Objective To improve the analysis method of the blood components of Yinchenhao decoction （YCHD） in vivo and explore its anti-hepatocellular carcinoma mechanism. Methods Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry （UPLC-Q-TOF/MS） was used to collect and analyze blood samples from mice. The mice were given a single dose of YCHD with a concentration of 0.1 g/ml and a dose of 25 ml/kg, and then the samples were collected 2 h post–administration, which was to systematically study the chemical components of YCHD in vivo. Network pharmacological methods were used to screen the components and targets of YCHD, and the targets of hepatocellular carcinoma; The common targets of YCHD and hepatocellular carcinoma were identified for GO enrichment and KEGG enrichment. Molecular docking was performed on the main targets to verify the binding ability between the active ingredients and the core targets. The relative mRNA expression levels of serine/threonine-protein kinase（AKT1） and tumor protein p53（TP53） in liver tissues were analyzed via qPCR, including the following mouse groups: mice with concanavalin A（Con-A）-induced acute liver injury without preventive administration, mice with Con-A-induced acute liver injury that received 14 d preventive oral administration of YCHD, and untreated control mice. Results ①The active ingredients of YCHD in the blood were identified by retrieving the data from the in vitro component analysis. They were chrysophanol, herniarin, aloe-emodin, and monotropein. ②The mechanism of action of the blood components against hepatocellular carcinoma （HCC） was further analyzed using network pharmacological methods, and a total of 30 components of YCHD were screened for 213 targets and 215 HCC targets. ③There were 17 intersection targets between YCHD and hepatocellular carcinoma, including AKT1, TP53, receptor tyrosine-protein kinase erbB-2 （ERBB2）, myelocytomatosis oncogene （MYC）, interleukin-1β （IL-1β）, etc. The GO enrichment results indicated that these components were primarily involved in DNA replication，chromosome segregation，leukocyte mediated immunity，leukocyte cell-cell adhesion. The KEGG enrichment results demonstrated that these components were predominantly associated with diverse cancer pathways. Additionally, the results indicated involvement in the citrate cycle （TCA cycle）, pyruvate metabolism, and p53 signaling pathway, ect. ④The results of molecular docking showed that chrysophanol, herniarin, and aloe - emodin had strong binding abilities with AKT1, TP53, ERBB2, MYC, and IL-1β. ⑤The relative expression of AKT1 and TP53 mRNA was significantly higher in the modelling group than in the control group. The relative expression of AKT1 and TP53 mRNA was significantly lower in the drug administration group than in the modelling group. Conclusion There were 4 blood components in YCHD, among which chrysophanol, herniarin, and aloe-emodin may act on AKT1, TP53, ERBB2, MYC, IL-1β and then participated in the regulation of cancer signaling pathways and p53 signaling pathway to play a role in the treatment of HCC.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

The rich club, as a community of highly interconnected nodes, serves as the topological center of the network. However, the similarities and differences in how the rich club supports functional integration and segregation in the brain across different species remain unknown. In this study, we first detected and validated the rich club in the structural networks of mouse, monkey, and human brains using neuronal tracing or diffusion magnetic resonance imaging data. Further, we assessed the role of rich clubs in functional integration, segregation, and balance using quantitative metrics. Our results indicate that the presence of a rich club facilitates whole-brain functional integration in all three species, with the functional networks of higher species exhibiting greater integration. These findings are expected to help to understand the relationship between brain structure and function from the perspective of brain evolution.
Animals ; Humans ; Brain/diagnostic imaging* ; Mice ; Male ; Nerve Net/diagnostic imaging* ; Macaca ; Female ; Neural Pathways/diagnostic imaging* ; Magnetic Resonance Imaging ; Biological Evolution ; Adult ; Diffusion Magnetic Resonance Imaging ; Brain Mapping ; Species Specificity ; Mice, Inbred C57BL

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Rho proteins and the Rho-associated protein kinase(ROCK)signaling pathway are cruci-al components of intracellular signaling cascades.Rho proteins,which belong to the small GTPase family,play a pivotal role in regulating essential elements of the cytoskeleton within cells.ROCK functions as a downstream effector protein kinase of Rho,modulating various biological processes,including cell morphology,migration,and proliferation.Recent studies have underscored the signifi-cance of the ROCK signaling pathway in the replication of a diverse group of viruses.Furthermore,it has been discovered that some viruses disrupt cellular contraction,adhesion,and migration through the Rho/ROCK pathway,subsequently influencing the immune response triggered by vi-ral infections and affecting the tight junctions between cells.This article primarily reviews the re-search progress regarding the Rho/ROCK signaling pathway and its key signaling molecules,Rho and ROCK,in terms of their activation and regulation of viral replication and tight junction pro-teins between cells.

Objective:To develop a laser-induced graphene (LIG)-based multimodal electrochemical sensor for monitoring the burn wound microenvironment and to evaluate its performance.Methods:This study was an experimental study. LIG three-electrode substrates were functionalized with L-lactate oxidase, polyaniline, and sortase A to fabricate lactate sensor, pH sensor, and bacterial sensor, respectively, thereby constituting the LIG-based multimodal electrochemical sensor. An electrochemical workstation was used to assess the electrochemical performance of the lactate sensor and bacterial sensor by cyclic voltammetry, with voltammetric response curves being plotted. An electrochemical workstation was used to assess the lactate sensor's response to lactate by chronoamperometry (with current-time curve being recorded and calibration curve being plotted during the test in the L-lactic acid solution with a molar concentration of 10-60 mmol/L), the pH sensor's response to pH by open-circuit potential measurement (with open-circuit potential-time curve being recorded and calibration curve being plotted during the test in the standard buffer solutions with pH values ranging from 3 to 8), and the bacterial sensor's response to bacteria by differential pulse voltammetry (with current-voltage curve being recorded and calibration curve being plotted during the test in gradient suspensions of Staphylococcus aureus ranging from 1×103-1×10? colony forming unit (CFU)/mL). The sample size for all the above experiments was 3. The correlation analysis was performed on the current value of the lactate sensor and the lactate concentration, the average value of steady-state open circuit potential of the pH sensor and the pH value, and the peak current value of the bacterial sensor and the bacterial concentration value. Each of the prepared standard test system solutions for lactate, pH value, and bacteria were all aliquoted into 30 samples. The lactate concentration, pH value, and bacterial concentration were determined by the lactate sensor and a L-lactate assay kit, the pH sensor and a precision pH meter, and the bacterial sensor and a microvolume spectrophotometer, respectively. Fifteen pairs of matched data were selected according to the random number table method for comparison, and the correlation analysis was performed on the measured values of each sensor and the reference values of the corresponding standard methods. Results:The voltammetric response curves showed that the lactate sensor and the bacterial sensor exhibited distinct oxidation peak currents at oxidation peak potentials of approximately 0.74 and 0.65 V, respectively. In the lactate sensor, the change in current after addition of phosphate buffered solution was (0.025±0.041) μA, which was significantly lower than that after addition of L-lactate solution (0.228±0.117) μA ( t=2.85, P<0.05). In the L-lactic acid solution with a molar concentration of 10-60 mmol/L, the current value of the lactate sensor was significantly linearly correlated with the lactate concentration ( r=0.98, P<0.05). In the standard buffer solutions with pH values ranging from 3 to 8, the average value of steady-state open circuit potential of the pH sensor was significantly linearly correlated with the corresponding pH values ( r=0.96, P<0.05). In gradient suspensions of Staphylococcus aureus ranging from 1×103 to 1×10? CFU/mL, the peak current value of the bacterial sensor was significantly linearly correlated with the logarithm of bacterial concentration ( r=0.95, P<0.05). There were no statistically significant differences between the lactate concentrations measured by the lactate sensor and by the L-lactate assay kit, pH values measured by the pH sensor and by the precision pH meter, and logarithmic bacterial concentrations measured by the bacterial sensor and by the microvolume spectrophotometer ( P>0.05), but there were significant positive correlations between the two (with r values of 0.97, 0.96, and 0.95, respectively, P<0.05). Conclusions:After functional modification, the developed LIG-based multimodal electrochemical sensor enables accurate monitoring of lactate concentration, pH value, and bacterial load in the burn wound microenvironment with the results being of high sensitivity and stability. This platform provides a reliable new approach for non-invasive monitoring of the critical indicators of burn wound microenvironment, which shows great prospects for clinical application.

BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Objective: To examine the mediating effect of resilience on AIDS-related stress and patient-reported outcome among elderly cases with HIV/AIDS, so as to provide the basis for promoting mental health and improving health outcomes of this population. Methods: From June to July 2024, elderly cases with HIV/AIDS receiving treatment in the infectious diseases department of a tertiary-level hospital in Sichuan Province and undergoing follow-up management at 12 community health service centers in Wuhou District, Chengdu City, Sichuan Province, were selected as study participants using convenience sampling method. Data on demographic information, duration since confirmed diagnosis and the most recent CD4+T lymphocyte count were collected through questionnaire surveys. The Chinese versions of the HIV/AIDS Stress Scale, the Chinese versions of the 10-item Connor-Davidson Resilience Scale, and the Patient-Reported Outcome Scale for Elderly HIV/AIDS Patients were used to assess AIDS-related stress, resilience, and patient-reported outcome, respectively. Structural equation modeling was performed using Mplus 8.3 software to analyze the mediating effect of resilience on AIDS-related stress and patient-reported outcome. The Bootstrap method was employed to test the significance of the mediating effect. Results: A total of 424 elderly HIV/AIDS cases were included, with a mean age of (62.04±8.73) years. Among them, 315 (74.29%) were males and 109 (25.71%) were females. The median scores were 23.00 (interquartile range, 11.00) points for AIDS-related stress, 30.00 (interquartile range, 7.00) points for resilience, and 363.45 (interquartile range, 53.03) points for the total score of patient-reported outcome. Resultsof the mediation effect analysis revealed that AIDS-related stress had a direct negative effect on patient-reported outcome (β=-0.608, 95%CI: -0.742 to -0.465). It also exerted an indirect negative effect on patient-reported outcome through the mediating role of resilience (β=-0.258, 95%CI: -0.364 to -0.158), with the mediating effect accounting for 29.79% of the total effect. Conclusion AIDS-related stress among elderly cases with HIV/AIDS can directly or indirectly negatively affect patient-reported outcome through resilience.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective:To investigate the differences in prosthesis implantation accuracy, biomechanical indicators, and 2-year postoperative clinical outcomes between robotic-assisted traditional posterior approach (RA-PLA) and robotic-assisted direct anterior approach (RA-DAA) in total hip arthroplasty (THA).Methods:This study is a prospective randomized controlled trial. Patients with unilateral femoral head ischemic necrosis or primary hip osteoarthritis who meet the inclusion and exclusion criteria and were admitted to the Department of Orthopedics,Xinqiao Hospital, Army Medical University from May to September 2022. Divided into RA-PLA group and RA-DAA group through central randomization. Use cumulative and fitting methods to analyze the learning curve of robotic surgery and eliminate cases before the inflection point of the learning curve. Compare the abduction angle and anteversion angle of acetabular cup implantation between two groups of patients, as well as the rate of falling into the safe zone, the difference in length between the two lower limbs, hip joint eccentricity, rotation center height, the complete accuracy of prosthesis planning (the number of cases in which acetabular cup prosthesis, femoral stem prosthesis specifications, and neck shaft angle were completely consistent with surgical planning during surgery/total cases×100%), patient reported outcome indicators (including Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC), and 12 item Short Form Health Survey (SF-12) score) and clinical outcomes. Data comparison was conducted using independent sample t-test, Wilcoxon rank sum test, chi square test, Fisher′s exact probability method, or repeated measures analysis of variance. Results:A total of 98 patients were included in this study, with 48 in the RA-PLA group and 50 in the RA-DAA group. After excluding cases before the inflection point of the learning curve, 30 patients were included in each group. There was no statistically significant difference in baseline data between the two groups before surgery (all P>0.05). There was no significant difference in the values of the anterior tilt angle and abduction angle between the two groups of acetabular cups compared to preoperative planning (all P>0.05). The proportion of patients who fell into the Lewinnek and Callanan safe zones was 90.0% (27/30) and 96.7% (29/30), respectively ( χ2=0.268, P=0.605). There was no significant difference in postoperative lower limb length, hip joint eccentricity, and rotation center height deviation and grading between the two groups (all P>0.05). The complete accuracy of prosthesis planning in the RA-DAA group was higher than that in the RA-PLA group (86.7% (26/30) compared to 63.3% (19/30), χ2=4.356, P=0.037).All patients were followed up for more than 2 years. In terms of postoperative HHS, WOMAC, and SF-12 score, there was no statistically significant difference in the inter group effect comparison (all P>0.05), but there was a significant statistical significance in the time effect (all P<0.05). There was no significant difference in the incidence of perioperative complications and adverse events between the RA-DAA group and the RA-PLA group (20.0% (6/30) vs. 13.3% (4/30), χ2=0.480, P=0.488). Conclusions:RA-DAA and RA-PLA techniques can achieve similar clinical efficacy after two years of surgery, and both can achieve similar reconstruction accuracy in terms of acetabular cup implantation angle, lower limb length, hip joint eccentricity, and rotation center height. The accuracy of prosthesis planning in RA-DAA is higher.