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Background. Cognitive impairment is the leading cause of traumatic brain injury- (TBI-) related disability; however, the underlying pathogenesis of this dysfunction is not completely understood. Methods. Using an isobaric tagging for relative and absolute quantitation- (iTRAQ-) based quantitative proteomic approach, serum samples from healthy control subjects, TBI patients with cognitive impairment, and TBI patients without cognitive impairment were analysed to identify differentially expressed proteins (DEPs) related to post-TBI cognitive impairment. In addition, DEPs were further analysed using bioinformatic platforms and validated using enzyme-linked immunosorbent assays (ELISA). Results. A total of 56 DEPs were identified that were specifically related to TBI-induced cognitive impairment. Bioinformatic analysis revealed that a wide variety of cellular and metabolic processes and some signaling pathways were involved in the pathophysiology of cognitive deficits following TBI. Five randomly selected DEPs were validated using ELISA in an additional 105 cases, and the results also supported the experimental findings. Conclusions. Despite limitations, our findings will facilitate further studies of the pathological mechanisms underlying TBI-induced cognitive impairment and provide new methods for the research and development of neuroprotective agents. However, further investigation on a large cohort is warranted. [ABSTRACT FROM AUTHOR]

Heteroresistance is a poorly understood mechanism of resistance which refers to a phenomenon where there are different subpopulations of seemingly isogenic bacteria which exhibit a range of susceptibilities to a particular antibiotic. In the current study, we identified a multidrug-resistant, carbapenemase-positive K. pneumoniae strain SWMUF35 which was classified as susceptible to amikacin and resistant to meropenem by clinical diagnostics yet harbored different subpopulations of phenotypically resistant cells, and has the ability to form biofilm. Population analysis profile (PAP) indicated that SWMUF35 showed heteroresistance towards amikacin and meropenem which was considered as co-heteroresistant K. pneumoniae strain. In vitro experiments such as dual PAP, dual Times-killing assays and checkerboard assay showed that antibiotic combination therapy (amikacin combined with meropenem) can effectively combat SWMUF35. Importantly, using an in vivo mouse model of peritonitis, we found that amikacin or meropenem monotherapy was unable to rescue mice infected with SWMUF35. Antibiotic combination therapy could be a rational strategy to use clinically approved antibiotics when monotherapy would fail. Furthermore, our data warn that antibiotic susceptibility testing results may be unreliable due to undetected heteroresistance which can lead to treatment failure and the detection of this phenotype is a prerequisite for a proper choice of antibiotic to support a successful treatment outcome. • Carbapenem-resistant K. pneumoniae has become a cause of nosocomial infections and posed challenges on treatments. • Heteroresistance could lead to treatment failure and is difficult to detect by methods employed by clinical laboratories. • Amikacin is often combined with carbapenems against multi-drug resistant K. pneumoniae. • Reports of amikacin and meropenem heteroresistant K. pneumoniae in China has not been previously reported. [ABSTRACT FROM AUTHOR]

Human aging is invariably accompanied by a decline in renal function, a process potentially exacerbated by uremic toxins originating from gut microbes. Based on a registered household Chinese Guangxi longevity cohort (n = 151), we conducted comprehensive profiling of the gut microbiota and serum metabolome of individuals from 22 to 111 years of age and validated the findings in two independent East Asian aging cohorts (Japan aging cohort n = 330, Yunnan aging cohort n = 80), identifying unique age-dependent differences in the microbiota and serum metabolome. We discovered that the influence of the gut microbiota on serum metabolites intensifies with advancing age. Furthermore, mediation analyses unveiled putative causal relationships between the gut microbiota (Escherichia coli, Odoribacter splanchnicus, and Desulfovibrio piger) and serum metabolite markers related to impaired renal function (p-cresol, N-phenylacetylglutamine, 2-oxindole, and 4-aminohippuric acid) and aging. The fecal microbiota transplantation experiment demonstrated that the feces of elderly individuals could influence markers related to impaired renal function in the serum. Our findings reveal novel links between age-dependent alterations in the gut microbiota and serum metabolite markers of impaired renal function, providing novel insights into the effects of microbiota-metabolite interplay on renal function and healthy aging., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Abstract: Studies have shown that rapid rehabilitation surgery has a positive effect on recovery after major orthopedic surgery. However, very few studies have examined the impact of fast track surgery on physical and psychological rehabilitation in patients who have undergone total hip replacement.This study aimed to investigate the value of the rapid rehabilitation surgical model for patients undergoing total hip arthroplasty during the perioperative period.We conducted a prospective cohort study that included patients who underwent total hip arthroplasty at our hospital from January 2015 to December 2018. We divided the patients into 2 groups - the rapid rehabilitation group and the conventional rehabilitation group - and compared their length of hospital stay, time to off-bed activity, pain score, Self-Rating Anxiety Scale scores, Self-Rating Depression Scale scores, complication rate, and rate of satisfaction during hospitalization.A total of 348 patients were included in the study. Of these, 180 received rapid rehabilitation nursing and 168 patients received conventional nursing. Compared with the patients in the conventional rehabilitation group, those in the rapid rehabilitation group had shorter hospital stays (11.5 ± 1.2 day vs 15.5 ± 2.3 day, P = .021), resumed off-bed activities sooner (20.5 ± 3.4 hours vs 61.8 ± 4.7 hours, P = .001, had less postoperative pain (4.0 ± 1.2 vs 6.5 ± 1.1, P < .001), and lower anxiety and depression scores (anxiety score: 24.4 ± 2.1 vs 47.9 ± 2.9; depression score: 25.8 ± 1.8 vs 43.7 ± 1.7, P < .001).The application of rapid rehabilitation surgery in total hip arthroplasty can accelerate patients' postoperative recovery, relieve anxiety and depression, and increase the patient's satisfaction with the treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Branched-chain amino acids (BCAAs) and telomere length are biologically associated with healthy aging. However, the association between them and their interaction on frailty remain unclear in humans. Here, a cross-sectional study based on residents from Guangxi longevity county was conducted to investigate the association of serum BCAAs, peripheral leukocyte telomere length (LTL) and frailty. A total of 1,034 subjects aged 20 to 110 years were recruited in the study. The real-time qPCR method and a targeted metabolomics approach based on isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) method were used for measurement of LTL and BCAAs, respectively. A frailty score defined as the proportion of accumulated deficits based on 24 aging-related items was used assess the health status of elderly subjects. First, we found that a higher concentration of BCAAs was significantly associated with longer LTL only in middle-aged subjects, independent of age and BMI (P < 0.05). In the oldest-old subjects, we identified a significantly inverse association between BCAAs and frailty score (P < 0.001), even after adjustment for age and BMI (P < 0.05). Additionally, we recognized a statistically significant synergetic interaction between BCAAs and LTL on frailty score in the oldest-old subjects by the general linear model (P = 0.042), although we did not find any significant association between LTL and frailty score. In summary, our findings suggest a potentially protective effect of circulating BCAAs on LTL and frailty based on the subjects from longevity county in East Asia and indicate a potential synergetic interaction between BCAAs and LTL in healthy aging.

Human longevity involves genetic, nutritional, environmental and many other factors playing a key role in healthy aging. Previous studies have shown that mineral metabolism and homeostasis are associated with lifespan extension. However, the majority of them have focused on a limited number of elements and ignored the complex relationship between them. In this study, we carried out a network-based approach to investigate the urinary ionome of nonagenarians and centenarians (longevity group) when compared with their biologically unrelated and younger family members (control group) from a Han Chinese population. Several differentially changed elements were identified, almost all of which showed an elevated level in the longevity group. Correlation analysis of the ionome revealed significant element-element interactions in each group. We then divided each group into distinct subgroups according to age ranges, and built the elemental correlation network for each of them. Significant elemental correlations and correlation changes involving all examined elements were identified within or between different subgroups, implying a highly dynamic and complex crosstalk among the elements during human life. Finally, more similar elemental patterns were observed between extremely old and middle-aged people. Overall, our data reveal new relationship between urinary minerals and human longevity, which may extend our understanding of the mechanism of healthy aging., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)