ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

Background/Aims: The long noncoding RNA DUXAP8 is a pivotal regulator in cancer pathogenesis, but the molecular mechanism underlying the role of DUXAP8 in colon cancer progression is underexplored. Methods: In addition to bioinformatic analyses, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess DUXAP8, microRNA-378a-3p, FOXQ1 expression in colon cancer tissues, and clinical data were analyzed to determine the correlation between DUXAP8 expression and colon cancer patient outcomes. Nuclear/cytoplasmic RNA fractionation was utilized to analyze the subcellular distribution of DUXAP8. Dual-luciferase and RNA immunoprecipitation assays were performed to confirm the binding of DUXAP8/FOXQ1 and microRNA-378a-3p. After cell transfection, qRT-PCR was performed to evaluate the modulatory relationship of DUXAP8/microRNA-378a-3p/FOXQ1. Cell Counting Kit-8, MTT, scratch healing, and Transwell assays were performed to evaluate the impact of DUXAP8/microRNA-378a-3p/ FOXQ1 expression on colon cancer cell functions. Results: The results revealed that the expression of DUXAP8 and FOXQ1 was upregulated in colon cancer tissues, while the expression of microRNA-378a-3p was down-regulated. The increased DUXAP8 expression was positively correlated with lymph node metastasis and TNM stage. Dual-luciferase and RNA immunoprecipitation assays demonstrated that DUXAP8 was a sponge for microRNA-378a-3p and targeted the ability of microRNA-378a-3p to regulate FOXQ1.In addition, functional experiment results revealed that overexpressed DUXAP8 facilitated the growth and migratory ability of colon cancer cells. DUXAP8 also reversed the tumor-suppressive effect of microRNA-378a-3p. However, silencing FOXQ1 could reverse the cancer-promoting effects of high DUXAP8 expression. Conclusions DUXAP8 expression was significantly increased in colon cancer, which was associated with lymph node metastasis and unfavorable outcomes in colon cancer patients. DUXAP8may hasten malignant progression of colon cancer cells through its effects on microRNA-378a-3p/FOXQ1.

Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

Background/Aims: The long noncoding RNA DUXAP8 is a pivotal regulator in cancer pathogenesis, but the molecular mechanism underlying the role of DUXAP8 in colon cancer progression is underexplored. Methods: In addition to bioinformatic analyses, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess DUXAP8, microRNA-378a-3p, FOXQ1 expression in colon cancer tissues, and clinical data were analyzed to determine the correlation between DUXAP8 expression and colon cancer patient outcomes. Nuclear/cytoplasmic RNA fractionation was utilized to analyze the subcellular distribution of DUXAP8. Dual-luciferase and RNA immunoprecipitation assays were performed to confirm the binding of DUXAP8/FOXQ1 and microRNA-378a-3p. After cell transfection, qRT-PCR was performed to evaluate the modulatory relationship of DUXAP8/microRNA-378a-3p/FOXQ1. Cell Counting Kit-8, MTT, scratch healing, and Transwell assays were performed to evaluate the impact of DUXAP8/microRNA-378a-3p/ FOXQ1 expression on colon cancer cell functions. Results: The results revealed that the expression of DUXAP8 and FOXQ1 was upregulated in colon cancer tissues, while the expression of microRNA-378a-3p was down-regulated. The increased DUXAP8 expression was positively correlated with lymph node metastasis and TNM stage. Dual-luciferase and RNA immunoprecipitation assays demonstrated that DUXAP8 was a sponge for microRNA-378a-3p and targeted the ability of microRNA-378a-3p to regulate FOXQ1.In addition, functional experiment results revealed that overexpressed DUXAP8 facilitated the growth and migratory ability of colon cancer cells. DUXAP8 also reversed the tumor-suppressive effect of microRNA-378a-3p. However, silencing FOXQ1 could reverse the cancer-promoting effects of high DUXAP8 expression. Conclusions DUXAP8 expression was significantly increased in colon cancer, which was associated with lymph node metastasis and unfavorable outcomes in colon cancer patients. DUXAP8may hasten malignant progression of colon cancer cells through its effects on microRNA-378a-3p/FOXQ1.

Background/Aims: The long noncoding RNA DUXAP8 is a pivotal regulator in cancer pathogenesis, but the molecular mechanism underlying the role of DUXAP8 in colon cancer progression is underexplored. Methods: In addition to bioinformatic analyses, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess DUXAP8, microRNA-378a-3p, FOXQ1 expression in colon cancer tissues, and clinical data were analyzed to determine the correlation between DUXAP8 expression and colon cancer patient outcomes. Nuclear/cytoplasmic RNA fractionation was utilized to analyze the subcellular distribution of DUXAP8. Dual-luciferase and RNA immunoprecipitation assays were performed to confirm the binding of DUXAP8/FOXQ1 and microRNA-378a-3p. After cell transfection, qRT-PCR was performed to evaluate the modulatory relationship of DUXAP8/microRNA-378a-3p/FOXQ1. Cell Counting Kit-8, MTT, scratch healing, and Transwell assays were performed to evaluate the impact of DUXAP8/microRNA-378a-3p/ FOXQ1 expression on colon cancer cell functions. Results: The results revealed that the expression of DUXAP8 and FOXQ1 was upregulated in colon cancer tissues, while the expression of microRNA-378a-3p was down-regulated. The increased DUXAP8 expression was positively correlated with lymph node metastasis and TNM stage. Dual-luciferase and RNA immunoprecipitation assays demonstrated that DUXAP8 was a sponge for microRNA-378a-3p and targeted the ability of microRNA-378a-3p to regulate FOXQ1.In addition, functional experiment results revealed that overexpressed DUXAP8 facilitated the growth and migratory ability of colon cancer cells. DUXAP8 also reversed the tumor-suppressive effect of microRNA-378a-3p. However, silencing FOXQ1 could reverse the cancer-promoting effects of high DUXAP8 expression. Conclusions DUXAP8 expression was significantly increased in colon cancer, which was associated with lymph node metastasis and unfavorable outcomes in colon cancer patients. DUXAP8may hasten malignant progression of colon cancer cells through its effects on microRNA-378a-3p/FOXQ1.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective To explore strategies for further subdivision of DRG in gastrointestinal surgery cases,providing references to enhance the differentiation of DRG subgroups.Methods A total of 5 108 gastrointestinal surgery cases were selected from a tertiary grade A hospital and a tertiary hospital in Hubei Province,spanning from January 2019 to June 30,2023,and another secondary hospital's data from 2020 and 2021.It employs single factor analysis and multiple linear regression analysis to identify factors influencing case costs.Additionally,the opinions of nine clinicans were gathered regarding factors affecting resource consumption in gastrointestinal surgery cases.The four selected case groups were further subdivided considers the peak characteristics of disease costs.It compares subdivided groups with the DRG Payment Subgroups Scheme(Version 2.0).Results Groups GB1,GB2,GC1,and GC2 were subdivided into 7,4,7,and 6 DRG groups,respectively.The coefficient of variation of each subdivided DRG were reduced,homogeneity was increased,and inter-group differentiation was increased.The results were consistent with the DRG Payment Subgroups Scheme(Version 2.0).Conclusion Based on DRG grouping,the DRG groups can be further subdivided according to the peak characteristics presented by case costs.This subdivision strategy is helpful to provide new ideas for case grouping of Medicare payment.

AIM To explore the relieving effect of Er Miao Wan on atopic dermatitis in mice.METHODS In vivo experiment:BALB/c mice were randomly divided into normal group,model group,dexamethasone group(2 mg/kg)and high,medium and low dose groups of Er Miao Wan(4.68,2.34 and 1.17 g/kg).The mouse model of atopic dermatitis was established by repeatedly smearing DNCB solution,and the model was given orally for 21 days.The skin lesion condition on the back of mice,ear swelling degree,and the weight difference between ear lobes were observed and recorded.HE staining was used to observe the histopathological changes in the skin lesion tissues of mice.Toluidine blue(TB)staining was used to observe the infiltration of mast cells in skin lesions.The expression of macrophage marker F4/80 in skin lesions was detected by IHC.The serum levels of TSLP,IL-4,IL-5 and total IgE were detected by ELISA.In vitro experiment:RAW264.7 cells in logarithmic growth period were given 400,200 and 100 μg/mL Er Miao Wan for intervention.Cell proliferation was detected by CCK-8 method.NO level in cell supernatant was detected by Griess method.TNF-α,IL-1 β and IL-6 levels in cell supernatant were detected by ELISA method.The expressions of proteins related to the MAPK/NF-κB signaling pathway in cells was detected by Western blot.RESULTS In vivo experiment:Compared with the model group,the scores of back skin lesions,the swelling degree of right ear and the weight difference between left and right ear pieces in the high-dose group of Er Miao Wan decreased(P＜0.05,P＜0.01),the thickness of skin lesions decreased,the infiltration of mast cells and macrophages decreased(P＜0.05,P＜0.01),and the inflammatory factors TSLP,IL-4,IL-5 and total IgE levels in serum decreased(P＜0.05,P＜0.01),and the expression of F4/80 in the skin lesions decreased(P＜0.01).In vitro experiment:Compared with the model group,the levels of NO,TNF-α,IL-1 β and IL-6 in Er Miao Wan 400 and 200 μg/mL groups decreased(P＜0.05,P＜0.01),and the phosphorylation levels of P38,JNK and P65 proteins decreased(P＜0.05,P＜0.01).CONCLUSION Er Miao Wan can alleviate skin lesion inflammation in DNCB-induced atopic dermatitis mice,and its mechanism may be related to inhibiting the activation of MAPK/NF-κB signaling pathway of macrophage,reducing macrophage infiltration and reducing Th2 cytokines.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.