Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Calpain: the regulatory point of myocardial ischemia-reperfusion injury.

Calpain is a conserved cysteine protease readily expressed in several mammalian tissues, which is usually activated by Ca2+ and with maximum activity at neutral pH. The activity of calpain is tightly regulated because its aberrant activation will nonspecifically cleave various proteins in cells. Abnormally elevation of Ca2+ promotes the abnormal activation of calpain during myocardial ischemia-reperfusion, resulting in myocardial injury and cardiac dysfunction. In this paper, we mainly reviewed the effects of calpain in various programmed cell death (such as apoptosis, mitochondrial-mediated necrosis, autophagy-dependent cell death, and parthanatos) in myocardial ischemia-reperfusion. In addition, we also discussed the abnormal activation of calpain during myocardial ischemia-reperfusion, the effect of calpain on myocardial repair, and the possible future research directions of calpain.

The Fra-1: Novel role in regulating extensive immune cell states and affecting inflammatory diseases.

Fra-1(Fos-related antigen1), a member of transcription factor activator protein (AP-1), plays an important role in cell proliferation, apoptosis, differentiation, inflammation, oncogenesis and tumor metastasis. Accumulating evidence suggest that the malignancy and invasive ability of tumors can be significantly changed by directly targeting Fra-1. Besides, the effects of Fra-1 are gradually revealed in immune and inflammatory settings, such as arthritis, pneumonia, psoriasis and cardiovascular disease. These regulatory mechanisms that orchestrate immune and non-immune cells underlie Fra-1 as a potential therapeutic target for a variety of human diseases. In this review, we focus on the current knowledge of Fra-1 in immune system, highlighting its unique importance in regulating tissue homeostasis. In addition, we also discuss the possible critical intervention strategy in diseases, which also outline future research and development avenues.

Targeting C-C Chemokine Receptor 5: Key to Opening the Neurorehabilitation Window After Ischemic Stroke.

Stroke is the world's second major cause of adult death and disability, resulting in the destruction of brain tissue and long-term neurological impairment; induction of neuronal plasticity can promote recovery after stroke. C-C chemokine receptor 5 (CCR5) can direct leukocyte migration and localization and is a co-receptor that can mediate human immunodeficiency virus (HIV) entry into cells. Its role in HIV infection and immune response has been extensively studied. Furthermore, CCR5 is widely expressed in the central nervous system (CNS), is engaged in various physiological activities such as brain development, neuronal differentiation, communication, survival, and learning and memory capabilities, and is also involved in the development of numerous neurological diseases. CCR5 is differentially upregulated in neurons after stroke, and the inhibition of CCR5 in specific regions of the brain promotes motor and cognitive recovery. The mechanism by which CCR5 acts as a therapeutic target to promote neurorehabilitation after stroke has rarely been systematically reported yet. Thus, this review aims to discuss the function of CCR5 in the CNS and the mechanism of its effect on post-stroke recovery by regulating neuroplasticity and the inflammatory response to provide an effective basis for clinical rehabilitation after stroke.

[Identification of a recurrent mutation in the ROR2 gene in a Chinese family with brachydactyly type B].

OBJECTIVE: To identify the disease-causing mutation in a Chinese family with brachydactyly type B (BDB). METHODS: Genomic DNA was extracted from peripheral blood samples of family members. Exons 8 and 9 of the ROR2 gene were amplified by polymerase chain reaction (PCR) and sequenced directly. Furthermore, the PCR products showing mutation were cloned into pMD18T vector and the insert fragments were sequenced. RESULTS: A 1398-1399 insA heterozygous mutation was detected in the patient. This mutation had been found in German families with BDB. CONCLUSION: To the authors' knowledge, it is the first report on identification of the ROR2 pathogenic mutation in Chinese patients with BDB.

[Heterogeneous phenotypes in Chinese glycogen storage disease type Ia patients with homozygous G727T mutation].

UNLABELLED: Glycogen storage disease (GSD) type Ia is an autosomal recessive disorder caused by a deficiency of glucose-6-phosphatase (G6Pase). The gene that encodes G6Pase was mapped to 17q21. The molecular genetic basis of GSD type Ia in the mainland Chinese population has not been explored. OBJECTIVE: To analyze the G6Pase gene mutations, and to compare the phenotypic features and the response to the corn starch treatment among patients who share the same mutation. METHODS: With the consent of the parents and their children, the authors studied 18 families with clinically diagnosed GSD type Ia from our long time follow-up groups. Direct DNA sequencing of all 5 exons and the exon-intron boundaries of G6Pase gene were done on the blood specimens. Seven of the 18 patients, male 2 and female 5, aged 1.5 to 16 years, were homozygous for same mutation. The clinical symptoms, signs and the serum biochemical values before and after treatment were compared in these 7 patients. RESULTS: The 7 patients were homozygous of G-->T transversion at the nucleotide 727 in exon 5 (G727T), which has previously been reported to cause abnormal splicing. The parents were heterozygous of the G727T mutation. All the patients exhibited typical features of GSD type Ia with variable severity, including hypoglycemia, hepatomegaly, kidney enlargement, growth retardation, bleeding diathesis, lactic acidemia, hyperlipidemia, and hyperuricemia. Two of the patients had repeated hypoglycemic seizures before the age of 2 years. One had moderate splenomegaly when he came to our clinic at the age of 16, the spleen size was reduced to 2 cm below the left costal margin after 5-year treatment. His sister, homozygous of G727T, did not show splenomegaly. One had multiple hepatic adenoma since the age of 5 years. Four had 5-year-delayed bone age when they started treatment at the age of 9 to 16 years, the bone age reached normal after 2 - 3 years treatment. No matter when they started corn starch treatment, the height increase in the first year was most obvious with an average of 10 cm. All the patients had abnormal liver function before treatment, 5 had constant slightly elevated liver enzymes with the treatment. All had normal urinalysis test, but the urine beta(2)- microglobulin was elevated. CONCLUSIONS: G727T mutation may be the major cause of GSD type Ia in China. Patients with the same mutation could have variable phenotypic characteristics, and the response to the corn starch treatment was different. The diagnosis of GSD type Ia can be based on clinical and biochemical abnormalities combined with mutation analysis instead of enzyme assays on liver biopsy.