Refraction/reflection reversal in two-dimensional acoustic metagratingsa).

Unlike acoustic metasurfaces that rely solely on phase gradients, acoustic metagratings (AMs) operate based on both phase gradients and grating diffraction, thus further extending the generalized Snell's law (GSL). In particular, AMs can achieve reversal of refraction and reflection based on the parity of the number of wave propagations inside the AMs. So far, discussions of this GSL extension have largely been applied to one-dimensional periodic AMs, while the designs of two-dimensional (2D) periodic AMs and their performance in three-dimensional (3D) space have been quite limited. Here, we study the GSL extension in 3D space and experimentally demonstrate a series of functional 2D periodic AMs. The designed AMs can achieve sound refraction/reflection under any incidence angle in 3D space, without restrictions to certain critical ranges; adjusting incident angles only enables the reversal of refraction and reflection. Additionally, we demonstrate two types of dual-layer sound lenses based on two AMs, whose reversal of refraction and reflection can be realized by simply attaching or separating the two AMs. Our work paves the way to complex 3D wavefront manipulation of AMs, which may find potential use in practical acoustic devices.

Acoustofluidic Virus Isolation via Bessel Beam Excitation Separation Technology.

The isolation of viruses from complex biological samples is essential for creating sensitive bioassays that assess the efficacy and safety of viral therapeutics and vaccines, which have played a critical role during the COVID-19 pandemic. However, existing methods of viral isolation are time-consuming and labor-intensive due to the multiple processing steps required, resulting in low yields. Here, we introduce the rapid, efficient, and high-resolution acoustofluidic isolation of viruses from complex biological samples via Bessel beam excitation separation technology (BEST). BEST isolates viruses by utilizing the nondiffractive and self-healing properties of 2D, in-plane acoustic Bessel beams to continuously separate cell-free viruses from biofluids, with high throughput and high viral RNA yield. By tuning the acoustic parameters, the cutoff size of isolated viruses can be easily adjusted to perform dynamic, size-selective virus isolation while simultaneously trapping larger particles and separating smaller particles and contaminants from the sample, achieving high-precision isolation of the target virus. BEST was used to isolate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from human saliva samples and Moloney Murine Leukemia Virus from cell culture media, demonstrating its potential use in both practical diagnostic applications and fundamental virology research. With high separation resolution, high yield, and high purity, BEST is a powerful tool for rapidly and efficiently isolating viruses. It has the potential to play an important role in the development of next-generation viral diagnostics, therapeutics, and vaccines.

Development of a 3D Hydrogel SERS Chip for Noninvasive, Real-Time pH and Glucose Monitoring in Sweat.

Traditional diagnostic methods, such as blood tests, are invasive and time-consuming, while sweat biomarkers offer a rapid physiological assessment. Surface-enhanced Raman spectroscopy (SERS) has garnered significant attention in sweat analysis because of its high sensitivity, label-free nature, and nondestructive properties. However, challenges related to substrate reproducibility and interference from the biological matrix persist with SERS. This study developed a novel ratio-based 3D hydrogel SERS chip, providing a noninvasive solution for real-time monitoring of pH and glucose levels in sweat. Encapsulating the probe molecule (4-MBN) in nanoscale gaps to form gold nanoflower-like nanotags with internal standards and integrating them into an agarose hydrogel to create a 3D flexible SERS substrate significantly enhances the reproducibility and stability of sweat analysis. Gap-Au nanopetals modified with probe molecules are uniformly dispersed throughout the porous hydrogel structure, facilitating the effective detection of the pH and glucose in sweat. The 3D hydrogel SERS chip demonstrates a strong linear relationship in pH and glucose detection, with a pH response range of 5.5-8.0 and a glucose detection range of 0.01-5 mM, with R2 values of 0.9973 and 0.9923, respectively. In actual sweat samples, the maximum error in pH detection accuracy is only 1.13%, with a lower glucose detection limit of 0.25 mM. This study suggests that the ratio-based 3D hydrogel SERS chip provides convenient, reliable, and rapid detection capabilities with substantial application potential for analyzing body fluid pH and glucose.

Real-world pharmacovigilance analysis of galsulfase: a study based on the FDA adverse event reporting system (FAERS) database.

Background: Associated with enzyme deficiencies causing glycosaminoglycans (GAGs) accumulation, mucopolysaccharidosis type VI (MPS VI) is lysosomal storage disorder. In the treatment of MPS VI, galsulfase (Naglazyme) is commonly used as an enzyme replacement therapy (ERT). There remains a need for comprehensive real-world data on its safety and associated adverse events (AEs). Objective: An analysis of the FDA Adverse Event Reporting System (FAERS) database will be conducted to identify potential risks and adverse reactions associated with galsulfase in real-life settings. Methods: The FAERS database was used to extract data from Q2 2005 to Q4 2023. A total of 20,281,876 reports were analyzed after duplicate elimination, with 3,195 AE reports related to galsulfase identified. The association between galsulfase and AEs was investigated by utilizing four algorithms: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS). The analysis focused on the timing of onset, signs of AEs, and clinical significance. Results: Twenty seven organ systems were involved, and significant system organ classes (SOCs) included respiratory, thoracic and mediastinal disorders, and infections and infestations. At the PT level, 72 PTs corresponding to 15 SOCs were identified, with some AEs not previously mentioned in the product label. AEs associated with galsulfase had a median onset time of 1,471 days, with over half of the cases occurred within the first 5 years of treatment initiation. Conclusion: This investigation delivers an exhaustive and indicative assessment of galsulfase's safety profile, grounded in authentic, real-world evidence. The findings emphasis the importance of continuous safety surveillance and the emergence of new AEs. The identification of previously unreported urologic adverse events, such as glomerulonephritis membranous and nephritic syndrome, warrants further investigation. The study emphasizes the need for enhanced pharmacovigilance to ensure patient safety and the effectiveness of galsulfase treatment.

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.

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.

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.

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.

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.

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.

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.

Clinical efficacy and safety of lymphocyte apheresis combined with plasma exchange in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage / 中华危重病急救医学

Objective:To analyze and summarize the clinical efficacy and safety of lymphocyte apheresis combined with plasma exchange in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage.Methods:A observational study was conducted. A total of 69 hepatitis B virus-related liver failure at the ascending stage patients who were hospitalized at Affiliated Guangzhou Eighth People's Hospital of Guangzhou Medical University from January 2016 to December 2020 were enrolled in this study. The patients were grouped according to their condition and wishes, including 38 patients treated with conservative medical treatment (control group) and 31 patients treated with lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment (study group). Clinical data were compared between the two groups 1-4 weeks after treatment, including dynamic changes of total bilirubin (TBil), international normalized ratio (INR), alanine aminotransferase (ALT), model for end-stage liver disease (MELD) score, and the rate of clinical improvement at 4 weeks after treatment. In addition, the adverse effects and dynamic changes of white blood cell count (WBC), lymphocyte count (LYM), platelet count (PLT), and hemoglobin (Hb) within 4 weeks after treatment were compared between the two groups.Results:Both groups showed significant improvement in clinical parameters after 1-4 weeks of initiation of therapy. The improvement of TBil, INR and MELD score at 1-4 weeks after treatment were significantly better in the treatment group than those in the control group [TBil (μmol/L): 248 (117, 335) vs. 398 (328, 464) at 1 week, 173 (116, 278) vs. 326 (184, 476) at 2 weeks, 107 (84, 235) vs. 355 (129, 467) at 3 weeks, 70 (61, 172) vs. 290 (82, 534) at 4 weeks; INR: 1.72±0.70 vs. 2.13±0.69 at 1 week, 1.67±0.61 vs. 2.28±1.35 at 2 weeks, 1.65±0.75 vs. 2.15±0.92 at 3 weeks, 1.61±0.93 vs. 2.19±1.17 at 4 weeks; MELD score: 18.35±5.32 vs. 23.38±4.56 at 1 week, 16.47±5.16 vs. 23.71±7.94 at 2 weeks, 16.30±5.75 vs. 22.64±6.99 at 3 weeks, 14.63±6.76 vs. 20.97±8.19 at 4 weeks], with significant differences (all P < 0.05). In addition, ALT levels at 1 week and 2 weeks after treatment in the study group were significantly lower than those in the control group [U/L: 128 (93, 206) vs. 240 (167, 436) at 1 week, 64 (42, 110) vs. 85 (69, 143) at 2 weeks, both P < 0.05]. The rate of clinical improvement at 4 weeks after treatment in the study group was 54.84% (17/31), which was significantly higher than that in the control group [28.95% (11/38)], with statistically significant difference ( P < 0.05). There was no significant difference in the rate of new infection between the study group and the control group [22.58% (7/31) vs. 34.21% (13/38), P > 0.05]. Additionally, expect that the PLT level at 1 week after treatment in the study group was significantly lower than that in the control group (×10 9/L: 101±42 vs. 128±59, P < 0.01), there was no significant difference in WBC, LYM or Hb at different time points after treatment between the two groups. Conclusion:Clinical efficacy of lymphocyte apheresis combined with plasma exchange based on comprehensive medical treatment in the treatment of patients with hepatitis B virus-related liver failure at the ascending stage is superior to conservative medical treatment alone, which can improve clinical improvement rate and recovery rate of liver function with high safety.

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.

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.

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.

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.