ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment. The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients, particularly those exposed to adverse social, economic, political, and environmental factors which exacerbate the risk of this disorder. The pathogenesis of depressive disorder is multifaceted, encompassing oxidative stress, neuroplasticity alterations, neuroinflammation, neurotransmitter system imbalances, and intestinal microecological disruptions, among others. Clinically, conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis. This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism. However, the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs. Mitogen-activated protein kinase (MAPK) is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes, including cell growth, differentiation, stress adaptation, and inflammatory response. It is instrumental in maintaining cellular homeostasis and regulating cellular responses. Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis. However, what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear. Modulating MAPK has been shown to influence the onset and progression of depressive disorder, though the precise mechanism remains elusive. Within the MAPK family, aberrant activity of extracellular signal-regulated kinase (ERK) can damage hippocampal neurons and overactivate microglia, precipitating depressive disorder. Excessive activation of c-Jun N-terminal kinase (JNK) results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex, and suppresses the expression of neurotrophic factors. p38, a key regulator in inflammatory reactions, can induce neuroinflammation when overactive, leading to depressive disorder. ERK, JNK, and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules. Consequently, these sub-pathways form a complementary and coordinated regulatory network. In addition, MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets, and there is a lack of identification of their markers and screening for subgroups. The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder, suggesting that MAPK could serve as a potential therapeutic target for this disorder. As for the study of ERK, different models of depressive disorder have contradictory effects on its activity. The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models. In the future, it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder. Research shows that classic clinical drugs, novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway. Research on MAPK remains limited, particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers. Although inhibitors face challenges, they also possess significant advantages and developmental potential. This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder, in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.

Endovascular thrombectomy for acute large-vessel occlusion in patients with active cancer remains a difficult clinical decision. Multiple cohort studies and meta-analyses indicate that, when standard imaging and clinical criteria are applied, reperfusion success is high and symptomatic intracranial hemorrhage is broadly comparable with non-cancer populations, arguing against categorical exclusion. At the same time, registries show lower 90-day functional independence and higher 90-day mortality in active-cancer cohorts—effects likely driven by malignancy-related systemic factors and pre-existing functional compromise rather than procedural harm. This narrative review synthesizes efficacy and safety signals, highlights decision-grade outcomes that are seldom reported—early neurological change, performance status around 90 days, and whether systemic anticancer therapy is started or resumed. It sets out a clinical–ethical–economic framework to support selection, consent, and aftercare, including a pragmatic pathway for under-resourced settings based on non-contrast computed tomography (CT) or single-phase CT angiography where advanced perfusion imaging or magnetic resonance imaging are unavailable. We outline an Asia–Pacific collaborative program designed to identify subgroups that may benefit from reperfusion and initiation of active cancer care.

ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

Objective: o analyze the epidemic characteristics of five sexually transmitted diseases (STDs), including syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infection in Yangzhou City, Jiangsu Province from 2019 to 2023, so as to provide the reference for the prevention and control strategies of STDs. Methods: Data of the onset time and diagnostic types of STDs cases in Yangzhou City from 2019 to 2023 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The temporal, regional and population characteristics of five types of STDs was analyzed using the descriptive epidemiological method. Results: A total of 10 895 cases of STDs were reported in Yangzhou City from 2019 to 2023, with an average annual reported incidence rate of 47.83/105. The average annual reported incidence rates of syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infections were 41.11/105, 2.83/105, 2.59/105, 0.43/105 and 0.85/105, respectively. The reported incidence rate of STDs showed a decreasing trend from 2019 to 2023 (P<0.05), with an average annual growth rate of -3.44%. The reported incidence rates of syphilis and gonorrhea showed a decreasing trend (both P<0.05), with average annual growth rates of -4.26% and -6.47%, respectively. The reported incidence rate of genital Chlamydia trachomatis infection showed an increasing trend (P<0.05), with an average annual growth rate of 22.32%. Baoying County, Guangling District and Hanjiang District had the top three reported incidence rates of STDs, at 56.61/105, 55.61/105 and 46.50/105, respectively. The average annual reported incidence rate of STDs among males was higher than that among females (53.19/105 vs. 42.54/105, P<0.05). The STD cases were primarily people aged 50 years and above, with 6 641 cases accounting for 60.95%. The occupations of STD cases were mainly farmers, housekeepers and unemployed, with 4 670 and 3 273 cases accounting for 42.86% and 30.04%, respectively. Conclusions The overall reported incidence of STDs in Yangzhou City from 2019 to 2023 showed a downward trend, while the reported incidence of genital Chlamydia trachomatis infection showed an upward trend. The individuals aged 50 years and above, farmers, housekeepers and the unemployed were identified as high-risk groups for STDs.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.

OBJECTIVE: To explore the clinical effect of personalized puncture planning before surgery using Picture Archiving and Communication System (PACS) in the treatment of osteoporotic vertebral compression fractures in the elderly. METHODS: A total of 69 elderly patients with osteoporotic vertebral compression fractures treated by percutaneous vertebroplasty from January 2020 20 to December 2021 with more than 1 year of follow-up were analyzed retrospectively. Thirty-four patients were individualized for preoperative planning with PACS software (observation group), including 8 males and 26 females, with a mean age of (73.30±7.96) years old;and 35 patients were treated with conventional treatment (control group), including 7 males and 28 females, with a mean age of (77.30±7.84) years old. The operation time, the amount of cement injection, cement leakage rate, bone watertight diffusion and refracture within 1 year between two groups were observed and compared. The Cobb's angle, low back pain visual analogue scale(VAS) and the modified Oswsetry disability indexes(ODI) before surgery and 1 day, 1 year after surgery were compared between two groups. RESULTS: Both groups successfully completed the operation without serious surgical complications, 2 refractures occurred in the control group. The operation time in the observation group was(41.9±11.9) min, which was less than that in the control group (52.7±13.6) min (P<0.05). There was no significant difference in the cement injection volume between two groups (P>0.05). Two cases of cement leakage in the observation group was less than 8 in the control group (P<0.05). The bone cement distribution index of two groups had significant difference(P<0.05). There were no significant differences between two groups in Cobb's angle of the injured vertebras and ODI before and 1 day after surgery(P>0.05), however, the comparative differences were statistically significant at 1 year after surgery(P<0.05). There was no significant difference in the VAS between two groups at each time period(P>0.05). CONCLUSION Using the PACS software to plan personalized puncture scheme can reduce the operation time, reduce the cement leakage rate, improve the diffusion of bone cement and longer maintain the postoperative form of vertebral body and the functional state of patients' lumbar back.
Humans ; Male ; Female ; Aged ; Vertebroplasty/methods* ; Fractures, Compression/diagnostic imaging* ; Spinal Fractures/diagnostic imaging* ; Osteoporotic Fractures/diagnostic imaging* ; Aged, 80 and over ; Retrospective Studies ; Radiology Information Systems

PURPOSE: Assessing fluid responsiveness relying on central venous oxygen saturation (ScvO₂) yields varied outcomes across several studies. This study aimed to determine the ability of the change in ScvO₂ (ΔScvO₂) to detect fluid responsiveness in ventilated septic shock patients and potential influencing factors. METHODS: In this prospective, single-center study, all patients conducted from February 2023 to January 2024 received fluid challenge. Oxygen consumption was measured by indirect calorimetry, and fluid responsiveness was defined as an increase in cardiac index (CI) ≥ 10% measured by transthoracic echocardiography. Multivariate linear regression analysis was conducted to evaluate the impact of oxygen consumption, arterial oxygen saturation, CI, and hemoglobin on ScvO₂ and its change before and after fluid challenge. The Shapiro-Wilk test was used for the normality of continuous data. Data comparison between fluid responders and non-responders was conducted using a two-tailed Student t-test, Mann Whitney U test, and Chi-square test. Paired t-tests were used for normally distributed data, while the Wilcoxon signed-rank test was used for skewed data, to compare data before and after fluid challenge. RESULTS: Among 49 patients (31 men, aged (59 ± 18) years), 27 were responders. The patients had an acute physiology and chronic health evaluation II score of 24 ± 8, a sequential organ failure assessment score of 11 ± 4, and a blood lactate level of (3.2 ± 3.1) mmol/L at enrollment. After the fluid challenge, the ΔScvO₂ (mmHg) in the responders was greater than that in the non-responders (4 ± 6 vs. 1 ± 3, p = 0.019). Multivariate linear regression analysis suggested that CI was the only independent influencing factor of ScvO₂, with R² = 0.063, p = 0.008. After the fluid challenge, the change in CI became the only contributing factor to ΔScvO₂ (R² = 0.245, p < 0.001). ΔScvO₂ had a good discriminatory ability for the responders and non-responders with a threshold of 4.4% (area under the curve = 0.732, p = 0.006). CONCLUSION ΔScvO₂ served as a reliable surrogate marker for ΔCI and could be utilized to assess fluid responsiveness, given that the change in CI was the sole contributing factor to the ΔScvO₂. In stable hemoglobin conditions, the absolute value of ScvO₂ could serve as a monitoring indicator for adequate oxygen delivery independent of oxygen consumption.
Humans ; Shock, Septic/blood* ; Male ; Female ; Middle Aged ; Prospective Studies ; Oxygen Saturation ; Aged ; Fluid Therapy ; Oxygen/blood* ; Oxygen Consumption ; Adult

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals