Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-Specific Transcriptome and Molecular Subtype.

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predicted consensus molecular subtypes in patients with metastatic colorectal cancer. Analysis of plasma evRNA also enabled monitoring of changes in transcriptomic subtype under treatment selection pressure and identification of molecular pathways associated with recurrence. This approach also revealed expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of using transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to the identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling. SIGNIFICANCE: The development of an approach to interrogate molecular subtypes, cancer-associated pathways, and differentially expressed genes through RNA sequencing of plasma extracellular vesicles lays the foundation for liquid biopsy-based longitudinal monitoring of patient tumor transcriptomes.

Modulating Th1/Th2 drift in asthma-related immune inflammation by enhancing bone mesenchymal stem cell homing through targeted inhibition of the Notch1/Jagged1 signaling pathway.

Asthma, a disease intricately linked to immune inflammation, is significantly influenced by the immune regulatory effect of bone mesenchymal stem cells (BMSCs). This study aims to investigate changes in the homing of BMSCs in bronchial asthma, focusing on the Notch homolog (Notch)1/Jagged1 signaling pathway's role in regulating T helper 1(Th1)/T helper 2(Th2) drift. Additionally, we further explore the effects and mechanisms of homologous BMSCs implantation in asthma-related immune inflammation. Following intervention with BMSCs, a significant improvement in the pathology of rats with asthma was observed. Simultaneously, a reduction in the expression of inflammatory cells and inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin(IL)-4, and IL-13 was observed in bronchoalveolar lavage fluid (BALF). Furthermore, there was an increase in the expression of Th1 cytokine Interferon-γ（IFN-γ）and the transcription factor T-box expressed in T cell (T-bet), while the expression of Th2 cytokine IL-13 and transcription factor GATA binding protein (GATA)-3 decreased in lung tissue. This indicates that the Th1/Th2 drift leans towards Th1, which a crucial in ameliorating asthma inflammation. Importantly, inhibition of the Notch1 signaling pathway led to an increased expression of the Stromal cell-derived factor-1(SDF-1)/C-X-C motif chemokine receptor (CXCR)4 chemokine axis. Consequently, the homing ability of bone marrow mesenchymal stem cells to asthma-affected lung tissue was significantly enhanced. BMSCs demonstrated heightened efficacy in regulating the cytokine/chemokine network and Th1/Th2 balance, thereby restoring a stable state during the immune response process in asthma. In conclusion, inhibiting the Notch signaling pathway enhances the expression of the SDF-1 and CXCR4 chemokine axis, facilitating the migration of allogeneic BMSCs to injured lung tissues. This, in turn, promotes immune regulation and improves the Th1/Th2 imbalance, thereby enhancing the therapeutic effect on asthmatic airway inflammation.

Discrete element simulation of vibration compaction of slag subgrade.

In this study, to improve the compaction quality and parameters of slag, discrete element models of irregular rock particles (10-60 mm) and circular soil particles (5 mm) were established based on on-site slag screening results. The motion of the vibratory roller was captured by coupling the roadbed model with the roller model in a simulation in which the roller vibrated and compacted the slag subgrade. The results indicated that (1) the best compaction was achieved when the small particle content was 40%, the medium particle content was 20%, and the large particle content was 40%. (2) When the slag was dominated by small rock particles, the optimum compaction frequency was 28 Hz, and when large rock particles dominated, the optimum compaction frequency was 33 Hz. (3) Rock particles were the primary particles that experienced stress in the vibration compaction, and the compressive force and displacement depended on the particle size. (4) The longitudinal and vertical displacements and rotation angles of the soil and rock particles were examined. The results of this study are conducive for advancing the understanding of slag compaction and improving the working efficiency and compaction quality of rollers.

Study of the mechanism of action of sand therapy on atherosclerosis based on the two-phase flow-Casson model.

BACKGROUND: Sand therapy is a non-pharmacological physiotherapy method that uses the natural environment and resources of Xinjiang to treat through the heat transfer and magnetic effects of sand. OBJECTIVE: Employing the two-phase flow-Casson blood flow model, we investigate the mechanism of atherosclerosis prevention via sand therapy, offering a biomechanical theoretical rationale for the prevention of atherosclerosis through sand therapy via the prism of computational fluid dynamics (CFD). METHODS: Sand therapy experiments were conducted to obtain popliteal artery blood flow velocity, and blood was considered as a two-phase flow composed of plasma and red blood cells, and CFD method was applied to analyze the hemodynamic effects of Casson's blood viscosity model before and after sand therapy. RESULTS: (1) The blood flow velocity increased by 0.24 m/s and 0.04 m/s at peak systolic and diastolic phases, respectively, after sand therapy; the axial velocity of blood vessels increased by 28.56% after sand therapy. (2) The average red blood cell viscosity decreased by 0.00014 Pa ⋅ s after sand therapy. (3) The low wall shear stress increased by 1.09 Pa and the high wall shear stress reached 41.47 Pa after sand therapy. (4) The time-averaged wall shear stress, shear oscillation index and relative retention time were reduced after sand therapy. CONCLUSION: The increase of blood flow velocity after sand therapy can reduce the excessive deposition of cholesterol and other substances, the decrease of erythrocyte viscosity is beneficial to the migration of erythrocytes to the vascular center, the increase of low wall shear stress has a positive effect on the prevention of atherosclerosis, and the decrease of time-averaged wall shear stress, shear oscillation index and relative retention time can reduce the occurrence of thrombosis.

Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Clinical characteristics and influencing factors of chronic obstructive pulmonary disease in patients with non-small cell lung cancer in Hubei province / 公共卫生与预防医学

Objective To analyze the clinical characteristics and influencing factors of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) in Hubei province, and to provide a theoretical basis for the diagnosis and treatment of NSCLC patients with COPD. Methods A total of 246 NSCLC patients admitted to our hospital from 2018 to 2020 were selected and divided into control group (without COPD, n=125) and observation group (with COPD, n=121) according to COPD. The clinical characteristics of chest pain, hemoptysis, emasculation, atelectasis and pleural effusion were compared between the two groups. The values of FEV1/FVC, RV/TLC and DLCO in the two groups were measured by pulmonary function detector. The age, gender, smoking, smoking history, proportion of lung squamous cell carcinoma, TNM stage and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression were used to analyze the risk factors of COPD in NSCLC patients. Results Among 246 NSCLC patients, 121 patients (49.19%) were complicated with COPD, including 76 males and 45 females, and there was a statistical difference between the two groups (χ2=4.891, P>0.05). The average age of the observation group (61.02±4.82) was significantly higher than that of the control group (59.76±4.73) (t=2.069, P0.05). Male (OR=2.982), smoking history (OR=2.623) and lung squamous cell carcinoma (OR=3.147) were risk factors for COPD in NSCLC patients (P<0.05). Conclusions NSCLC patients with COPD are more common in male smokers in Hubei Province, often accompanied by pleural effusion , severe hemoptysis and other symptoms , and their lung function is decreased. Early detection and standardized treatment of COPD in the treatment of NSCLC can improve the prognosis of patients.

Electroacupuncture ameliorates cardiac dysfunction in myocardial ischemia model rats: a potential role of the hypothalamic-pituitary-adrenal axis.

OBJECTIVE: To verify the hypothesis that electroacupuncture inhibits the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis regulating the expression of glial fibrillary acidic protein (GFAP) in the hippocampus of acute myocardial ischemia (AMI) rats. METHODS: Sixty-six healthy male Sprague-Dawley rats were randomly divided into five groups: Sham, AMI (Model), electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment (EA), non-acupoint electroacupuncture (Control), and Model + corticosterone (Model + CORT). AMI was induced occlusion of the left anterior descending coronary artery, followed by 3 d of electroacupuncture at Shenmen (HT7)-Tongli (HT5) segment. In the Control group, electroacupuncture was applied at points lying 5 and 10 mm from the base of the tail. The AMI + CORT group was injected with CORT (20 mg/kg) in saline. Hemorheology, electrocardiography (ECG), hematoxylin and eosin staining, and expression of glycogen phosphorylase BB (GPBB) and heart-type fatty acid-binding protein (H-FABP) were used to assess cardiac function. The effects of adrenocorticotropic hormone (ACTH) and CORT were evaluated by enzyme-linked immunosorbent assay. Protein expression in the Sham and Model groups were screened by tandem mass tag-based quantitative proteomics analysis. Protein expression was evaluated by Western blotting (vimentin and GFAP) and immunofluorescence staining (GFAP). RESULTS: Compared with the Sham group, the hemorheology indicators, heart rate, ECG-ST segment elevation, and GPBB and H-FABP levels were higher in Model rats. The EA group showed reductions in these indicators compared with the Model group. Similarly, in Model rats, the expression of ACTH and CORT were significantly increased compared with the Sham group. The EA group also showed reduced expression of ACTH and CORT. Importantly, proteomics analysis showed that vimentin was differentially expressed in Model rats. Compared with the Sham group, vimentin and GFAP expression in the hippocampus was increased in the Model group but decreased in the AMI + EA group. Additionally, intraperitoneal injection of CORT aggravated the expression of GPBB, H-FABP and GFAP. CONCLUSIONS: Our results suggested that electroacupuncture may protect against cardiac injury induced by AMI through regulation of HPA axis hyperactivity, and that hippocampal GFAP may play an important role in the regulation.

Programmable DNA hydrogel provides suitable microenvironment for enhancing autophagy-based therapies in intervertebral disc degeneration treatment.

The pathogenesis of intervertebral disc degeneration (IVDD) is attributed to metabolic dysregulation within the extracellular matrix and heightened apoptosis of nucleus pulposus cells (NPC). Therefore, a potential therapeutic strategy for managing IVDD involves the reestablishment of metabolic equilibrium within the extracellular matrix and the suppression of excessive myeloid cell apoptosis. The microRNA, miR-5590, displays marked differential expression in degenerative nucleus pulposus (NP) tissues and exerts a direct influence on the regulation of DDX5 expression. This, in turn, modulates mammalian target of rapamycin (mTOR) phosphorylation, thereby impacting autophagy and apoptosis. However, ensuring the smooth delivery of miRNA to a specific injury site poses a significant challenge. To address this issue, a multifunctional DNA hydrogel was developed and subsequently loaded with miR-5590 via spherical nucleic acids (SNAs) for the treatment of IVDD. The hydrogel, which exhibits versatility, has the potential to be administered through injection at the site of injury, resulting in a consistent and prolonged release of miR-5590. This leads to the creation of a genetic microenvironment within the NP, which triggers the onset of autophagy in NPCs and subsequently suppresses apoptosis. As a result, this process regulates the metabolic equilibrium within the extracellular matrix, thereby impeding the in vitro and in vivo progression of IVDD. The amalgamation of miRNAs and biomaterials offers a promising therapeutic strategy for the management of IVDD in clinical settings.

Comparative analysis of clinicopathological characteristics of central necrotizing breast cancer and basal cell-like breast cancer.

Purpose: This study aims to compare the clinicopathological and immunohistochemical characteristics of centrally necrotizing carcinoma of the breast (CNC) and basal-like breast cancer (BLBC), as well as to analyze the characteristics of the molecular typing of the CNC. Methods: The clinicopathological features of 69 cases of CNC and 48 cases of BLBC were observed and compared. EnVision immunohistochemical staining was performed to detect the expressions of hypoxia-inducible factor 1α (HIF-1α), breast cancer susceptibility gene 1 (BRCA1), and vascular endothelial growth factor (VEGF) in CNC and BLBC. Results: The age of the 69 patients ranged from 32 to 80 years, with an average of 54.55 years. Gross examination showed that most tumors were well-defined single central nodules with a diameter of 1.2~5.0 cm. Microscopically, there is a large necrotic or acellular area in the center of the tumor, mainly composed of tumor coagulative necrosis with varying degrees of fibrosis or hyaline degeneration. A small amount of cancer tissue remained in the form of a ribbon or small nest around the necrotic focus. Among 69 cases of CNC, the proportion of basal cell type (56.5%) was significantly higher than that of lumen type A (18.84%), lumen type B (13.04%), HER2 overexpression (5.8%), and nonexpression (5.8%). A total of 31 cases were followed up for 8~50 months, with an average of 33.94 months. There have been nine cases of disease progression. When compared to BLBC, there were no significant differences in BRCA1 and VEGF protein expression in response to CNC (p > 0.05), but there were significant differences in protein expression in HIF-1α (p < 0.05). Conclusion: The molecular typing of CNC showed that over half of those were BLBC. No statistically significant difference in the expression of BRCA1 was observed between CNC and BLBC; thus, we predict that targeted therapy for BRCA1 in BLBC may also have considerable effects in CNC patients. The expression of HIF-1α is significantly different in CNC and BLBC, and perhaps HIF-1α can be used as a new entry point to distinguish between the two. There is a significant correlation between the expression of VEGF and HIF-1α in BLBC, and there was no significant correlation between the expression levels of the two proteins in CNC.

Influence of the Anatomical Structure on the Hemodynamics of Iliac Vein Stenosis.

Few reports study the effects of the anatomical structure of the iliac vein on hemodynamics and the methods to reduce and delay in-stent thrombosis. The anatomical structure of iliac vein stenosis was used to establish vascular models with different stenosis rates, taper angle, and left branch tilt angle in the work. The influence of anatomical structure on hemodynamics was revealed through theoretical research and in vitro experimental verification. A real iliac vein model was built based on computed tomography angiography (CTA) images, and hemorheological parameters including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI) and relative residence time (RRT) were analyzed by computational fluid dynamics (CFD). The results showed that iliac vein stenosis could significantly increase the wall shear stress (WSS) of the blood vessels at the stenosis site and outside the intersection area, which was easy to produce eddy currents in the distal blood vessels. With the increased taper angle, the proportion of low-wall shear stress areas and the risk of thrombosis increased. A small tilt angle could aggravate the influence of narrow blood vessels on the blood flow characteristics and vascular wall. The numerical simulation results were consistent with the theoretical research results, and the experimental study verified the correctness of the simulation. The work is helpful to further understand the hemodynamic characteristics of the iliac vein, providing a scientific reference for clinical treatment and diagnosis.

Return to sports WeChat applet for evaluating the rehabilitation effects after anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To clarify the intervention guidance of return to sports WeChat applet and evaluate the rehabilitation effectiveness after anterior cruciate ligament (ACL) reconstruction.@*METHODS@#Between September 2020 and September 2022, 80 patients who met the selection criteria and underwent ACL anatomical single bundle reconstruction were selected as the research objects. According to the double-blind random method, they were divided into the applet group and the regular group, with 40 cases in each group. Patients in the applet group were rehabilitated under the guidance of the return to sports WeChat applet, and the patients were asked to perform the test once a month after operation, including patients' subjective scores [Tegner score, knee injury and osteoarthritis outcome score (KOOS), International Knee Documentation Committee (IKDC) score, American Hospital for Special Surgery (HSS) score], psychological assessment [ACL recovery sports injury scale (ACL-RSI) score], jumping test, balance test, bending angle test. Patients in the regular group were followed up by doctors and nurses regularly by telephone every month. All the patients were reexamined at 3, 6, 9, and 12 months after operation, and the range of motion of the knee joint with 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, and internal and external displacement) recorded by Opti_Knee three-dimensional knee joint motion measurement gait analysis system was observed. The anterior tibial translation difference (ATTD) was measured by Ligs knee measuring instrument when a forward thrust of 120 N was applied to the posterior part of the proximal tibia. Tegner score, IKDC score, KOOS score (including KOOS-Pain score, KOOS-Symptoms score, KOOS-Activities of daily living score, KOOS-Sport score, and KOOS-Quality of life score), HSS score, ACL-RSI score, jumping ability, balance ability, patients' satisfaction with the rehabilitation process, and ACL healing grading according to ACL continuity and signal intensity shown by MRI.@*RESULTS@#There were significant differences in various indicators between different time points after operation in the two groups ( P<0.05). At 3 months after operation, except that the ACL-RSI score of the applet group was significantly higher than that of the regular group ( P<0.05), there was no significant difference in the other indicators between the two groups ( P>0.05). At 6 months after operation, the ACL-RSI score, IKDC score, Tegner score, KOOS scores of different items, HSS score, balance and jumping ability of the applet group were significantly higher than those of the regular group ( P<0.05), and there was no significant difference in the other indicators between the two groups ( P>0.05). At 9 months after operation, there was no significant difference in all indicators between the two groups ( P>0.05). At 12 months after operation, 27 cases (67.5%) in the applet group and 21 cases (52.5%) in the regular group returned to sport, with a significant difference of the return to sports incidence between the two groups [ RR(95% CI)=1.50 (1.00, 2.25), P=0.049]. In the applet group, 27 cases were very satisfied with the rehabilitation process, 10 cases were satisfied, 2 cases were basically satisfied, and 1 case was not satisfied, while 19, 13, 5, and 3 cases in the regular group, respectively. The satisfaction degree of the applet group was significantly better than that of the regular group ( P=0.049). MRI examination of the two groups showed that the ACL was continuous without secondary rupture or necrosis. The ACL healing grade of the applet group was 31 cases of grade 1 and 9 cases of grade 2, and that of the regular group was 28 cases of grade 1 and 12 cases of grade 2, there was no significant difference in ACL healing grade between the two groups ( P=0.449).@*CONCLUSION@#The application of return to sports WeChat applet in the rehabilitation of patients after ACL reconstruction can significantly reduce the fear of return to sports and improve the rate of return to sports. The return to sports WeChat applet is convenient to operate, with high utilization rate and high patient compliance, which significantly improves the satisfaction.

Effect of Suanzaoren Decoction on expression of ionotropic glutamate receptors and synaptic plasticity in hippocampus of anxiety rats / 中国中药杂志

This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P<0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P<0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P<0.01), and significantly increased levels of GABA(P<0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P<0.05, P<0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.

Progress in evaluation of return to sports after anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To summarize the evaluation methods of return to sports (RTS) after anterior cruciate ligament reconstruction (ACLR) in recent years, in order to provide reference for clinical practice.@*METHODS@#The literature related to the RTS after ACLR was searched from CNKI, Wanfang, PubMed, and Foreign Medical Information Resources Retrieval Platform (FMRS) databases. The retrieval range was from 2010 to 2023, and 66 papers were finally included for review. The relevant literature was summarized and analyzed from the aspects of RTS time, objective evaluation indicators, and psychological evaluation.@*RESULTS@#RTS is the common desire of patients with ACL injury and doctors, as well as the initial intention of selecting surgery. A reasonable and perfect evaluation method of RTS can not only help patients recover to preoperative exercise level, but also protect patients from re-injury. At present, the main criterion for clinical judgement of RTS is time. It is basically agreed that RTS after 9 months can reduce the re-injury. In addition to time, it is also necessary to test the lower limb muscle strength, jumping, balance, and other aspects of the patient, comprehensively assess the degree of functional recovery and determine the different time of RTS according to the type of exercise. Psychological assessment plays an important role in RTS and has a good clinical predictive effect.@*CONCLUSION@#RTS is one of the research hotspots after ACLR. At present, there are many related evaluation methods, which need to be further optimized by more research to build a comprehensive and standardized evaluation system.

Research on phase modulation to enhance the feature of high-frequency steady-state asymmetric visual evoked potentials / 生物医学工程学杂志

High-frequency steady-state asymmetric visual evoked potential (SSaVEP) provides a new paradigm for designing comfortable and practical brain-computer interface (BCI) systems. However, due to the weak amplitude and strong noise of high-frequency signals, it is of great significance to study how to enhance their signal features. In this study, a 30 Hz high-frequency visual stimulus was used, and the peripheral visual field was equally divided into eight annular sectors. Eight kinds of annular sector pairs were selected based on the mapping relationship of visual space onto the primary visual cortex (V1), and three phases (in-phase[0º, 0º], anti-phase [0º, 180º], and anti-phase [180º, 0º]) were designed for each annular sector pair to explore response intensity and signal-to-noise ratio under phase modulation. A total of 8 healthy subjects were recruited in the experiment. The results showed that three annular sector pairs exhibited significant differences in SSaVEP features under phase modulation at 30 Hz high-frequency stimulation. And the spatial feature analysis showed that the two types of features of the annular sector pair in the lower visual field were significantly higher than those in the upper visual field. This study further used the filter bank and ensemble task-related component analysis to calculate the classification accuracy of annular sector pairs under three-phase modulations, and the average accuracy was up to 91.5%, which proved that the phase-modulated SSaVEP features could be used to encode high- frequency SSaVEP. In summary, the results of this study provide new ideas for enhancing the features of high-frequency SSaVEP signals and expanding the instruction set of the traditional steady state visual evoked potential paradigm.

Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics / 中国中药杂志

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Positive effects of Xuebijing injection on intestinal microbiota and metabolite spectrum in septic rats / 中华危重病急救医学

OBJECTIVE@#To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites.@*METHODS@#A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis.@*RESULTS@#At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities.@*CONCLUSIONS@#Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.

Intervention effect and mechanism of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis mice / 中国药房

OBJECTIVE To study the intervention effect of Hippophae rhamnoides oil on glucocorticoid resistance in superantigen-induced atopic dermatitis （AD） mice，and to explore the mechanism of action. METHODS Fifty mice were randomly divided into 5 groups，i.e. normal control group （group A），model group （group B），dexamethasone intervention group （positive control，group C），H. rhamnoides oil intervention group （group D），dexamethasone+H. rhamnoides oil intervention group （group E），with 10 mice in each group. Except for group A，other groups were given 2，4-dinitrochlorobenzene+staphylococcal enterotoxin B to induce the AD mice model. Starting from the 7th day of the experiment，groups C，D and E were given dexamethasone （1.5 mg/kg） and/or H. rhamnoides oil （10 mL/kg） intragastrically，once a day，for 28 consecutive days. After the last medication，the pathomorphological changes of ear tissue were observed by 节作用。E-mail：57667478@qq.com HE staining； the serum levels of immunoglobulin E （IgE） and interleukin 4 （IL-4） were detected by enzyme-linked immunosorbent assay. Positive cell count of glucocorticoid receptor α （GRα） and GRβ in the ear tissue of mice was detected by tyramide signal amplification. The expressions of GRα protein，GRβ protein，and protein kinase B （AKT）/ribosomal protein S6 kinase 1，S6K1 （S6K1） signaling pathway-related proteins were determined by Western blot assay. RESULTS Compared with group B，the skin inflammation in the left ear of the mice was significantly reduced in groups C，D and E，the serum levels of IgE and IL-4 were decreased significantly in groups D and E （P＜ 0.05），while the number of GRα positive cells and GRα protein expression were increased significantly （P＜0.05）； the protein levels of G protein inhibitory subunit 1 （Gαi1），Gαi3，phosphorylated S6K1 （p-S6K1） and phosphorylated AKT （p-AKT） were decreased significantly （P＜0.05）； the number of GRβ positive cells and protein expression of GRβ was decreased significantly in group E（P＜0.05）. Compared with group C，the skin inflammation in the left ear of the mice was almost clear away in group E，the serum levels of IgE and IL-4 were decreased significantly （P＜0.05）； the number of GRα positive cells and GRα protein expression were increased significantly in groups D and E （P＜0.05）； the protein levels of GRβ，Gαi1，p-S6K1 and p-AKT were all decreased significantly in groups D and E（P＜0.05）； and protein level of Gαi3 was decreased significantly in group E （P＜0.05）. CONCLUSIONS H. rhamnoides oil has an intervention effect on superantigen-induced glucocorticoid resistance of AD mice，which may be exerted by inhibition of the Gαi1/3-induced AKT/S6K1 signaling pathway.

Modified Sanpiantang Treats Nitroglycerin-induced Migraine in Rats via p38 MAPK/iNOS Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo decipher the mechanism of modified Sanpiantang in the treatment of nitroglycerin-induced migraine in rats. MethodSeventy-two Wistar rats were randomized into the control， model （nitroglycerin， 10 mg·kg-1）， positive control （rizatriptan， 0.89 mg·kg-1）， and high- （12.96 g·kg-1）， medium- （6.48 g·kg-1）， and low-dose （3.24 g·kg-1） modified Sanpiantang groups. The rat model of migraine was established by intraperitoneal injection of 10 mg·kg-1 nitroglycerin. The behavioral test was carried out to measure the mechanical pain thresholds （MPT） of the periorbital region and hindpaw after successful modeling. The serum levels of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， and interleukin-1β （IL-1β） in rats were determined by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was employed to determine the expression of inducible nitric oxide synthase （iNOS） in the trigeminal nucleus caudalis （TNC）. Western blot was employed to determine the protein levels of iNOS and phospho-p38 mitogen-activated protein kinase （p-p38 MAPK） in the TNC. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to measure the mRNA levels of iNOS， p38 MAPK， and IL-1β in the TNC. ResultCompared with the control group， the model group showed decreased MPT （P<0.01）， elevated serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.01）， and up-regulated expression levels of p38 MAPK， iNOS， and IL-1β in the TNC （P<0.05， P<0.01）. Compared with the model group， modified Sanpiantang increased the MPT （P<0.05）， and the medium-dose group showed the most significant effect （P<0.01）. In addition， modified Sanpiantang down-regulated the mRNA levels of iNOS， p38 MAPK， and IL-1β and the protein levels of p-p38 MAPK and iNOS in the TNC of migraine rats （P<0.05， P<0.01） and lowered the serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.05， P<0.01）. ConclusionModified Sanpiantang may treat migraine by down-regulating the expression of pro-inflammatory factors such as NO， TNF-α， IFN-γ， and IL-1β in the p38 MAPK/iNOS signaling pathway to reduce the neurogenic inflammation.

Therapeutic effect and prognostic factors of vitrectomy for proliferative diabetic retinopathy in patients with chronic renal failure / 中华眼底病杂志

Objective:To investigate the efficacy and prognostic factors of pars plana vitrectomy (PPV) in the treatment of proliferative diabetic retinopathy (PDR) with chronic renal failure (CRF).Methods:A retrospective study. From January 2016 to June 2021, a total of 82 eyes of 58 patients diagnosed with PDR combined with CRF and treated with PPV in Department of Ophthalmology, The Second Hospital of Hebei Medical University were included in the study. There were 32 cases in males and 26 cases in females. The mean age was (48.45±10.41) years. The course of renal failure was (4.15±3.23) years, and the course of diabetes was (14.45±6.71) years. All patients undergo best-corrected visual acuity (BCVA). The BCVA examination was performed using the international standard Snellen visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity for recording. The mean number of logMAR BCVA was 2.04±0.82 (0.7-2.8). The duration of vitreous hemorrhage averaged (2.65±1.55) months. There were 38 eyes (46.3%, 38/82) with traction retinal detachment; 32 eyes had a history of panretinal photocoagulation (PRP) treatment (39.0%, 32/82). All eyes were treated with 25G PPV. Patients with traction retinal detachment were treated with intravitreal injection of anti-vascular endothelial growth factor (VEGF) 3 days before surgery. Opacification of the lens affected the operation operator combined with phacoemulsification. Biochemical indexes such as hemoglobin, glycosylated hemoglobin, albumin, creatinine, uric acid, and alternative treatment (non-dialysis/hemodialysis/peritoneal dialysis) were collected. Postoperative follow-up time was ≥6 months. χ2 test or Fisher's exact test were used for comparison between groups. A logistic regression model was used for multivariate analysis, and Spearman correlation analysis was used to evaluate the correlations between variables. Results:At 6 months after surgery, the mean logMAR BCVA was 1.16±0.57. Compared with logMAR BCVA before surgery, the difference was statistically significant ( t=-0.837, P<0.001); 44 eyes had BCVA ≥0.1 and 38 eyes had BCVA <0.1. Postoperative vitreous hemorrhage (PVH) was observed in 17 eyes after surgery (20.7%, 17/82). PVH occurred in 15 (46.9%, 15/32), 1 (2.3%, 1/44), and 1 (16.7%, 1/6) eyes in patients without dialysis, hemodialysis and peritoneal dialysis, respectively. There was significant difference between those without dialysis and those on hemodialysis ( χ2=26.506, P<0.05). There was no significant difference between peritoneal dialysis patients and those without dialysis and hemodialysis patients ( χ2=2.694, 2.849; P>0.05). PVH occurred in 3 (10.0%, 3/30) and 14 (27.0%, 14/52) eyes of vitreous cavity filled with silicone oil and perfusion fluid, respectively. The difference was statistically significant ( χ2=3.315, P<0.05); 1 (33.3%, 1/3) and 10 (71.4%, 10/14) eyes were treated with PPV again, respectively, and the difference was statistically significant ( P<0.05). Neovascular glaucoma (NVG) occurred in 12 eyes (14.6%, 12/82). Logistic regression analysis showed that age [odds ratio ( OR) =0.911, P<0.05], diabetic retinopathy (DR) stage ( OR=7.229, P<0.05), renal failure duration ( OR=0.850, P<0.05), operation time ( OR=1.135, P<0.05) was an independent risk factor for poor vision prognosis. Diabetes duration ( OR=1.158, P<0.05), renal failure duration ( OR=1.172, P<0.05) and alternative therapy were independent factors affecting the occurrence of PVH. Diabetes duration ( OR=1.138, P<0.05) and renal failure duration ( OR=1.157, P<0.05) were independent risk factors for postoperative NVG. Spearman correlation analysis showed that PVH was strongly correlated with post-operative NVG ( r=0.469, P<0.01). There was no significant correlation between blood glucose, hemoglobin, creatinine and blood urea nitrogen and prognosis of postoperative vision, PVH and NVG occurrence ( P>0.05). Conclusions:In PDR patients with CRF, DR Stage, age, renal failure course and operation duration are correlated with vision prognosis. Compared with those who do not receive alternative therapy, hemodialysis treatment can reduce the occurrence of PVH and NVG after surgery.

Clinicopathological diagnosis and treatment of undifferentiated(embryonal) sarcoma of the liver / 中华普通外科杂志

Objective:To investigate the clinicopathological features, differential diagnosis, treatment and prognosis of undifferentiated embryonal sarcoma of the liver (UESL).Methods:Five UESL cases operated on at Hunan Provincial People's Hospital from 2014 to 2021 were retrospectively analyzed. H&E and immunohistochemical staining were done for pathological observation.Results:The 5 UESL patients(two boys,three girls) were 0.5 to 15 years old, all underwent radical surgical resection. In 3 cases tumors located in right liver, 1 in left liver, 1 in both lobes. Radiographically and visually, the tumor is a large cystic solid mass, microscopically composed of myxoid stroma and undifferentiated stromal cells, with pleomorphic tumor giant cells and characteristic eosinophilic bodies. All 5 patients are now alive after surgical resection: 1 patient achieved disease-free survival of more than 91 months after surgery alone. Two patients had recurrence after surgery and received surgical resection plus chemotherapy or chemotherapy alone. They achieved survival of more than 35 and 16 months, respectively. Two patients were treated with chemotherapy or chemotherapy plus radiotherapy after surgery and survived more than 49 and 31 months without recurrence, respectively.Conclusions:UESL is a rare and highly malignant mesenchymal tumor with characteristic pathologic morphology. Radical resection is the key to the treatment for UESL, and chemotherapy and radiotherapy should be carried out after surgery.