Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

BACKGROUND:Macrophages play a key role in the occurrence and progression of lung diseases,and autophagy plays an important role in maintaining environmental homeostasis and functional stability in macrophages.It has been suggested that macrophage autophagic activity has two sides in lung inflammatory diseases.OBJECTIVE:To summarize the relationship between macrophage autophagy and lung diseases,thereby providing reference for exploring the prevention and treatment strategies of lung inflammatory diseases by targeting macrophage autophagy.METHODS:Literature retrieval was performed in CNKI and PubMed for relevant literature published from database inception to September 2024.The search terms were"macrophage autophagy,efferocytosis,macrophage polarization,acute lung injury,pneumonia,chronic obstructive pulmonary disease,pulmonary fibrosis,asthma"in Chinese and English,respectively.The search results were included or excluded based on the selection criteria,and 100 papers that met the criteria were finally included in the review.RESULTS AND CONCLUSION:(1)The obstruction of autophagy flow will induce the polarization imbalance of macrophages and impair their efferocytosis,resulting in the increase of M1 macrophages and aggravating inflammation.(2)The judgment of autophagic activity should be based on whether the autophagy flow is smooth or not,and it is essential to evaluate the degradation ability of autophagy.Some studies failed to comprehensively detect the degradation ability of autophagy lysosomes to assess whether the autophagy flow is unobtrusive.As a result,the so-called two-sided view of pulmonary macrophage autophagy in pulmonary inflammatory diseases in such studies is actually related to the one-sided judgment of autophagy activity.(3)The pathological manifestations vary across different pulmonary diseases and even at different stages of the same disease.Activation of macrophage autophagy plays a positive role in regulating pulmonary inflammatory homeostasis in conditions such as acute lung injury,infectious pneumonia,mild chronic obstructive pulmonary disease,early-stage pulmonary fibrosis,and secondary asthma.However,in the severe fibrotic stage of chronic obstructive pulmonary disease and the progressive stage of pulmonary fibrosis,the activation of pulmonary macrophage autophagy aggravates pulmonary fibrosis,reflecting the dual nature of macrophage autophagy.In allergic asthma,autophagy is activated in lung-resident macrophages but suppressed in infiltrating monocyte-derived macrophages from circulation.The former is closely related to airway stenosis,and the latter aggravates pneumonia disorders.Therefore,identifying the types and progression stages of lung diseases,along with accurately assessing autophagic activity,is crucial for future investigations into the relationship between macrophage autophagy and disease pathogenesis,thereby facilitating the development of therapeutic strategies in the future.

Triple-negative breast cancer (TNBC) remains a refractory subtype of breast cancer due to its resistance to various therapeutic strategies. In this study, we introduce a "brake-release and accelerator-pressing" approach to engineer a microneedle patch embedded with copper-doped Prussian blue nanoparticles (Cu-PB) and the ferroptosis inducer sorafenib (SRF) for raised chemodynamic (CDT)/photothermal (PTT) combination therapy against TNBC. Upon transdermal insertion, the dissolving microneedles swiftly disintegrate and facilitate the release of SRF. Under gentle external light exposure, copper ions (Cu²⁺) and iron ions (Fe³⁺) were liberated from Cu-PB. The direct chelation of Cu²⁺ and the indirect suppression by SRF, collectively attenuate glutathione peroxidase 4 (GPX4) enzymatic function, destabilizing the cellular redox equilibrium (referred to as the "brake-release" strategy). The release of Cu²⁺ and Fe³⁺ ions instigates a Fenton/Fenton-like reaction within tumor cells, further yielding hydroxyl radicals and elevating reactive oxygen species (ROS) concentrations (referred to as the "accelerator-pressing" strategy). This overwhelming ROS accumulation, coupled with the impaired clearance of resultant lipid peroxides (LPO), ultimately triggers a robust ferroptosis cell death response. In summary, this study presents an innovative combinatorial therapeutic strategy based on dual-ferroptosis induction for TNBC, implying a promising therapeutic platform for developing ferroptosis-centered treatments for this aggressive breast cancer subtype.

Objective To explore the correlation between triglyceride-glucose(TyG)index and hyperuricemia in men with normal fasting blood glucose(FPG)levels.Methods A total of 309 men with normal FPG who participated in a health examination at the Ninth Medical Center of the People's Liberation Army General Hospital in April 2024 were enrolled in this study.All the subjects were divided into the normal uric acid(NUA,n=218)group and the hyperuricemia(HUA,n=91)group according to serum uric acid(SUA)levels.Results Scr,TG,weight,SBP,DBP,BMI,ALT,AST,γ-GGT,and TyG index were higher in the HUA group than in the NUA group(P<0.05).Pearson and Spearman correlation analysis showed that SUA were positively correlated with Scr,eGFR,TG,weight,SBP,DBP,BMI,ALT,AST,γ-GGT and TyG(P<0.05),and negatively correlated with HDL-C(P<0.05).Logistic regression analysis showed that after adjusting for confounding factors,TyG index remained an important influencing factor for HUA.ROC curve analysis showed that the area under the ROC curve of TyG index predicting hyperuricemia in men with normal FPG was 0.665,with an cutoff value of 8.45.Conclusions TyG index in men with normal FPG are influencing factors for hyperuricemia,indicating that hyperuricemia has a close association with insulin resistance,and is an important component of metabolic syndrome.

Objective To determine the effect of limb dominance on landing biomechanics and lower limb functional outcomes in patients with anterior cruciate ligament reconstruction(ACLR).Methods Forty-nine participants were recruited and divided into the ACLR on dominant limb(ACLR-D)group,ACLR on nondominant limb(ACLR-ND)group and healthy control group.Single-leg jump landing,knee isokinetic muscle strength,Y balance,and single-leg hop distance were tested on both limbs of all participants.Kinematics and kinetics data during the single-leg jump landing were collected by an infrared motion capture system and a force platform,and knee joint muscle strength was collected using the isokinetic muscle strength testing system.Two-way mixed-design ANOVAs were used to observe the effects of limb and group on the outcomes of each test.Results The non-surgical limbs had greater knee valgus,knee external rotation angles and knee valgus moments during single-leg jump landing in the ACLR-D group compared with those in the ACLR-ND group,and the ACLR-D group had significantly smaller bilateral knee flexion angles than the control group.There were no differences in knee muscle strength,Y-balance composite scores and single-leg hop distance between ACLR-D and ACLR-ND groups,but the Y balance scores in the ACLR-ND group were smaller than those in the control group.Conclusions Limb dominance has no effects on knee muscle strength,dynamic postural control,and single-leg hop function in ACLR patients.The non-surgical limbs of ACLR-D patients are at a higher risk of ACL injury due to the presence of greater knee valgus and external rotation angles and knee valgus moments.

Objective:To observe the improving effect of acupuncture and Tuina(Chinese therapeutic massage)combined with Ba Duan Jin(Eight-brocade Exercise)on motor function in patients with Parkinson disease(PD)in the early and middle stages.Methods:Seventy patients with early-or middle-stage PD were randomly divided into a control group and an observation group,with 35 patients in each group.The control group was given conventional treatment such as oral levodopa hydrochloride tablets;the observation group was treated with acupuncture,Tuina,and Ba Duan Jin in addition to the control group's treatment.Acupuncture and Tuina were administered twice a week,and Ba Duan Jin was performed five times a week.Each course of treatment lasted 4 weeks,and a total of 3 courses were completed.The changes in the unified Parkinson disease rating scale Ⅲ(UPDRS Ⅲ)score,Berg balance scale(BBS)score,15-meter walking speed,and 6-minute walk distance were compared between the two groups.Results:The total effective rate in the observation group was 93.6%,which was significantly higher than 45.7%in the control group(P<0.01).After 4,8,and 12 weeks of treatment,the UPDRS Ⅲ score in the observation group was significantly lower than the previous score(P<0.05);the BBS score was significantly higher than the previous score(P<0.05),and the 6-minute walk distance also significantly increased compared to the previous result(P<0.05).After 8 and 12 weeks of treatment,the 15-meter walking speed in the observation group was significantly higher than that before treatment and the previous measurement(P<0.05).In comparison with the control group,the observation group showed significantly lower UPDRS Ⅲ scores after 8 and 12 weeks of treatment(P<0.05).Additionally,after 4,8,and 12 weeks of treatment,the observation group had significantly higher BBS scores,15-meter walking speed,and the 6-minute walk distance than the control group(P<0.05).There were no significant differences in the above indicators before and after treatment in the control group(P>0.05).Conclusion:The addition of acupuncture,Tuina,and Ba Duan Jin to Western medication treatment can effectively improve motor function,balance ability,and walking ability in patients with early-or middle-stage PD.

Objective:To explore the prognostic differences between liver resection and transarterial chemoembolization (TACE) in patients with Budd-Chiari syndrome (BCS) complicated by hepatocellular carcinoma (HCC) and to identify independent risk factors affecting patient survival.Methods:The clinical and follow-up data of 103 patients with stage Ⅰa-Ⅲa BCS complicated by HCC treated at the First Affiliated Hospital of Zhengzhou University from Aug 2015 to Sep 2023 were retrospectively analyzed.Results:Patients were divided into two groups based on their initial treatment choices: the liver resection group ( n=20) and the TACE group ( n=83). Before propensity score matching(PSM), the median overall survival in the liver resection group was 42 months longer than in the TACE group (74 months vs. 32 months, P=0.002). After PSM, the median overall survival remained significantly longer in the liver resection group by 39 months (74 months vs. 35 months, P=0.032). In terms of disease-free survival, before PSM, the liver resection group was 30-month longer than the TACE group (42 months vs. 12 months, P=0.001). After PSM, the difference in median disease-free survival between the two groups was 23 months (35 months vs. 12 months, P=0.018). Multivariate Cox regression analysis identified treatment modality and maximum tumor diameter as independent risk factors for overall survival, while treatment modality was the only independent factor for disease-free survival. Conclusions:Liver resection significantly prolongs both overall survival and disease-free survival in resectable HCC in BCS patients compared to TACE. Treatment modality and tumor size are key prognostic factors influencing overall survival.

Objective:To analyze the total amount,institutional flow and development trend of total Traditional Chinese Medicine(TCM)costs in China from 2018 to 2022,and to study the changes of total TCM costs in different primary healthcare institutions.Methods:The total TCM costs were accounted for using the institutional flow method and the case-base aggregation method.Results:From 2018 to 2022,the total TCM costs of primary healthcare organizations in China accounted for a rising proportion,with a stable growth trend,in which the total flow to community and township health centers accounted for a higher proportion,the proportion of total TCM costs of primary institutions in rural areas declined,and there was a negative growth in the village clinics;the growth rate of primary drug costs slowed down,and the growth rate of medical costs showed a wave-like change,with an overall increase in the amount of financial subsidies and subsidies from the higher level.Conclusion:The TCM service capacity of primary healthcare institutions nationwide has been developing steadily,and should continue to expand the existing advantages and build up a solid position for grassroots TCM service in China;the TCM service capacity of China's rural areas still needs to be improved;it is needed to continue to enhance the capacity of primary technical services of Chinese medicine practitioners and rationalizing the role of pharmaceutical services,and the percentage of financial and higher-level subsidies for primary healthcare institutions has been rising fluctuatingly.