Mitochondria, the primary energy-producing organelles of the cell, also serve as signaling hubs and participate in diverse physiological and pathological processes, including apoptosis, inflammation, oxidative stress, neurodegeneration, and tumorigenesis. As semi-autonomous organelles, mitochondrial functionality relies on nuclear support, with mitochondrial biogenesis and homeostasis being stringently regulated by the nuclear genome. This interdependency forms a bidirectional signaling network that coordinates cellular energy metabolism, gene expression, and functional states. During mitochondrial damage or dysfunction, retrograde signals are transmitted to the nucleus, activating adaptive transcriptional programs that modulate nuclear transcription factors, reshape nuclear gene expression, and reprogram cellular metabolism. This mitochondrion-to-nucleus communication, termed “mitochondrial retrograde signaling”, fundamentally represents a mitochondrial “request” to the nucleus to maintain organellar health, rooted in the semi-autonomous nature of mitochondria. Despite possessing their own genome, the “fragmented” mitochondrial genome necessitates reliance on nuclear regulation. This genomic incompleteness enables mitochondria to sense and respond to cellular and environmental stressors, generating signals that modulate the functions of other organelles, including the nucleus. Evolutionary transfer of mitochondrial genes to the nuclear genome has established mitochondrial control over nuclear activities via retrograde communication. When mitochondrial dysfunction or environmental stress compromises cellular demands, mitochondria issue retrograde signals to solicit nuclear support. Studies demonstrate that mitochondrial retrograde signaling pathways operate in pathological contexts such as oxidative stress, electron transport chain (ETC) impairment, apoptosis, autophagy, vascular tension, and inflammatory responses. Mitochondria-related diseases exhibit marked heterogeneity but invariably result in energy deficits, preferentially affecting high-energy-demand tissues like muscles and the nervous system. Consequently, mitochondrial dysfunction underlies myopathies, neurodegenerative disorders, metabolic diseases, and malignancies. Dysregulated retrograde signaling triggers proliferative and metabolic reprogramming, driving pathological cascades. Mitochondrial retrograde signaling critically influences tumorigenesis and progression. Tumor cells with mitochondrial dysfunction exhibit compensatory upregulation of mitochondrial biogenesis, excessive superoxide production, and ETC overload, collectively promoting metastatic tumor development. Recent studies reveal that mitochondrial retrograde signaling—mediated by altered metabolite levels or stress signals—induces epigenetic modifications and is intricately linked to tumor initiation, malignant progression, and therapeutic resistance. For instance, mitochondrial dysfunction promotes oncogenesis through mechanisms such as epigenetic dysregulation, accumulation of mitochondrial metabolic intermediates, and mitochondrial DNA (mtDNA) release, which activates the cytosolic cGAS-STING signaling pathway. In normal cells, miR-663 mediates mitochondrion-to-nucleus retrograde signaling under reactive oxygen species (ROS) regulation. Mitochondria modulate miR-663 promoter methylation, which governs the expression and supercomplex stability of nuclear-encoded oxidative phosphorylation (OXPHOS) subunits and assembly factors. However, dysfunctional mitochondria induce oxidative stress, elevate methyltransferase activity, and cause miR-663 promoter hypermethylation, suppressing miR-663 expression. Mitochondrial dysfunction also triggers retrograde signaling in primary mitochondrial diseases and contributes to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Current therapeutic strategies targeting mitochondria in neurological diseases focus on 5 main approaches: alleviating oxidative stress, inhibiting mitochondrial fission, enhancing mitochondrial biogenesis, mitochondrial protection, and insulin sensitization. In AD patients, mitochondrial morphological abnormalities and enzymatic defects, such as reduced pyruvate dehydrogenase and α-ketoglutarate dehydrogenase activity, are observed. Platelets and brains of AD patients exhibit diminished cytochrome c oxidase (COX) activity, correlating with mitochondrial dysfunction. To model AD-associated mitochondrial pathology, researchers employ cybrid technology, transferring mtDNA from AD patients into enucleated cells. These cybrids recapitulate AD-related mitochondrial phenotypes, including reduced COX activity, elevated ROS production, oxidative stress markers, disrupted calcium homeostasis, activated stress signaling pathways, diminished mitochondrial membrane potential, apoptotic pathway activation, and increased Aβ42 levels. Furthermore, studies indicate that Aβ aggregates in AD and α‑synuclein aggregates in PD trigger mtDNA release from damaged microglial mitochondria, activating the cGAS-STING pathway. This induces a reactive microglial transcriptional state, exacerbating neurodegeneration and cognitive decline. Targeting the cGAS-STING pathway may yield novel therapeutics for neurodegenerative diseases like AD, though translation from bench to bedside remains challenging. Such research not only deepens our understanding of disease mechanisms but also informs future therapeutic strategies. Investigating the triggers, core molecular pathways, and regulatory networks of mitochondrial retrograde signaling advances our comprehension of intracellular communication and unveils novel pathogenic mechanisms underlying malignancies, neurodegenerative diseases, and type 2 diabetes mellitus. This review summarizes established mitochondrial-nuclear retrograde signaling axes, their roles in interorganellar crosstalk, and pathological consequences of dysregulated communication. Targeted modulation of key molecules and proteins within these signaling networks may provide innovative therapeutic avenues for these diseases.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

Objective:To explore the clinical value of the three-dimensional fat suppression fast spoiled gradient echo (3D-FS-FSPGR) MRI sequence in the preoperative evaluation of congenital radial polydactyly.Methods:The data of children with congenital radial polydactyly who underwent surgical treatment in the Department of Orthopedics at Shanxi Children’s Hospital from May 2021 to April 2022 were retrospectively analyzed. Preoperative X-ray examinations and MRI 3D-FS-FSPGR sequence scans were performed on the children. Radiologists first described the morphological characteristics of the articular cartilage, and then orthopedic surgeons performed the Wassel classification based on the X-ray and MRI imaging result, focusing on the bifurcation level, morphology, and articular surface of the phalangeal and metacarpal cartilage. The corresponding surgical method was selected according to the Wassel classification, and intraoperative incision exploration was used as the gold standard. Six months after surgery, the surgical outcome was evaluated using the modified Tada scoring system [with a total score of 0-7, and classified as excellent: >5 points, good: 3-5 points, and poor: <3 points; the excellent and good rate = (excellent + good) cases/total number of cases × 100%]. The appearance, function and recurrence of the operated finger were evaluated 1 year after surgery. Descriptive statistics were performed using SPSS 26.0 software, and the Kappa coefficient was used to evaluate the consistency of the Wassel classification result between radiographs, MRI 3D-FS-FSPGR sequences and intraoperative exploration respectively.Results:A total of 45 children (55 fingers) with congenital radial polydactyly were enrolled, including 25 males and 20 females, aged 5 to 60 months, with the median age of 9 months. Unilateral findings were seen in 35 cases and bilateral findings in 10 cases. MRI 3D-FS-FSPGR imaging sequences clearly demonstrated the level of cartilage bifurcation and bone tissue growth and development, which were consistent with intraoperative exploration findings. The accuracy of the MRI 3D-FS-FSPGR Wassel classification was 100% (55/55), and the accuracy of the X-ray Wassel classification was 81.8% (45/55). Disagreements were found in the classifications of five fingers: three with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅲ, and two with X-ray classifications of Wassel type Ⅳ but actually classified as type Ⅴ. The Kappa coefficients were all >0.85. All patients were followed up for 1 year. The modified Tada score showed excellent in 41 fingers, good in 6 fingers, and poor in 8 fingers, for an excellent and good rate of 85.5% (47/55). At final follow-up, the reconstructed thumbs showed significant improvement in appearance, with normal bone axis restoration, no deviation of the digits, and normal nail appearance. There was no significant scarring or contracture. Functions of thumb flexion, extension, grasping, and opposition were good. There was no postoperative deformity or recurrence.Conclusion:MRI 3D-FS-FSPGR sequences can accurately classify congenital radial polydactyly preoperatively, optimize the surgical incision and osteotomy alignment, and achieve excellent surgical outcomes.

Background: Oxidative stress causes fatal damage to follicular keratinocytes (FKCs) and is a common pathophysiology of many hair disorders. Objective: This study investigated the protective effects of Red ginseng extract (RGE) and its main ginsenosides against oxidative hair damage using an in vitro organ model of human hair follicles. Methods: We examined whether RGE and its constituent ginsenosides could prevent oxidative damage induced by H 2 O 2 in FKCs by suppressing apoptosis and promoting hair growth. Results: RGE and its main ginsenoside, G-Rb1, significantly inhibited reactive oxygen species production and apoptosis in FKCs. Furthermore, they effectively alleviated the inhibition of hair growth induced by oxidative damage and inhibited the transition of hair from the anagen to the telogen stage. The hair cycle and apoptosis were associated with the modulation of p53 and Bax/Bcl2 signaling. Conclusion RGE and G-Rb1 can effectively mitigate the oxidative damage caused by FKCs, thereby affecting hair growth and hair cycles.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective To explore the effects of the Otago Exercise Program(OEP)on activities of daily living,muscle strength,balance,and physical function in older adults with sarcopenia,to compare OEP with conventional exercise training,and to provide a basis for clinical rehabilitation programs for older adults with sarcopenia.Methods In this randomized controlled trial,120 older adults clinically diagnosed with sarcopenia were enrolled.The participants were randomly assigned to the OEP intervention group(experimental group)and the conventional exercise intervention group(control group),with 60 in each group.The experimental group underwent 12 weeks of OEP training,three times a week,with each session lasting 45 minutes.The control group underwent conventional exercise training following the same schedule.The Modified Barthel Index was used as the primary outcome measure to assess activities of daily living.Secondary outcome measures included muscle strength,gait stability,dynamic balance,and physical function status,evaluated using grip strength,6-meter walking speed,the Timed Up and Go Test(TUGT),and the Short Physical Performance Battery(SPPB).Results A total of 120 older adults with sarcopenia were included.The mean age of the participants was(80.17±8.48)years.Baseline data before treatment showed no statistically significant differences between the two groups.Both groups completed the treatment within 12 weeks without experiencing any adverse events.The baseline data for the experimental group were as follows,MBI at(67.00±22.76)points,hand grip strength at(15.29±4.94)kg,gait speed at(0.61±0.26)m/s,TUGT time at(15.05±6.74)s,and SPPB score at(6.17±1.40)points,while the corresponding post-intervention findings were as follows,(78.72±15.83)points,(17.67±5.83)kg,(0.77±0.28)m/s,(13.49±6.16)s,and(9.25±1.71)points,respectively.The experimental group showed improvements in all measures from baseline to post-intervention(P＜0.05 for all measures).As for the control group,the baseline data for the corresponding measures were as follows,(67.20±22.12)points,(15.00±5.35)kg,(0.58±0.23)m/s,(17.29±6.90)s,and(6.00±1.24)points,respectively.The post-intervention findings increased to(71.13±20.28)points,(15.47±5.72)kg,(0.64±0.28)m/s,(16.50±6.99)s,and(6.73±1.61)points,respectively,but the changes were not statistically significant(P＞0.05).Furthermore,an intergroup comparison of intervention effects(post-intervention minus preintervention)revealed significant differences in mean changes from baseline.The experimental group demonstrated improvements of(+11.72±6.32)points in modified Barthel Index,(+11.72±6.32)kg in grip strength,(+0.16±0.09)m/s in gait speed,(—1.56±1.32)s in TUGT time,and(—1.56±1.32)points in SPPB score.In contrast,the control group showed smaller changes of(+3.93±5.65)points,(+0.47±1.37)kg,(+0.06±0.07)m/s,(—0.79±1.54)s,and(+0.73±1.12)points,respectively(all P＜0.05).Intergroup comparisons revealed superior outcomes in the experimental group across all measures.Conclusion OEP significantly enhances activities of daily living,improves muscle strength,balance,and physical function in older adults,and is more effective than conventional rehabilitation exercise programs,making it suitable for extensive clinical application.

Objective:To observe the clinical efficacy and Effects on gastrointestinal dynamics and inflammatory factors levels of combined treatment with electromagnetic stimulation and Shugan Qingwei Tang for reflux esophagitis(RE).Methods:142 cases of liver and stomach depression heat type RE patients who were treated in our hospital from April 2021 to May 2023 were selected.The patients were divided into control group(conventional drug therapy combined with electromagnetic stimulation)and study group(Shugan Qingwei decoction was added to the control group)by random number table method,with 71 cases each.The curative effect,gastrointestinal dynamics indexes,inflammatory factors and adverse reactions were observed between the two groups.Results:Compared with control group after treatment,the clinical total effective rate,serum gastrin(GAS),and motilin(MTL)were higher,while serum tumor necrosis factor-α(TNF-α),c-reactive protein(CRP),interleukin-1β(IL-1β),and interleukin-6(IL-6)were lower in the study group(P＜0.05).There were no obvious adverse reactions between both groups.Conclusion:The combination therapy of Shugan Qingwei Tang and electromagnetic stimulation can improve the clinical treatment effect,improve gastrointestinal function,reduce the level of inflammatory factors,and has good safety for RE patients.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.

Objective:To observe the clinical efficacy and Effects on gastrointestinal dynamics and inflammatory factors levels of combined treatment with electromagnetic stimulation and Shugan Qingwei Tang for reflux esophagitis(RE).Methods:142 cases of liver and stomach depression heat type RE patients who were treated in our hospital from April 2021 to May 2023 were selected.The patients were divided into control group(conventional drug therapy combined with electromagnetic stimulation)and study group(Shugan Qingwei decoction was added to the control group)by random number table method,with 71 cases each.The curative effect,gastrointestinal dynamics indexes,inflammatory factors and adverse reactions were observed between the two groups.Results:Compared with control group after treatment,the clinical total effective rate,serum gastrin(GAS),and motilin(MTL)were higher,while serum tumor necrosis factor-α(TNF-α),c-reactive protein(CRP),interleukin-1β(IL-1β),and interleukin-6(IL-6)were lower in the study group(P＜0.05).There were no obvious adverse reactions between both groups.Conclusion:The combination therapy of Shugan Qingwei Tang and electromagnetic stimulation can improve the clinical treatment effect,improve gastrointestinal function,reduce the level of inflammatory factors,and has good safety for RE patients.

Objective:To provide novel genetic biomarkers for the diagnosis and treatment of sepsis,bioinformatics analysis was used to screen differentially expressed genes and identify Hub genes in sepsis.Methods:Gene Expression Omnibus(GEO)database was used to retrieve gene expression datasets of sepsis and screen for differentially expressed genes(DEGs).Protein-protein interaction(PPI)network analysis,Gene Ontology(GO)analysis,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were used to clarify the molecular mechanism of DEGs,and Hub genes were screened.Results:A total of 361 DEGs were identified,including 163 up-regulated genes and 198 down-regulated genes.Enrichment analysis revealed that these DEGs were primarily involved in antigen processing and presentation,T cell biology,cell adhesion molecules,and T cell receptor signaling pathways.CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1 were determined as optimal diagnostic biomarkers for sepsis.Conclusions:This study elucidated 10 Hub genes(CD4,TP53,PTPRC,LCK,ITGAM,ZAP70,CD247,CD2,CD3E,and HSP90AB1)as potential biomarkers for the diagnosis and treatment of sepsis.However,since the the generalizability of these Hub genes in patients with sepsis remains unvalidated,further experimental verification is still needed in the future.