Prognostic value of platelet count-related ratios on admission in patients with pyogenic liver abscess.

OBJECTIVE: The purpose of the current study was to evaluate the association between C-reactive protein-to-platelet ratio (CPR), neutrophil-to-lymphocyte*platelet ratio (NLPR) and fibrinogen-to-platelet ratio (FPR) and the prognoses of pyogenic liver abscess (PLA) patients. METHODS: A cohort of 372 patients with confirmed PLA were enrolled in this retrospective study between 2015 and 2021. Laboratory data were collected on admission within 24 h. The demographic characteristics and clinical features were recorded. Risk factors for outcomes of PLA patients were determined via multivariate logistic regression analyses, and optimal cut-off values were estimated by using the receiver operating characteristic (ROC) curve analysis. RESULTS: Out of 372 patients, 57.8% were men, 80 (21.5%) developed sepsis, and 33 (8.9%) developed septic shock. The levels of CPR, NLPR and FPR were significantly increased in the development of sepsis, and prolonged hospital stays in PLA patients. The multivariate logistic regression analysis indicated that the CPR (OR: 2.262, 95% CI: 1.586-3.226, p < 0.001), NLPR (OR: 1.118, 95% CI: 1.070-1.167, p < 0.001) and FPR (OR: 1.197, 95% CI: 1.079-1.329, p = 0.001) were independent risks of PLA patients with sepsis, and NLPR (OR: 1.019, 95% CI: 1.004-1.046, p = 0.019) was shown to be an independent predictor of prolonged hospital stays. The ROC curve results showed that the three biomarkers had different predictive values, and CPR proved to work best, with a ROC value of 0.851 (95% CI: 0.807-0.896, p < 0.001) for sepsis. CONCLUSION: Higher levels of CPR, NLPR and FPR were associated with a higher risk of poor outcomes. Moreover, a high CPR level performed best when predicting the clinical outcome in PLA patients.

Antibiotic Sensitivity of Proteus mirabilis Urinary Tract Infection in Patients with Urinary Calculi.

Background: The study's objective was to determine Proteus mirabilis susceptibility in individuals with urinary tract infections and stones to antibiotics and prescribe optimal antimicrobial treatment. Methods: Nonrepetitive Proteus mirabilis strains were isolated from urine specimens obtained from 317 patients diagnosed with urinary stones from January, 2018, to December, 2021. A VITEK mass spectrometer was used for species identification, and a VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). Susceptibility to imipenem and cefoperazone/sodium sulbactam was tested by the disc diffusion method (K-B method). The antibiotic sensitivity of the strains was analyzed by sex and season. Results: A total of 317 patients were reviewed: 202 females (63.7%) and 115 males (36.3%). Proteus mirabilis infections were observed during spring (21.8%, n = 69), summer (26.2%, n = 83), autumn (33.8%, n = 107), and winter (18.2%, n = 57). Proteus mirabilis infections in females were diagnosed most often during the fall (24.3%, n = 77) and during the summer in males (11.0%, n = 35) (p = 0.010). Female patients responded best to levofloxacin (p = 0.014), and male patients responded best to sulfamethoxazole (p = 0.023). Seasonal variation in antibiotic sensitivity was confirmed, with significantly higher rates in the winter for cefuroxime (p = 0.002) and sulfamethoxazole (p = 0.002). Significant seasonal increases were also found in levofloxacin sensitivity during the summer (p = 0.005). Conclusions: Highly effective antibiotics such as cefoxitin and ceftazidime should be used empirically by considering antibiotic sensitivity changes by sex, season, and year. Regional studies should be conducted frequently.

Clinical features and development of Sepsis in Klebsiella pneumoniae infected liver abscess patients: a retrospective analysis of 135 cases.

BACKGROUND: Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis. METHODS: This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed. RESULTS: A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient. CONCLUSION: Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.

Hepatitis B virus infection and risk of non-alcoholic fatty liver disease: A population-based cohort study.

BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD) has been studied extensively, the potential risk factors for NAFLD among chronic hepatitis B (CHB) patients have not been fully known. METHODS: A population-based cohort of adult CHB patients without a history of alcohol drinking or NAFLD were recruited and followed up from October 2012 to January 2015 in Jiangsu province, China. Using Cox proportional hazards regression model, potential risk factors including viral and metabolic factors for NAFLD were evaluated. RESULTS: Two thousand three hundred and ninety-three adult CHB patients (mean age 50.7 ± 13.2 years) were included in the cohort. With 4429 person-years of follow-up, 283 individuals progressed to NAFLD with an incidence rate of 63.89/1000 person-years. Overweight and obese CHB patients had an increased risk of NAFLD (overweight adjusted hazard ratio [HR], 3.10; 95% CI, 2.29-4.18; obese HR, 8.52; 95%CI, 5.93-12.25) compared to normal weight carriers. The incidence of NAFLD was associated with concurrent type 2 diabetes mellitus (DM) (HR, 1.88; 95%CI, 1.15-3.08). However, no associations between viral factors with NAFLD incidence rate were identified. In a subgroup of participants with concurrent type 2 DM, detectable HBV DNA levels were negatively associated with the development of NAFLD (HR, 0.37; 95%CI, 0.14-0.98). There was super-multiplicative interaction between BMI and gender with respect to incidence of NAFLD, with an ROR of 2.08 (95%CI, 1.02-4.23). CONCLUSION: Metabolic factors play an important role in the presence of NAFLD among Chinese CHB patients. However, viral replication factors are not related to NAFLD except among those with concurrent type 2 DM.

Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance and seroconversion in hepatitis B e antigen-negative chronic infection patients: A population-based prospective cohort.

Seroclearance of hepatitis B surface antigen (HBsAg) has been widely studied; however, seroconversion of HBsAg and characteristics of viral load among hepatitis B e antigen (HBeAg)-negative chronic infection patients after HBsAg lost is not clear. We performed a large-scale study in a HBeAg-negative chronic infection cohort to evaluate spontaneous HBsAg seroclearance incidence from October 2012 to April 2017 in Jiangsu province, China. We also elucidated the characteristics of HBsAg seroconversion and hepatitis B virus (HBV) DNA detectability among patients who cleared HBsAg. A total of 2997 HBeAg-negative chronic infection patients (mean age 52.3 ± 12.9 years at baseline) were included. With 10 519 person-years of follow-up, 348 patients successfully spontaneously cleared HBsAg, with an incidence rate of 3.31 per 100 person-years. Patients with HBV DNA detectable ~1999 IU/mL at baseline had a lower probability of HBsAg seroclearance relative to those with undetectable HBV DNA, with a hazard ratio of 0.31 (95% CI = 0.23, 0.41). HBsAg seroconversion occurred in 37.3% of those patients who cleared HBsAg. The geometric mean of anti-HBs among those with HBsAg conversion was 79.4 mIU/mL. Female had a higher HBsAg seroconversion rate (P = 0.011). Among those with HBsAg seroclearance, 11.2% still had HBV DNA levels of higher than 100 IU/mL. Patients with higher HBV DNA at baseline had a higher risk of detectable HBV DNA levels even after HBsAg seroclearance (P < 0.001). This study reveals HBsAg seroconversion rates and HBV DNA undetectability epidemiological characteristics of patients with HBsAg seroclearance and suggests that monitoring HBV DNA is needed when managing HBeAg-negative chronic patients, even after clearing HBsAg.

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.

Identification of the sites of 4-hydroxy-2-nonenal and neprilysin adduction using a linear trap quadrapole Velos Pro-Orbitrap Elite mass spectrometer.

Amyloid-ßdegrading enzyme neprilysin (NEP) plays a pivotal role in eliminating Aß The oxidized modification of NEP by 4-hydroxy-2-nonenal (HNE) may reduce the clearance of Aß in cultured cells and Alzheimer's disease (AD) brains. The aim of this research is to study whether HNE could modify the NEP protein and identify the specific sites of HNE-NEP modification using a linear trap quadrapole (LTQ) Velos Pro-Orbitrap Elite mass spectrometer. NEP activity was determined after SH-SY5Y cells had incubated with HNE (20 µM) for 24 hours. To identify the sites of NEP modification, samples of both native and HNE-modified NEP digested by trypsin were analyzed using a LTQ Velos Pro-Orbitrap Elite mass spectrometer. The NEP peptide sequence information from the fragment ion masses was used to search for the sites of NEP adduction. HNE-treated cells showed a 60% loss of NEP activity. NEP was covalently adducted at Lys 93, Lys 472 by HNE via Michael addition. Compared to the control group, the sites of modified peptide in NEP showed a consistent 156 Da increased in m/z, which provides sequence information and might contribute to further studies on drug design and the therapeutics of AD.

PEG300 Protects Mitochondrial Function By Upregulating PGC-1α to Delay Central Nervous System Oxygen Toxicity in Mice.

Central nervous system oxygen toxicity (CNS-OT) is a complication of hyperbaric oxygen (HBO) treatment, with limited prevention and treatment options available. In this study, we aimed to explore the effect of polyethylene glycol 300 (PEG300) on CNS-OT and underlying mechanisms. Motor and cognitive functions of mice in normobaric conditions were evaluated by Morris water maze, passive active avoidance, and rotarod tests. HBO was applied at 6 atmospheres absolute (ATA) for 30 min after drug administration. The latency period of convulsion in mice was recorded, and hippocampal tissues were extracted for biochemical experiments. Our experimental results showed that PEG300 extended the convulsion latencies in CNS-OT mice, reduced oxidative stress and inflammation levels in hippocampal tissues. Furthermore, PEG300 preserved mitochondrial integrity and maintained mitochondrial membrane potential in hippocampal tissue by upregulating Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α). This protective effect was enhanced following the administration of ZLN005, an agonist of PGC-1a. Hence, our study suggests that PEG300 might exert protective effects by upregulating PGC-1α expression and preserving mitochondrial health, offering promising prospects for CNS-OT treatment.

Metagenomic next-generation sequencing testing from the perspective of clinical benefits.

BACKGROUND AND AIMS: Metagenomic next-generation sequencing (mNGS) provided promising supports to rapid pathogen diagnosis. However, summary of scientific application strategy based on clinical practice study is still necessary for enhancing clinical benefits. MATERIALS AND METHODS: We conducted a retrospective analysis of 775 samples from patients with suspected infectious diseases (IDs). Based on final diagnosis, diagnostic performance, clinical relevance and clinical impact of mNGS among various clinical settings were assessed, and influencing factors were deeply explored. RESULTS: 84.26 % tests were clinically relevant; sample, but not sequencing, was the influencing factor. 40.77 % tests contributed to positive clinical impact, while 0.13 % and 59.10 % to negative and no impact respectively. mNGS utility in patients with IDs, definite infection site, BALF and CSF contributed to higher positive impacts. Days of empirical treatment before sampling ≤ 5 in ICU and ≤ 2 or between 11 and 20 in non-ICU, and reporting in 2 days brought about higher clinical benefit rates. Characteristic pathogen spectrum between ICU and non-ICU cases were revealed. CONCLUSIONS: Our findings highlighted clinical benefits from mNGS varied among different clinical settings, and elucidated choices on patients, samples, sampling and reporting time were four key factors. Rational strategy should be concerned to promote scientific application of mNGS and better improve clinical value.

Bacteremia Caused by a Serotype Ob5 Vibrio cholerae Strain in a Cirrhotic Patient in China.

The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

Value of the Prognostic Nutritional Index in Surgery for Crohn Disease in China and the Effects on Outcome: A Retrospective Study.

PURPOSE: To investigate the value of the Prognostic Nutritional Index (PNI) in the surgery of Crohn Disease and examine the ability of PNI to predict poor outcomes with surgery. METHODS: One hundred fifty-seven patients were divided into a good nutrition group (PNI ≥40) and a poor nutrition group (PNI <40). The retrospective univariate analysis, logistic regression multivariate analysis, and receiver operating characteristic (ROC) curve analysis were used to screen out independent risk factors for postoperative complications and postoperative recurrences that required reoperation. RESULTS: Penetrating behavior was an independent risk factor for postoperative complications. Emergency surgery, penetrating behavior, hypoalbuminemia, and low PNI were independent risk factors for reoperation. By the receiver operating characteristic analysis, low PNI was superior to hypoproteinemia in predicting postsurgical recurrence. CONCLUSIONS: PNI is a good marker for predicting surgical recurrence, but it cannot predict postoperative complications. The nutritional status in patients before elective surgery can be modified to improve PNI. It can reduce surgical recurrence to a minimum level.

Clinical Value of Sampling Time of Metagenomic Next-Generation Sequencing in Patients with Severe Pneumonia.

Objective: Severe pneumonia is a common infectious disease with high morbidity and mortality. Early etiological diagnosis is crucial for improving the prognosis. The aim of this study is to evaluate the clinical value of sampling time of mNGS in patients with severe pneumonia. Methods: This retrospective study enrolled 105 patients with severe pneumonia. mNGS was performed on bronchoalveolar lavage fluid (BALF). Patients were divided into the sampling time ≤ 72h vs sampling time >72h groups and survivors vs non-survivors groups according to their sampling time and prognosis. Clinical characteristics, the adjustment of antibiotics and clinical prognostic value were evaluated. Results: Our study showed that, early sampling of mNGS can significantly shorten the mechanical ventilation time (p = 0.007) and hospitalization time (p = 0.004). In the non-survivors group, CURB-65, SOFA, and APACHE II scores were higher. Age (OR: 1.051, 95% CI: 1.004-1.100, p = 0.034), chronic respiratory diseases (OR: 4.639, 95% CI: 1.260-17.082, p = 0.021), immunosuppression (OR: 5.008, 95% CI: 1.617-15.510, p = 0.005) and SOFA score on the day of mNGS sampling (OR: 1.492, 95% CI: 1.212-1.837, p < 0.001) were independent risk factors of in-hospital mortality. The most common pathogens were Klebsiella pneumoniae and Human gammaherpesvirus 4. The proportion of appropriate and targeted antibiotics adjusted was significantly higher than that in the sampling time > 72h group, and the proportion of antifungal and antiviral agents adjusted was lower. In the early sampling group, it was significantly decreased in the CRP, PCT level and NEU% at discharge. Conclusion: This study demonstrated that early sampling of mNGS could shorten the time of mechanical ventilation and hospitalization of patients with severe pneumonia. Patients with higher SOFA score on the day of sampling had a poorer prognosis. It emphasizes that early sampling of mNGS has a positive value.

Mitochondrial dynamics in neurological diseases: a narrative review.

Background and Objective: The mitochondrion is a crucial organelle for aerobic respiration and energy metabolism. It undergoes dynamic changes, including changes in its shape, function, and distribution through fission, fusion, and movement. Under normal conditions, mitochondrial dynamics are in homeostasis. However, once the balance is upset, the nervous system, which has high metabolic demands, will most likely be affected. Recent studies have shown that the imbalance of mitochondrial dynamics is involved in the occurrence and development of various neurological diseases. However, whether the regulation of mitochondrial dynamics can be used to treat neurological diseases is still unclear. We aimed to comprehensively analyze mitochondrial dynamics regulation and its potential role in the treatment of neurological diseases. Methods: A comprehensive literature review was carried out to understand the mechanisms and applications of mitochondrial dynamics in neurological diseases based on the literature available in PubMed, Web of Science, and Google Scholar. Key Content and Findings: This review discusses the molecular mechanisms related to mitochondrial dynamics and expounds upon the role of mitochondrial dynamics in the occurrence and development of neurodegenerative diseases, epilepsy, cerebrovascular disease, and brain tumors. Several clinically tested drugs with fewer side effects have been shown to improve the mitochondrial dynamics and nervous system function in neurological diseases. Conclusions: Disorders of mitochondrial dynamics can cause various neurological diseases. Elucidation of mechanisms and applications involved in mitochondrial dynamics will inform the development of new therapeutic targets and strategies for neurological diseases. Dynamin-related protein 1 (Drp1), as a highly relevant molecular for mitochondrial dynamics, might be a potential target for treating neurological diseases in the future.

Clinical Diagnosis Application of Metagenomic Next-Generation Sequencing of Plasma in Suspected Sepsis.

Purpose: We analyzed the clinical concordance of mNGS test results from blood samples and improved the clinical efficiency of mNGS in the diagnosis of suspected sepsis pathogens. Patients and Methods: In this study, 99 samples of suspected blood flow infection were included for plasma mNGS, and the correlation between mNGS results and blood culture results, serum inflammatory indices, clinical symptoms and antibiotic treatment was analyzed, as well as the comparison with the detection rate of BALF pathogens, as well as the classification of different pathogens in the mNGS results were analyzed. Results: The mNGS pathogen detection rate was higher than that of traditional blood culture (83.02% vs 35.82%). The rate of the mNGS results being consistent with the clinical diagnosis was also higher than that of traditional blood culture (58.49% vs 20.75%). This study shows that bacteria and fungi are the main pathogens in sepsis, and viral sepsis is very rare. In this study, 32% of sepsis patients were secondary to pneumonia. Compared with the pathogen detection rate using alveolar lavage fluid, the detection rate from plasma mNGS was 62.5%. Samples were also easy to sample, noninvasive, and more convenient for clinical application. Conclusion: This study shows that compared with blood culture, the detection rate of mNGS pathogen that meets the diagnosis of sepsis is higher. We need a combination of multiple indicators to monitor the early diagnosis and treatment of sepsis.

The clinical significance of in-house metagenomic next-generation sequencing for bronchoalveolar lavage fluid diagnostics in patients with lower respiratory tract infections.

Objective: Metagenomic next-generation sequencing (mNGS) technology has the potential to detect a wide range of pathogenic microorganisms. However, reports on the diagnostic value and clinical significance of different platforms of mNGS for patients with lower respiratory tract infections (LRTIs) remain scarce. Methods: A total of 306 patients with suspected LRTIs were enrolled from January 2019 to December 2021. The diagnostic performance of conventional methods and mNGS on bronchoalveolar lavage fluid (BALF) were compared. BALF mNGS was performed using a commercial and an in-house laboratory. The diagnostic value and the clinical implications of mNGS for LRTIs were analyzed for the different platforms. Results: The positive rate of mNGS in the in-house group was higher than that in the commercial group (85.26% vs. 70.67%, p < 0.001). mNGS significantly increased the pathogen detection rate compared with conventional methods [from 70.67% vs. 22.67% (p < 0.001) to 85.26% vs. 30.77% (p < 0.001)]. The pathogens detected using mNGS included bacteria, fungi, viruses, and atypical pathogens. The in-house platform performed well on a wider spectrum of microbial distribution. Furthermore, it showed an advantage in detecting mixed pathogens in immunocompromised patients. Among the mNGS positive cases, 34 (32.0%) cases had their antibiotics adjusted in the commercial group, while 51 (38.3%) cases had a change of treatment in the in-house group. Moreover, the turnaround time of mNGS and the time from mNGS to discharge in the in-house group were significantly shorter than those in the commercial group. Conclusion: In-house mNGS had a higher detection rate and can show a wider spectrum of pathogens, with potential benefits for the clinic by shortening the turnaround time and hospitalization, and it may be more suitable for clinical microbiology laboratories.

Epidemiology and Molecular Characteristics of mcr-9 in Citrobacter spp. from Healthy Individuals and Patients in China.

With the globally prevailing carbapenemase-producing (CP) Citrobacter spp., polymyxin antibiotics have been reconsidered as one of the last-resort treatment options. Our study was conducted to investigate the prevalence of mcr-9 in Citrobacter species. From October to November 2021, 650 fecal samples and 215 Citrobacter isolates were collected from healthy individuals and infected patients, respectively. Isolates were screened for the presence of the mcr-9 gene by the PCR method. mcr-9-carrying strains were identified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Due to the susceptibility to colistin, Citrobacter spp. isolates were first induced to increase the expression of mcr-9 on China blue agar plates containing colistin and were then subjected to conjugation experiments. Whole-genome sequencing was performed on the Illumina NovaSeq PE150 system. The prevalence of mcr-9 in the Citrobacter genus from healthy guts and infected patients was 0.62% and 1.86%, respectively. In all mcr-9-positive strains, MICs of polymyxin B were observed at ≤2 µg/mL, displaying a nonresistant phenotype. As for conjugation experiments, only one isolate successfully transferred the mcr-9 gene to Escherichia coli C600. Whole-genome sequencing showed that eight mcr-9-positive Citrobacter isolates carried mcr-9 and genes encoding resistance to beta-lactam antibiotics, including blaCMY, blaDHA, blaSHV, blaTEM, and blaCTX-M. We also discovered that mcr-9 could be located on the pKPC-CAV1321 plasmid. Our study investigated the prevalence of mcr-9 in Citrobacter spp. in both healthy individuals and infected patients and described the carriage of mcr-9 on the pKPC-CAV1321 plasmid for the first time. IMPORTANCE The emergence of mcr homologues posed a serious threat to the therapeutic efficiency of polymyxin antibiotics. Citrobacter freundii is generally regarded as an opportunistic pathogen associated with a variety of nosocomial infections. In this study, we investigated the prevalence of mcr-9 in Citrobacter spp. isolates from healthy individuals and infected patients and highlighted the importance of the rational use of antibiotics. In addition, this epidemiological investigation is the first to describe the carriage of mcr-9 on plasmid pKPC-CAV1321 and confirms the horizontal transfer of this plasmid. Our research may shed new light on further studies of mcr-9 dissemination in humans.

Isorhamnetin promotes functional recovery in rats with spinal cord injury by abating oxidative stress and modulating M2 macrophages/microglia polarization.

Spinal cord injury (SCI), mostly caused by sports injuries, falls, or traffic accidents, is a major cause of disability. The aim of current work was to investigate the therapeutic effect of isorhamnetin (ISO) on functional recovery in rats with SCI. The male adult rats were exposed to a clip-compression SCI and treated with ISO. ISO treatment improved locomotor function and reduced the loss of motor neurons in SCI rats. Treatment with ISO markedly relieved SCI-induced hypersensitivities to mechanical and thermal stimulation in rats. ISO treatment activated nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway and abated oxidative stress in injured spinal cords. ISO treatment partly suppressed microglial and glial activation and reduced expression of inflammatory cytokines including TNF-α, monocyte chemotactic protein-1 (MCP-1), and IL-1ß in injured spinal cords. More importantly, ISO treatment promoted M2 macrophage activation in the injured region. lipopolysaccharide (LPS) or IL-4 was employed to stimulate macrophages/microglia into M1 or M2 phenotype in cultured BV2 cells in vitro. ISO treatment enhanced the expression of characteristic microglial anti-inflammatory polarization markers in BV2 cells. In conclusions, ISO treatment promotes functional recovery in rats with SCI by abating oxidative stress and modulating M1/M2 macrophage polarization.

Successful thrombolytic therapy in acute ischemic stroke after reversal of warfarin: a case report.

It is essential for acute ischemic stroke (AIS) patients to receive timely revascularization. However, intravenous thrombolysis (IVT) is not recommended for AIS patients with warfarin associated hypocoagulability. Meanwhile, monotherapy of coagulation factors or vitamin K is unable to reverse anticoagulation of warfarin in emergency. Thus, developing an effective IVT strategy poses a challenging task for these fragile population. Herein, an 82-year-old male, on regular administration with warfarin because of nonvalvular atrial fibrillation (NVAF), suffered from AIS and had an elevated international normalized ratio value of 1.72 and prolonged prothrombin time of 18.2 s at stroke onset. For normalizing INR, combination of 4 factor prothrombin complex concentrate, fresh frozen plasma and vitamin K1 were administrated. Finally, the patient successfully received recombinant tissue plasminogen activator (rt-PA), with an obviously neurological improvement. This case shows a feasible role of IVT therapy with rt-PA after reversal of coagulation regarding AIS patients with warfarin-related hypocoagulability.

In vitro Activity of Contezolid Against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus, and Strains With Linezolid Resistance Genes From China.

Contezolid is a novel oxazolidinone, which exhibits potent activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). In this study, the in vitro activity of contezolid was compared with linezolid (LZD), tigecycline (TGC), teicoplanin (TEC), vancomycin (VA), daptomycin (DAP), and florfenicol (FFC) against MRSA and VRE strains isolated from China. Contezolid revealed considerable activity against MRSA and VRE isolates with MIC90 values of 0.5 and 1.0 µg/mL, respectively. For VRE strains with different resistance genotypes, including vanA- and vanM-type strains, contezolid did not exhibit significantly differential antibacterial activity. Furthermore, the antimicrobial activity of contezolid is similar to or slightly better than that of linezolid against MRSA and VRE strains. Subsequently, the activity of contezolid was tested against strains carrying linezolid resistance genes, including Staphylococcus capitis carrying cfr gene and Enterococcus faecalis carrying optrA gene. The results showed that contezolid exhibited similar antimicrobial efficacy to linezolid against strains with linezolid resistance genes. In general, contezolid may have potential benefits to treat the infections caused by MRSA and VRE pathogens.

Acoustic Bessel Vortex Beam by Quasi-Three-Dimensional Reflected Metasurfaces.

Vortex beams have a typical characteristic of orbital angular momentum, which provides a new degree of freedom for information processing in remote communication and a form of non-contact manipulation for trapping particles. In acoustics, vortex beams are generally observed on the surface of a metamaterial structure or in a waveguide with a hard boundary owing to the characteristic of easy diffusion in free space. The realization of an acoustic vortex beam with a long-distance propagation in free space still remains a challenge. To overcome this, we report a type of acoustic Bessel vortex (ABV) beam created by a quasi-three-dimensional reflected metasurface in free space based on phase modulation. By using the Bessel and vortex phase profiles, we can realize an ABV beam with the high performances of both Bessel and vortex beams, and its effective propagation distance is larger than 9.2λ in free space. Beyond that, we discuss the bandwidth and topological charge of the ABV beam in detail, and the fractional bandwidth can reach about 0.28. The proposed ABV beam has the advantages of a high-performance vortex, long-distance propagation, and broad bandwidth, which provide a new pathway for designing multifunctional vortex devices with promising applications.