ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

BACKGROUND:Growth factor is the key effect molecule that plays a role in platelet-rich plasma in clinical treatment.There are differences in the concentration of growth factor after different activators activate platelet-rich plasma,which is an important factor affecting clinical efficacy. OBJECTIVE:To analyze the influence of different activators on the mass concentration of growth factors in platelet-rich plasma. METHODS:Totally 12 healthy volunteers were recruited to collect EDTA-K2 anticoagulant venous blood.Secondary centrifugation was used to prepare platelet-rich plasma.The difference in mass concentrations of growth factors was compared between venous blood and platelet-rich plasma.The platelet-rich plasma was mixed with four activators(normal saline,thrombin,calcium gluconate,calcium gluconate+thrombin)according to the volume ratio of 10:1,and incubated in a constant temperature water bath at 37 °C for 30 minutes.After centrifugation,the supernatant was extracted and the mass concentration of growth factor was detected.The bacterial growth in supernatant was measured by blood agar plate.Pearson correlation was used to analyze the correlation between different activators and the mass concentration of growth factor in platelet-rich plasma,and the correlation between the value of thrombocytometer and the mass concentration of growth factors in platelet-rich plasma. RESULTS AND CONCLUSION:(1)The mass concentrations of platelet-derived growth factor-BB,platelet-derived growth factor-AB,vascular endothelial growth factor,and epidermal growth factor in platelet-rich plasma were 8.7,22.2,2.3,and 2.8 times of those in venous blood,respectively(P<0.05).(2)Compared with normal saline group,the mass concentrations of platelet-derived growth factor BB,platelet-derived growth factor AB,vascular endothelial growth factor,and epidermal growth factor were increased in the thrombin group,calcium gluconate group,and calcium gluconate+thrombin group(P<0.05).The mass concentration of platelet-derived growth factor BB in the thrombin group and calcium gluconate group was higher than that in the calcium gluconate+thrombin group(P<0.05),and the mass concentration of platelet-derived growth factor AB in the thrombin group was higher than that in the calcium gluconate group and calcium gluconate+thrombin group(P<0.05).Epidermal growth factor mass concentration in the thrombin group was lower than that in the calcium gluconate group and calcium gluconate+thrombin group(P<0.05).(3)The results of blood agar plate test showed no bacterial growth in the supernatant of the four groups.(4)Pearson correlation analysis showed that the mass concentration of platelet-derived growth factor BB in platelet-rich plasma was strongly positively correlated with thrombin(r=0.683,P<0.05),and the mass concentration of vascular endothelial growth factor was strongly positively correlated with thrombin,calcium gluconate,calcium gluconate+thrombin stimulant(r=0.730,0.789,0.686,P<0.05).There was no correlation between the value of thrombocytometer and the mass concentration of four kinds of growth factors(P>0.05).(5)The results suggest that different activators have an impact on the concentration of growth factors in platelet-rich plasma.It is suggested to choose different activators to improve clinical efficacy according to different growth factor mass concentrations and treatment needs.

Objective To study the spatial distribution of the incidence of pulmonary tuberculosis in Hubei Province and its influencing factors, so as to improve the theoretical basis for scientific development of tuberculosis prevention and control measures in the future. Methods The data of reported incidence of tuberculosis and related influencing factors in various counties and districts of Hubei Province in 2020 were collected. Global Moran's I index, hotspot analysis and geographically weighted regression (GWR) model analysis were used to calculate the spatial autocorrelation of the incidence of tuberculosis, and to analyze the influencing factors affecting the incidence rate of tuberculosis. Results There were obvious regional differences in the space distribution of the incidence rate of tuberculosis. Hot spot analysis showed positive spatial correlation and obvious clustering. The GWR model (AICc=784.251) in this study had higher AICc value compared to the ordinary least squares regression (OLS) model (AICc=804.2585). The GWR model showed that the increase in the proportion of the population aged 65 and above and the proportion of the ethnic minority population had a significant promoting effect on the increase of the incidence rate of tuberculosis, and there was significant spatial heterogeneity. The effect of PM_2.5 concentration on the incidence rate of pulmonary tuberculosis varied in different regions, and the degree of effect was also different. Conclusion The proportion of people aged 65 and above and the proportion of ethnic minorities may significantly influence the incidence of pulmonary tuberculosis. The effect of PM_2.5 concentration varies in different regions, so targeted measures should be formulated according to the situation in different regions.

In order to meet the need of autonomous control of patients with severe limb disorders, this paper designs a nursing bed control system based on motor imagery-brain computer interface (MI-BCI). In view of the low decoding performance of cross-subjects and the dynamic fluctuation of cognitive state in the existing MI-BCI technology, the neural network structure optimization and user interaction feedback enhancement are improved. Firstly, the optimized dual-branch graph convolution multi-scale neural network integrates dynamic graph convolution and multi-scale convolution. The average classification accuracy is higher than that of multi-scale attention temporal convolution network, Gram angle field combined with convolution long short term memory hybrid network, Transformer-based graph convolution network and other existing methods. Secondly, a dual visual feedback mechanism is constructed, in which electroencephalogram (EEG) topographic map feedback can improve the discrimination of spatial patterns, and attention state feedback can enhance the temporal stability of signals. Compared with the single EEG topographic map feedback and non-feedback system, the average classification accuracy of the proposed method is also greatly improved. Finally, in the four classification control task of nursing bed, the average control accuracy of the system is 90.84%, and the information transmission rate is 84.78 bits/min. In summary, this paper provides a reliable technical solution for improving the autonomous interaction ability of patients with severe limb disorders, which has important theoretical significance and application value.
Humans ; Brain-Computer Interfaces ; Deep Learning ; Electroencephalography ; Feedback, Sensory ; Neural Networks, Computer ; Beds

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Chronic, unresolved inflammation correlates with persistent hepatic injury and fibrosis, ultimately progressing to hepatocellular carcinoma (HCC). Bisdemethoxycurcumin (BDMC) demonstrates therapeutic potential against HCC, yet its mechanism in preventing hepatic "inflammation-carcinoma transformation" remains incompletely understood. In the current research, clinical HCC specimens underwent analysis using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) to evaluate the expression of fibrosis markers, M2 macrophage markers, and CXCL12. In vitro, transforming growth factor-β1 (TGF-β1)-induced LX-2 cells and a co-culture system of LX-2, THP-1, and HCC cells were established. Cell functions underwent assessment through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and Transwell assays. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting and immunofluorescence evaluated the differential expression of molecules. The interaction between β-catenin/TCF4 and CXCL12 was examined using co-immunoprecipitation (Co-IP), dual luciferase, and chromatin immunoprecipitation (ChIP) assays. A DEN-induced rat model was developed to investigate BDMC's role in liver fibrosis-associated HCC (LFAHCC) development in vivo. Our results showed that clinical HCC tissues exhibited elevated fibrosis and enriched M2 macrophages. BDMC delayed liver fibrosis progression to HCC in vivo. BDMC inhibited the inflammatory microenvironment induced by activated hepatic stellate cells (HSCs). Furthermore, BDMC suppressed M2 macrophage-induced fibrosis and HCC cell proliferation and metastasis. Mechanistically, BDMC repressed TCF4/β-catenin complex formation, thereby reducing CXCL12 transcription in LX-2 cells. Moreover, CXCL12 overexpression reversed BDMC's inhibitory effect on macrophage M2 polarization and its mediation of fibrosis, as well as HCC proliferation and metastasis. BDMC significantly suppressed LFAHCC development through CXCL12 in rats. In conclusion, BDMC inhibited LFAHCC progression by reducing M2 macrophage polarization through suppressing β-catenin/TCF4-mediated CXCL12 transcription.
Animals ; Liver Neoplasms/etiology* ; Humans ; Carcinoma, Hepatocellular/immunology* ; Liver Cirrhosis/complications* ; Macrophages/drug effects* ; Male ; Rats ; Chemokine CXCL12/genetics* ; Diarylheptanoids/pharmacology* ; Rats, Sprague-Dawley ; beta Catenin/genetics*

AIM:To investigate the therapeutic effects of chrysin on nonalcoholic steatohepatitis(NASH).METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,model group,and chrysin group.The mice in control group were fed with normal diet,and those in model and chrysin groups were fed with methio-nine-and choline-deficient(MCD)diet.After 5 weeks of adaptation,the mice in chrysin group received chrysin treatment(20 mg/kg)by continuous lavage for 6 weeks,while those in control and model groups were given equal volume of saline.During the experiment,the health condition of the mice was monitored.Liver morphology was examined after the mice were sacrificed.Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-den-sity lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured using a biochemical analyzer.Liver tissue TG and TC levels were measured using assay kits.Liver cell damage and inflammation were assessed by hematoxylin-eosin(HE)staining and F4/80 immunohistochemistry staining.The ex-tent of liver lipid deposition was explored by oil red O staining.Masson staining and Sirius red staining were performed to assess liver fibrosis.Immunohistochemistry was performed to analyze the expression of fibrosis-related molecules.RE-SULTS:Compared with control group,the mice in model group showed significant decrease in body weight,liver wet weight,and liver volume.Serum TG,LDL-C,ALT and AST levels,as well as liver TG and TC levels were significantly elevated,and HDL-C levels were decreased in model group.Pathological staining showed significant inflammatory cell in-filtration,lipid deposition,and liver fibrosis.After the treatment with chrysin,increased body weight and liver weight,a reddish appearance of the liver,relatively smooth surface,and sharp liver edges were observed.Serum TG,LDL-C,AST and ALT levels,and liver TG levels were significantly reduced by chrysin.Inflammatory cell infiltration,lipid deposition,and liver tissue fibrosis were also significantly attenuated by chrysin.CONCLUSION:Chrysin shows a potential as a can-didate drug for the treatment of NASH by inhibiting hepatic steatosis,inflammation,and liver fibrosis.

Objective:To investigate the effects of remimazolam on hemodynamics during the induction of general anesthesia and postoperative cognitive function in patients undergoing cardiac valve replacement surgery.Methods:A randomized controlled study was conducted involving 80 patients who underwent heart valve replacement surgery at Yan'an University Affiliated Hospital from January 2020 to December 2023. The patients were randomly assigned to either a control group or an observation group, with 40 patients in each group. The control group received routine general anesthesia, while the observation group received additional remimazolam during the routine anesthesia process. Hemodynamic parameters were compared between the two groups at different time points: heart rate and mean arterial pressure were recorded before anesthesia induction (T1), at the beginning of anesthesia induction (T2), 5 minutes after anesthesia induction (T3), at the time of tracheal intubation (T4), and 5 minutes after tracheal intubation (T5). The level of anesthesia during induction was compared between the two groups. Cognitive function in both groups was evaluated before and immediately after surgery. Additionally, the incidence of anesthesia-related adverse events during the perioperative period was compared between the two groups.Results:At T4 and T5, the heart rates in the observation group were (79.23 ± 10.22) beats/min and (78.54 ± 9.94) beats/min, respectively, and the mean arterial pressures were (115.64 ± 21.04) mmHg (1 mmHg = 0.133 kPa) and (108.61 ± 17.99) mmHg. Both values were significantly lower than those in the control group [heart rate: (84.51 ± 10.35) beats/min, (84.31 ± 10.08) beats/min, mean arterial pressure: (130.06 ± 19.25) mmHg, (121.62 ± 18.61) mmHg, t = 2.30, 2.58, 3.20, 3.18, all P < 0.05]. The time taken for the EEG bi-frequency index to drop below 60 and the EEG bi-frequency index before tracheal intubation in the observation group were both significantly lower than those in the control group ( t = 3.03, 3.14, both P < 0.05). Immediately after surgery, the Mini-Mental State Examination (MMSE) score in the control group showed a significant decrease ( t = 6.43, P < 0.05), while the MMSE score in the observation group did not change significantly ( t = 0.60, P > 0.05). Moreover, the immediate postoperative MMSE score in the observation group [(26.98 ± 2.97) points] was significantly higher than that in the control group [(23.15 ± 2.78) points, t = -5.95, P < 0.05]. There was no statistically significant difference in the incidence of anesthesia-related adverse events between the two groups (χ2 = 0.66, P > 0.05). Conclusion:Remimazolam can maintain hemodynamic stability during the induction of anesthesia in patients undergoing cardiac valve replacement surgery, facilitate the rapid attainment of satisfactory sedation, and reduce immediate postoperative cognitive dysfunction. Furthermore, the use of remimazolam in conjunction with routine general anesthesia does not significantly increase anesthesia-related risks, demonstrating a high level of safety.

Objective:To study the prevalence and association factors of depressive and anxiety disorders in the hypertensive population.Methods:Using the database obtained from the 2013 China Chronic Disease and Risk Factor Surveillance and the 2013-2015 China Mental Health Survey,4 861 hypertensive residents were used as study subjects.And using the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)as diagnostic criterion for depressive and anxiety disorders,the 12-month prevalence was calculated.Multifactorial lo-gistic regression models were used to explore the association factors of hypertension comorbid depressive and anxie-ty disorders.Results:The 12-month prevalence rates of depressive disorders and anxiety disorders were 4.1％and 5.0％in 4 861 hypertensive residents.Chinese Han[OR(95％CI):2.00(1.01-3.93)],lack of sleep[OR(95％CI):1.82(1.34-2.48)],having myocardial infarction[OR(95％CI):2.35(1.18～4.67)]and stroke in the past year[OR(95％CI):2.10(1.19-3.72)],and chronic obstructive pulmonary disease[OR(95％CI):2.11(1.11-4.05)]were risk factors of hypertension comorbid depressive disorder.Hypertensive people with controlled blood pressure[OR(95％CI):2.01(1.30-3.13)]had a higher risk of co-morbid depressive disorder than those with blood pressure above the normal range on this measurement.Chinese Han[OR(95％CI):2.51(1.32-4.80)],Southwest China[OR(95％CI):1.64(1.02-2.63)],and lack of sleep[OR(95％CI):1.45(1.09-1.93)]were risk factors of hypertension comorbid anxiety disorder.Former but current non-smoking[OR(95％CI):0.48(0.23-0.99)]was a protective factor of hypertension comorbid anxiety disorder.Conclusion:The 12-month prevalence of anxiety disorder was higher than that of depressive disorder in this hypertensive population.Both Han and sleep deprived hypertensive people had a higher risk of comorbid depressive and anxiety disorders.