This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology* ; Receptor, Notch1/genetics* ; Signal Transduction/drug effects* ; Mice ; Animals ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia/drug effects* ; Cell Survival/drug effects* ; Membrane Potential, Mitochondrial/drug effects* ; Humans

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Objective:To understand the prevalence of peer-recommended self-HIV testing in men who have sex with men (MSM), and provide clue for identifying key individuals who can promote self-HIV testing.Methods:Data were derived from the self-HIV testing kits application system operated by Shijiazhuang Tongxing Non-Governmental Organization from July 1, 2022 to May 31, 2024. Statistical analysis was conducted by using software SPSS 29.0, and χ2 test was used to analyze differences between groups. Visual analysis of recommendation networks was performed by using software yEd Graph Editor 3.24. Results:A total of 1 574 MSM applied for HIV self-testing kits. The majority of the MSM were unmarried (74.7%), with education level of college or abvoe (65.5%), and employed (53.2%). Among them, 54.8% (862/1 574) reported consistent condom use at each sex in the past three months, while 37.2% (585/1 574) uploaded their HIV test results. Additionally, 53 MSM (3.4%) recommended self-HIV testing to other MSM. Notably, MSM aged ≥30 years and MSM who had occasional condoms use at each sex in the past three months were more likely to recommend self-HIV testing to other MSM. The 53 MSM collectively recommended self-HIV testing to another 740 MSM, the average was 13.9 MSM recommended by 1 MSM. Among MSM who accepted recommendation, 3 HIV-positive cases were identified, indicating that 1 HIV infection was detected by 17.7 recommendations. In the four-round recommendation, 10 MSM participated in more than one round recommendation, all of them were HIV prevention volunteers. Others only participating in one round were common MSM. Eleven MSM recommended self-HIV testing to two or more MSM.Conclusions:Peer-recommendation has high efficiency in the promotion of self-HIV testing, with HIV prevention volunteers serving as the primary force and the common MSM acting as a supportive force. Future efforts should be made to fully use key individuals to promote self-HIV testing.

Objective:To understand the prevalence of peer-recommended self-HIV testing in men who have sex with men (MSM), and provide clue for identifying key individuals who can promote self-HIV testing.Methods:Data were derived from the self-HIV testing kits application system operated by Shijiazhuang Tongxing Non-Governmental Organization from July 1, 2022 to May 31, 2024. Statistical analysis was conducted by using software SPSS 29.0, and χ2 test was used to analyze differences between groups. Visual analysis of recommendation networks was performed by using software yEd Graph Editor 3.24. Results:A total of 1 574 MSM applied for HIV self-testing kits. The majority of the MSM were unmarried (74.7%), with education level of college or abvoe (65.5%), and employed (53.2%). Among them, 54.8% (862/1 574) reported consistent condom use at each sex in the past three months, while 37.2% (585/1 574) uploaded their HIV test results. Additionally, 53 MSM (3.4%) recommended self-HIV testing to other MSM. Notably, MSM aged ≥30 years and MSM who had occasional condoms use at each sex in the past three months were more likely to recommend self-HIV testing to other MSM. The 53 MSM collectively recommended self-HIV testing to another 740 MSM, the average was 13.9 MSM recommended by 1 MSM. Among MSM who accepted recommendation, 3 HIV-positive cases were identified, indicating that 1 HIV infection was detected by 17.7 recommendations. In the four-round recommendation, 10 MSM participated in more than one round recommendation, all of them were HIV prevention volunteers. Others only participating in one round were common MSM. Eleven MSM recommended self-HIV testing to two or more MSM.Conclusions:Peer-recommendation has high efficiency in the promotion of self-HIV testing, with HIV prevention volunteers serving as the primary force and the common MSM acting as a supportive force. Future efforts should be made to fully use key individuals to promote self-HIV testing.

AIM To evaluate the quality of Tibetan medicine"Sangdi"based on HPLC fingerprints combined with chemometrics.METHODS The analysis was performed on a 30 ℃ thermostatic Welch Ultimate AQ-C18 column(250 mm × 4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.2％phosphoric acid flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 245 nm,after which cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were performed,the contents of gentiopicroside,sweroside,mangiferin,isoorientin,8-hydroxy-1,3,5-trimethoxyxanthone(R2)and 1,8-dihydroxy-3,7-dimethoxyxanthone(R3)were determined.RESULTS There were 18 common peaks in the fingerprints for 15 batches of samples with the similarities of more than 0.90.Six constituents showed good linear relationships within their own ranges(R 2 ≥ 0.999 2),whose average recoveries were 96.93％-103.58％with the RSDs of 0.82％-2.9％.Various batches of samples were clustered into 2 categories,4 principal components demonstrated the accumulative variance contribution rate of 86.404％,mangiferin,gentiopicroside and isoorientin were taken as quality difference markers.CONCLUSION This stable,reliable and reproducibe method can provide a reference for the comprehensive quality evaluation of"Sangdi".

This article explored the specific mechanism by which ginsenoside Rg_1 regulates cellular autophagy to attenuate hypoxia/reoxygenation(H/R) injury in HL-1 cardiomyocytes through the microRNA155(miR-155)/neurogenic gene Notch homologous protein 1(Notch1)/hairy and enhancer of split 1(Hes1) pathway. An HL-1 cell model with H/R injury was constructed, and ginsenoside Rg_1 and/or Notch1 inhibitor DAPT and miR-155 mimics were used to treat cells. Cell counting kit(CCK)-8 was used to detect the relative viability of HL-1 cells with H/R injury. The lactate dehydrogenase(LDH) content in cell culture medium supernatant was detected by using an LDH assay kit, and autophagosome in cells was observed by transmission electron microscopy. The level of autophagy in cells was detected through the mono-dansyl-cadaverine(MDC) detection method. Fluorescence quantitative polymerase chain reaction was used to detect the mRNA levels of miR-155, Notch1, Hes1, and microtubule-associated protein1 light chain 3(LC3), and Western blot was used to detect the protein expression levels of Notch1, Hes1, LC3Ⅰ, and LC3Ⅱ. The results show that after H/R injury, the activity of HL-1 cells decreases, and LDH leakage increases. Besides, the number of intracellular autophagosomes increases, and the mRNA level of LC3 and the LC3Ⅱ/LC3Ⅰ ratio are elevated. In addition, ginsenoside Rg_1 can increase cell activity, decrease LDH leakage and the number of intracellular autophagosomes, and reduce the mRNA level of LC3 and the LC3Ⅱ/LC3Ⅰ ratio. Therefore, it plays a cardioprotective role by inhibiting autophagy, and Notch1 inhibitor or miR-155 overexpression can inhibit the effect of ginsenoside Rg_1, promote autophagy, and aggravate H/R injury in HL-1 cells. Ginsenoside Rg_1 can inhibit the reduction of Notch1 and Hes1 mRNA levels and protein expressions and the increase in miR-155 mRNA levels caused by H/R injury, while Notch1 inhibitors or miR-155 overexpression show the opposite effect. In summary, ginsenoside Rg_1 can regulate autophagy through the miR-155/Notch1/Hes1 pathway to alleviate H/R injury in HL-1 cardiomyocytes.
Ginsenosides/pharmacology* ; MicroRNAs/metabolism* ; Autophagy/drug effects* ; Receptor, Notch1/genetics* ; Transcription Factor HES-1/genetics* ; Mice ; Animals ; Cell Line ; Signal Transduction/drug effects* ; Myocytes, Cardiac/cytology* ; Cell Hypoxia/drug effects*

Humans ; Cohort Studies ; Body Mass Index ; Percutaneous Coronary Intervention ; Coronary Artery Disease ; Inflammation ; Treatment Outcome ; Risk Factors

Objective:By detecting the levels of proteins in the Toll-like receptor-4/nuclear factor-κB （TLR4/NF-κB） signaling pathway and downstream proinflammatory cytokines in peripheral blood of patients with Meniere's disease （MD）, Pittsburgh Sleep Quality Index （PSQI） scores were collected to investigate the correlation between sleep disorders and MD and the role of TLR4/NF-κB signaling pathway in mediating sleep disorders inducing MD. Methods:Thirty-two MD patients and 20 family members of patients without middle ear and inner ear related diseases were selected. Basic data, PSQI and fasting peripheral blood of all subjects were collected. Enzyme linked immunosorbent assay.The levels of interleukin-1β（IL-1β）, tumor necrosis factor-α（TNF-α）, monocyte chemokine-1（MCP-1）, Toll-like receptor 4（TLR4） and nuclear factor-κB（NF-κB） in peripheral blood were detected by ELISA, and the data were statistically analyzed. Results:①PSQI score of MD group was higher than that of normal control group, and the difference was statistically significant（P<0.01）; The scores of every factors of PSQI in MD group were higher than those in normal control group, and the scores of factors 2, 4 and 6 were significantly different from those in normal control group. ②In the MD group, there were 18 patients with sleep disorders, with a prevalence rate of 56.25%, including 6 males with a prevalence rate of 50.00% and 12 females with a prevalence rate of 60.00%. ③The levels of five test indexes in MD group, sleep disorder group and non-sleep disorder group were higher than those in control group, and the levels of TLR4 and NF-κB in MD group were significantly different from those in control group（P<0.05）. The levels of IL-1β, TNF-α, TLR4 and NF-κB in sleep disorder group were significantly different from those in control group（P<0.05）. The levels of five test indexes in non-sleep disorder group were not statistically significant compared with those in control group. The levels of five test indexes in the MD sleep disorder group were higher than those in the MD group and the non-sleep disorder group, with no statistical significance. The levels of five test indexes in MD group were higher than those in non-sleep disorder group, with no statistical significance（P>0.05）. Conclusion:①Sleep disorders may be one of the important predisposing factors of some MD, and the effects of sleep disorders on MD are different between the sexes. ②Sleep disorders may activate TLR4/NF-κB signaling pathway to induce MD. The selection of TLR4/NF-κB signaling pathway related proteins and downstream pro-inflammatory factor inhibitors to intervene MD may provide a new idea for protecting the hearing balance function of MD.
Female ; Humans ; Male ; Meniere Disease ; NF-kappa B/metabolism* ; Signal Transduction ; Sleep Deprivation ; Toll-Like Receptor 4 ; Tumor Necrosis Factor-alpha/metabolism*