ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

The neurophysiological mechanisms by which exercise improves cognitive function have not been fully elucidated. A comprehensive and systematic review of current domestic and international neurophysiological evidence on exercise improving cognitive function was conducted from multiple perspectives. At the molecular level, exercise promotes nerve cell regeneration and synaptogenesis and maintains cellular development and homeostasis through the modulation of a variety of neurotrophic factors, receptor activity, neuropeptides, and monoamine neurotransmitters, and by decreasing the levels of inflammatory factors and other modulators of neuroplasticity. At the cellular level, exercise enhances neural activation and control and improves brain structure through nerve regeneration, synaptogenesis, improved glial cell function and angiogenesis. At the structural level of the brain, exercise promotes cognitive function by affecting white and gray matter volumes, neural activation and brain region connectivity, as well as increasing cerebral blood flow. This review elucidates how exercise improves the internal environment at the molecular level, promotes cell regeneration and functional differentiation, and enhances the brain structure and neural efficiency. It provides a comprehensive, multi-dimensional explanation of the neurophysiological mechanisms through which exercise promotes cognitive function.
Animals ; Humans ; Brain/physiology* ; Cognition/physiology* ; Exercise/physiology* ; Nerve Regeneration/physiology* ; Neuronal Plasticity/physiology*

Objective : To investigate the effects and underlying mechanisms of high mobility group nucleosome-binding domain protein 2(HMGN2) on lung adenocarcinoma cells. Methods : This work first analyzed the association between HMGN2 and lung adenocarcinoma tissues using The Cancer Genome Atlas(TCGA) database. Lung adenocarcinoma tissues and adjacent normal tissues were collected to compare the differential expression levels of HMGN2. The expression of HMGN2 mRNA in lung adenocarcinoma cell lines A549 and NC-H1299 were detected by qRT-PCR and Western blot. HMGN2 expression was knocked down using si-RNA technology, with the control group transfected with an equivalent amount of NC-siRNA, and the si-RNA group transfected with si-HMGN2. Stable transfected cell lines were established based on si-RNA knockdown efficiency. The effects of HMGN2 knockdown on the growth, movement, and spread of lung adenocarcinoma cells were assessed using CCK-8, Transwell assays, scratch assays, colony formation assays, and EdU assays. Transcriptome sequencing analysis revealed pathways related to tumorigenesis associated with HMGN2. The relative expression levels of MAPK pathway proteins after HMGN2 knockdown were detected by Western blot. Results : HMGN2 mRNA expression was significantly elevated in lung cancer tissues and lung adenocarcinoma cell lines(P<0.05). After HMGN2 knockdown, cell proliferation, migration, and invasion were significantly reduced(P<0.05), and the phosphorylation levels of the MAPK signaling pathway markedly decreased(P<0.05). Conclusion HMGN2 enhances the proliferation, migration, and invasion of lung adenocarcinoma cells, and its mechanism may be closely related to the activation of the MAPK signaling pathwayviaphosphorylation.

Objective To analyze the relationship between different degrees of cerebral venous sinus stenosis and the trans-stenotic pressure gradient using a 3D-printed hemodynamic simulation system for cerebral venous sinuses.Methods Based on the double elastic cavity model,a complete morphological model of the superior sagittal sinus,transverse sinus,and sigmoid sinuses was constructed using 3D printing technology.An in vitro hemodynamic simulation system incorporating pulsatile blood flow was established to simulate the hemodynamic environment of cerebral venous sinus stenosis.Using this system,both unilateral dominant drainage and bilateral balanced drainage were simulated.The degree of stenosis and the pressure upstream and downstream of the stenosis were measured.The pressure difference and pressure ratio were calculated to analyze the correlation between stenosis degree and the trans-stenotic pressure gradient.Results In the unilateral dominant drainage model,as the stenosis severity increased,the upstream pressure increased,whereas the downstream pressure remained relatively stable,leading to an increased pressure gradient between the two ends.The regression equation for stenosis degree(X)and pressure gradient(pressure difference ΔP)was:YΔP=1.962X-1.417(R=0.867,R2=0.753,P<0.001).In the bilateral balanced drainage model of cerebral venous sinuses,when the stenosis degree on one side of the model increased,the pressure gradient between the two ends changed slightly and eventually reached a stable state.The regression equation between X and ΔP was:YΔP=0.62X+1.047(R=0.98,R2=0.96,P<0.001).Conclusions Stenosis in cerebral venous sinuses with unilateral dominant drainage has a more significant impact on the pressure gradient,while unilateral stenosis in bilateral cerebral venous sinuses with balanced drainage has a smaller impact on the pressure gradient.This result suggests that for bilateral venous sinus stenosis,stent implantation can be prioritized in one side of the cerebral venous sinuses.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Objective To investigate the population composition,seasonal dynamics,and infestation levels of cockroaches in Lanzhou,China,and to provide information for the scientific development of cockroach control strategies.Methods Monitoring was conducted at three locations using the sticky trap method.Habitats included farm product markets,catering establishments,hotels,hospitals,and residential areas.Results From 2016 to 2023,the average cockroach density was 0.77 insects per board,with an average infestation rate of 10.84%.Blattella germanica was the dominant species.Seasonal density of cockroaches showed an approximately unimodal distribution,peaking in September.The highest average density and infestation rates were observed in farm product markets.Conclusions Cockroach density and infestation levels in Lanzhou remained relatively low.A comprehensive prevention and control strategy focusing on environmental management in key areas should be implemented according to the seasonal fluctuations.

Objective To analyze the risk factors for increased drainage volume after open transforaminal lumbar interbody fusion(TLIF),and to establish a predictive model and then validate it.Methods The clinical data of 680 patients who underwent open TLIF at the General Hospital of Northern Theater Command from January 2016 to December 2019 were collected and the patients were randomly divided into the training group(n=476)and the validation group(n=204).Taking the predictive factors screened out by LASSO regression analysis as independent variables,a multivariate Logistic regression predictive model was constructed.The model was internally validated through the receiver operating characteristic(ROC)curve,Hosmer-Lemeshow goodness-of-fit test,and calibration curve,and its clinical utility was assessed via decision curve analysis(DCA).Results LASSO regression analysis screened out four predictive variables:age,number of surgical segments,operative duration,and intraoperative blood loss.The multivariate Logistic regression predictive model demonstrated that age≥60 years,number of surgical segments≥4,operative duration≥2 hours,and intraoperative blood loss≥200 mL were independent influencing factors for the increased postoperative drainage volume in patients undergoing TLIF(P<0.05).ROC curve analysis revealed an area under the curve(AUC)of 0.816(95%CI:0.798 to 0.867)in the training group and 0.783(95%CI:0.685 to 0.823)in the validation group,indicating that the predictive model had good discriminatory ability.Additionally,the Hosmer-Lemeshow goodness-of-fit test and calibration curve indicated that the predictive model had a good degree of fit,and the predicted probability was basically consistent with the actual probability,demonstrating a good calibration.The DCA results confirmed that this predictive model could be applied in clinical practice.Conclusion The risk factors for increased drainage volume after open TLIF include age,number of surgical segments,operative duration,and intraoperative blood loss.The predictive model established based on these factors demonstrates good performance,and it can be applied in clinical guidance for the selection of drainage tube removal time after TLIF.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.