic surgeries were encountered, conversion to laparotomy was the ultimate treatment.</p

Chemoproteomics Reveals Unexpected Lysine/Arginine-Specific Cleavage of Peptide Chains as a Potential Protein Degradation Machinery

Proteins can undergo oxidative cleavage by in vitro metal-catalyzed oxidation (MCO) in either the α-amidation or the diamide pathway. However, whether oxidative cleavage of polypeptide-chain occurs in biological systems remains unexplored. We describe a chemoproteomic approach to globally and site-specifically profile electrophilic protein degradants formed from peptide backbone cleavages in human proteomes, including the known N-terminal α-ketoacyl products and >1000 unexpected N-terminal formyl products. Strikingly, such cleavages predominantly occur at the carboxyl side of lysine (K) and arginine (R) residues across native proteomes in situ, while MCO-induced oxidative cleavages randomly distribute on peptide/protein sequences in vitro. Furthermore, ionizing radiation-induced reactive oxygen species (ROS) also generate random oxidative cleavages in situ. These findings suggest that the endogenous formation of <i>N</i>-formyl and <i>N</i>-α-ketoacyl degradants in biological systems is more likely regulated by a previously unknown mechanism with a trypsin-like specificity, rather than the random oxidative damage as previously thought. More generally, our study highlights the utility of quantitative chemoproteomics in combination with unrestricted search tools as a viable strategy to discover unexpected chemical modifications of proteins labeled with active-based probes

A Chemoproteomic Platform To Assess Bioactivation Potential of Drugs

Reactive metabolites (RM) formed from bioactivation of drugs can covalently modify liver proteins and cause mechanism-based inactivation of major cytochrome P450 (CYP450) enzymes. Risk of bioactivation of a test compound is routinely examined as part of lead optimization efforts in drug discovery. Here we described a chemoproteomic platform to assess <i>in vitro</i> and <i>in vivo</i> bioactivation potential of drugs. This platform enabled us to determine reactivity of thousands of proteomic cysteines toward RMs of diclofenac formed in human liver microsomes and living animals. We pinpointed numerous reactive cysteines as the targets of RMs of diclofenac, including the active (heme-binding) sites on several key CYP450 isoforms (1A2, 2E1 and 3A4 for human, 2C39 and 3A11 for mouse). This general platform should be applied to other drugs, drug candidates, and xenobiotics with potential hepatoxicity, including environmental organic substances, bioactive natural products, and traditional Chinese medicine

Data File 1: Assessment of eye length changes in accommodation using dynamic extended-depth OCT

LT and AEL changes from each trial at each accommodative level for each subject after removing trials with errant subject behavior, excessive noise in biometry, or issues in acquisition. Originally published in Biomedical Optics Express on 01 May 2017 (boe-8-5-2709

Visualization 1: Assessment of eye length changes in accommodation using dynamic extended-depth OCT

Example video of a disaccommodative response to a 6 D stimulus by a 23 y.o. subject Originally published in Biomedical Optics Express on 01 May 2017 (boe-8-5-2709