Objective: To investigate the regulatory effect of Jieduan Niwan Formula (JDNWF) drug-containing serum on AMPK-mediated mitochondrial quality control in D-GalN-induced HepG2 cells. Methods: Twenty male Wistar rats were randomly divided into blank control and JDNWF-containing serum groups, 10 rats per group. The JDNWF-containing serum group was gavaged with JDNWF (21.7 g/kg), whereas the blank control group was gavaged with saline. Blood was collected to prepare JDNWF-containing and blank control serum. Cell viability, mitochondrial damage indicators, and MQC pathway protein expression levels were evaluated to determine the optimal volume fraction of JDNWF. HepG2 cells were divided into control, D-GalN, DMSO, AMPK inhibitor, JDNWF drug-containing serum, and JDNWF drug-containing serum plus AMPK inhibitor groups, and corresponding drug interventions were administered to each group. Cells were collected after the interventions, and the CCK-8 assay was used to measure cell viability, the 2′-7′-dichlorodihydrofluorescein diacetate fluorescent probe was used to detect reactive oxygen species (ROS) levels, JC-1 was used to detect mitochondrial membrane potential, thiobarbituric acid was used to measure malondialdehyde (MDA) levels, WST-8 was used to measure superoxide dismutase (SOD) activity, and western blotting was used to detect the expression levels of mitochondrial quality control-related proteins, including p-AMPK, AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1. Results: 5% JDNWF drug-containing serum most significantly restored cell viability, mitochondrial damage markers, and MQC pathway protein expression in the model group. Therefore, it was chosen for intervention in subsequent experiments. Compared to the control group, the cell viability of the D-GalN, DMSO, and AMPK inhibitor groups was significantly reduced (P<0.01). In contrast, the heterogeneity of mitochondrial membrane potential, ROS, and MDA levels was significantly increased (P<0.01), and SOD activity was significantly decreased (P<0.01). The p-AMPK, PGC-1α, NRF1, TFAM, MFN2, and DRP1 protein expression levels were significantly decreased (P<0.01). After JDNWF drug-containing serum intervention, compared to the DMSO group, cell viability significantly increased (P<0.01), mitochondrial membrane potential heterogeneity, ROS, and MDA levels significantly decreased (P<0.01), SOD activity significantly increased (P<0.01), and p-AMPK, PGC-1α, NRF1, TFAM, and MFN2 protein expression levels significantly increased (P<0.01), whereas DRP1 protein expression significantly decreased (P<0.01). Compared to the JDNWF drug-containing serum group, the cell viability in the JDNWF plus AMPK inhibitor group significantly decreased (P<0.01), mitochondrial membrane potential heterogeneity and ROS levels significantly increased (P<0.01), MDA levels significantly increased (P<0.05), SOD activity significantly decreased (P<0.05), p-AMPK, PGC-1α, NRF1, and TFAM protein expression levels significantly decreased (P<0.01), MFN2 protein expression significantly decreased (P<0.05), and DRP1 protein expression significantly increased (P<0.01). Conclusion JDNWF drug-containing serum may restore mitochondrial function and improve D-GalN-induced HepG2 cell injury by regulating AMPK-mediated mitochondrial quality control.

Stroke is a critical health issue in China, and carotid artery stenosis and plaque play key roles in its prevalence. Despite the acknowledged significance of this condition, detailed information regarding the prevalence of carotid artery stenosis and plaque across the Chinese population has been scarce. This study analyzed data from the China Stroke High-risk Population Screening and Intervention Program for 2020-2021, focusing on 194 878 Chinese adults aged 40 years and above. It assessed the prevalence of carotid artery stenosis and plaque and identified their associated risk factors. Results revealed a standardized prevalence of 0.40% for carotid artery stenosis and 36.27% for carotid plaque. Notably, the highest rates of stenosis were observed in north and south China at 0.61%, while southwestern China exhibited the highest plaque prevalence at 43.17%. Key risk factors included older age, male gender, hypertension, diabetes, stroke, smoking, and atrial fibrillation. This study highlights significant geographical and demographic disparities in the prevalence of these conditions, underlining the urgent need for targeted interventions and policy reforms. These measures are essential for reducing the incidence of stroke and improving patient outcomes, addressing this significant health challenge in China.
Humans ; China/epidemiology* ; Male ; Female ; Prevalence ; Middle Aged ; Carotid Stenosis/epidemiology* ; Risk Factors ; Aged ; Adult ; Plaque, Atherosclerotic/epidemiology* ; Stroke/epidemiology* ; Aged, 80 and over

Objective:To investigate the protective effect of prunetin on the neurons in the rats with cerebral ischemia reperfusion injury(CIRI),and to clarify its possible mechanisms.Methods:Thirty-six SD rats were randomly divided into sham operation group,model group,low dose of prunetin group(3.5 mg·kg-1),medium dose of prunetin group(7.0 mg·kg-1),high dose of prunetin group(14.0 mg·kg-1),and positive drug edaravone(Eda)group(n=6).Zealonga method was used to evaluate the neurological function damage of the rats in various groups;open field experiment was used to evaluate the autonomous motor function;Triphenyltetrazolium chlorde(TTC)staining was used to evaluate the areas of cerebral infarction of the rats in various groups;HE staining and Nissl staining were used to observe the pathomorphology of brain tissue of the rats in various groups.Additionally,twenty-one SD rats were randomly divided into sham operation group,model group,prunetin group,c-Jun N-terminal kinase(JNK)inhibitor group,p38 inhibitor group,JNK inhibitor+prunetin group,and p38 inhibitor+prunetin group(n=3).TUNEL staining was used to detect the positive rates of apoptosis of neurons of the rats in various groups;Western blotting method was used to detect the expression levels of apoptosis-related proteins and JNK/p38 signaling pathway-related proteins in brain tissue of cerebral infarction side of the rats in various groups.Results:Compared with sham operation group,the neurological deficit score of rats in model group was significantly increased(P＜0.001),the total motor distance was shortened(P＜0.001),and the ratio of cerebral infarction area was increased(P＜0.001).In sham group,the neuronal structure in the rat brain tissue was clear and well-organized,with an abundance of Nissl bodies and no apparent pathological changes observed.Compared with model group,the neurological deficit scores of the rats in medium and high doses of prunetin groups were decreased(P＜0.05),total motor distances of rats were increased(P＜0.05),and the cerebral infarction areas of rats were decreased(P＜0.05);the neurons showed disarrayed arrangement,cytoplasmic condensation,nuclear consolidation,and lysing and deletion of Nissl bodies were decreased.Compared with sham operation group,the positive rate of apoptosis of neurons in model group was significantly increased(P＜0.001),the expression level of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and cleaved Caspase-3 proteins in brain tissue of the rats were significantly increased(P＜0.05 or P＜0.01).Compared with model group,the positive rats of apoptosis of neurons of the rats in prunetin group were decreased(P＜0.05),the expression level of Bcl-2 protein in brain tissue of the rats was increased(P＜0.001),and the expression levels of Bax and cleaved Caspase-3 proteins were significantly decreased(P＜0.05).Compared with inhibitor groups,the positive rates of apoptosis of neurons in inhibitor+prunetin groups were decreased(P＜0.01),and the expression levels of p-JNK and p-p38 proteins in brain tissue of the rats as well as the ratios of p-JNK/JNK and p-p38/p38 were decreased(P＜0.05).Conclusion:Prunetin has the effect of reducing the neurological function damage,decreasing the area of cerebral infarction,reducing the pathological damage,and inhibiting neuronal apoptosis in the rats,and its mechanism may be related to inhibiting neuronal apoptosis through regulating the JNK/p38 signaling pathway.

Objective:To discuss the protective effect of TUG-891 on ischemic stoke(IS)induced by ischemia-hypoxia,and to clarify its potential mechanism.Methods:A total of 60 healthy male C57BL/6 mice were randomly divided into sham operation group(n=20),model group[distal middle cerebral artery occlusion(dMCAO)group,n=20],and model+TUG-891 group(dMCAO+TUG-891 group,n=20).After modeling,the mice were intraperitoneally injected with TUG-891 solution(35 mg·kg?1·d?1)for 3 consecutive days.Modified neurological severity score(mNSS)and rotarod test were used to evaluate the neurological function of the mice in various groups;2,3,5-triphenyltetrazolium chloride(TTC)staining was used to observe the cerebral infarction volumes of the mice in various groups;biochemical method was used to detect the malondialdehyde(MDA)level and superoxide dismutase(SOD)activity in the supernatant of brain tissue of the mice in various groups;Hematoxylin-Eosin(HE)and NISSL staining were used to observe the pathomerphology of brain tissue of the mice in various groups;terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL)staining was used to detect the apoptotic indexes of neuronal cells in brain tissue of the mice in various groups;Western blotting method was used to detect the expression levels of glucose-regulated protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),phosphorylated PERK(p-PERK),and C/EBP homologous protein(CHOP)proteins in brain tissue of the mice in various groups.Results:The mNSS and rotarod test results shoued that compared with sham operation group,the mNSS of the mice in dMCAO group was significantly increased(P<0.01),and the time on the rod was significantly decreased(P<0.01);compared with dMCAO group,the mNSS of the mice in dMCAO+TUG-891 group was decreased(P<0.05),and the time on the rod was increased(P<0.05).The TTC staining results shoued that compared with sham operation group,the volume of white infarct foci in the cerebral cortex of the mice in dMCAO group was increased(P<0.01);compared with dMCAO group,the cerebral infarction volume of the mice in dMCAO+TUG-891 group was significantly decreased(P<0.01).The HE staining results showed that compared with sham operation group,the cortex of the mice in dMCAO group was severely damaged,manifested by disordered arrangement of neuronal cells and obvious nuclear pyknosis in the infarct area,and the morphology of cortical infarct area of the mice in dMCAO+TUG-891 group was improved;the NISSL staining results showed that the Nissl bodies in the cortical infarct area of the mice in dMCAO group became thinner,elongated,and lost more.The pathological damage of brain tissue of the mice in dMCAO+TUG-891 group was significantly improved.Compared with sham operation group,the MDA level in brain tissue of the mice in model group was significantly increased(P<0.01),and the SOD activity was decreased(P<0.01);compared with model group,the MDA level in brain tissue of the mice in TUG-891 group was significantly decreased(P<0.01),and the SOD activity was significantly increased(P<0.01).The TUNEL staining results showed that compared with sham operation group,the apoptotic index of neuronal cells in brain tissue of the mice in dMCAO group was increased(P<0.01);compared with dMCAO group,the apoptotic index of neuronal cells in brain tissue of the mice in dMCAO+TUG-891 group was decreased(P<0.01).Compared with sham operation group,the expression levels of GRP78,p-PERK,and CHOP proteins in brain tissue of the mice in dMCAO group were increased(P<0.05);compared with dMCAO group,the expression levels of GRP78,p-PERK,and CHOP proteins in brain tissue of the mice in dMCAO+TUG-891 group were decreased(P<0.05).Conclusion:TUG-891 can alleviate neurological injury caused by ischemic stroke,and its mechanism may be related to the inhibition of endoplasmic reticulum stress and apoptosis.

ObjectiveTo explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.MethodWe used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin (55 mg/kg), geniposide (5 mg/kg), or their 11:1 combination. Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining, Evans blue assay, enzyme-linked immunosorbent assay, and Western blot.ResultsThe results revealed that the nuclear factor-kappa B (NF-κB) signaling pathway is inhibited in combination treatment of cerebral ischemia. Ten targets were identified as key nodes in the protein–protein interaction network: interleukin 6 (IL-6), interleukin-1β, interleukin 18, C–C motif ligand 2, C–C motif ligand 4, interleukin 10, interferon-γ-inducible protein 10, C–C motif ligand 3, tumor necrosis factor-α (TNF-α), interleukin-1α. The baicalin-geniposide combination significantly reduced infarct volume, improved neurological deficits, and alleviated brain edema/blood–brain barrier leakage compared with monotherapy. Additionally, it significantly inhibited toll-like receptor 4 (TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-α and IL-6 levels.ConclusionThe baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.

Objective:To investigate the therapeutic effect of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive positive pressure ventilation (NPPV) on patients with pulmonary edema caused by seawater drowning.Methods:A retrospective analysis method was used. Based on the Utstein database of emergency drowning in the First Hospital of Qinhuangdao, the clinical data of patients with seawater drowning pulmonary edema admitted to the emergency medicine department of the First Hospital of Qinhuangdao from January 1, 2019 to December 31, 2022 were collected. The patients were divided into NPPV group and HFNC group according to different ventilation methods. The general data, endotracheal intubation rate in 7 days, arterial blood gas analysis indexes [arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), arterial oxygen saturation (SaO 2)] and hemodynamic indexes (systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, blood lactic acid) before and after treatment, length of stay in intensive care unit (ICU), oxygen therapy comfort of the two groups were compared. Results:A total of 54 patients were enrolled, including 21 patients in the NPPV group and 33 patients in the HFNC group. There were no significant differences in gender, age, state of consciousness and other general information between the two groups. Compared with NPPV group, the rate of endotracheal intubation in HFNC group within 7 days was significantly lower [24.2% (8/33) vs. 33.3% (7/21), P < 0.05]. Before treatment, there were no significant differences in arterial blood gas analysis and hemodynamics between the two groups. After treatment, the above indexes in both groups were significantly improved compared with those before treatment, and PaO 2, SaO 2, systolic blood pressure, diastolic blood pressure and mean arterial pressure in HFNC group were significantly higher than those in NPPV group [PaO 2 (mmHg, 1 mmHg≈0.133kPa): 93.56±6.37 vs. 82.14±6.25, SaO 2: 1.02±0.09 vs. 0.95±0.11, systolic blood pressure (mmHg): 117.37±8.43 vs. 110.42±8.38, diastolic blood pressure (mmHg): 79.43±7.61 vs. 72.21±4.32, mean arterial pressure (mmHg): 92.34±6.32 vs. 85.12±5.38], PaCO 2, heart rate and blood lactic acid were significantly lower than those in NPPV group [PaCO 2 (mmHg) : 34.26±5.63 vs. 37.24±6.22, heart rate (times/min): 73.38±7.56 vs. 86.25±5.41, blood lactic acid (mmol/L): 1.38±0.36 vs. 2.25±1.14], and the differences were statistically significant (all P < 0.05). In addition, the length of ICU stay in HFNC group was significantly shorter than that in NPPV group (days: 13.30±2.38 vs. 16.27±4.26), and the comfort rate of oxygen therapy was significantly higher than that in NPPV group [66.7% (22/33) vs. 42.8% (9/21)], with statistical significance (all P < 0.05). Conclusion:HFNC can improve the oxygenation of patients with pulmonary edema caused by seawater drowning, improve hemodynamics, reduce the rate of tracheal intubation, shorten the length of ICU stay, and improve the comfort of oxygen therapy, which has certain clinical application value.

Objective To analyze the medication law and academic thoughts of national TCM master Qian Ying in the treatment of chronic hepatitis B through data mining.Methods Totally 168 cases of chronic hepatitis B treated by Professor Qian Ying from Mar.2000 to Dec.2020 were retrospectively collected,and the properties,tastes and tropism meridians,core prescriptions and drug groups of the prescription drugs were analyzed by using the famous doctor inheritance platform.Results Totolly 168 medical cases involved 168 patients and 227 kinds of Chinese materia medica,with a total frequency of 2 158 times.The characteristics of properties,tastes and tropism meridians showed that the main property was cold,and the main taste was bitter,and the main meridian was liver meridian.34 kinds of high-frequency Chinese materia medica(mainly were tonics,heat-clearing medicines,and medicines for activating blood circulation and reducing stasis),28 kinds of core Chinese materia medica,10 pairs of highly co-occurring drugs,and 10 potential drug groups were mined.Conclusion Professor Qian Ying believes that the pathogenesis of chronic hepatitis B is deficiency in nature and excess in superficiality,and the treatment focuses on tonifying deficiency.It is often treated from the liver and emphasizes the harmonization of liver,spleen and kidney.Tonifying deficiency,clearing heat,promoting blood circulation and removing blood stasis are the main treatment methods,followed by dispelling dampness,promoting qi,eliminating phlegm,opening stagnation and relieving the exterior,etc.He pays attention to the harmonization of body and use,is good at using multiple methods.

Objective To investigate and evaluate the nutrition status in serum 25-hydroxy vitamin D[25(OH)D]levels of 0～12 years old children in Xi'an.Methods A total of 2 670 patients aged 0～12 years old who underwent routine physical examinations in Children's Health Department of the Second Hospital of Air Force Medical University were selected from March 2020 to July 2023,and the 25(OH)D data of these patients were conducted in retrospective analysis.The nutritional status of vitamin D in these children of different genders,ages and seasons were also analyzed.Results ①This study included 2 670 children aged 0～12 years old in Xi'an,with the average level of serum 25(OH)D was 40.80±18.00 ng/ml.Among them,38 cases(1.42%)had serum 25(OH)D deficiency,333 cases(12.47%)had serum 25(OH)D insufficience,and 2 299 cases(86.11%)had sufficient serum 25(OH)D.②There was a statistically significant difference in serum 25(OH)D levels among different age groups(H=1 524.23,P=0.000).The group aged 1～<4 has the highest value of 52.51±13.57 ng/ml,while the group aged 8～12 has the lowest value of 21.65±6.75 ng/ml.③The levels of serum 25(OH)D in summer(39.44±17.46 ng/ml)were lower than those in spring(41.96±17.76 ng/ml)and autumn(42.71±18.15 ng/ml),with statistical significant differences(Z=101.57,-134.06,all P<0.01).However,the deficiency and inadequate rate of serum 25(OH)D in winter(18.95%)was higher than those in spring,summer and autumn(13.52%,12.75%,12.36%),with statistical significant differences(χ2=14.32,P=0.026).④There was no statistically significant difference in serum 25(OH)D levels between genders(H=0.933,P=0.351).However,the deficiency and inadequate rate of serum 25(OH)D in boys(12.51%)was lower than that in girls(15.46%),and the difference was statistically significant(χ2=9.257,P=0.010).Conclusion The nutritional status of serum 25(OH)D in children aged 0～12 years in Xi'an area is comparatively fine,and it is necessary to strengthen the intake and supplementation of vitamin D in over 3 years old children.

ObjectiveTo evaluate the effectiveness and safety of neck seven-line method combined with periauricular acupuncture as salvage treatment for sudden hearing loss in non-acute stage. MethodsSixty-six patients with non-acute stage of sudden hearing loss with a disease duration of 15-90 days were randomly divided into 33 cases each in treatment group and control group. The treatment group was given neck seven-line method combined with acupuncture at periauricular points； the control group used sham acupuncture and sham electroacupuncture at the same points. Both groups were treated 3 times a week for 6 weeks. The pure tone average hearing threshold of impaired frequencies were examined before treatment， after treatment finish and at follow-up （week 10）， and the difference between pure tone average hearing threshold of impaired frequencies before and after treatment was calculated； calculate the proportion of patients with ≥10 dB improvement in pure tone average hearing threshold of impaired frequency after treatment and at follow-up； compare the patients' Tinnitus Evaluation Scale （TEQ） scores， Chinese Medicine Quality of Life Assessment Scale （CQ-11D） health utility values and the difference between before and after treatment， and record the occurrence of adverse events. ResultsThe pure tone average of impaired frequency in the treatment group were （50.57±18.07） dB and （47.70±17.42） dB at post-treatment and follow-up respectively， and （54.38±21.77） dB and （53.36±20.99） dB in the control group at post-treatment and follow-up. Compared with the pre-treatment period， the pure tone average hearing threshold of impaired frequency in the two groups significantly decreased （P＜0.05） at post-treatment and follow-up. The difference of pure tone average hearing threshold of impaired frequency in the treatment group after treatment and at the follow-up visit compared to that before treatment was lower than those in the control group （P＜0.05）. After treatment， 13 patients （39.39%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in pure tone average hearing threshold of impaired frequency； at the follow-up visit， 18 patients （54.55%） in the treatment group and 10 patients （30.30%） in the control group showed improvement of ≥10 dB in the pure tone average hearing threshold of impaired frequency， and there was no statistical significance for comparison between groups at the time of post-treatment and follow-up （P＞0.05）. The TEQ score of the treatment group significantly lower than that before treatment （P＜0.05）； the TEQ score of the treatment group and the difference between before and after treatment significantly lower than that of the control group （P＜0.05）. The difference in CQ-11D health utility values and the difference between before and after treatment were not statistically significant between the two groups （P＞0.05）. Eight cases of acupuncture-related adverse events occurred among 66 patients， including subcutaneous haematomas after needling， severe pain during needling and needle fainting， which disappeared after symptomatic treatment and did not affect the following treatment. ConclusionNeck seven-line method combined with periauricular acupuncture could be used as salvage treatment for sudden hearing loss in non-acute stage to improve the pure tone average hearing threshold of impaired frequency， alleviate tinnitus， with safety.

ObjectiveTo investigate the ameliorative effect and mechanism of total saponins of Codonopsis Radix （TSC） on learning and memory impairment induced by D-galactose in aging mice. MethodTwenty-four male C57BL/6J mice were randomly assigned into four groups （n=6）： normal group， model group （200 mg·kg^-1 D-galactose）， TSC group （200 mg·kg^-1）， and donepezil group （3 mg·kg^-1）. After one week of pre-treatment， the mice in the model， TSC， and donepezil groups were administrated with corresponding agents for 8 weeks. In the ninth week， the Morris water maze test was performed to assess the learning and memory abilities. Histopathological changes in the brain were evaluated by hematoxylin-eosin （HE） and Nissl staining. Immunohistochemistry was used to detect the expression of nuclear factor kappa-B （NF-κB）， tumor necrosis factor-α （TNF-α）， and brain-derived neurotrophic factor （BDNF） in the brain tissue. The serum levels of glutathione peroxidase （GSH-Px）， catalase （CAT）， superoxide dismutase （SOD）， malondialdehyde （MDA）， TNF-α， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） were measured by enzyme-linked immunosorbent assay， on the basis of which the effects of TSC on neuroinflammation and memory impairment in D-galactose-induced aging mice were assessed. ResultCompared with the normal group， the model group exhibited decreased cognitive function， decreased activities of CAT， SOD， and GSH-Px in the serum （P<0.01）， and upregulated levels of MDA， TNF-α， IL-1β， and IL-18 （P<0.01）. In addition， partial neuronal damage and degeneration were observed in the hippocampus and cortex of the model group， accompanied by downregulated BDNF expression （P<0.05） and upregulated NF-κB and TNF-α expression （P<0.05）. Compared with the model group， TSC alleviated D-galactose-induced cognitive dysfunction， enhanced the activities of CAT， SOD， and GSH-Px （P<0.01）， lowered MDA， TNF-α， IL-1β， and IL-18 levels （P<0.01）， and ameliorated the pathological changes in the hippocampus and cerebral cortex. Additionally， TSC upregulated BDNF expression （P<0.05， P<0.01） and downregulated NF-κB and TNF-α expression （P<0.05， P<0.01） in the hippocampus and cerebral cortex. ConclusionTSC exerts a protective effect on cognitive dysfunction induced by D-galactose in aging mice by inhibiting oxidative stress and inflammation.