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.

Objective To evaluate the surgical efficacy of unilateral pneumonectomy for the treatment of tuberculous destroyed lung, analyze the causes of severe postoperative complications, and explore clinical management strategies. Methods A retrospective analysis was conducted on the clinical data of patients with tuberculous destroyed lung who underwent unilateral pneumonectomy at the Public Health Clinical Center of Chengdu from 2017 to 2023. Postoperative severe complications were statistically analyzed. Patients were divided into a non-severe complication group and a severe-complication group, and the causes, management, and outcomes of complications were analyzed. Results A total of 134 patients were included, comprising 69 males and 65 females, with a mean age of 17-73 (40.43±12.69) years. There were 93 patients undergoing left pneumonectomy and 41 patients undergoing right pneumonectomy. Preoperative sputum smear was positive in 35 patients, all of which converted to negative postoperatively. There were 58 patients with hemoptysis preoperatively, and none experienced hemoptysis postoperatively. Postoperative incisional infection occurred in 8 (5.97%) patients, and postoperative pulmonary infection in 26 (19.40%) patients. Severe postoperative complications occurred in 17 (12.69%) patients, including empyema in 9 (6.72%) patients, bronchopleural fistula with empyema in 1 (0.75%) patient, severe pneumonia in 3 (2.24%) patients, postpneumonectomy syndrome in 1 (0.75%) patient, chylothorax in 1 (0.75%) patient, ketoacidosis in 1 (0.75%) patient, and heart failure with severe pneumonia in 1 (0.75%) patient. Perioperative mortality occurred in 2 (1.49%) patients, both of whom underwent right pneumonectomy. Multivariate logistic regression analysis revealed that a history of ipsilateral thoracic surgery, concomitant Aspergillus infection, and greater blood loss were independent risk factors for severe complications following unilateral pneumonectomy for tuberculous destroyed lung (P<0.05). Conclusion Unilateral pneumonectomy for patients with tuberculous destroyed lung can significantly improve the clinical cure rate, sputum conversion rate, and hemoptysis cessation rate. However, there is a certain risk of severe perioperative complications and mortality, requiring thorough perioperative management and appropriate management of postoperative complications.

OBJECTIVE To explore the effects of Polygala tenuifolia compatibility on toxicity， anti-inflammatory and analgesic efficacy of sand-ironing Strychnos nux-vomica （SS）. METHODS The preparation of SS single decoction， SS-P. tenuifolia core-removed （PC） （1∶2.5） or （1∶5） combined decoction， and SS-PC （1∶5） mixture were carried out to investigate their median lethal dose （LD50）. Using aspirin as positive control， the number of writhing movements， analgesic rate， pain latency， ear swelling degree and inflammation inhibition rate induced by the above-mentioned medicinal liquids in mice were compared. The contents of the active and toxic components， strychnine and brucine， in the above-mentioned medicinal liquids were also determined. RESULTS The LD50 values of SS single decoction， SS-PC （1∶2.5） combined decoction， SS-PC （1∶5） combined decoction and SS- PC （1∶5） mixture were 302.00， 614.47， 1 445.44 and 1 778.28 mg/kg， respectively. Compared with control group， the number of writhing movements and ear swelling degree in the mice of the above-mentioned medicinal liquid groups were reduced or decreased significantly （P＜0.05 or P＜0.01）； pain latency [at 90 and 120 minutes in the SS single decoction group， at 60 and 90 minutes in the SS-PC （1∶2.5） combined decoction group， and at 60，90， 120 minutes in the SS-PC （1∶5） combined decoction group and SS-PC （1∶5） mixture group] was significantly prolonged （P＜0.05 or P＜0.01）； analgesic rates of the respective medicinal liquids were 39.30%， 70.87%， 80.00% and 82.46%， and inflammation inhibition rates were 38.08%，TD 57.89%， 76.47% and 50.46%； analgesic and anti-inflammatory effects of combined decoction and mixture were generally better than those of the single decoction （P＜0.05 or P＜0.01）. In the above-mentioned four medicinal liquids， the total contents of strychnine were 0.71%， 0.42%， 0.47% and 0.64%， and the total contents of brucine were 0.88%， 0.63%， 0.57% and 0.88%， respectively. CONCLUSIONS The combination of P. tenuifolia can reduce the toxicity of SS and enhance its anti-inflammatory and analgesic effects. Moreover， there is a tendency for the toxicity-reducing and efficacy-enhancing effects to increase with the increasing dosage of P. tenuifolia. Additionally， the combined decoction of SS and P. tenuifolia can reduce the contents of the active and toxic components， strychnine and brucine， in SS.

Objective:To investigate the predictive value of preoperative aspartate aminotransferase to alanine aminotransferase ratio (AAR) for early recurrence after radical resection of single small hepatocellular carcinoma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 137 patients who underwent radical resection of liver cancer at the General Hospital of Ningxia Medical University from January 2017 to July 2021. These patients were categorized into a recurrence group ( n = 72) and a non-recurrence group ( n = 65) based on early postoperative recurrence. Univariate and multivariate logistic regression analyses were conducted in the training cohort to identify independent risk factors for early recurrence of small hepatocellular carcinomas. Subsequently, the AARs were grouped, and patients with similar propensity scores estimated by the logistic model were matched 1:1 using the Propensity Score Match method with a caliper value of 0.02 to eliminate confounders. Logistic regression analysis was then repeated to assess the predictive value of the matched AAR for postoperative recurrence in patients with single small hepatocellular carcinoma. Results:Univariate analysis revealed that age ( χ2 = 4.22, P = 0.040), the ratio of fibrinogen to albumin ( χ2 = 8.26, P = 0.004), and the AAR ( χ2 = 5.83, P = 0.016) were significantly associated with early recurrence of small liver cancer after radical resection. Multivariate logistic regression analysis further identified age ( P = 0.042), the ratio of fibrinogen to albumin ( P = 0.024), and the AAR ( P = 0.018) as independent risk factors for early recurrence of single small hepatocellular carcinoma following radical surgery. After excluding confounding factors using the Propensity Score Match method, 25 patient pairs were successfully matched. Post-matching logistic regression analysis revealed that an AAR > 0.74 ( P = 0.005) and age > 60 years ( P = 0.024) were independent risk factors for early recurrence in patients with single small hepatocellular carcinoma following radical resection. Conclusion:Preoperative AAR is an independent risk factor for early recurrence in patients with single small hepatocellular carcinoma following surgery, demonstrating excellent predictive value.

Objective To observe the effect of coronary reperfusion therapy on the differential ex-pression of plasma exosomal miRNAs in patients with acute myocardial infarction(AMI).Meth-ods Three elderly male AMI patients undergoing coronary reperfusion therapy in our hospital from October to November 2022 were recruited in this study.The venous blood samples were col-lected at admission and 2 and 24 h after recanalization.MiRNA-sequencing was used to screen the differentially expressed miRNAs which were commonly expressed in the plasma exosomes of the 3 patients.Bioinformatics analysis was performed on the target genes,and then the differentially expressed miR-499a-5p was verified by qPCR.Results Compared with the plasma exosomal miRNAs at admission,there were 418 up-regulated and 406 down-regulated miRNAs at 2 h after operation,and 320 up-regulated and 225 down-regulated miRNAs at 24 h after operation(P＜0.05);Compared with the miRNAs at 2 h after operation,there were 344 up-regulated and 350 down-regulated ones at 24 h after operation(P＜0.05).Kyoto Encyclopedia of Genes and Ge-nomes enrichment analysis showed that the differentially expressed miRNAs were enriched in phosphatidylinositol-3-kinase-protein kinase B,hypoxia-inducible factor 1,and vascular smooth muscle contraction pathways.Gene Ontology analysis indicated that the molecular functions of dif-ferentially expressed miRNA target genes were mainly enriched in protein binding and DNA bind-ing;cellular components were mainly enriched in cell membrane and cytoplasm;and biological processes were mainly enriched in signaling and transcription of DNA templates.The miR-499a-5p level was significantly lower at 2 h postoperatively than at admission[(0.577±0.020)vs(1.000± 0.023),P＜0.05],and at 24 h postoperatively than at 2 h postoperatively[(0.068±0.006)vs(0.577±0.020),P＜0.05].Conclusion Plasma exosomal miRNAs can be used as a biomarker for early diagnosis of elderly AMI patients and for predicting the efficacy of reperfusion therapy.

Based upon the underlying mechanism and pathological evidence of tissue injury of antibody-mediated rejection (AMR) , four etiological and symptomatic therapies were proposed for managing AMR, including etiological treatment of AMR including antibody-targeting, B cell or plasma cell-targeting therapies; strategies for preventing antibody-mediated endothelial damage: an inhibition of complement/antibody dependent cell-mediated pathways; anticoagulant & thrombolytic therapies for thrombotic microangiopathy secondary to endothelial damage ; anti-inflammatory therapies for acute/chronic vascular inflammation secondary to endothelial damage. Etiological treatment is essential for preventing and treating AMR while symptomatic measures, such as anticoagulant, thrombolytic and antiinflammatory therapies, are stressed. Finally the authors devised therapeutic strategies for AMR in 4 different patient groups of non-sensitized allograft recipients, sensitized allograft recipients, individuals with active AMR and those with chronic active AMR.

Objective To prepare asenapine maleate microemulsion gel(ASPM-Emulgel)and evaluate its brain targeting by nasal administration.Methods The prescription composition and dosage of asenapine maleate microemulsion(ASPM-Emul)was determined according to the equilibrium solubility of asenapine maleate(ASPM)in different oils,emulsifiers,co-emulsifiers and the compatibility results of excipients,and ASPM-Emul was prepared into a gel with carbomer 940 as the gel matrix.The particle size distribution and microstructure of ASPM-Emul were investigated.The in vitro release rates and permeability in sheep nasal mucosa of ASPM-Emul and ASPM Emulgel were compared using the Franz diffusion cell method.The nasal ciliary toxicity of ASPM-Emulgel was investigated using the in vivo toad maxillary model method.Brain targeting of ASPM-Emulgel by nasal administration in rats was evaluated.Results According to the results of equilibrium solubility and compatibility,Maisine 35-1,Tween 80 and Transcutol P were selected as the oil phase,emulsifier and co-emulsifier of ASPM-Emul,respectively,with the ratio of 4 ∶ 4 ∶ 2.ASPM-Emul was a light blue semi-transparent microemulsion with a particle size of(73.6±7.4)nm.The microemulsion was regularly spherical and uniformly dispersed under transmission electron microscopy.The results of in vitro release and permeation showed that the release rate of ASPM-Emul was relatively fast,while the release rate of ASPM-Emulgel remained stable.However,the permeability of the two formulations in sheep nasal mucosa was basically similar.ASPM-Emul and ASPM-Emulgel showed no significant toxicity to nasal cilia of toad.Compared with the tail vein ASPM group,the drug content in the brain of ASPM-Emul and ASPM-Emulgel significantly increased after nasal administration,both exhibiting significant brain targeting,and the drug targeting efficiency(DTE)of ASPM-Emulgel was higher.Conclusion The preparation of ASPM into microemulsion gel can significantly improve the brain targeting after nasal administration,and is expected to improve the clinical therapeutic effect of ASPM.

Objective To analyze changes in neuromuscular control during sit-to-stand(STS)in older adults with hallux valgus(HV)through muscle synergy,and thus to explore the effect of falls in older adults with HV.Methods Four groups of subjects were included in this study,13 young controls(YC);12 young HVgroup(HVY);14 healthy elderly controls(EC);and 15 elderly HV group(HVE).All subjects completed the STS maneuver in an armless chair,and EMG data were integrated using non-negative matrix factorization to compare muscle synergies in the YC,HVY,EC,and HVE groups;plantar pressures(COP),ground reaction forces(GRF),and fall scores(FES-I)were collected.Results Compared with YC group,HVY,EC,and HVE groups had lower relative activation amplitude of abductor hallucis and lateral gastrocnemius in STS preparation phase;meanwhile,EC and HVE groups needed more muscle activation to maintain stability of trunk and foot-ankle joints in STS stabi-lization phase;and HVE group needed more co-contractions of thigh muscles to maintain stability of the knee joint.The COP,FES-I of HVE group was higher than that of the other groups(P<0.05).Conclusion In STS,healthy older adults and older adults with HV required more muscle activation to maintain trunk and ankle stability;older adults with HV required more co-contraction of the thigh muscles to maintain knee stability;in addition to this,older adults with HV were more prone to falls.

Objective To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture.Methods From October 2019 to May 2021,14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame,including 9 males and 5 females.The age ranged from 33 to 69 years.All the 14 patients had fresh closed fractures without femur,tibia and fibula fracture.Surgery was complet-ed from 4 to 7 d after hospital admission.During the operation,the X-ray carbon bed was used,the pelvic ring was reduced by Starr pelvis reduction frame,and pelvic ring fracture was treated by orthopedic robot.Operation time,bleeding volume,fluo-roscopy times of single screw placement,fracture reduction quality,affected limb function and complications were observed.Radiological reduction was evaluated using Matta scoring standard,and clinical efficacy was evaluated by Majeed pelvic func-tion scoring system at the final follow-up.Results All of 14 patients successfully completed the operation,the operation time was 84 to 141 min,the bleeding volume was 20 to 50 ml,and the fluoroscopy times of single screw insertion was 4 to 9 times.All of 14 patients were followed up for 12 to 24 months.The healing time was 3 to 7 months.No complications such as fracture of internal fixation,screw loosening,infection and nerve injury were found.According to the evaluation criteria of Matta imag-ing reduction,9 cases were excellent,4 cases were good,and 1 case was fair.At the final follow-up,Majeed pelvic function scoring system was used:10 cases were excellent,4 cases were good.Conclusion The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple,time-saving,less trauma,less complications and effective.

Objective:To investigate the predictive values of clinical test indexes and imaging indexes for early postoperative recurrence of hepatitis B virus (HBV)-related small hepatocellular carcinoma.Methods:Clinical case data of 163 patients with HBV-related small hepatocellular carcinoma undergoing radical hepatectomy at the Department of Hepatobiliary Surgery in the General Hospital of Ningxia Medical University from January 2017 to August 2021 were retrospectively collected. The patients were categorized into 87 cases in an early recurrence group and 76 cases in a non-early recurrence group according to whether or not they had recurrence within 2 years after surgery. After excluding the covariance of various indicators, independent risk factors for postoperative tumor recurrence were established using univariate analysis and multivariate logistic regression analysis. A clinical prediction model was constructed and presented visually in a nomogram diagram, and the predictive ability of the nomogram diagram model was evaluated using receiver operating characteristic curves as well as calibration curves. Cox regression analysis was used to determine the relationship between independent risk factors and time to recurrence.Results:Univariate analysis showed that in the early recurrence group, the number and proportion of patients with preoperative gamma-glutamyl transferase to lymphocyte count ratio (GLR) > 35.79 [41.38% (36/87)], tumor multiplicity [25.29% (22/87)], the presence of peritumoral edema [45.98% (40/87)], intratumoral small arterial clusters [50.58% (44/87)], and age ≥ 60 years [74.71% (65/87)] were significantly higher than those in the non-early recurrence group ( χ2 = 5.73, 3.78, 3.97, 3.73, 3.75, all P < 0.05). Multivariate logistic regression analysis showed that GLR > 35.79 and the presence of peritumoral edema were independent risk factors for early recurrence after radical hepatectomy of HBV-related small hepatocellular carcinomas [odds ratio ( OR) = 2.22, 1.99, 95% confidence interval ( CI): 1.10-4.59, 1.00-3.99, P < 0.05]. The nomogram diagram prediction model was established, with a C index of 0.70 (95% CI: 0.60-0.79) in the receiver operating characteristic curve and a Brier Score of 0.22 in the calibration curve, which demonstrated good model differentiation and accuracy. Cox regression analysis showed that a GLR > 35.79 and the presence of peritumoral edema were risk factors affecting the time to recurrence after resection of HBV-associated small hepatocellular carcinomas. Conclusion:GLR > 35.79 and the presence of peritumoral edema are independent risk factors for early recurrence after radical hepatectomy of HBV-related small hepatocellular carcinoma. The constructed clinical prediction model has good predictive efficacy.