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.

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.

Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Objective:To explore the clinical manifestations,diagnosis,pathological features and treatment of small-cell carci-noma of the prostate(SCCP).Methods:We conducted a retrospective analysis of the clinical and pathological data of 2 cases of confirmed SCCP treated from November 2017 to March 2018,and reviewed relevant literature.Results:Both the patients had the symptoms of frequent,urgent and difficult urination,with an elevated level of PSA and grades Ⅱ-Ⅲ enlargement of the prostate at palpation.One underwent prostate puncture biopsy and the other received transurethral 1470 laser vaporization resection of the tumor.Postoperative pathology indicated prostate adenocarcinoma accompanied by SCCP in both of the cases.One of them was treated by eto-poside-platinum(EP)chemotherapy and died of systemic multiple organ failure 20 months after diagnosis,while the other underwent endocrine therapy and has lived with tumor up to the present day.Conclusion:The incidence rate of SCCP is low,its malignancy is high,and its prognosis is poor.The average survival of the patient is about 7 to 10 months after diagnosis.Currently there is no effec-tive management of the dissease,except by relying on the experience of the treatment of small-cell lung cancer,with chemotherapy as the main option.

Phthalate esters are plasticizers that people are often exposed to in daily life.They are closely related to our lives and generally exist in the air,soil and water.Studies show that the exposure to phthalates is associated with male reproductive damage.When the concentration of phthalates reaches a certain level in the body,it can reduce the count and motility of sperm,induce abnor-malities in the reproductive system and organs,and affect male fertility.This review summarizes the advances in the studies of the met-abolic pathway of phthalate esters in the human body,the mechanism underlying their damage to the male reproductive system and their antagonistic effect.

Objective To explore the safety and management mode of hysteroscopy in three different modes:outpatient,daily and inpatient.Methods The quality control data of patients who underwent hysteroscopic surgery in Hysterscopy Centre,Obstetrics and Gynecology Hospital,Fudan University from Jan 2019 to Dec 2021 were collected through the electronic information system of the hospital and the monthly quality control report of hysteroscopy center.The amount of surgery,the proportion of grade Ⅳsurgery,the analysis of operation types,the indicator including complications,and unanticipated secondary surgery were retrospectively analyzed.Results From 2019 to 2021,5 162 outpatient hysteroscopic patients,15 331 daily hysteroscopic patients and 5 942 inpatient hysteroscopic patients were admitted in our hospital.The age of inpatient hysteroscopic patients was significantly older than those of outpatient and daily patients(P<0.001).In the past three years,the proportion of daily hysteroscopy gradually increased,and the proportion of inpatient hysteroscopy gradually decreased(P<0.001).The total percentage of grade Ⅳ hysteroscopic surgery was 12.9%,in which inpatient was higher than daily,and daily was higher than outpatient(P<0.001).The incidence of complications and accidents during hysteroscopy was 0.117%(31/26 435),including 17 cases of uterine perforation,7 cases of hysteroscopy failure,3 cases of excessive intraoperative bleeding,2 cases of fluid overload,1 case of intestinal injury,and 1 case of anesthesia accident.The incidence of hysteroscopy in outpatient,daily and inpatient were 0.020%(1/5 162),0.137%(21/15 331)and 0.151%(9/5 942)respectively.Conclusion Hysteroscopy in outpatient,daily and inpatient are all safe and reliable.Outpatient and daily hysteroscopy can improve the efficiency of medical services,which has gradually become a trend.

The purpose of this study was to identify the tick species native to Xindi Township,Yumin County,Xinjiang,China.Preliminary morphological identification of parasitic ticks collected from animals in the area was conducted with an ultra-depth of field three-dimensional VHX 600 digital stereo microscope.Total DNA of the ticks was extracted,amplified by PCR based on the COI and ITS2 gene loci,and the posi-tive PCR products were sequenced.The sequence were a-ligned with reference sequences from the NCBI database were aligned with the Basic Local Alignment Search Tool.A genet-ic phylogenetic tree was generated with the neighbor-joining method of MEGA 7.0 software to determine the evolutionary biological characteristics of ticks.Morphological identification showed that the ticks collected from Xindi Township of Yu-min County were consistent with the characteristics of Hya-lomma asiaticum.An evolutionary tree based on the COI and ITS2 gene sequences showed that the ticks collected in this study were clustered with known H.asiaticum sequences.The PCR products of COI and ITS2 were sequenced and compared,which confirmed that the collected tick species were H.asiaticum,in agreement with the morphological and molecular biological results.These findings help to clarify the distribution of ticks in Xindi Township of Xinjiang,and provide basic data for the analysis of tick genetic and evolutionary characteristics,as reference for surveillance and control of ticks in the Xinjiang Uygur Autonomous Region.

Quinic acid(QA)has antioxidant,anticancer and anti-inflammatory effects,but its pro-tective effect against bovine mastitis remains to be further investigated.The aim of this study was to investigate the inhibitory effects and mechanisms of quinic acid(QA)on lipopolysaccharide(LPS)-induced inflammation and pyroptosis in bovine mammary epithelial cells(MAC-T)and mouse mammary tissues.The CCK-8 method was applied to screen the treatment concentration of QA in MAC-T cells.The ELISA method was used to detect the expression levels of inflammatory factors,oxidative stress factors and pyroptosis indicators.The distribution of CD3 in mouse mam-mary tissues was detected by the immunohistochemical method.p65 nuclear translocation was measured by immunofluorescence.Western blot was performed to test the protein and phosphoryl-ation levels of NF-κB,the inflammasome of NOD-like receptor(NLRP3),Caspase-11 and gasder-min D(GSDMD).The results showed that QA(20,40 and 60 mg/L)significantly increased the activity of MAC-T cells(P＜0.05).QA treatment significantly reduced LPS-induced expression of inflammatory factors(TNF-α,IL-1β and IL 6),oxidative stress indicators(COX-2 and iNOS)and pyroptosis indicators(ROS,LDH and IL-18)in both MAC-T cells and mouse mammary tissues in a manner of dose-dependence(P＜0.05).Moreover,after intraperitoneal injection of QA at 5,10 and 20 mg/kg,respectively,the expression of T-lymphocyte marker CD3 induced by LPS was sig-nificantly downregulated in mouse breast tissues(P＜0.05).In addition,QA significantly de-creased the LPS-induced expression of NF-κB(IκBα,p65,p-IκBα and p-p65),inflammasome(NL-RP3,ASC and Caspase-1),Caspase-11 and DSDMD in both MAC-T cells and mouse mammary tis-sues,and inhibited p65 nuclear transfer in MAC-T cells(P＜0.05).Overall,the above results indi-cate that QA inhibits inflammatory response and pyroptosis through NF-κB and NLRP3 inflamma-some in both MAC-T cells and mouse mammary tissues.The results of this study provide novel da-ta on the prevention and treatment of mastitis by plant active ingredients.

Objective:To investigate the clinical efficacy of continuous veno-venous hemodia-filtration (CVVHDF) combined with hemoperfusion (HP) HA380 in the treatment of heat stroke patients with multiple organ dysfunction syndrome (MODS).Methods:A retrospective and observational study was conducted. A total of 15 patients with heat stroke combined with MODS who were admitted to the department of intensive care unit (ICU)of Suizhou Central Hospital/Hubei University of Medicine from July to September 2022 were selected as the study objects. All 15 patients were treated with CVVHDF combined with HA380 based on the comprehensive management strategy for severe illness. Organ function indicators [including total bilirubin (TBil), aspartate aminotransferase (AST), creatine kinase (CK), lactate dehydrogenase (LDH), creatinine (Cr), cardiac troponin T (cTnT), myoglobin (Myo), MB isoenzyme of creatine kinase (CK-MB), sequential organ failure assessment (SOFA)] and inflammatory indicators [including white blood cell count (WBC), neutrophil count (NEU), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6)] were collected. The improvements of the above indexes at admission, after the first HP, after the second HP, after the third HP, and on the 5th day of treatment were compared. Combined with the clinical outcome of patients, the comprehensive efficacy of CVVHDF combined with HA380 in the treatment of severe heat radiation disease was evaluated.Results:There were 10 males and 5 females among the 15 patients. The average age was (64.5±11.5) years old. There were 6 cases of classical heat stroke and 9 cases of exertional heat stroke. Glasgow coma scale (GCS) was 3-8 at admission; SOFA score was 9-17 within 12 hours after admission; acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) was 25-45 within 24 hours after admission. After treatment, the IL-6 level and SOFA score gradually decreased, and there were significant differences in the decrease after the second HP compared to admission [IL-6 (ng/L): 48.37 (15.36, 113.03) vs. 221.90 (85.87, 425.90), SOFA: 8.3±3.3 vs. 11.1±2.4, both P < 0.05]. The PCT level reached its peak after the first HP [12.51 (6.07, 41.65) μg/L], and then gradually decreased, and the difference was statistically significant after the third HP [1.26 (0.82, 5.40) μg/L, P < 0.05]. Compared those at admission, Cr level significantly improved after the first HP (μmol/L: 66.94±25.57 vs. 110.80±31.13, P < 0.01), Myo significantly decreased after the second HP [μg/L: 490.90 (164.98, 768.05) vs. 3?000.00 (293.00, 3?000.00), P < 0.05], After the third HP, the CK level also showed significant improvement [U/L: 476.0 (413.0, 922.0) vs. 2?107.0 (729.0, 2?449.0), P < 0.05]. After CVVHDF combined with 3 times HP treatment, the patient's inflammatory response was gradually controlled and organ function gradually recovered. On the 5th day of the disease course, WBC, PCT and IL-6 levels were significantly improved compared to admission, and AST, CK, LDH, Cr, Myo, CK-MB, and SOFA score were significantly corrected compared with those on admission. The 24-hour survival rate of 15 patients was 86.67%, and the 24-hour, 7-day and 28-day survival rates were both as high as 73.33%. The average mechanical ventilation time of 11 surviving patients was (101.8±22.0) hours, the average continuous renal replacement therapy (CRRT) time was (58.8±11.0) hours, the average length of ICU stay was (6.3±1.0) days, and the average total hospitalization was (14.6±5.2) days. Conclusion:CVVHDF combined with HP HA380 in the treatment of heat stroke patients with MODS can effectively improve organ function and alleviate the inflammatory storm, which is an effective means to improve the rescue rate and reduce the mortality of severe heat stroke patients.