ObjectiveThis study aimed to investigate the intervention effect of Renqing Mangjue on the malignant transformation of gastric mucosal epithelial cells induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） and to explore its molecular mechanism in preventing precancerous lesions of gastric cancer based on the cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG）/mitogen-activated protein kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodsHuman gastric mucosal epithelial cells （GES-1） were initially induced by MNNG to establish a precancerous cell model （MC cells）. The effective concentration of MNNG for inducing malignant transformation in GES-1 cells was screened using the cell proliferation activity decection （CCK-8） assay， and the effective concentration of Renqing Mangjue for inhibiting the proliferation of transformed GES-1 cells was also determined. GES-1 cells were divided into a blank control group， a model group， and treatment groups with Renqing Mangjue at concentrations of 1， 3， 10， and 30 mg·L^-1. Furthermore， the effects of Renqing Mangjue on the migratory ability and epithelial-mesenchymal transition （EMT） characteristics of GES-1 malignant transformed cells were evaluated using Transwell migration assays， wound healing assays， and real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR）. Additionally， candidate chemical components and target sites of Renqing Mangjue were obtained from the TCMIP v2.0 database， and disease targets at various stages of gastric cancer precursors were sourced from the Gene Expression Omnibus （GEO） database. Pathway enrichment analysis was performed using the Metascape database to predict the potential mechanisms of action of Renqing Mangjue. Finally， the protective mechanism of Renqing Mangjue against gastric cancer precursors was validated through Western blot analysis. ResultsAt a concentration of 20 μmol·L^-1， MNNG exhibited an inhibition rate of approximately 50% on GES-1 cells （P<0.01）， and at this concentration， the GES-1 cells displayed biological characteristics indicative of malignant transformation. In contrast， Renqing Mangjue had no significant effect on the proliferation of normal GES-1 cells， but significantly inhibited the proliferation of MC cells （P<0.01） and markedly reduced their migratory capacity （P<0.01）. Moreover， it also increased the mRNA expression level of E-cadherin during the EMT process （P<0.05）， while inhibiting the expression of both N-cadherin and the transcription factor Snail mRNA （P<0.05， P<0.01）. Network predictions suggested that Renqing Mangjue may prevent gastric cancer precursors through modulating the cGMP/PKG and MAPK/ERK signaling pathways. Furthermore， Western blot results indicated that Renqing Mangjue upregulated the expression of PKG and NPRB （B-type natriuretic peptide receptor） proteins in the cGMP/PKG pathway （P<0.01）， while downregulating the expression of the downstream proteins MEK and ERK （P<0.05， P<0.01）. ConclusionIn summary， Renqing Mangjue can prevent gastric cancer precursors by inhibiting the proliferation and migration of malignant transformed GES-1 cells， thereby delaying the EMT process. The underlying mechanisms may be related to the activation of the cGMP/PKG pathway and the inhibition of the MEK/ERK signaling pathway.

This study aims to develop a fully automated method for tooth segmentation and root canal measurement based on cone beam computed tomography (CBCT) images, providing objective, efficient, and accurate measurement results to guide and assist clinicians in root canal diagnosis grading, instrument selection, and preoperative planning. The method utilized Attention U-Net to recognize tooth descriptors, cropped regions of interest (ROIs) based on the center of mass of these descriptors, and applied an integrated deep learning method for segmentation. The segmentation results were mapped back to the original coordinates and position-corrected, followed by automatic measurement and visualization of root canal lengths and angles. The results indicated that the Dice coefficient for segmentation was 96.42%, the Jaccard coefficient was 93.11%, the Hausdorff Distance was 2.07 mm, and the average surface distance was 0.23 mm, all of which surpassed existing methods. The relative error of the root canal working length measurement was 3.15% (< 5%), the curvature angle error was 2.85 °, and the correct classification rate of the treatment difficulty coefficient was 90.48%. The proposed methods all achieved favorable results, which can provide an important reference for clinical application.
Cone-Beam Computed Tomography/methods* ; Deep Learning ; Humans ; Dental Pulp Cavity/diagnostic imaging* ; Image Processing, Computer-Assisted/methods*

The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

Evoked Potentials ; Social Isolation ; Attention ; Humans

ObjectiveTo identify the pharmacodynamic material basis of Ruyi Zhenbaowan in relieving neuropathic pain by integrating the calculation of biological network proximity and pharmacokinetic characterization. MethodThe interaction network of "drug candidate target-related gene of disease" was constructed by Cytoscape 3.8.2， and the average shortest path value of each drug putative target acting on neuropathic pain-related genes in this network was calculated by Pesca 3.8.0 tool so as to evaluate the network proximity between them， and screen prescription candidate targets with strong intervention efficiency and their corresponding potential effect components. After that， plasma and cerebrospinal fluid samples were collected from rats after administration of Ruyi Zhenbaowan at set time points， and the contents of potential effect components in samples was quantified by ultra performance liquid chromatography-quadrupole-ion trap mass spectrometry（UPLC-Q-TRAP/MS）， and drug concentration-time curves were plotted， then the pharmacokinetic parameters were calculated by DAS 2.1.1. ResultBy evaluating the network proximity between candidate targets and neuropathic pain-related genes in the interaction network， a total of 40 putative targets of Ruyi Zhenbaowan with strong intervention effects on neuropathic pain-related genes， such as estrogen receptor 1（ESR1）， cyclic adenosine monophosphate（cAMP）-dependent protein kinase catalytic subunit alpha（PRKACA） and protein kinase B1 （Akt1）， and 10 corresponding potential effect components， such as glycyrrhizic acid and betulinic acid， were obtained. Pharmacokinetic characterization showed that among the 10 potential effect components， gallic acid， apigenin-7-O-glucuronide， glycyrrhizic acid and apigenin were well absorbed and metabolized in plasma and cerebrospinal fluid， with long onset time and good bioavailability. ConclusionFrom the perspective of efficacy-target-constituent-pharmacokinetic， this study analyzes the main effective materials of Ruyi Zhenbaowan， such as glycyrrhizic acid， gallic acid， apigenin-7-O-glucuronide and apigenin， which have a high exposure in plasma or cerebrospinal fluid and have a strong intervention effect on neuropathic pain. The related results provide reliable experimental evidences for clarifying the material basis and developing quality standards of Ruyi Zhenbaowan.

OBJECTIVE To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart. METHODS By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1. RESULTS Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01). CONCLUSION Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart. METHODS By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1. RESULTS Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01). CONCLUSION Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.

Objective To explore the left and right ventricular myocardial strain and dyssynchrony in patients with Micra AV leadless pacing implantation,and to further analyze the impact of implantation site on myocardial strain and dyssynchrony.Methods A retrospective study was conducted on 43 patients with Micra AV implantation and 20 patients with high-degree atrioventricular block(Ⅱdegree typeⅡandⅢdegree atrioventricular block)at the Department of Cardiology,Zhongshan Hospital from April 2023 to December 2023.The demographic information and clinical characteristics of the patients were collected.Echocardiography and speckle tracking imaging techniques were used to obtain conventional echocardiographic parameters,myocardial strain,and dyssynchrony indices of patients in the two groups,including global longitudinal strain(GLS),free wall longitudinal strain(FWLS),peak strain dispersion(PSD)of 18 left ventricular segments,PSD of 6 right ventricular segments,and other indices.According to the implantation location of Micra AV,the patients were further divided into middle group(right ventricular septum),high group(right ventricular inflow tract),and low group(apical region),and the differences in myocardial strain and dyssynchrony indices among the three subgroups were compared.Results The left ventricular GLS(LVGLS),right ventricular GLS(RVGLS),and right ventricular FWLS(RVFWLS)of the Micra AV group were significantly lower than those of the conduction block group(P＜0.001),and the right ventricular dyssynchrony of the Micra AV group was significantly higher than that of the conduction block group(P＜0.05).Comparison of myocardial strain and dyssynchrony at different implantation sites showed that the LVGLS of the high implantation group was significantly higher than that of the middle and low implantation groups,and the left ventricular dyssynchrony index Yu was significantly lower than that of the middle group(P＜0.05);the right ventricular ejection fraction(RVEF)of the low implantation group was significantly lower than that of the high group,and the right ventricular 6-segment PSD was significantly higher than that of the middle and high implantation groups(P＜0.05).Conclusions Compared with patients with high-degree atrioventricular block,patients with Micra AV leadless pacing have reduced left and right ventricular strain,and the implantation of low position had greater effect.

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Objective:To observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV).Methods:A retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance.Results:Compared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant ( F=77.402, P<0.001). There was no significant difference in BCVA between any two groups at different time points after treatment ( P>0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease ( r=-0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant ( F=112.480, P<0.001). There were statistically significant differences in different follow-up time before and after treatment ( P<0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion:Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.

This study aimed to explore the effects of akebiaquinata and dandelion extracts in impro-ving intestinal redox homeostasis in weaned rabbits.In the trial,120 35-day-old Ira rabbits weig-hing(1.22±0.08)kg were randomly divided into 4 groups according to the two-factor design,namely group C(basal diet),group D(basal diet+0.5％dandelion extract),group A(basal diet+0.5％akebiaquinata extract),and group DA(basal diet+0.5％dandelion extract+0.5％akebia-quinata extract),with 10 replicates in each group.The adapt period was one week and the experi-mental period was four weeks.At the last day,serum,liver tissue,jejunum and ileal mucosa samples were collected and stored for measurement.The results showed that:(1)First week,the average daily weight gain of group C was significantly lower than that of group D and group A(P＜0.05),and the feed weight ratio was significantly higher than that of group D and group A(P＜0.05).(2)The content of reactive oxygen species(ROS)in liver and serum was significantly reduced in akebiaquinata extract(P＜0.01),and the content of serum ROS in dandelion extract was significantly reduced(P＜0.01),and there were significant and extremely significant interac-tions in liver and serum,respectively.Extracts of akebiaquinata and dandelion were effective in re-ducing the levels of oxidative damage markers in tissues and serum,but increasing the content of malondialdehyde in liver tissues.(3)Akebiaquinata extract significantly increased the activity of glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)in serum(P＜0.01),and significantly reduced the activity of T-AOC in liver(P＜0.01)and superoxide dismutase in je-junum and liver(P＜0.05).Dandelion extract significantly increased the activity of T-AOC in ser-um and GSH-Px in jejunum(P＜0.05).The extracts of akebiaquinata and dandelion had a signifi-cant interaction effect on peroxidase in serum(P＜0.05).(4)The expression of Kelch-like ECH-as-sociated protein 1(Keap1)and NAD(P)H:quinone oxidoreductase 1(NQO1)genes in the jejunum was significantly and extremely significantly reduced by akebiaquinata extract.The extracts of ake-biaquinata and dandelion had significant interaction effects on ileal NQO1,Heme oxygenase1 and Superoxide dismutase 2(P＜0.05)and Keap1(P＜0.01).The expression of NQO1 gene in liver tis-sue was significantly reduced by akebiaquinata extract(P＜0.05).Dandelion and Akebiaquinata ex-tracts can reduce the content of reactive oxygen species in vivo and alleviate oxidative damage.At the same time,dandelion and akebiaquinata extract can work together to regulate antioxidant gene expression and antioxidant enzyme activity through the Nrf2-Keap1 signaling pathway to maintain intestinal redox homeostasis and relieve intestinal oxidative stress.