ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

ObjectiveTo explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction， and their regulatory role in mitophagy. MethodsSixty male C57BL/6 mice were randomly assigned to six groups： sham-operated group， model group， Qingxin Jieyu granules low-， medium-， and high-dose groups （1.3， 2.6， 5.2 g·kg^-1）， and sacubitril valsartan sodium group （0.03 g·kg^-1）， with 10 mice per group. Except for the sham-operated group， all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model. Ultrasound was used to measure left ventricular parameters， including end-diastolic and end-systolic diameters （LVIDd， LVIDs）， diastolic and systolic posterior wall thickness （LVPWd， LVPWs）， end-diastolic and end-systolic volumes （LV Vold， LV Vols）， left ventricular ejection fraction （LVEF）， and fractional shortening （LVFS）. Additionally， the heart mass index and heart weight/tibia length ratio of mice were calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify brain natriuretic peptide （BNP）， creatine kinase isoenzyme （CK-MB）， angiotensinⅡ （AngⅡ）， and lactate dehydrogenase （LDH） levels in the serum of mice. Histological analysis using hematoxylin-eosin （HE） and Masson staining was conducted to examine morphological changes in myocardial tissue. Immunohistochemistry assessed the expression of vascular growth factors， including basic fibroblast growth factor （bFGF） and vascular endothelial growth factor （VEGF）. Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice. Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase （p-AMPK） and phosphorylated mammalian target of rapamycin （p-mTOR） proteins in myocardial tissue from each experimental group. ResultsCompared to the sham-operated group， the model group mice exhibited significantly elevated levels of LV Vold， LV Vols， LVIDd， LVIDs， cardiac mass index， heart weight/tibia length ratio， BNP， LDH， and p-mTOR protein expression （P<0.05）， along with decreased levels of LVPWd， LVPWs， LVEF， LVFS， and p-AMPK protein expression （P<0.05）. The model group also displayed substantial inflammatory cell infiltration， collagen deposition in myocardial cells， reduced expression of bFGF and VEGF， mitochondrial swelling， and cristae fragmentation. Compared to the model group， the sacubitril/valsartan group and mid-dose Qingxin Jieyu granules group showed significant reductions in LVIDs， LV Vold， LV Vols， BNP， CK-MB， LDH， and p-mTOR protein expression （P<0.05）， coupled with increases in LVEF， LVFS， and p-AMPK expression （P<0.05）. Improvements were observed across all treatment groups， including reduced inflammatory cell infiltration and collagen deposition， increased bFGF and VEGF expression， alleviated mitochondrial swelling， and the presence of autophagosomes and lysosomes. ConclusionThe results show that Qingxin Jieyu granules can regulate mitochondrial autophagy in myocardial tissue and inhibit ventricular remodeling to improve cardiac performance， by up-regulating the p-AMPK expression in the myocardial tissue of mice with ventricular remodeling after myocardial infarction， and down-regulating the p-mTOR expression.

Objective: To examine the association between moderate-to-vigorous physical activity (MVPA) and weight adjusted waist index (WWI) with psychological sub health in middle school students,so as to provide a basis for mental health intervention and promotion. Methods: From September to November 2023, a stratified cluster random sampling method was used to survey 47 372 middle school students aged 12-17 in Jiangsu, Xinjiang, Guangdong, Jilin and Henan provinces from eastern, western, southern, northern and central of China. MVPA, WWI, and psychological subhealth were assessed, with WWI categorized into quartiles ( Q 1- Q 4). Data were analyzed using χ 2 test, Logistic regression analysis and Logistic regression analysis of generalized linear models. Results: The overall prevalence of psychological sub health among middle school students was 21.0%, with higher rates in boys(21.4%) than girls(20.5%) ( χ 2=6.49, P <0.05). The detection rates of emotional problems, behavioral problems and social adaptation difficulties in middle school students were 27.8%, 26.9% and 17.5%, respectively. The combination of MVPA and WWI groups was used as independent variables, and the covariates were adjusted to perform Logistic regression analysis of generalized linear model;while the Q 1 group with MVPA>60 min/d was used as the reference group, the Q 4 group with MVPA<30 min/d had the highest risk of psychological sub health detection( OR =1.58, 95% CI =1.38-1.81),and the detection risks of psychological sub health among middle school students in Q 1- Q 3 groups were 1.34(1.17-1.53), 1.30(1.13-1.49) and 1.42(1.24- 1.62 )( P <0.01). Conclusions MVPA and WWI are significantly associated with psychological sub health in middle school students. Lower MVPA and higher WWI in middle school students correlate with increased sub health risks. Interventions should aim to enhance MVPA levels and reduce WWI to improve mental well being in middle school students.

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

The redistribution of body fluids towards the head will lead to cardiovascular dysfunction when exposed to microgravity environment.De-gravity unloading can cause degenerative adaptation of nerves and muscles,posing numerous challenges for astronauts returning to the Earth's gravitational environment.In severe cases,it can even threaten the health and safety of astronauts.Although exercise is the most effective weightlessness protection measure,the current weightlessness protection programs based on traditional exercise are too time-consuming.High intensity interval training(HIIT),an efficient training strategy,is widely used in competitive sports and it can rapidly improve human physical performance in the short term through a combination of high-intensity exercise with small and low intervals or active rest repetitions.The use of different modes of HIIT training combinations can simultaneously improve cardiovascular health and neuromuscular function.HIIT may be a more effective strategy for preventing weight loss during exercise.Through a systematic review of the classification,mechanism of action,and determining factors of training effectiveness of HIIT,and a feasibility analysis of implementing HIIT in space microgravity environments,it is proposed that HIIT may become an optimization strategy for current space station astronaut exercise programs,thereby more effectively saving resources.Therefore,it is necessary to take ground-based simulated microgravity experiment to deeply study and fully verify various HIIT training schemes which might be used for astronauts to counter microgravity effects.

Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule(QXJYG)against atherosclerosis(AS)based on network pharmacology.Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology.Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline,atorvastatin(13.15 mg/kg),or QXJYG at 0.99,1.98,and 3.96 g/kg for 8 weeks(n=6).Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta.Blood lipids and serum levels of Ang II,ET-1,TXA2,PGI2,and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA.The expressions of LOX-1,PPARγ,RXRα,p-P65,VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry.Results The rat models of AS showed obvious abdominal aorta wall thickening,increased pulse wave velocity and pulse index,decreased inner diameter of the abdominal aorta,elevated levels of TC,LDL-C,Ang II,ET-1 and TXA2,and lowered levels of HDL-C and PGI2.QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta,decreased serum levels of TC,LDL-C,Ang II,ET-1 and TXA2,and increased the levels of HDL-C and PGI2.Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism,PPAR and NF-κB pathways.Consistently,treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1,P-P65,VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats.Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level,reducing LOX-1 expression,activating PPARγ and RXRα,and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta.

Objective A quality control(QC)system based on the electronic portal imaging device(EPID)system was used to realize the Multi-Leaf Collimator(MLC)position verification and dose verification functions on Primus and VenusX accelerators.Methods The MLC positions were calculated by the maximum gradient method of gray values to evaluate the deviation.The dose of images acquired by EPID were reconstructed using the algorithm combining dose calibration and dose calculation.The dose data obtained by EPID and two-dimensional matrix(MapCheck/PTW)were compared with the dose calculated by Pinnacle/TiGRT TPS for γ passing rate analysis.Results The position error of VenusX MLC was less than 1 mm.The position error of Primus MLC was significantly reduced after being recalibrated under the instructions of EPID.For the dose reconstructed by EPID,the average γ passing rates of Primus were 98.86%and 91.39%under the criteria of 3%/3 mm,10%threshold and 2%/2 mm,10%threshold,respectively.The average γ passing rates of VenusX were 98.49%and 91.11%,respectively.Conclusion The EPID-based accelerator quality control system can improve the efficiency of accelerator quality control and reduce the workload of physicists.

Objective:To investigate the protective effects and mechanisms of targeted inhibition of type 3 deiodinase (Dio3) on skeletal muscle mitochondria in sepsis.Methods:① In vivo experiments: adeno-associated virus (AAV) was employed to specifically target Dio3 expression in the anterior tibial muscle of rats, and a septic rat model was generated using cecal ligation and puncture (CLP). The male Sprague-Dawley (SD) rats were divided into shNC+Sham group, shD3+Sham group, shNC+CLP group, and shD3+CLP group by random number table method, with 8 rats in each group. After CLP modeling, tibial samples were collected and Western blotting analysis was conducted to assess the protein levels of Dio3, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), and silence-regulatory protein 1 (SIRT1). Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was utilized to examine mRNA expression of genes including thyroid hormone receptors (THRα, THRβ), monocarboxylate transporter 10 (MCT10), mitochondrial DNA (mtDNA), and PGC1α. Transmission electron microscopy was employed to investigate mitochondrial morphology. ② In vitro experiments: involved culturing C2C12 myoblasts, interfering with Dio3 expression using lentivirus, and constructing an endotoxin cell model by treating cells with lipopolysaccharide (LPS). C2C12 cells were divided into shNC group, shD3 group, shNC+LPS group, and shD3+LPS group. Immunofluorescence colocalization analysis was performed to determine the intracellular distribution of PGC1α. Co-immunoprecipitation assay coupled with Western blotting was carried out to evaluate the acetylation level of PGC1α. Results:① In vivo experiments: compared with the shNC+Sham group, the expression of Dio3 protein in skeletal muscle of the shNC+CLP group was significantly increased (Dio3/β-Tubulin: 3.32±0.70 vs. 1.00±0.49, P < 0.05), however, there was no significant difference in the shD3+Sham group. Dio3 expression in the shD3+CLP group was markedly reduced relative to the shNC+CLP group (Dio3/β-Tubulin: 1.42±0.54 vs. 3.32±0.70, P < 0.05). Compared with the shNC+CLP group, the expression of T3-regulated genes in the shD3+CLP group were restored [THRα mRNA (2 -ΔΔCt): 0.67±0.05 vs. 0.33±0.01, THRβ mRNA (2 -ΔΔCt): 0.94±0.05 vs. 0.67±0.02, MCT10 mRNA (2 -ΔΔCt): 0.65±0.03 vs. 0.57±0.02, all P < 0.05]. Morphology analysis by electron microscopy suggested prominent mitochondrial damage in the skeletal muscle of the shNC+CLP group, while the shD3+CLP group exhibited a marked improvement. Compared with the shNC+Sham group, the shNC+CLP group significantly reduced the number of mitochondria (cells/HP: 10.375±1.375 vs. 13.750±2.063, P < 0.05), while the shD3+CLP group significantly increased the number of mitochondria compared to the shNC+CLP group (cells/HP: 11.250±2.063 vs. 10.375±1.375, P < 0.05). The expression of mtDNA in shNC+CLP group was markedly reduced compared with shNC+Sham group (copies: 0.842±0.035 vs. 1.002±0.064, P < 0.05). Although no difference was detected in the mtDNA expression between shD3+CLP group and shNC+CLP group, but significant increase was found when compared with the shD3+Sham group (copies: 0.758±0.035 vs. 0.474±0.050, P < 0.05). In the shD3+CLP group, PGC1α expression was significantly improved at both transcriptional and protein levels relative to the shNC+CLP group [PGC1α mRNA (2 -ΔΔCt): 1.49±0.13 vs. 0.68±0.06, PGC1α/β-Tubulin: 0.76±0.02 vs. 0.62±0.04, both P < 0.05]. ② In vitro experiments: post-24-hour LPS treatment of C2C12 cells, the cellular localization of PGC1α became diffuse; interference with Dio3 expression promoted PGC1α translocation to the perinuclear region and nucleus. Moreover, the acetylated PGC1α level in the shD3+LPS group was significantly lower than that in the shNC+LPS group (acetylated PGC1α/β-Tubulin: 0.59±0.01 vs. 1.24±0.01, P < 0.05), while the expression of the deacetylating agent SIRT1 was substantially elevated following Dio3 inhibition (SIRT1/β-Tubulin: 1.04±0.04 vs. 0.58±0.03, P < 0.05). When SIRT1 activity was inhibited by using EX527, PGC1α protein expression was notably decreased compared to the shD3+LPS group (PGC1α/β-Tubulin: 0.92±0.03 vs. 1.58±0.03, P < 0.05). Conclusion:Inhibition of Dio3 in skeletal muscle reduced the acetylation of PGC1α through activating SIRT1, facilitating nuclear translocation of PGC1α, thereby offering protection against sepsis-induced skeletal muscle mitochondrial damage.

Objective:To evaluate the effect of low-dose esketamine for postoperative analgesia on the postoperative depression in patients with gastrointestinal tumors.Methods:This study was a prospective randomized controlled trial. Eighty patients, aged 18-64 yr, with a body mass index of 18-25 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, scheduled for elective radical resection of the gastrointestinal tumor under general anesthesia from June to November 2023 in our hospital, were divided into 2 groups ( n=40 each) using a random number table method: esketamine group (group E) and control group (group C). Each patient received postoperative patient-controlled intravenous analgesia(PCIA). The PCIA solution in group E contained esketamine 0.5 mg/kg, dezocine 0.5 mg/kg, dexmetomidine 1.5 μg/kg and flurbiprofen ester 100 mg in 100 ml of normal saline. The PCIA solution in group C contained dezocine 0.5 mg/kg, dexmetomidine 1.5 μg/kg and flurbiprofen ester 100 mg in 100 ml of normal saline. The Hospital Anxiety and Depression Scale (HADS) was used to assess the patients′ anxiety and depression at 1 day before operation (T 0) and 2 days after operation (T 1). The Quality of Recovery-15 scale was used to evaluate the early postoperative recovery quality. Visual analog scale scores, the pressing times of patient-controlled analgesia and the number of rescue analgesia were recorded within 2 days after operation. The occurrence of drug-related adverse reactions was also recorded. Results:Seventy-eight patients were finally included, with 39 cases in group E and 39 cases in group C. Compared with group C, the postoperative HADS-depression scale score and incidence of depression were significantly decreased, the Quality of Recovery-15 scale score was increased, the visual analog scale scores were decreased ( P<0.05), and no significant changes were found in the postoperative HADS-anxiety scale score and incidence of anxiety, the pressing times of patient-controlled analgesia and the number of rescue analgesia in group E ( P>0.05). Visual hallucination was found at 1 day after operation in one patient and relieved at 2 days after operation in group E. There was no significant difference in the incidence of postoperative dizziness, nausea and vomiting between the two groups ( P>0.05). Conclusions:Postoperative analgesia with 0.5 mg/kg esketamine can alleviate postoperative depressive symptoms, enhance the efficacy of analgesia and improve the early postoperative recovery quality in patients with gastrointestinal tumors.

BACKGROUND:The effect of electroacupuncture on the proliferation and differentiation of hippocampal oligodendrocytes in model mice with Alzheimer's disease remains poorly understood while demyelinating reaction related to oligodendrocytes is a common pathological reaction of Alzheimer's disease. OBJECTIVE:To investigate the effects and mechanism of electroacupuncture stimulation of"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)in Alzheimer's disease model mice on the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes. METHODS:Forty 6-week-old SPF APP/PS1 transgenic male Alzheimer's disease model mice were randomly divided into electroacupuncture group(n=20)and Alzheimer's disease model group(n=20).Healthy male C57BL/6J mice of the same age were used as normal controls(n=20).The mice in the electroacupuncture group received electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)for 16 weeks(20 minutes/day and one day off a week).After electroacupuncture,Morris water maze was used to detect the changes of learning and memory function.Immunohistochemistry was utilized to detect hippocampal dentate gyrus β-amyloid senile plaques.The expression of BrdU/NeuN and BrdU/GALC in the hippocampal dentate gyrus was detected by immunofluorescence double labeling.Western blot assay was used to detect the expression levels of neuron specific protein Nestin and oligodendrocyte specific protein GALC in the hippocampus.mRNA and protein levels of Notch1 and Hes1 in the hippocampus were detected by real-time fluorescence quantitative PCR and western blot assay. RESULTS AND CONCLUSION:(1)Compared with the normal control group,the ability of learning and memory in the Alzheimer's disease model group decreased significantly;hippocampal dentate gyrus β-amyloid senile plaques increased significantly(P<0.01);the expression of GALC and Nestin in the hippocampus decreased significantly(P<0.01,P<0.05).(2)Compared with the Alzheimer's disease model group,the learning and memory ability of the electroacupuncture group was significantly increased;β-amyloid senile plaque in the hippocampal dentate gyrus decreased significantly(P<0.01).BrdU/NeuN double labeled positive cells in the hippocampal dentate gyrus and Nestin protein expression in the hippocampus increased significantly(P<0.01,P<0.05);GALC expression in hippocampus increased significantly(P<0.01).The mRNA and protein levels of Notch1 in the hippocampus were significantly increased(P<0.05,P<0.01).The mRNA and protein levels of Hes1 in the hippocampus decreased significantly(P<0.05).(3)These findings indicate that electroacupuncture at"Baihui"(GV 20),"Fengfu"(GV 16)and bilateral"Shenshu"(BL 23)of the Alzheimer's disease model infant mice can promote the proliferation and differentiation of endogenous neural stem cells to neurons and oligodendrocytes,which may be regulated through the Notch1/Hes1 pathway.