Objective Myocardial ischemia-reperfusion injury (MIRI) is a secondary condition following the reestablishment of blood flow to the heart, resulting in myocardial damage such as cardiomyocyte death, ferroptosis, fibrosis, and hypertrophy. However, there is still a lack of targeted therapeutic drugs to date.Aldometanib is a newly developed activator of AMP-activated protein kinase (AMPK) located on the lysosomal membrane, which exhibits significant pharmacological potential. Nevertheless, its role in MIRI remains incompletely understood. Methods This study assessed aldometanib's impact on myocardial ischemia-reperfusion injury using H9c2 and AC16 cardiomyocyte lines as in vitro models. Results Experimental data demonstrated that aldometanib promoted cardiomyocyte proliferation, reduced oxidative stress, and alleviated inflammatory responses. Furthermore, we identified that aldometanib could inhibit ferroptosis in cardiomyocytes. Mechanistically, our investigations revealed that aldometanib exerted a cardioprotective effect by alleviating cardiomyocyte damage through the regulation of mitochondrial function. Specifically, aldometanib enhanced mitophagy by activating lysosomal AMPK. Additionally, we found that aldometanib exerted an antioxidant effect via Nrf2, thereby mitigating ferroptosis. In animal models, we preliminarily confirmed that aldometanib treatment attenuated tissue damage and functional impairment following myocardial ischemia-reperfusion, further supporting its therapeutic potential. Conclusions This study uncovers the protective effect of aldometanib against MIRI and its underlying mechanism, providing experimental evidence and a potential candidate drug for targeting MIRI.

The correlation between socio-economic status (SES) and bone-related diseases garners increasing attention, prompting a bidirectional Mendelian randomization (MR) analysis in this study. Genetic data on SES indicators (average total household income before tax, years of schooling completed, and Townsend Deprivation Index at recruitment), femoral neck bone mineral density (FN-BMD), heel bone mineral density (eBMD), osteoporosis, and five different sites of fractures (spine, femur, lower leg-ankle, foot, and wrist-hand fractures) were derived from genome-wide association summary statistics of European ancestry. The inverse variance weighted method was employed to obtain the causal estimates, complemented by alternative MR techniques, including MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Furthermore, sensitivity analyses and multivariable MR were performed to enhance the robustness of our findings. Higher educational attainment exhibited associations with increased eBMD (β: .06, 95% confidence interval [CI]: 0.01-0.10, P = 7.24 × 10-3), and reduced risks of osteoporosis (OR: 0.78, 95% CI: 0.65-0.94, P = 8.49 × 10-3), spine fracture (OR: 0.76, 95% CI: 0.66-0.88, P = 2.94 × 10-4), femur fracture (OR: 0.78, 95% CI: 0.67-0.91, P = 1.33 × 10-3), lower leg-ankle fracture (OR: 0.79, 95% CI: 0.70-0.88, P = 2.05 × 10-5), foot fracture (OR: 0.78, 95% CI: 0.66-0.93, P = 5.92 × 10-3), and wrist-hand fracture (OR: 0.83, 95% CI: 0.73-0.95, P = 7.15 × 10-3). Material deprivation appeared to increase the risk of spine fracture (OR: 2.63, 95% CI: 1.43-4.85, P = 1.91 × 10-3). A higher FN-BMD level positively affected increased household income (β: .03, 95% CI: 0.01-0.04, P = 6.78 × 10-3). All these estimates were adjusted for body mass index, type 2 diabetes, smoking initiation, and frequency of alcohol intake. The MR analyses show that higher educational levels is associated with higher eBMD, reduced risk of osteoporosis and fractures, while material deprivation is positively related to spine fracture. Enhanced FN-BMD correlates with increased household income. These findings provide valuable insights for health guideline formulation and policy development.

Background: Depression is prevalent among older adults, and internet-delivered psychological interventions (IDPIs) have emerged as a promising solution. Aim: To explore the landscape of IDPIs for late-life depression, examining current characteristics, psychotherapies, intervention strategies, facilitators, and barriers. Method: Guided by a PRISMA-guided scoping review, we systematically searched five electronic databases. Results: 25 relevant studies were identified. IDPIs were used for treatment, prevention, and assessment. Internet-based cognitive behavioral therapy was the most common psychotherapy. Seven strategies to provide tailored services include psychotherapy courses, professional involvement, mood and progress tracking, virtual community, timed reminders, additional learning resources, and gamification elements. Barriers contained cognitive impairment, low digital literacy, device inaccessibility, limited depression awareness, adherence issues, and acclimation time, while facilitators included prior treatment experience, real-life character stories, strong client-worker bonds, and integration into daily care routines. Conclusion: IDPIs present an accessible and convenient avenue for older adults. Future directions suggest exploring minimalist interventions, diverse strategies, and optimized implementation to amplify IDPIs impact among this vulnerable group. (c) 2023 Elsevier Inc. All rights reserved.

Abstract Background: Unintentional injury was the leading cause of death and disability among individuals younger than 49 years globally in 2019. However, the association between serum CK-MB levels and clinical value in polytrauma patients with nonmyocardial contusion remains unclear. Methods: This was a single-center, retrospective study. Demographic and clinical data were extracted from the Hospital Information System (HIS) at the Third Xiangya Hospital of Central South University. A total of 287 patients were included in the study. Patients were divided into a normal group (CK-MB ≤25 U/L) and an abnormal group (CK-MB >25 U/L) based on a low CK-MB level. Further clinical and follow- up data were analyzed by using univariate and multivariate logistic regression.Finally, disease-free survival and overall survival were calculated by the Kaplan– Meier method. Results: Multivariate logistic regression demonstrated that CK-MB (OR: 1.023, 95% CI: 1.006-1.040) was an independent risk factor for predicting in-hospital mortality in polytrauma patients with nonmyocardial contusion. Compared with normal CK-MB levels, CK-MB elevation was associated with a longer length of ICU stay (7.38±13.13 vs. 3.16±5.86 days, P =0.004) and total length of hospital stay (24.73±23.04 vs. 18.29±14.63 days, P =0.015) and was more likely to result in arrhythmia during hospitalization (19.29% vs. 10%, P =0.048). Moreover, the follow-up data showed that patients with CK-MB elevation were more likely to have cardiopalmus after discharge (15.00% vs. 5.68%, P =0.027). Conclusion: Our findings suggested that elevated CK-MB played an important role in the prognosis of polytrauma patients with nonmyocardial contusion, and a higher level of CK-MB indicated a poor prognosis.

Engaging in physical activity and exercise is one of the important ways for health promotion.However,older adults are often physically inactive or have a sedentary lifestyle and have poor compliance with physical activity.Exergaming program with their unique advantages could make physical activity a more joyful experience and motivate older adults to participate in physical activity.Promoting older adults'health through engagement in exergaming programs is still in the early stage,and still faces many challenges.Analyzing the challenges and difficulties faced by exergaming program for older adults and exploring in-depth strategies to promote the implementation of exergaming program for older adults are of great significance for the design and implementation of sports games for older adults.

Vissers-Bodmer Syndrome (VIBOS) is an autosomal dominant disorder caused by variants in the CNOT1 gene. It is characterized by systemic developmental and language-motor delay, intellectual disabilities, growth and behavioral abnormalities, hypotonia, and distal skeletal defects, such as deformities of the hands and feet. This syndrome becomes evident during infancy and can display a highly variable phenotype. Thirty-nine individuals with heterozygous de novo CNOT1 variants were first reported in 2019. Herein, we report a child with VIBOS who exhibited delayed motor development for over 4 years, along with hypotonia and atypical facial features. Notably, the patient developed short stature as the primary characteristic without any intellectual disability or organic nervous system lesions. Genetic testing revealed a de novo base duplication variant in exon 5 of the CNOT1 gene, NM_016284.5(CNOT1):c.316_317dup(p.Pro107Serfs*10). Importantly, the pathogenicity of this specific variant has not been reported in relevant literature. This study reports a new variant, thereby enriching the variant spectrum of CNOT1 associated with VIBOS, and contributes to the genetic counseling of affected families.

Catalytic nanomedicine can in situ catalytically generate bactericidal species under external stimuli to defend against bacterial infections. However, bacterial biofilms seriously impede the catalytic efficacy of traditional nanocatalysts. In this work, MoSe2 nanoflowers (NFs) as piezoelectric nanozymes were constructed for dual-driven catalytic eradication of multi-drug-resistant bacterial biofilms. In the biofilm microenvironment, the piezoelectricity of MoSe2 NFs was cascaded with their enzyme-mimic activity, including glutathione oxidase-mimic and peroxidase-mimic activity. As a result, the oxidative stress in the biofilms was sharply elevated under ultrasound irradiation, achieving a 4.0 log10 reduction of bacterial cells. The in vivo studies reveal that the MoSe2 NFs efficiently relieve the methicillin-resistant Staphylococcus aureus bacterial burden in mice under the control of ultrasound at a low power density. Moreover, because of the surface coating of antioxidant poly(ethyleneimine), the dual-driven catalysis of MoSe2 NFs was retarded in normal tissues to minimize the off-target damage and favor the wound healing process. Therefore, the cascade of piezoelectricity and enzyme-mimic activity in MoSe2 NFs reveals a dual-driven strategy for improving the performance of catalytic nanomaterials in the eradication of bacterial biofilms.

BackgroundMotoric cognitive risk syndrome (MCR) is a pre-dementia symptom strongly predicting cognitive decline and dementia. Although advancements in elucidating the epidemiology of MCR, the evidence about the association between sarcopenia, sarcopenia parameters, and MCR remains scarce.ObjectivesThe purpose of this study was to determine the associations between sarcopenia, sarcopenia parameters, and MCR among community-dwelling Chinese older adults.MethodsA total of 4,184 community-dwelling older adults from the China Health and Retirement Longitudinal Study (CHARLS) in the 2011 waves were included. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria. Sarcopenia parameters included handgrip strength (HGS), height-adjusted appendicular skeletal muscle mass (ASM/Ht2), and five-times sit-to-stand test time (FTSSTT). MCR was defined as subjective cognitive complaints and slow gait speed without dementia or impaired mobility. The associations between sarcopenia, sarcopenia parameters, and MCR were conducted using the logistic regression model. The restricted cubic spline with four knots were performed to determine the nonlinear and linear relationships between HGS, ASM/Ht2, FTSSTT, and MCR.ResultsThe prevalence of MCR in wave 2011 of CHARLS was 11.2%. After adjustment for potential confounders, we found sarcopenia [odd ratio (OR) (95% CI): 1.70 (1.13 ~ 2.54), p = 0.011], lower HGS [0.97 (0.96 ~ 0.99), p = 0.001], and more FTSSTT [1.12 (1.10 ~ 1.15), p < 0.001] were significantly associated with a higher risk of MCR. There was an inverse linear dose–response between HGS and MCR (p for overall = 0.008, p for nonlinearity =0.776). The nonlinear relationship between FTSSTT and MCR was found (p for overall <0.001, p for nonlinearity = 0.025) with FTSSTT ≥29 s being associated with a higher risk of MCR. A dose–response relationship was not found between ASM/Ht2 and MCR (p for overall =0.589).ConclusionSarcopenia, lower HGS, and higher FTSSTT are associated with MCR among older adults in China, while the latter two exhibit a dose–response relationship with MCR. It is suggested that timely identification and management of sarcopenia and its parameters may help delay the progression of cognitive impairment and promote healthy aging.

Congenital sodium diarrhea(CSD)is a monogenic disor-der caused by specific genetic defects that increase sodium content in the stool,resulting in intractable diarrhea.The disease was first reported by Holmberg in 1985[1].

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

Genistein, a naturally occurring phytoestrogen and a member of the large class of compounds known as isoflavones, exerts protective effects in several diseases. Recent studies indicate that genistein plays a critical role in controlling body weight, obesity-associated insulin resistance, and metabolic disorders, but its target organs in reversing obesity and related pathological conditions remain unclear. In this study, we showed that mice supplemented with 0.2% genistein in a high-fat diet for 12 weeks showed enhanced metabolic homeostasis, including reduced obesity, improved glucose uptake and insulin sensitivity, and alleviated hepatic steatosis. We also observed a beiging phenomenon in the white adipose tissue and reversal of brown adipose tissue whitening in these mice. These changes led to enhanced resistance to cold stress. Altogether, our data suggest that the improved metabolic profile in mice treated with genistein is likely a result of enhanced adipose tissue function.

Objective:To investigate the clinical characteristic, gene mutations and genotype-phenotype correlation of 21-hydroxylase deficiency (21-OHD) in Hunan.Methods:A total of 48 patients with 21-OHD who were admitted to the Department of Pediatrics, the Second Xiangya Hospital, Central South University from March 2016 to March 2017 were collected.According to the clinical manifestations and biochemical characteristics of the patients, they were divided into salt wasting (SW) and simple virilizing (SV). Sanger sequencing combined with multiplex ligation-dependent probe amplification(MLPA) were used to detect the mutations of CYP21A2 gene.The patients were divided into 3 groups according to their mutations severity: severe mutation group, moderate mutation group and unknown mutation group.Then, the correlation between genotype and phenotype was analyzed. Results:(1) Forty-eight 21-OHD patients included 28 SW cases and 20 SV cases, and the first visiting age of SW was younger than that of SV, and the difference was statistically significant ( U=44.5, P<0.05). The SW cases had high incidence rate of adrenal crisis and the SV patients were liable to advanced bone age and precocious puberty.(2) Forty-four patients were detected abnormal gene mutation and the positive rate of genetic diagnosis was 91.7%.Fourteen mutation types including I2G, Del, I173N, R357W, R484fs(c.1451_1452delGGinsC, c.1450dupC), R483fs, G111Vfs*21, Q319X, c.292+ 1G>A, c.377C>G, E6Cluster, p.H393Q and m. 1647C>T, were found in 88 alleles.The most frequent mutations were I2G(36.4%), I173N(20.4%), and Del(22.7%). p.H393Q and m. 1647C>T were 2 novel mutations.I2G (47.3%) and Del (27.3%) were the most frequent mutations in SW cases, and I173N (48.5%) was the most frequent mutation in SV cases.(3) Severe mutation was in 29 patients, including 26 SW, and moderate mutation was in 13 patients, including 12 SW.The percentage of SW in severe mutation group was 89.7% and SV in moderate mutation was 92.3%. Conclusions:I2G, I173N and Del were the frequent mutations of 21-OHD in Hunan, and the total percen-tage was 79.5%.Genotype of 21-OHD has strong correlation with clinical phenotype, which can effectively predict SW by severe mutation and predict SV by moderate mutation.

Objective:To investigate the behavioral problems of children with congenital adrenal hyperplasia (CAH), and to explore the influencing factors, thus providing evidence for their prevention and interventions.Methods:A case-control study was carried out.A total of 25 children with CAH who were aged 4-16 and regularly followed up in the Outpatient Department of the Second Xiangya Hospital, Central South University from June 1, 2017 to March 31, 2019 were enrolled in the study group, and 50 age-and gender-matched healthy children in Hunan Province were selected as the healthy control group.The parents of the selected subjects were investigated with the Achenbach Child Behavior Checklist (CBCL) to evaluate children′s behavior problems.SPSS 22.0 software was applied to statistical analysis.Results:(1) The scores of externalizing behaviors, aggressive factors and behavior problems in 4-to 5-year-old male children in the CAH group were significantly higher than those in the healthy control group [(12.440±8.353) scores vs.(5.060±5.230) scores, (9.670±6.481) scores vs.(4.110±4.157) scores, (22.110±13.062) scores vs.(12.890±9.405) scores] ( t=2.829, 2.711, 2.109, respectively, all P<0.05). There was no significant difference in the scores of other behavior problems and influencing factors between the CAH group and the healthy control group (all P>0.05). (2) The influencing factor of behavioral problems was progesterone ( β=0.567). Testoste-rone not only was the influencing factor of externalizing and internalizing behaviors ( β=0.582, 0.497, respectively), but also affected the behavior of physical complaints, violation of discipline and social withdrawal ( β=0.735, 0.531 and 0.492, respectively). The factor influencing the schizoid behavior was the initial treatment age ( β=0.402). Conclusions:Four- to 5-year-old male children with CAH have behavioral problems, among which aggression and externalizing behaviors are more common.The increase of testosterone may cause the problems of internalizing and externalizing behaviors in children with CAH, and has a great impact on physical complaints, social withdrawal, and discipline violation.The increase of progesterone may lead to the behavior problems of the children.The older the initial treatment age, the more serious the schizoid behavior problem may be.

OBJECTIVE To study the clinical features of children with adenovirus pneumonia and hemophagocytic lymphohistiocytosis (HLH). METHODS A retrospective analysis was performed on the mediacal data of 7 children with adenovirus pneumonia and HLH from March to September, 2019. RESULTS The age of these children ranged from 11 months to 5 years, and among these children, 5 were aged <2 years and 5 were boys. None of these children had underlying diseases. All children were hospitalized due to persistent high fever and cough, and the peak temperature of fever was 39°C to 41°C. With disease progression, 7 children developed hepatomegaly and 6 developed splenomegaly. Routine blood test results showed reductions in two or three lineages of blood cells, with increases in serum ferritin (SF), C-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH). Phagocytosis of blood cells was observed in 6 children. Radiological examination of lungs showed pneumonia changes. All 7 children were diagnosed with human adenovirus type 7 infection based on pathogenic metagenome detection. No abnormality was found by HLH gene detection and the children were diagnosed with secondary HLH. All children received intravenous immunoglobulin. Among these children, 4 received dexamethasone and etoposide chemotherapy, 3 received dexamethasone alone, and 4 received plasma exchange. Of the 7 children, 2 died and 5 were recovered. Compared with those who survived, the children who died had significantly greater reductions in the three lineages of blood cells and significantly greater increases in serum levels of CRP, PCT, SF, and LDH. CONCLUSIONS The children with adenovirus pneumonia and HLH have main clinical features of persistent high fever, progressive reductions in two or three lineages of peripheral blood cells, and involvement of other organ systems, including hepatosplenomegaly. Significant increases in serum levels of CRP, PCT, SF, and LDH may suggest a poor prognosis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the specific mechanism of the disease remains unknown, and effective treatments are still lacking. It was reported that Nuclear enriched abundant transcript 1 (NEAT1) obviously was up-regulated in NAFLD model. But the role and underlying mechanism of NEAT1 in NAFLD is unclear. Methods: HepG2 cells were treated by free fatty acids (FFA) and C57BL/6J mice were treated by high-fat diet to establish NAFLD in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of NEAT1, ROCK1, and miR-146a-5p. Western blotting and qRT-PCR were used for measuring expression of protein and mRNA level, respectively. Dual luciferase assay was used to detect the target relationship. Oil Red O staining was used to measure the lipid accumulation. HE staining was used for observing pathological feature of liver tissues. Results: High levels of NEAT1 and ROCK1, and low level of miR-146a-5p were identified in NAFLD models. NEAT1 could target miR-146a-5p to promote ROCK1 expression. Knockdown of NEAT1, overexpression of miR-146a-5p and knockdown of ROCK1 inhibited lipid accumulation through activating AMPK pathway. Conclusion: NEAT1 may regulate NAFLD through miR-146a-5p targeting ROCK1, and further affect AMPK/SREBP pathway. This study may provide a new thought for the treatment of NAFLD.