Efficacy of ceftazidime-avibactam in the treatment of carbapenem-resistant Klebsiella pneumoniae infections: Focus on solid organ transplantation recipients.

INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a new option to treat KPC- and OXA-48 carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. However, clinical evidence is limited regarding its use in treating CRKP infections, especially in solid organ transplantation (SOT) recipients. In this study, we assessed the efficacy of CAZ-AVI in treating CRKP infections in both the general population and the SOT recipients in comparison with other antibiotic regimens. METHODS: This is a single-centre retrospective cohort study of patients admitted between January 1, 2018 and June 30, 2021 with the diagnosis of CRKP infections receiving either CAZ-AVI or other regimens ≥ 72 hours and clinical outcomes were analysed. RESULTS: Of 200 patients with CRKP infections, 67 received CAZ-AVI, 133 received other regimens, and 50 were SOT recipients. In the SOT cohort, 30 patients received CAZ-AVI, and 20 received other regimens. The overall 30-day mortality was 38% in the SOT cohort. Compared with patients receiving other regimens, CAZ-AVI therapy resulted in lower 30-day mortality (23.3% vs. 60%, P = 0.014) and 90-day mortality (35.7% vs. 86.7%, P = 0.003), higher clinical cure (93.3% vs. 40%, P < 0.001) and microbiological clearance. Similar promising results of CAZ-AVI were also shown in the whole population cohort. Moreover, clinical outcomes of SOT recipients receiving CAZ-AVI were not inferior to those without SOT. CONCLUSIONS: CAZ-AVI therapy was associated with better clinical outcomes in CRKP infections in both the general population and SOT recipients. Considering the limitations of the present study, well-conducted RCTs are still warranted to confirm these findings.

Use of the Serum Level of Cholinesterase as a Prognostic Marker of Nonfatal Clinical Outcomes in Patients Hospitalized with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) contributes to a poor prognosis. Reliable biomarkers to predict adverse outcomes during hospitalization are important. Aim: To investigate the relationship between the serum cholinesterase (ChE) level and adverse clinical outcomes, including hypoxemia severity, hypercapnia, duration of hospital stay (DoHS), and noninvasive ventilation (NIV) requirement, in patients with AECOPD. Methods: Patients hospitalized with AECOPD in the Wuhu Hospital of Traditional Chinese Medicine between January 2017 and December 2021 were included. Results: A total of 429 patients were enrolled. The serum ChE level was significantly lower in patients with hypercapnia, who required NIV during hospitalization and who had a DoHS of >10 days, with an oxygenation index < 300. The ChE level was correlated negatively with the C-reactive protein level and neutrophil-to-lymphocyte ratio and correlated positively with the serum albumin level. Multivariate logistic regression analysis indicated that a serum ChE level of ≤4116 U/L (OR = 2.857, 95% CI = 1.46-5.58, p = 0.002) was associated significantly with NIV requirement. Conclusions: The serum ChE level was correlated significantly with complicating severe hypoxemia, hypercapnia, prolonged DoHS, and the need for NIV in patients hospitalized with AECOPD. The serum ChE level is a clinically important risk-stratification biomarker in patients hospitalized with AECOPD.

Combined Proteomic and Metabolomic Analyses Reveal the Comprehensive Regulation of Stropharia rugosoannulata Mycelia Exposed to Cadmium Stress.

The potential of Stropharia rugosoannulata as a microbial remediation material for cadmium (Cd)-contaminated soil lies in its capacity to absorb and accumulate Cd in its mycelia. This study utilized the TMT and LC-MS techniques to conduct integrated proteomic and metabolomic analyses with the aim of investigating the mycelial response mechanisms of S. rugosoannulata under low- and high-Cd stresses. The results revealed that mycelia employed a proactive defense mechanism to maintain their physiological functions, leading to reduced sensitivity to low-Cd stress. The ability of mycelia to withstand high levels of Cd stress was influenced primarily by the comprehensive regulation of six metabolic pathways, which led to a harmonious balance between nitrogen and carbohydrate metabolism and to reductions in oxidative stress and growth inhibition caused by Cd. The results provide valuable insights into the molecular mechanisms involved in the response of S. rugosoannulata mycelia to Cd stress.

Sweat Sensor Based on Wearable Janus Textiles for Sweat Collection and Microstructured Optical Fiber for Surface-Enhanced Raman Scattering Analysis.

Wearable sweat sensors provide real-time monitoring of biomarkers, enabling individuals to gain real-time insight into their health status. Current sensors primarily rely on electrochemical mechanisms, limiting their capacity for the concurrent detection of multiple analytes. Surface-enhanced Raman scattering spectroscopy offers an alternative approach by providing molecular fingerprint information to facilitate the identification of intricate analytes. In this study, we combine a wearable Janus fabric for efficient sweat collection and a grapefruit optical fiber embedded with Ag nanoparticles as a sensitive SERS probe. The Janus fabric features a superhydrophobic side in contact with the skin and patterned superhydrophilic regions on the opposite surface, facilitating the unidirectional flow of sweat toward these hydrophilic zones. Grapefruit optical fibers feature sharp tips with the ability to penetrate transparent dressings. Its microchannels extract sweat through capillary force, and nanoliter-scale volumes of sweat are sufficient to completely fill them. The Raman signal of sweat components is greatly enhanced by the plasmonic hot spots and accumulates along the fiber length. We demonstrate sensitive detection of sodium lactate and urea in sweat with a detection limit much lower than the physiological concentration levels. Moreover, the platform shows its capability for multicomponent detection and extends to the analysis of real human sweat.

The Effect of Mushroom Dietary Fiber on the Gut Microbiota and Related Health Benefits: A Review.

Mushroom dietary fiber is a type of bioactive macromolecule derived from the mycelia, fruiting bodies, or sclerotia of edible or medicinal fungi. The use of mushroom dietary fiber as a prebiotic has recently gained significant attention for providing health benefits to the host by promoting the growth of beneficial microorganisms; therefore, mushroom dietary fiber has promising prospects for application in the functional food industry and in drug development. This review summarizes methods for the preparation and modification of mushroom dietary fiber, its degradation and metabolism in the intestine, its impact on the gut microbiota community, and the generation of short-chain fatty acids (SCFAs); this review also systematically summarizes the beneficial effects of mushroom dietary fiber on host health. Overall, this review aims to provide theoretical guidance and a fresh perspective for the prebiotic application of mushroom dietary fiber in the development of new functional foods and drugs.

Intravenous Polymyxin B as Adjunctive Therapy to High-Dose Tigecycline for the Treatment of Nosocomial Pneumonia Due to Carbapenem-Resistant Acinetobacter baumannii and Klebsiella pneumoniae: A Propensity Score-Matched Cohort Study.

Although the combination of polymyxin and tigecycline is widely used in treating carbapenem-resistant bacterial infections, the benefit of this combination is still uncertain. To assess whether adding polymyxin B to the high-dose tigecycline regimen would result in better clinical outcomes than the high-dose tigecycline therapy in patients with pneumonia caused by carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii, we conducted a propensity score-matched cohort study in a single center between July 2019 and December 2021. Of the 162 eligible patients, 102 were included in the 1:1 matched cohort. The overall 14-day mortality in the matched cohort was 24.5%. Compared with high-dose tigecycline, the combination therapy was not associated with better clinical outcomes, and showed similar 14-day mortality (OR, 0.72, 95% CI 0.27-1.83, p = 0.486), clinical cure (OR, 1.09, 95% CI 0.48-2.54, p = 0.823), microbiological cure (OR, 0.96, 95% CI 0.39-2.53, p = 0.928) and rate of nephrotoxicity (OR 0.85, 95% CI 0.36-1.99, p = 0.712). Subgroup analyses also did not demonstrate any statistical differences. Based on these results, it is reasonable to recommend against adding polymyxin B to the high-dose tigecycline regimen in treating pneumonia caused by carbapenem-resistant K. pneumoniae and A. baumannii.

ALTERATION IN SHEAR WAVE ELASTOGRAPHY IS ASSOCIATED WITH ACUTE KIDNEY INJURY: A PROSPECTIVE OBSERVATIONAL PILOT STUDY.

ABSTRACT: Background: Kidney stiffness could change during kidney disease. We hypothesize that acute kidney injury (AKI) would increase renal stiffness. Therefore, evaluating kidney Young's modulus (YM; a measure of tissue stiffness) using shear wave elastography (SWE) might help to diagnose AKI. Methods: This research was divided into two studies. Study A: Male C57BL/6 mice were used to observe kidney YM changes induced by sepsis-associated AKI, which was established by cecal ligation and puncture (CLP). Study B included 54 consecutive critically ill patients with or without AKI. Changes in renal YM were observed. Results: Study A: CLP mice showed a significantly higher kidney YM compared with the sham group. The YM gradually increased from CLP 0 hours to CLP 24 hours, and presented a fair relationship with the renal tubular injury score ( R2 = 0.71) and serum creatinine ( R2 = 0.73). Study B: YM was easily accessible, and the intraclass correlation coefficient ranged from 0.62 to 0.84. Kidney YM was higher in AKI patients and gradually increased from non-AKI to AKI III patients. Furthermore, the YM in the upper, middle, and lower poles of the renal cortex presented a fair relationship with kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin ( R2 ranging from 0.4 to 0.58), and the areas under the curve of the above five indicators for the diagnosis of AKI were 0.7, 0.73, 0.70, 0.74, and 0.79, respectively. Conclusion: SWE-derived estimates of renal stiffness are higher in AKI patients and sepsis-associated AKI mice. However, it has no advantage over NGAL and KIM-1. Trial Registration: Chinese Clinical Trial Registry No: ChiCTR2200061725. Retrospectively registered July 1, 2022, https://www.chictr.org.cn/showproj.aspx?proj=169359 .

Integrated physiologic and proteomic analysis of Stropharia rugosoannulata mycelia in response to Cd stress.

Soil Cd pollution seriously threatens environment and human health. Due to its ability to absorb and accumulate Cd in mycelia, Stropharia rugosoannulata could be a potential candidate for bioremediation of Cd-contaminated soils; however, the response mechanism of mycelia to Cd stress is still unclear. In this study, the physiologic and proteomic differences of S. rugosoannulata mycelia under 0.2 mg/L (low) and 2 mg/L (high) Cd stress were investigated. The results showed that Cd accumulation and mycelial growth inhibition exhibited a concentration-depended trend. Analysis of antioxidant system indicated that SOD, GR, GSH, GSSG and ASA played key roles in resisting the toxic effects of Cd. Via proteome analysis, 24 and 267 differentially expressed proteins (DEPs) were observed under low and high Cd stress, respectively. GO and KEGG analysis found that the mycelial growth inhibition might due to the down-regulation of some DEPs involved in "valine, leucine and isoleucine biosynthesis" and "tyrosine metabolism"; the certain tolerance to high Cd stress might attribute to the regulation of DEPs referred to energy metabolism and antioxidant system-related pathways, maintaining cellular energy homeostasis and removing ROS. These results provide a theoretical basis for further elucidation of response mechanisms in S. rugosoannulata to Cd stress.

Prognostic Value of Serum Cholinesterase Levels for In-Hospital Mortality among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Cholinesterase (ChE) is associated with the pathogenesis of chronic obstructive pulmonary disease (COPD), including chronic airway inflammation and oxidation/antioxidant imbalance. However, the relationship between serum ChE levels and survival outcomes of patients hospitalized with acute exacerbations of COPD (AECOPD) is unknown. In this retrospective single-center study, we investigated the ability of the serum ChE level to predict in-hospital death in patients hospitalized with AECOPD. The clinicopathological data, including serum ChE levels as well as clinical and biochemical indicators were extracted for 477 patients from the hospital records and analyzed. Our results demonstrated that AECOPD patients with lower serum ChE levels were associated with increased mortality, frequent hospitalization due to acute exacerbations (AE) in the past year, and longer hospital stay. The optimal cutoff value for the serum ChE level was 4323 U/L. The area under the ROC curve (AUC) values for predicting in-hospital mortality based on the serum ChE level was 0.79 (95% confidence interval (CI), 0.72-0.85). Multivariate logistic regression analysis demonstrated that serum ChE level ≤ 4323 U/L (odds ratio (OR) 9.09, 95% CI 3.43-28.3, p < 0.001), age-adjusted Charlson comorbidity index (aCCI), and the number of hospitalizations due to AE in the past year were independent risk factors for predicting the in-hospital mortality of AECOPD patients. In conclusion, our study demonstrated that low serum ChE levels were associated with significantly higher in-hospital mortality rates of patients hospitalized with AECOPD. Therefore, serum ChE level is a promising prognostic predictor of hospitalized AECOPD patients.

Controlled fiber core mode and surface mode interaction for enhanced SERS performance.

Three-dimensional surface-enhanced Raman scattering (SERS) platform based on microstructure fibers has many advantages for rapid liquid detection due to its microfluidic channels and light guidance. The fiber mode field distribution determines the light-analyte interaction strength but has rarely been studied in SERS applications. In this paper, we numerically and experimentally investigate the mode field distribution in suspended-core fibers decorated with gold nanoparticles. The interaction between the core mode and surface mode is controlled by changing the density of gold nanoparticles on the inner surface. The avoided crossing wavelength shifts linearly to red with the decrease of the nanoparticle spacing. With an optimized nanoparticle spacing of 20 nm, the avoided crossing occurs near the laser wavelength of 633 nm, which greatly increases the power ratio in the liquid channels and hence improves the SERS performance. The detection limit for crystal violet was 10-9 M, and the enhancement factor was 108. The avoided crossing mechanism can be applied to all fiber SERS probes for sensitivity improvement.

Pragmatic Comparison of Piperacillin/Tazobactam versus Carbapenems in Treating Patients with Nosocomial Pneumonia Caused by Extended-Spectrum ß-Lactamase-Producing Klebsiella pneumoniae.

The effectiveness of piperacillin/tazobactam for managing nosocomial pneumonia caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is unknown. To answer this question, we conducted a retrospective cohort study in two tertiary teaching hospitals of patients admitted between January 2018 and July 2021 with a diagnosis of nosocomial pneumonia caused by ESBL-producing K. pneumoniae receiving either piperacillin/tazobactam or carbapenems within 24 h from the onset of pneumonia for at least 72 h. Clinical outcomes, including 28-day mortality and 14-day clinical and microbiological cure, were analyzed. Of the 136 total patients, 64 received piperacillin/tazobactam and 72 received carbapenems. The overall 28-day mortality was 19.1% (26/136). In the inverse probability of treatment weighted cohort, piperacillin/tazobactam therapy was not associated with worse clinical outcomes, as the 28-day mortality (OR, 0.82, 95% CI, 0.23-2.87, p = 0.748), clinical cure (OR, 0.94, 95% CI, 0.38-2.35, p = 0.894), and microbiological cure (OR, 1.10, 95% CI, 0.53-2.30, p = 0.798) were comparable to those of carbapenems. Subgroup analyses also did not demonstrate any statistical differences. In conclusion, piperacillin/tazobactam could be an effective alternative to carbapenems for treating nosocomial pneumonia due to ESBL-producing K. pneumoniae when the MICs are ≤8 mg/L.

Effect of PCSK9 Inhibitor on Contrast-Induced Acute Kidney Injury in Patients with Acute Myocardial Infarction Undergoing Intervention Therapy.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to inhibit pyroptosis and apoptosis, which play important roles in the development and progression of contrast-induced acute kidney injury (CI-AKI). However, to the best of our knowledge, no studies have investigated the potential effect of PCSK9 inhibitors on the prevalence of CI-AKI after percutaneous coronary intervention (PCI). This study aimed to determine whether PCSK9 inhibitors are associated with the prevalence of CI-AKI. The medical records of 309 (mean age, 63.35 years; 71.84% male) patients with acute myocardial infarction who underwent PCI at our institution were retrospectively analyzed. Overall, 149 and 160 patients were assigned to the evolocumab and control groups, respectively. Serum creatinine levels were examined preoperatively and 24-72 h postoperatively and compared between groups. Data were grouped according to the occurrence of CI-AKI, and a univariate analysis was conducted to exclude suspected influencing factors that led to CI-AKI occurrence. After adjusting for confounding factors, a logistic regression analysis was performed to assess the association between evolocumab administration (independent variable) and CI-AKI occurrence (dependent variable). The prevalence of CI-AKI was significantly lower in the evolocumab group (6.7%) than in the control group (20.0%; p < 0.01).We further evaluated the correlation between exposure factor and outcome. The relative risk(RR) between the use of evolocumab and the occurrence of CI-AKI was 0.34(95% CI 0.17-0.66,p<0.01).This result indicate a significant association between the use of evolocumab and a reduction in the incidence of CI-AKI.The logistic regression analysis results revealed that evolocumab was significantly associated with CI-AKI. The use of PCSK9 inhibitors, hydration therapy, and statin administration appears promising for preventing CI-AKI in patients with acute myocardial infarction undergoing PCI.

Serum Creatinine/Cystatin C Ratio as a Predictor of In-hospital Mortality in Patients Hospitalized with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Low serum creatinine/cystatin C ratio (CCR) is associated with unfavorable characteristics in patients with chronic obstructive pulmonary disease (COPD); however, the relationship between CCR and in-hospital mortality of patients with acute exacerbation of COPD (AECOPD) is unexplored. Our objective was to assess the value of CCR for predicting in-hospital mortality of patients hospitalized with AECOPD. METHODS: Patients with AECOPD (n = 597) were retrospectively enrolled. Patient's clinical characteristics and laboratory tests, including serum cystatin C and creatinine, were reviewed. The prediction value of CCR was evaluated using area under the receiver operating characteristic curve (AUC) values. Factors potentially impacting in-hospital mortality were investigated using univariate and multivariate logistic regression analyses. RESULTS: Mortality rate during hospitalization was 10.05%. CCR was lower in non-surviving vs. survived patients (41.67 vs. 61.52, P < 0.001). AUC value for CCR for in-hospital mortality prediction was 0.79 [95% confidence interval (CI) 0.73-0.85]. On multivariate logistic regression analysis, in-hospital mortality was strongly associated with CCR < 52.27 [odds ratio (OR) 6.23, 95% CI (3.00-12.92), P < 0.001], age ≥ 81 years [OR 2.97, 95% CI (1.20-7.37), P = 0.019], oxygenation index < 300 [OR 3.28, 95% CI (1.27-8.44), P = 0.014], CRP > 8 mg/L [OR 1.84, 95% CI (1.15-2.95), P = 0.012], and D-dimer > 500 ng/L [OR 5.19, 95% CI (1.51-17.79), P = 0.009]. CONCLUSIONS: CCR was significantly lower, and is a potential prognostic indicator, in patients with AECOPD who died during hospitalization.

Comparative Proteomics Study on the Postharvest Senescence of Volvariella volvacea.

Volvariella volvacea is difficult to store after harvest, which restricts the production and circulation of V. volvacea fruiting bodies. Low-temperature storage is the traditional storage method used for most edible fungi. However, V. volvacea undergoes autolysis at low temperatures. When fruiting bodies are stored at 15 °C (suitable temperature), V. volvacea achieves the best fresh-keeping effect. However, the molecular mechanism underlying the postharvest senescence of V. volvacea remains unclear. Based on this information, we stored V. volvacea fruiting bodies at 15 °C after harvest and then analyzed the texture and phenotype combined with the results of previous physiological research. Four time points (0, 24, 60, and 96 h) were selected for the comparative proteomics study of V. volvacea during storage at 15 °C. A variety of proteins showed differential expressions in postharvest V. volvacea at 15 °C. Further comparison of the gene ontology (GO) enrichment analysis and KEGG pathways performed at different sampling points revealed proteins that were significantly enriched at several time points. At the same time, we also analyzed differentially expressed proteins (DEPs) related to the RNA transport, fatty acid biosynthesis and metabolism, and amino acid biosynthesis and metabolism pathways, and discussed the molecular functions of the PAB1, RPG1, ACC1, ADH3, ADH2, ALD5, and SDH2 proteins in postharvest V. volvacea senescence. Our results showed that many biological processes of the postharvest senescence of V. volvacea changed. Most importantly, we found that most RNA transport-related proteins were down-regulated, which may lead to a decrease in related gene regulation. Our results also showed that the expression of other important proteins, such as the fatty acid metabolism related proteins increased; and changes in fatty acid composition affected the cell membrane, which may accelerate the ripening and perception of V. volvacea fruiting bodies. Therefore, our research provides a reference for further studies on the aging mechanism of V. volvacea.

Influence of China's Carbon Emissions Trading Scheme on Green Innovation of Enterprises.

China's economic growth has entered "new normal," and the task of reducing carbon emissions has become more onerous. Hence, this study aimed to explore whether China's carbon emissions trading pilot policy stimulated corporate green innovation capabilities. The data pertained to the green patent data of the listed companies in Shanghai and Shenzhen stock exchanges during 2008-2018. Using a difference-in-difference-in-differences (DDD) method, the study took advantage of the variations across regions, across enterprises, and across years and obtained several novel findings. First, the pilot carbon emissions trading policy significantly stimulated the green innovation capabilities of emission control companies in the pilot areas compared with enterprises in nonpilot areas and the nonemission control list. Second, the effect of the policy on the improvement in corporate green innovation capabilities might be driven by the improvement in corporate input factor allocation efficiency and the additional benefits that could be obtained from the carbon trading market. Third, the positive effect of the policy on the green innovation capabilities of state-owned enterprises was more significant. Therefore, the establishment and promotion of a unified national carbon emissions trading market and supporting mechanisms should be accelerated to achieve the balance of stable economic growth and carbon emission task.

Carbon Transfer Decision Model Based on LMDI Method.

Establishing a coordinated governance mechanism for regional carbon emissions is an essential way to achieve carbon peak and carbon neutrality, while the study of interprovincial carbon emissions transfer is one of the important foundations of regional carbon emissions coordinated governance research. Based on the multiregional input-output (MRIO) model, this study calculated the carbon emissions from both the producers' perspective and the consumers' perspective and analyzed the interprovincial net carbon emissions transfer decision. Furthermore, the logarithmic mean Divisia index (LMDI) method was adopted to decompose the factors that affect the province's net carbon emissions into technological effect, structural effect, input-output effect, and scale effect. It was revealed that the input-output effect was the primary influencing factor of the net carbon transfer at the provincial level.

Research progress on the carcinogenesis mechanism of inflammation in ulcerative colitis: a narrative review.

OBJECTIVE: In this review, we have summarized the influence of inflammation-related pathological mechanisms on the development of ulcerative colitis (UC) to colorectal cancer (CRC). BACKGROUND: UC is a chronic inflammatory bowel disease (IBD) of unknown etiology that affects the colon and rectum. Long-term inflammation of UC may greatly increase the risk of CRC, and the secretion of inflammatory factors and sustained inflammation may be key drivers of UC-associated CRC progression. Compared with the general population, the risk of CRC in patients with UC is 2.4 times higher, and the mortality rate of patients with UC is higher than that of those with sporadic CRC. The use of non-steroidal anti-inflammatory drugs can reduce the probability of UC transforming into CRC. METHODS: Literatures about inflammation and UC were extensively reviewed to analyze and discuss. CONCLUSIONS: We believe that the mechanism of continuous inflammation that promotes cancer in UC may be the result of the mutual influence of intestinal microbes, inflammatory signals, and tissue remodeling. The invasion of intestinal microorganisms activates inflammatory signals and promotes the secretion of inflammatory factors which intensifies the remodeling of the extracellular matrix (ECM) and recruits immune cells. Eventually, a mutually engendering circuit of microbial invasion, release of inflammatory mediators, and remodeling of ECM is formed, which triggers continuous inflammation and promotes development of CRC.