Expansion and transmission dynamics of high risk carbapenem-resistant Klebsiella pneumoniae subclones in China: An epidemiological, spatial, genomic analysis.

AIMS: Carbapenem-resistant Klebsiella pneumonia (CRKP) is a global threat that varies by region. The global distribution, evolution, and clinical implications of the ST11 CRKP clone remain obscure. METHODS: We conducted a multicenter molecular epidemiological survey using isolates obtained from 28 provinces and municipalities across China between 2011 and 2021. We integrated sequences from public databases and performed genetic epidemiology analysis of ST11 CRKP. RESULTS: Among ST11 CRKP, KL64 serotypes exhibited considerable expansion, increasing from 1.54% to 46.08% between 2011 and 2021. Combining our data with public databases, the phylogenetic and phylogeography analyses indicated that ST11 CRKP appeared in the Americas in 1996 and spread worldwide, with key clones progressing from China's southeastern coast to the inland by 2010. Global phylogenetic analysis showed that ST11 KL64 CRKP has evolved to a virulent, resistant clade with notable regional spread. Single-nucleotide polymorphism (SNP) analysis identified BMPPS (bmr3, mltC, pyrB, ppsC, and sdaC) as a key marker for this clade. The BMPPS SNP clade is associated with high mortality and has strong anti-phagocytic and competitive traits in vitro. CONCLUSIONS: The high-risk ST11 KL64 CRKP subclone showed strong expansion potential and survival advantages, probably owing to genetic factors.

IL-27 in combination with anti-PD-1 can be anti-cancer or pro-cancer.

Interleukin-27 (IL-27) is known to play opposing roles in immunology. The present paper considers, specifically, the role IL-27 plays in cancer immunotherapy when combined with immune checkpoint inhibitor anti-PD-1. We first develop a mathematical model for this combination therapy, by a system of Partial Differential Equations, and show agreement with experimental results in mice injected with melanoma cells. We then proceed to simulate tumor volume with IL-27 injection at a variable dose F and anti-PD-1 at a variable dose g. We show that in some range of "small" values of g, as f increases tumor volume decreases as long as fFc(g), where Fc(g) is a monotone increasing function of g. This demonstrates that IL-27 can be both anti-cancer and pro-cancer, depending on the ranges of both anti-PD-1 and IL-27.

Blood culture quality and turnaround time of clinical microbiology laboratories in Chinese Teaching Hospitals: A multicenter study.

PURPOSE: Blood culture (BC) remains the gold standard for the diagnosis of bloodstream infections. Improving the quality of clinical BC samples, optimizing BC performance, and accelerating antimicrobial susceptibility test (AST) results are essential for the early detection of bloodstream infections and specific treatments. METHODS: We conducted a retrospective multicenter study using 450,845 BC specimens from clinical laboratories obtained from 19 teaching hospitals between 1 January 2021 and 31 December 2021. We evaluated key performance indicators (KPIs), turnaround times (TATs), and frequency distributions of processing in BC specimens. We also evaluated the AST results of clinically significant isolates for four different laboratory workflow styles. RESULTS: Across the 10 common bacterial isolates (n = 16,865) and yeast isolates (n = 1011), the overall median (interquartile range) TATs of AST results were 2.67 (2.05-3.31) and 3.73 (2.98-4.64) days, respectively. The specimen collections mainly occurred between 06:00 and 24:00, and specimen reception and loadings mainly between 08:00 and 24:00. Based on the laboratory workflows of the BCs, 16 of the 19 hospitals were divided into four groups. Time to results (TTRs) from specimen collection to the AST reports were 2.35 (1.95-3.06), 2.61 (1.98-3.32), 2.99 (2.60-3.87), and 3.25 (2.80-3.98) days for groups I, II, III, and IV, respectively. CONCLUSION: This study shows the related BC KPIs and workflows in different Chinese hospitals, suggesting that laboratory workflow optimization can play important roles in shortening time to AST reports and initiation of appropriate timely treatment.

Exploring the third-generation tetracycline resistance of multidrug-resistant livestock-associated methicillin-resistant Staphylococcus aureus ST9 across healthcare settings in China.

BACKGROUND: The overuse of antibiotics in livestock is contributing to the burden of antimicrobial resistance in humans, representing a One Health challenge. Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has recently become a growing concern, and ST9 is the major LA-MRSA lineage in China and has emerged in clinical settings. METHODS: Antimicrobial susceptibility testing was used to evaluate the tetracycline resistance of ST9 MRSA collections, and gene cloning experiments were performed to explore the resistance mechanisms. Whole-genome sequencing and comparative genomics were used to analyse the genetic features of clinical ST9 isolates. A phylogenetic tree was constructed to investigate the relationship of human- and livestock-derived ST9 isolates. RESULTS: Clinical ST9 isolates were found to possess several types of resistance genes and resistance-related mutations and were multidrug-resistant. Notably, all clinical ST9 isolates were resistant to third-generation tetracyclines. Cloning experiments showed that both the acquisition of the tetracycline resistance gene tet(L)/tet(63) and a mutation in the rpsJ gene contributed to third-generation tetracycline resistance. Phylogenetic analysis showed that the ST9 isolates collected in healthcare systems were probably transmitted from livestock. The ST9 lineage underwent multiple interspecies recombination events and gained many resistance elements. Furthermore, the resistance to third-generation tetracyclines may have evolved under tetracycline pressure in livestock. CONCLUSIONS: The evolution of ST9 MRSA in livestock and transmission of this clone between humans and livestock highlight the importance of establishing control strategies with the One Health approach to reduce the burden of antibiotic resistance.

Whole genome analysis of echinocandin non-susceptible Candida Glabrata clinical isolates: a multi-center study in China.

BACKGROUND: Candida glabrata is an important cause of invasive candidiasis. Echinocandins are the first-line treatment of invasive candidiasis caused by C. glabrata. The epidemiological echinocandin sensitivity requires long-term surveillance and the understanding about whole genome characteristics of echinocandin non-susceptible isolates was limited. RESULTS: The present study investigated the echinocandin susceptibility of 1650 C. glabrata clinical isolates in China from August 2014 to July 2019. The in vitro activity of micafungin was significantly better than those of caspofungin and anidulafungin (P < 0.001), assessed by MIC50/90 values. Whole genome sequencing was conducted on non-susceptible isolates and geography-matched susceptible isolates. Thirteen isolates (0.79%) were resistant to at least one echinocandin. Six isolates (0.36%) were solely intermediate to caspofungin. Common evolutionary analysis of echinocandin-resistant and echinocandin-intermediate isolates revealed genes related with reduced caspofungin sensitivity, including previously identified sphinganine hydroxylase encoding gene SUR2. Genome-wide association study identified SNPs at subtelometric regions that were associated with echinocandin non-susceptibility. In-host evolution of echinocandin resistance of serial isolates revealed an enrichment for non-synonymous mutations in adhesins genes and loss of subtelometric regions containing adhesin genes. CONCLUSIONS: The echinocandins are highly active against C. glabrata in China with a resistant rate of 0.79%. Echinocandin non-susceptible isolates carried common evolved genes which are related with reduced caspofungin sensitivity. In-host evolution of C. glabrata accompanied intensive changing of adhesins profile.

Application of next-generation sequencing on diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with ANCA-associated vasculitis.

BACKGROUND: Mycoplasma hominis is one of the main opportunistic pathogenic mycoplasmas in humans which has a major impact on patients with bloodstream infections. Because it is difficult to detect or isolate, rapid and accurate diagnosis using improved methods is essential and still challenging for patients with bloodstream infection. CASE PRESENTATION: In this case, we reported the application of next -generation sequencing for the diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. After 9 days of combined treatment with levofloxacin, polymyxin B and meropenem, the patient's condition was gradually controlled and he was discharged without further complications. During the three-month outpatient follow-up, no recurrence of symptoms or clinical signs was reported. CONCLUSIONS: This successful application of next generation sequencing assisted the rapid diagnosis of Mycoplasma hominis bloodstream infection, provided a new perspective in the clinical approach and highlighted the potential of this technique in rapid etiological diagnosis.

Metagenomic next-generation sequencing for the diagnosis of Pneumocystis jirovecii Pneumonia in critically pediatric patients.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii Pneumonia (PCP) in critically pediatric patients. METHODS: Seventeen critically pediatric patients with PCP and sixty patients diagnosed with non-PCP pneumonia who were admitted in pediatric intensive care unit between June 2018 and July 2021 were enrolled. Conventional methods and mNGS for detecting Pneumocystis jirovecii (P. jirovecii) were compared. The patients' demographics, comorbidities, laboratory test results, antibiotic treatment response and 30 day mortality were analyzed. RESULT: The mNGS showed a satisfying diagnostic performance with a sensitivity of 100% in detecting P. jirovecii compared with Gomori methenamine silver staining (5.9%), serum (1,3)-ß-D-glucan (86.7%) and and LDH (55.6%). The diagnostic specificity of mNGS for PCP was higher than that of serum BDG (56.7%) and LDH (71.4%). In PCP group, over one thirds' cases had mixed infections. Compared with survivors, non-survivors had higher stringently mapped read numbers (SMRNs) in bronchoalveolar lavage fluid (BALF) sample (P < 0.05), suggesting SMRNs were closely associated with the severity of response. The detection for P. jirovecii by mNGS both in BALF and blood samples reached a concordance rate of 100%, and the SMRNs in the BALF were remarkably higher than that in blood samples. Initial antimicrobial treatment was modified in 88.2% of PCP patients based on the mNGS results. CONCLUSION: The mNGS is a potential and efficient technology in diagnosing PCP and shows a satisfying performance in the detection of co-pathogens. Both blood and BALF samples for mNGS are suggested for the presumptive diagnosis of PCP.

A simple in-host model for COVID-19 with treatments: model prediction and calibration.

In this paper, we provide a simple ODEs model with a generic nonlinear incidence rate function and incorporate two treatments, blocking the virus binding and inhibiting the virus replication to investigate the impact of calibration on model predictions for the SARS-CoV-2 infection dynamics. We derive conditions of the infection eradication for the long-term dynamics using the basic reproduction number, and complement the characterization of the dynamics at short-time using the resilience and reactivity of the virus-free equilibrium are considered to inform on the average time of recovery and sensitivity to perturbations in the initial virus free stage. Then, we calibrate the treatment model to clinical datasets for viral load in mild and severe cases and immune cells in severe cases. Based on the analysis, the model calibrated to these different datasets predicts distinct scenarios: eradication with a non reactive virus-free equilibrium, eradication with a reactive virus-free equilibrium, and failure of infection eradication. Moreover, severe cases generate richer dynamics and different outcomes with the same treatment. Calibration to different datasets can lead to diverse model predictions, but combining long- and short-term dynamics indicators allows the categorization of model predictions and determination of infection severity.

Redox-Active Covalent Organic Frameworks with Nickel-Bis(dithiolene) Units as Guiding Layers for High-Performance Lithium Metal Batteries.

Combining the chemistry of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) can bring new opportunities for the design of advanced materials with enhanced tunability and functionality. Herein, we constructed two COFs based on Ni-bis(dithiolene) units and imine bonds, representing a bridge between traditional MOFs and COFs. The Ni-bis(dithiolene)tetrabenzaldehyde as the 4-connected linker was initially synthesized, which was further linked by 4-connected tetra(aminophenyl)pyrene (TAP) or 3-connected tris(aminophenyl)amine (TAA) linkers into two COFs, namely, Ni-TAP and Ni-TAA. Ni-TAP shows a two-dimensional sql network, while TAA is a twofold interpenetrated framework with an ffc topology. They both exhibit a high Brunauer-Emmett-Teller surface area (324 and 689 m2 g-1 for Ni-TAP and Ni-TAA, respectively), a fairly good conductivity (1.57 × 10-6 and 9.75 × 10-5 S m-1 for Ni-TAP and Ni-TAA, respectively), and high chemical stability (a stable pH window of 1-14 for Ni-TAA). When applied in lithium metal batteries as an intermediate layer for guiding the uniform Li electrodeposition, Ni-TAP and Ni-TAA displayed impressive lithiophilicity and high Li-ion conductivity, enabling the achievement of smooth and dense Li deposition with a clear columnar morphology and stable Li plating/stripping behaviors with high Li utilization, which is anticipated to pave the way to upgrade Li metal anodes for application in high-energy-density battery systems.

Combined fragment-based machine learning force field with classical force field and its application in the NMR calculations of macromolecules in solutions.

We have developed a combined fragment-based machine learning (ML) force field and molecular mechanics (MM) force field for simulating the structures of macromolecules in solutions, and then compute its NMR chemical shifts with the generalized energy-based fragmentation (GEBF) approach at the level of density functional theory (DFT). In this work, we first construct Gaussian approximation potential based on GEBF subsystems of macromolecules for MD simulations and then a GEBF-based neural network (GEBF-NN) with deep potential model for the studied macromolecule. Then, we develop a GEBF-NN/MM force field for macromolecules in solutions by combining the GEBF-NN force field for the solute molecule and ff14SB force field for solvent molecules. Using the GEBF-NN/MM MD simulation to generate snapshot structures of solute/solvent clusters, we then perform the NMR calculations with the GEBF approach at the DFT level to calculate NMR chemical shifts of the solute molecule. Taking a heptamer of oligopyridine-dicarboxamides in chloroform solution as an example, our results show that the GEBF-NN force field is quite accurate for this heptamer by comparing with the reference DFT results. For this heptamer in chloroform solution, both the GEBF-NN/MM and classical MD simulations could lead to helical structures from the same initial extended structure. The GEBF-DFT NMR results indicate that the GEBF-NN/MM force field could lead to more accurate NMR chemical shifts on hydrogen atoms by comparing with the experimental NMR results. Therefore, the GEBF-NN/MM force field could be employed for predicting more accurate dynamical behaviors than the classical force field for complex systems in solutions.

Mathematical Modeling and Analysis of CD200-CD200R in Cancer Treatment.

CD200 is a cell membrane protein that binds to its receptor, CD200 receptor (CD200R). The CD200 positive tumor cells inhibit the cellular functions of M1 and M2 macrophages and dendritic cells (DCs) through the CD200-CD200R complex, resulting in downregulation of Interleukin-10 and Interleukin-12 productions and affecting the activation of cytotoxic T lymphocytes. In this work, we provide two ordinary differential equation models, one complete model and one simplified model, to investigate how the binding affinities of CD200R and the populations of M1 and M2 macrophages affect the functions of the CD200-CD200R complex in tumor growth. Our simulations demonstrate that (i) the impact of the CD200-CD200R complex on tumor promotion or inhibition highly depends on the binding affinity of the CD200R on M2 macrophages and DCs to the CD200 on tumor cells, and (ii) a stronger binding affinity of the CD200R on M1 macrophages or DCs to the CD200 on tumor cells induces a higher tumor cell density in the CD200 positive tumor. Thus, the CD200 blockade would be an efficient treatment method in this case. Moreover, the simplified model shows that the binding affinity of CD200R on macrophages is the major factor to determine the treatment efficacy of CD200 blockade when the binding affinities of CD200R on M1 and M2 macrophages are significantly different to each other. On the other hand, both the binding affinity of CD200R and the population of macrophages are the major factors to determine the treatment efficacy of CD200 blockade when the binding affinities of CD200R on M1 and M2 macrophages are close to each other. We also analyze the simplified model to investigate the dynamics of the positive and trivial equilibria of the CD200 positive tumor case and the CD200 deficient tumor case. The bifurcation diagrams show that when M1 macrophages dominate the population, the tumor cell density of the CD200 positive tumor is higher than the one of CD200 deficient tumor. Moreover, the dynamics of tumor cell density change from tumor elimination to tumor persistence to oscillation, as the maximal proliferation rate of tumor cells increases.

Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study.

BACKGROUND: Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China. METHODS: In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected. RESULT: Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883-48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066-31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663-46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228-6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226-32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI. CONCLUSION: In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.

Mathematical modeling of the eyespots in butterfly wings.

Butterfly wing color patterns are a representative model system for studying biological pattern formation, due to their two-dimensional simple structural and high inter- and intra-specific variabilities. Moreover, butterfly color patterns have demonstrated roles in mate choice, thermoregulation, and predator avoidance via disruptive coloration, attack deflection, aposematism, mimicry, and masquerade. Because of the importance of color patterns to many aspects of butterfly biology and their apparent tractability for study, color patterns have been the subjects of many attempts to model their development. Early attempts focused on generalized mechanisms of pattern formation such as reaction-diffusion, diffusion gradient, lateral inhibition, and threshold responses, without reference to any specific gene products. As candidate genes with expression patterns that resembled incipient color patterns were identified, genetic regulatory networks were proposed for color pattern formation based on gene functions inferred from other insects with wings, such as Drosophila. Particularly detailed networks incorporating the gene products, Distal-less (Dll), Engrailed (En), Hedgehog (Hh), Cubitus interruptus (Ci), Transforming growth factor-ß (TGF-ß), and Wingless (Wg), have been proposed for butterfly border ocelli (eyespots) which helps the investigation of the formation of these patterns. Thus, in this work, we develop a mathematical model including the gene products En, Hh, Ci, TGF-ß, and Wg to mimic and investigate the eyespot formation in butterflies. Our simulations show that the level of En has peaks in the inner and outer rings and the level of Ci has peaks in the inner and middle rings. The interactions among these peaks activate cells to produce white, black, and yellow pigments in the inner, middle, and outer rings, respectively, which captures the eyespot pattern of wild type Bicyclus anynana butterflies. Additionally, our simulations suggest that lack of En generates a single black spot and lack of Hh or Ci generates a single white spot, and a deficiency of TGF-ß or Wg will cause the loss of the outer yellow ring. These deficient patterns are similar to those observed in the eyespots of Vanessa atalanta, Vanessa altissima, and Chlosyne nycteis. Thus, our model also provides a hypothesis to explain the mechanism of generating the deficient patterns in these species.

Generalized energy-based fragmentation approach for calculations of solvation energies of large systems.

A generalized energy-based fragmentation (GEBF) approach has been combined with a universal solvation model based on solute electron density (SMD) to compute the solvation energies of general large systems (such as protein molecules) in solutions. In the GEBF-SMD method, the solvation energy of a target system could be combined by the corresponding solvation energies of various subsystems, each of which is embedded in the background point charges and surface charges on the surface of solute cavity at the positions of its atoms and neighbouring atoms outside of the subsystem. Our results show that the GEBF-SMD model could reproduce the conventional SMD solvation energies quite well for various proteins in solutions, and could significantly reduce the computational costs for the SMD calculations of large proteins. In addition, the GEBF-SMD approach is almost independent of the basis sets and the types of solvents (including protic, polar, and nonpolar ones). Also, the GEBF-SMD approach could reproduce the relative energies of various conformers of large systems in solutions. Therefore, the GEBF-SMD method is expected to be applicable for computing the solvation energies of a broad range of large systems.

A case series of medically managed Candida parapsilosis complex prosthetic valve endocarditis.

BACKGROUND: In recent years, Candida parapsilosis is recognized as a species complex and is composed of Candida parapsilosis sensu stricto, Candida orthopsilosis and Candida metapsilosis. Candida parapsilosis complex prosthetic valve endocarditis (PVE) is rare and the survival rate is still low despite of optimal therapeutic strategies. In our report, it is novel to report cases as Candida parapsilosis complex PVE at species and identify Candida parapsilosis using MALDI-TOF MS. Case presentation A series of 4 cases of Candida parapsilosis complex PVE from our institution was reported. Three were infected by Candida parapsilosis sensu stricto and one was infected by Candida metapsilosis. The condition of two cases got better and the other died. CONCLUSIONS: More attention should be paid to Candida parapsilosis complex PVE and early diagnosis and prompt antibiotic therapy may play a role in the treatment for Candida parapsilosis complex PVE. It is recommended to identify Candida parapsilosis complex at species level and MALDI-TOF MS as an easy, fast and efficient identification method is worth promoting in clinical microbiology.

In Vitro Activity of Imipenem/Relebactam Against Enterobacteriaceae Isolates Obtained from Intra-abdominal, Respiratory Tract, and Urinary Tract Infections in China: Study for Monitoring Antimicrobial Resistance Trends (SMART), 2015-2018.

BACKGROUND: Considering the increasing incidence of carbapenem-resistant Enterobacteriaceae in China, this study aimed to establish the in vitro effectiveness of imipenem/relebactam (IMI/REL) on clinical Enterobacteriaceae isolates derived from intra-abdominal infections (IAIs), respiratory tract infections (RTIs), and urinary tract infections (UTIs) in China between 2015 and 2018. METHODS: In total, 8781 Enterobacteriaceae isolates from IAI, RTI, and UTI samples were collected from 22 hospitals across 7 geographic regions of China. Susceptibility to antimicrobial drugs was tested using the Clinical and Laboratory Standards Institute broth microdilution and breakpoints, and IMI/REL activity was assessed using United States Food and Drug Administration guidelines. RESULTS: In 2015-2018, the most frequently identified Enterobacteriaceae species was Escherichia coli (n = 4676 [53.3%]), followed by Klebsiella pneumoniae (n = 2949 [33.6%]) and Enterobacter cloacae (n = 542 [6.2%]). The Enterobacteriaceae isolates showed 95.2% overall susceptibility to IMI/REL, of which the susceptibility rates in isolates from IAI, RTI, and UTI were 95.8%, 91.4%, and 96.6%, respectively. Overall, the susceptibilities of both intensive care unit (ICU) and non-ICU Enterobacteriaceae isolates to colistin were 92.9%, followed by IMI/REL (90.7% [95.9%]) and amikacin (83.3% [92.3%]). In addition, IMI/REL restored 66.3% susceptibility in imipenem-nonsusceptible Enterobacteriaceae. CONCLUSIONS: Given their high in vitro susceptibility, Enterobacteriaceae infections in China should be considered for IMI/REL treatment, especially with isolates that are not susceptible to carbapenems.

Determining the susceptibility of carbapenem resistant Klebsiella pneumoniae and Escherichia coli strains against common disinfectants at a tertiary hospital in China.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) infections have become a global health threat. Controlling CRE transmission in hospitals is increasingly dependent on the use of disinfectants to restrict the risk of infection. Here, the susceptibility of patient-derived carbapenem resistant Klebsiella pneumoniae (CRKP) and Escherichia coli (CREC) strains against three common disinfectants and the determinants of resistance to disinfectants were investigated. METHODS: The minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of three common chemical disinfectants: chlorhexidine, trichloroisocyanuric (TCCA) acid and Povidone iodine (PVP-I) against 50 CRE strains were measured. The drug-resistance genes -qacEΔ1, qacA/B and cepA-were determined using polymerase chain reaction. RESULTS: A total of 36 CRKP and 14 CREC strains were collected in our hospital from 2016 to 2018. The MIC ranges of 36 CRKP strains against chlorhexidine, TCCA and PVP-I were 8~512 mg/L, 64~128 mg/L and 8~128 mg/L, respectively. For 14 CREC strains, the MIC ranges against chlorhexidine, TCCA and PVP-I were 4~128 mg/L, 64~128 mg/L and 4~128 mg/L, respectively. Moreover, against chlorhexidine and PVP-I, the MIC90 of 36 CRKP strains was higher than that of 50 CSKP strains. The qacE△1 gene was detected in 15 isolates among 36 CRKP strains (41.7%), and 8 isolates among 14 CREC strains (57.1%); while the qacA/B gene was not detected. Specifically, the cepA gene was much more prevalent than the qacEΔ1; it reached over 80% among CRKP strains. Compared to the CSKP strains, the presence of the qacEΔ1 and cepA genes was significantly higher among the CRKP strains (p < 0.05). CONCLUSION: CRE strains collected from patients in our hospital exhibit various degree of resistance to the commonly used chemical disinfectants. It is of great help to keep monitoring the tendency of the reduced susceptibility of the pan-resistant strains against disinfectants, in order to effectively control and prevent the spread of the super resistant bacteria.

PLIN: A Network for Pseudo-LiDAR Point Cloud Interpolation.

LiDAR sensors can provide dependable 3D spatial information at a low frequency (around 10 Hz) and have been widely applied in the field of autonomous driving and unmanned aerial vehicle (UAV). However, the camera with a higher frequency (around 20 Hz) has to be decreased so as to match with LiDAR in a multi-sensor system. In this paper, we propose a novel Pseudo-LiDAR interpolation network (PLIN) to increase the frequency of LiDAR sensor data. PLIN can generate temporally and spatially high-quality point cloud sequences to match the high frequency of cameras. To achieve this goal, we design a coarse interpolation stage guided by consecutive sparse depth maps and motion relationship. We also propose a refined interpolation stage guided by the realistic scene. Using this coarse-to-fine cascade structure, our method can progressively perceive multi-modal information and generate accurate intermediate point clouds. To the best of our knowledge, this is the first deep framework for Pseudo-LiDAR point cloud interpolation, which shows appealing applications in navigation systems equipped with LiDAR and cameras. Experimental results demonstrate that PLIN achieves promising performance on the KITTI dataset, significantly outperforming the traditional interpolation method and the state-of-the-art video interpolation technique.

Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes.

Context: Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed.Objective: We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs).Materials and methods: RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy.Results: Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC50) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1ß in the culture supernatant (p < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs (p < 0.05).Conclusions: Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.

Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Data for a total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; P = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; P = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; P = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; P = 0.022), that combination therapy was superior to monotherapy (P = 0.036), that metallo-ß-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter (P = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.