Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.

Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Objective This study was to develop a HPLC-MS/MS method for determination of etomidate and etomidate acid in blood samples.Methods The blood samples were deproteinized with acetonitrile and supernatant was achieved by shake,sonication,centrifuge and filtration using 0.22 μm membrane.Then,supernatant was performed on an analytical column Poroshell 120 EC-C18(150 mm×3.0 mm,2.7 μm)and flowed with 0.1%formic acid(mobile phase A)and acetonitrile(mobile phase B).The gradient elution at a flow rate of 0.8 mL/min was determined using an electrospray ionization source in positive ion mode and multiple reaction monitoring mode.Results The linearities of etomidate and etomidate acid in blood samples were good within the corresponding range and the correlation coefficients(r)were over 0.9988.The limit of detection(LOD)of etomidate and etomidate acid were 19.94 and 40.25 ng/mL,and the limit of quantitation(LOQ)of them were 50 and 100 ng/mL,respectively.Moreover,matrix effects were ranged from 1.47%to 10.34%and recoveries ranged from 82.81%to 90.07%.The detection of a positive case using our method was successfully determined to be 1 138.89 and 3 126.41 ng/mL for the contents of etomidate and etomidate acid,respectively.Conclusion Our study has further confirmed that this method with simple pretreatment,little sample usage and wide linear range,can be successfully applied to the detection of forensic sciences on etomidate and etomidate acid.

ObjectiveTo investigate effect of conducting training of autism spectrum disorder （ASD） early screening skill on improving the ability to early identify ASD of medical staffs in primary care hospitals. MethodsIn September 2021， the training of ASD early screening skills was carried out for medical staffs from 20 primary care hospitals in Chengdu. After training， the training effect was evaluated. The numbers of referrals from primary care hospitals to superior hospitals， confirmed ASD as well as their average diagnostic age of children with ASD before and after training were used as evaluation indicators. ResultsAfter training， the number of children with suspected ASD referred by primary care hospitals was more than that before training ［（16.65±11.60） vs. （3.40±2.23）， t=5.431， P<0.01］， the number of children diagnosed with ASD was more than that before training［（6.85±4.93） vs. （2.45±1.67）， t=4.171， P<0.01］， and the differences were statistically significant. As for the diagnosed age of ASD children， after training， the average age was lower than that before training ［（34.95±11.67） vs. （42.2±14.64）， t=-2.553， P=0.019］. ConclusionTraining of ASD early screening skills for medical staffs in primary care hospitals may help to improve their ability to early screening ASD children.

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Objective:To explore the clinical application value of MRI in quantitative evaluation of anterior cruciate ligament mucoid degeneration (ACL-MD).Methods:From March to July 2020, 40 patients who were scheduled to undergo arthroscopic treatment were prospectively collected in the First Affiliated Hospital of Kunming Medical University.The anterior cruciate ligament tissue from the lateral edge of the tibial end was taken during the operation. Based on the pathologicalre sults, the patients were divided into the ACL-MD group ( n=19) and the normal group ( n=21). The sagittal plane three-dimensional steady-state rapid precession (3D-FIESTA), T 1 mapping, T 2 mapping, and T 2* mapping were performed before the knee joint surgery, and the scanned images were post-processed and analyzed to measure the T 1, T 2, and T 2* values of the tibial end of the anterior cruciate ligament.The relaxation time of the ACL-MD group and the normal group was compared using independent sample t test. The ROC curve was drawn using each parameter and the areas under the curve (AUC) for the diagnosis of ACL-MD were obtained.DeLong test was used to compare the differences of AUCs. Results:The T 1 [(1 291.9±273.4) ms], T 2 [(54.8±10.6) ms], and T 2* values [(30.6±6.4) ms] of anterior cruciate ligaments in the ACL-MD group were significantly higher than those in the normal group [ (1 087.0±121.0), (44.8±7.1), (20.4±4.8) ms; t=3.011, 3.473, 5.658, all P<0.001]. The AUCs of T 1, T 2, T 2* were 0.747, 0.764, 0.912, sensitivity of 63.2%, 63.2%, 100%, and the specificity of 100%, 95.2%, 76.2% in diagnosing ACL-MD. The AUC of the T 2* value was higher than those of the T 1 and T 2 values, and the differences were statistically significant ( Z=1.734, 2.162, P=0.043, 0.031). Conclusion:T 1, T 2, T 2*values measured by MRI quantitative imaging have high performance in assessing knee joint ACL-MD, and T 2* value has the largest AUC and the highest diagnostic efficiency.

Inhibitory GABAergic interneurons are fundamental elements of cortical circuits and play critical roles in shaping network activity. Dysfunction of interneurons can lead to various brain disorders, including epilepsy, schizophrenia, and anxiety. Based on the electrophysiological properties, cell morphology, and molecular identity, interneurons could be classified into various subgroups. In this study, we investigated the density and laminar distribution of different interneuron types and the co-expression of molecular markers in epileptic human cortex. We found that parvalbumin (PV) and somatostatin (SST) neurons were distributed in all cortical layers except layer I, while tyrosine hydroxylase (TH) and neuropeptide Y (NPY) were abundant in the deep layers and white matter. Cholecystokinin (CCK) neurons showed a high density in layers IV and VI. Neurons with these markers constituted ~7.2% (PV), 2.6% (SST), 0.5% (TH), 0.5% (NPY), and 4.4% (CCK) of the gray-matter neuron population. Double- and triple-labeling revealed that NPY neurons were also SST-immunoreactive (97.7%), and TH neurons were more likely to express SST (34.2%) than PV (14.6%). A subpopulation of CCK neurons (28.0%) also expressed PV, but none contained SST. Together, these results revealed the density and distribution patterns of different interneuron populations and the overlap between molecular markers in epileptic human cortex.
Adolescent ; Adult ; Brain Chemistry ; genetics ; physiology ; Cerebral Cortex ; metabolism ; pathology ; Child ; Cholecystokinin ; metabolism ; Epilepsy ; etiology ; pathology ; Female ; Gene Expression Regulation ; physiology ; Humans ; Interneurons ; metabolism ; Male ; Middle Aged ; Neuropeptide Y ; metabolism ; Parvalbumins ; metabolism ; Phosphopyruvate Hydratase ; metabolism ; Somatostatin ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism ; Young Adult

BACKGROUND/AIMS: Solitary hepatocellular carcinoma (HCC) is a subgroup of HCCs. We aimed to establish nomograms for predicting the survival of solitary HCC patients after hepatectomy. METHODS: A total of 538 solitary HCC patients were randomly classified into training and validation sets. A Cox model was used to identify predictors of overall survival (OS) in the training set. A nomogram was generated based on these predictors and was validated using the validation set. RESULTS: Tumor size, microvascular invasion, and major vascular invasion were significantly associated with OS in the training set. Nomograms were developed based on these predictors in the multivariate analysis. The C-index was 0.75 for the OS nomogram and 0.72 for the recurrence-free survival nomogram. Compared to the index of conventional staging systems for predicting survival (0.71 for Barcelona Clinic Liver Cancer, 0.66 for the seventh American Joint Committee on Cancer, 0.68 for Cancer of the Liver Italian Program, and 0.70 for Hong Kong Liver Cancer), the index of the OS nomogram was significantly higher. Moreover, the calibration curve fitted well between the predicted and observed survival rate. Similarly, in the validation set, the nomogram discrimination was superior to those of the four staging systems (p<0.001). CONCLUSIONS: The nomograms demonstrated good discrimination performance in predicting 3- and 5-year survival rates for solitary HCCs after hepatectomy.
Calibration ; Carcinoma, Hepatocellular* ; Discrimination (Psychology) ; Hepatectomy* ; Hong Kong ; Humans ; Joints ; Liver ; Liver Neoplasms ; Multivariate Analysis ; Nomograms* ; Prognosis ; Survival Rate

Objective To investigate the value of blood oxygenation level dependent(BOLD)fMRI in assessing the functional changes of the lumbar dorsal extensor muscles before and after exercise in healthy young people.Methods The changes of the R2*value of lumbar dorsal extensor group in 30 healthy young volunteers(15 males and 15 females)before and after exercise was prospectively studied.BOLD-fMRI scans were performed on healthy young volunteers before and after exercise, the exercise mode was to perform the upper body flexion and extension movement with a simple Rome stool.The scanned images were processed and analyzed, the cross-sectional area and R2* value of the lumbar dorsal extensor muscles (including the multifidus,the longissimus and the iliocostalis)were measured at the upper margin of the L3 and L4 vertebral body before and after exercise.The paired t test was used to compare CSA and R2*values of muscles before and after loading. The CSA and R2* value of different muscles in different sides were compared by independent sample t test. Pearson correlation analysis was used to analyze the relevance between CSA and R2* in muscle before and after exercise. Results After exercise, the R2* values of multifidus,longissimus and iliocostalis at the upper margin of the L4 vertebral body were[(39.2±8.6),(38.9± 7.7),(41.6±7.8)]Hz,significantly lower than before exercise[(46.1±6.9),(45.3±6.2),(46.0±6.7)]Hz(P<0.01);the changes of R2*values of the muscles between the left and right sides before and after the movements were not statistically significant(P>0.05).The R2*values of longissimus and iliocostalis at the upper margin of the L3 vertebral body were[(44.2±9.1),(46.6±9.3)]Hz,significantly lower than before exercise[(48.6±7.2),(49.7± 6.8)]Hz (P<0.01), but the R2* values of multifidus after loading was (43.9 ± 9.0)Hz, there was no statistical difference compared with before exercise (46.8 ± 6.6)Hz (P>0.05);there was a significant difference in the changes of R2*value before and after the movement between the left and right side of iliocostalis(P<0.05).A significant negative correlation between CSA and R2*value was found in the iliocostalis on the right side at the upper margin of L3 vertebral body and in the multifidus on the left side at the upper margin of L4 vertebral body,and the correlation coefficients were (-0.697,-0.616).Conclusion BOLD-fMRI can be a new way to assess the functional changes of the lumbar dorsal extensor group before and after exercise.

Traditional 3D ultrasound reconstruction system can just depict 3D anatomical structure, so it is very difficult to give an accurate assessment of the functionality of the heart. In this study, a dynamic 3D reconstruction method of tissue Doppler ultrasound heart images is set up based on the combination of 3D reconstruction and tissue Doppler imaging technique. Dynamic 3D acceleration field of heart movement is reconstructed to supply a new approach of accurate assessment of functionality of the heart. The key problem of vector interpolation and fusion imaging in the process of acceleration vector field reconstruction is solved. The 3D acceleration field of heart movement and anatomical structure is reconstructed separately from the original tissue Doppler acceleration images and showed in the same field. The experimental results testified that the 3D space relationship of acceleration and anatomical structure is correct and this method can supply more information for the assessment of heart functionality.
Echocardiography, Doppler ; Heart ; anatomy & histology ; Humans ; Image Processing, Computer-Assisted ; Movement