Joint association of TyG index and high sensitivity C-reactive protein with cardiovascular disease: a national cohort study.

BACKGROUND: Both the triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, and systemic inflammation are predictors of cardiovascular diseases; however, little is known about the coexposures and relative contributions of TyG index and inflammation to cardiovascular diseases. Using the nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS), we conducted longitudinal analyses to evaluate the joint and mutual associations of the TyG index and high-sensitivity C-reactive protein (hsCRP) with cardiovascular events in middle-aged and older Chinese population. METHODS: This study comprised 8 658 participants aged at least 45 years from the CHARLS 2011 who are free of cardiovascular diseases at baseline. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Cardiovascular events were defined as the presence of physician-diagnosed heart disease and/or stroke followed until 2018.We performed adjusted Cox proportional hazards regression and mediation analyses. RESULTS: The mean age of the participants was 58.6 ± 9.0 years, and 3988 (46.1%) were females. During a maximum follow-up of 7.0 years, 2606 (30.1%) people developed cardiovascular diseases, including 2012 (23.2%) cases of heart diseases and 848 (9.8%) cases of stroke. Compared with people with a lower TyG index (< 8.6 [median level]) and hsCRP < 1 mg/L, those concurrently with a higher TyG and hsCRP had the highest risk of overall cardiovascular disease (adjusted hazard ratio [aHR], 1.300; 95% CI 1.155-1.462), coronary heart disease (aHR, 1.294; 95% CI 1.130-1.481) and stroke (aHR, 1.333; 95% CI 1.093-1.628), which were predominant among those aged 70 years or below. High hsCRP significantly mediated 13.4% of the association between the TyG index and cardiovascular disease, while TyG simultaneously mediated 7.9% of the association between hsCRP and cardiovascular risk. CONCLUSIONS: The findings highlight the coexposure effects and mutual mediation between the TyG index and hsCRP on cardiovascular diseases. Joint assessments of the TyG index and hsCRP should be underlined for the residual risk stratification and primary prevention of cardiovascular diseases, especially for middle-aged adults.

Diabetes, glycemic control and arterial stiffness: a real-world cohort study in the context of predictive, preventive, and personalized medicine.

Background: Arterial stiffness is a major contributor to morbidity and mortality worldwide. Although several metabolic markers associated with arterial stiffness have been developed, there is limited data regarding whether glycemic control modifies the association between diabetes and arterial stiffness. For these reasons, identification of traits around diabetes will directly contribute to arterial stiffness and atherosclerosis management in the context of predictive, preventive, and personalized medicine (PPPM). Thus, this study aimed to explore the relationship of diabetes and glycemic control status with arterial stiffness in a real-world setting. Methods: Data of participants from Beijing Xiaotangshan Examination Center (BXEC) with at least two surveys between 2008 and 2019 were used. Cumulative hazards were presented by inverse probability of treatment weighted (IPTW) Kaplan-Meier curves. Cox models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Arterial stiffness was defined as brachial-ankle pulse wave velocity (baPWV) ≥1400 cm/s. Results: Of 5837 participants, the mean baseline age was 46.5±9.3 years, including 3791 (64.9%) males. During a median follow-up of 4.0 years, 1928 (33.0%) cases of incident arterial stiffness were observed. People with diabetes at baseline had a 48.4% (HR: 1.484, 95% CI: 1.250-1.761) excessive risk of arterial stiffness. Adherence to good glycemic control attenuated the relationship between diabetes and arterial stiffness (HR: 1.264, 95% CI: 0.950-1.681); while uncontrolled diabetes was associated with the highest risk of arterial stiffness (HR: 1.629, 95% CI: 1.323-2.005). Results were consistent using IPTW algorithm and multiple imputed data. Conclusion: Our study quantified that diabetes status is closely associated with an increased risk of arterial stiffness and supported that adherence to good glycemic control could attenuate the adverse effect of diabetes on arterial stiffness. Therefore, glucose monitoring and control is a cost-effective strategy for the predictive diagnostics, targeted prevention, patient stratification, and personalization of medical services in early vascular damages and arterial stiffness. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00347-z.

Triglyceride-glucose index, renal function and cardiovascular disease: a national cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. METHODS: This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). RESULTS: A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m2, those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131-3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. CONCLUSIONS: The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk.

The Role of Proton in High Power Density Vanadium Redox Flow Batteries.

To design high-performance vanadium redox flow batteries (VRFBs), the influence of proton on electrocatalysts cannot be neglected considering the abundance of proton in a highly acidic electrolyte. Herein, the impact of proton on metal oxide-based electrocatalysts in VRFBs is investigated, and a proton-incorporating strategy is introduced for high power density VRFBs, in addition to unraveling the catalytic mechanism. This study discloses that the metal oxide-based electrocatalyst (WO3) undergoes in situ surface reconstruction by forming H0.5WO3 after incorporating proton. Experimental and theoretical results precisely disclose the catalytic active sites. The battery with H0.5WO3 designed by a proton-incorporating strategy achieves an attractive power density of 1.12 W cm-2 and sustains more than 900 cycles without an obvious decay, verifying the outstanding electrochemical performance of H0.5WO3. This work not only sheds light on the influence of proton on electrocatalysts for rational design of advanced VRFBs catalysts but also provides guidelines for the fundamental understanding of the reaction mechanism, which is highly important for the application of VRFBs.

Association Between Osseointegration of Lower Extremity Amputation and Mortality Among Adults.

Importance: Transcutaneous osseointegration post amputation (TOPA) creates a direct linkage between residual bone and an external prosthetic limb, providing superior mobility and quality of life compared with a socket prosthesis. The causes and potential risks of mortality after TOPA have not been investigated. Objective: To investigate the association between TOPA and mortality and assess the potential risk factors. Design, Setting, and Participants: This observational cohort study included all patients with amputation of a lower extremity who underwent TOPA between November 1, 2010, and October 31, 2021, at a specialty orthopedic practice and tertiary referral hospital in a major urban center. Patients lived on several continents and were followed up as long as 10 years. Exposures: Transcutaneous osseointegration post amputation, consisting of a permanent intramedullary implant passed transcutaneously through a stoma and connected to an external prosthetic limb. Main Outcomes and Measures: Death due to any cause. The hypotheses tested-that patient variables (sex, age, level of amputation, postosseointegration infection, and amputation etiology) may be associated with subsequent mortality-were formulated after initial data collection identifying which patients had died. Results: A total of 485 patients were included in the analysis (345 men [71.1%] and 140 women [28.9%]), with a mean (SD) age at osseointegration of 49.1 (14.6) years among living patients or 61.2 (12.4) years among patients who had died. Nineteen patients (3.9%) died a mean (SD) of 2.2 (1.7) years (range, 58 days to 5 years) after osseointegration, including 17 (3.5%) who died of causes unrelated to osseointegration (most commonly cardiac issues) and 2 (0.4%) who died of direct osseointegration-related complications (infectious complications), of which 1 (0.2%) was coclassified as a preexisting health problem exacerbated by osseointegration (myocardial infarction after subsequent surgery to manage infection). No deaths occurred intraoperatively or during inpatient recuperation or acute recovery after index osseointegration (eg, cardiopulmonary events). Kaplan-Meier survival analysis with log-rank comparison and Cox proportional hazards regression modeling identified increased age (hazard ratio, 1.06 [95% CI, 1.02-1.09]) and vascular (odds ratio [OR], 4.73 [95% CI, 1.35-16.56]) or infectious (OR, 3.87 [95% CI, 1.31-11.40]) amputation etiology as risk factors. Notable factors not associated with mortality risk included postosseointegration infection and male sex. Conclusions and Relevance: These findings suggest that patients who have undergone TOPA rarely die of problems associated with the procedure but instead usually die of unrelated causes.

Abnormal brain activities in multiple frequency bands in Parkinson's disease with apathy.

Background: Apathy is among the most prevalent and incapacitating non-motor symptoms of Parkinson's disease (PD). PD patients with apathy (PD-A) have been reported to have abnormal spontaneous brain activity mainly in 0.01-0.08 Hz. However, the frequency-dependence of brain activity in PD-A remains unclear. Therefore, this study aimed to examine whether abnormalities in PD-A are associated with specific frequency bands. Materials and methods: Overall, 28 patients with PD-A, 19 PD patients without apathy (PD-NA), and 32 gender-, age-matched healthy controls (HCs) were enrolled. We collected resting-state functional magnetic resonance imaging (rs-fMRI) data, demographic information, and neuropsychological assessments, including apathy, depression, anxiety and cognitive function for every participant. The amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) were calculated in the conventional (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) frequency bands based on statistical parametric mapping (SPM12) and RESTplus V1.25. Two-sample t-tests were performed to compare the differences among the three groups. Results: PD-A reduced ALFF in the right anterior cingulate gyri in the slow-5 band and decreased fALFF in the right middle frontal gyrus in the conventional band, compared to patients with PD-NA. However, PerAF, ReHo, and DC could not distinguish PD-A from PD-NA in the three bands. PD-A had higher ALFF and fALFF in the left middle occipital gyrus and lower fALFF in the bilateral insula in the slow-5 band compared to the HCs. Furthermore, abnormal DC value in hippocampus and parahippocampus was observed separately in the conventional band and in the slow-4 band between PD-A and HCs. Moreover, PD-A and PD-NA showed lower ReHo in cerebellum in the three bands compared to the HCs. Conclusion: Our study revealed that PD-A and PD-NA might have different neurophysiological mechanisms. Concurrently, the ALFF in the slow-5 band and fALFF in the conventional band were sensitive in differentiating PD-A from PD-NA. The influence of apathy on the disease can be considered in the future research on PD, with the effects of frequency band taken into account when analyzing spontaneous brain activities in PD-A.

Non-invasive physical therapy as salvage measure for ischemic skin flap: A literature review.

This review focuses on the available evidence regarding the molecular mechanisms and treatment potential of several non-surgical physical therapies for managing flap ischemia to propose a non-invasive, economical, and simple treatment to improve flap survival. A review of the literature was conducted on the topics of various non-invasive methods for the treatment of ischemic necrosis of the distal end of the flap between 1988 and 2019. A total of 52 published studies were reviewed on the applications of hyperbaric oxygen therapy, electrical stimulation therapy, heat stress pretreatment, phototherapy, and vibration therapy to manage skin flap necrosis. The underlying molecular mechanisms of these physical therapies on revitalizing the dying skin flaps were discussed and preliminary clinical uses of these therapies to salvage the necrotic skin flaps were pooled and summarized for clarifying the safety and feasibility of these methods. Various physical therapy regimens have been ushered to manage necrotic development in cutaneous flaps. With the refinement of these new technologies and enhancement of related basic science research on vascular revitalization, the prevention and treatment of flap ischemia will enter a new era.

Complete androgen insensitivity syndrome caused by c.1769-1G > C mutation and activation of a cryptic splice acceptor site in the androgen receptor gene.

Androgen insensitivity syndrome (AIS) is the most common cause of 46,XY disorders of sex development (46,XY DSD). This syndrome is an X-linked recessive genetic disease characterized by resistance to the actions of androgens in an individual with a male karyotype and it is caused by mutations in the androgen receptor (AR) gene. We evaluated two siblings with primary amenorrhea, normal secondary sex characteristics, absence of uterus and ovaries, intra-abdominal testis, and elevated testosterone levels. Sequence analysis of the AR gene revealed a splice acceptor site mutation in intron 2 (c.1769-1G > C). The analysis of mRNA showed that this mutation resulted in the activation of a cryptic splice acceptor site located in intron 2 and in the synthesis of an aberrant mRNA transcript with 69 nucleotides insertion between exon 2 and exon 3, leading to an insertion of 23 amino acids in the AR protein instead of generating a premature termination codon. The additional 23 amino acids insertion affects AR intracellular trafficking by impairing its translocation from the cytoplasm to the nucleus after hormone stimulation. The c.1769-1G > C mutation provides new insights into the molecular mechanism involved in splicing defects and expands the spectrum of mutations associated with the androgen insensitivity syndrome.

Gold nanorods or nanospheres? Role of particle shape on tuning the shape memory effect of semicrystalline poly(ε-caprolactone) networks.

In this study, modified poly(ε-caprolactone) (PCL) tri-block copolymers were successfully synthesized through ring opening polymerization. The nanocomposite films containing either colloidal gold nanorods (AuNRs) or gold nanospheres (AuNSs) in the polymer matrix were fabricated without chemical modification to realize light-responsive shape memory behaviors. The localized surface plasmon resonance of AuNPs was utilized by irradiating the selective wavelength of light to create a photothermal effect. The polymer microstructures were investigated by NMR, and the thermal properties of the polymer networks were studied by TGA and DSC. The addition of AuNPs did not change the melting temperature, (T m) of the SMP. The AuNRs were fairly well dispersed within the PCL matrix as observed using SEM-EDAX analysis and as indicated from the uniform shape memory transitions of the SMP/AuNR nanocomposites. The shape memory behavior was quantitatively analyzed by cyclic thermomechanical tests using DMA. The laser-triggered shape memory properties of the nanocomposites were analyzed and the shape recovery process from a rectangular shaped film to a helical coil was demonstrated. The speed of SMP recovery was found to be dependent on the geometry and concentration of the AuNPs in the nanocomposite, as well as on the laser wavelength and intensity.

Mutational analysis of the androgen receptor gene in two Chinese families with complete androgen insensitivity syndrome.

Androgens are essential for normal male sex differentiation and are responsible for the normal development of male secondary sexual characteristics at puberty. The physiological effects of androgens are mediated by the androgen receptor (AR). Mutations in the AR gene are the most common cause of androgen insensitivity syndrome. The present study undertook a genetic analysis of the AR gene in two unrelated families affected by complete androgen insensitivity syndrome (CAIS) in China. In family 1, a previously reported nonsense mutation (G-to-A; p.W751X) was identified in exon 5 of the AR gene. In addition, a novel missense mutation was detected in exon 6 of the AR gene from family 2; this mutation resulted in a predicted amino acid change from phenylalanine to serine at codon 804 (T-to-C; p.F804S) in the ligand-binding domain (LBD) of AR. Computer simulation of the structural changes generated by the p.F804S substitution revealed marked conformational alterations in the hydrophobic core responsible for the stability and function of the AR-LBD. In conclusion, the present study identified two mutations from two unrelated Chinese families affected by CAIS. The novel mutation (p.F804S) may provide insights into the molecular mechanism underlying CAIS. Furthermore, it expands on the number of mutational hot spots in the international AR mutation database, which may be useful in the future for prenatal diagnosis and genetic counseling.

Identification of a novel frameshift mutation of the EXT2 gene in a family with multiple osteochondroma.

Multiple osteochondroma (MO), also known as multiple hereditary exostoses, is an autosomal dominant skeletal disorder with characteristic multiple cartilage-capped tumours (osteochondromas or exostoses) growing outward from the metaphyseal region of the long tubular bones. Mutations in exostosin glycosyltransferase 1 (EXT1) or EXT2 are the most commonly associated mutations with MO and are responsible for 70-95% of cases. In the present study, a genetic analysis was performed on a large family with MO using polymerase chain reaction and direct DNA sequencing of the entire coding regions of EXT1 and EXT2. Sanger sequencing identified a novel heterozygous frameshift mutation, c.119_120delCT (p.Thr40ArgfsX15), in exon 2 of the EXT2 gene in the proband and all other affected individuals, while this deleterious mutation was not detected in the healthy family members and normal controls. The c.119_120delCT mutation is located in the transmembrane region of the EXT2 protein and results in a truncated EXT2 protein lacking 665 amino acids at the C-terminus, which includes the critical exostosin and glycosyltransferase family 64 domains. Thus, the present study identified a novel causative frameshift mutation in EXT2 from a large MO family. This study is useful for extending the known mutational spectrum of EXT2, for understanding the genetic basis of MO in the patients studied, and for further application of mutation screening in the genetic counseling and subsequent prenatal diagnosis of this family.