Objective:To construct the intracranial venous sinus thrombosis (CVST) models under plateau hypoxia by simulating plateau hypoxic condition, and further clarify the role of plateau hypoxa in CVST.Methods:Forty-eight 8-week-old male SD rats were randomly divided into sham-operated group, plateau sham-operated group, CVST group, and plateau CVST group ( n=12). CVST models in the CVST group and plateau CVST group were established by ferric chloride wet dressing, and rats in the plateau CVST group were kept in a low-pressure oxygen chamber for 2 d immediately after modeling to simulate plateau hypoxic condition at an altitude of 5,000 m (barometric pressure of 54.047 kPa, oxygen concentration of 10%-11%, and temperature of 18-23 °C). Only the bone flap and dura mater were separated in rats of the sham-operated group, without low-pressure oxygen condition or filter paper dressing. Only the bone flap and dura mater were separated in rats of the plateau sham-operated group, with plateau hypoxic condition at an altitude of 5,000 m for 2 d and without filter paper dressing. Intracranial venous sinus blood flow was detected by Doppler flowmetry before and 48 h after modeling. At 6, 24, and 48 h after modeling, 4 rats in each group were sacrificed; blood vessels at the thrombus of superior sagittal sinus (blood vessels at the superior sagittal sinus in the sham-operated group and plateau sham-operated group) were cut out and weighed; meanwhile, water contents of the brain tissues were calculated. HE staining was employed in the brain, heart, liver, lung, and kidney tissues and veins, and toluidine blue staining was peformed in the brain tissues only at 48 h after modeling. Results:(1) Doppler flowmetry indicated that intracranial venous sinus blood flow was normal in the 4 groups before modeling; intracranial venous sinus blood flow signals were normal in the sham-operated group and plateau sham-operated group and obviously weakened in the CVST group and plateau CVST group 48 h after modeling. (2) No thrombus was formed in the sham-operated group 48 h after modeling. At 6, 24 and 48 h after modeling, the thrombus in the CVST group ([15.44±1.90] mg, [12.63±1.26] mg, and [7.85±0.68] mg) and plateau CVST group ([20.38±1.67] mg, [24.93±2.37] mg, and [20.90±1.30] mg) weighted significantly heavier than those in the plateau sham-operated group ([2.55±0.38] mg, [2.19±0.30] mg, [1.75±0.31] mg), and that in the plateau CVST group weighted significantly heavier than that in the CVST group ( P<0.05); the thrombus weight in both plateau sham-operated group and CVST group decreased sequentially at 6, 24 and 48 h after modeling, with significant differences ( P<0.05); whereas, the thrombus weight in the plateau CVST group at 24 h after modeling increased compared with that at 6 h after modeling, and that at 48 h after modeling decreased compared with that at 24 h after modeling, with significant differences ( P<0.05). (3) At 6 h after modeling, the brain water contents in the sham-operated group, plateau sham-operated group, CVST group and plateau CVST group were (77.56±0.52)%, (77.57±0.92)%, (78.91±0.53)%, and (78.90±0.63)%, respectively, with statistical differences ( P<0.05); the CVST group and plateau CVST group had increased water content compared with the sham-operated group and plateau sham-operated group without significant differences ( P>0.05). At 24 and 48 h after modeling, the brain water content among the 4 groups was not statistically different ( P>0.05). (4) HE staining and toluidine blue staining indicated limited infarction, neuronal edema, and necrotic apoptosis in the brain tissues of plateau CVST group at 24 h after modeling. HE staining showed no obvious pathological changes in the myocardium, liver, lung, or kidney tissues in the 4 groups. Conclusion:CVST models can be successfully established by simulating plateau hypoxic condition through ferric chloride wet dressing and feeding in low-pressure oxygen chamber.

AIM:This study aimed to investigate the mechanism by which celoside I enhances mitophagy in a model of optic nerve injury through regulation of reactive oxygen species(ROS)-mediated c-Jun N-terminal kinase(JNK)/c-Jun signaling pathway.METHODS:Twenty-four New Zealand white rabbits were randomly divided into four groups:sham surgery,model,mecobalamin,and experimental group.Optic nerve injury was induced in the model,mecobala-min,and experimental groups,while the sham surgery group underwent a sham procedure.The mecobalamin group re-ceived mecobalamin,the experimental group received celoside I,and the sham surgery and model groups received saline.Interventions were administered daily for 28 d.Various techniques including endoscopy,hematoxylin-eosin(HE)stain-ing,TUNEL method,immunofluorescence staining and Western blot were used to assess fundus condition,retinal mor-phology,apoptosis,ROS expression,and protein levels in the retina.RESULTS:Fundus examination revealed im-proved blood flow in the mecobalamin and experimental groups compared to the model group.Retinal morphology showed enhanced retinal ganglion cells(RGCs)in the mecobalamin and experimental groups.Apoptosis index was lower in the mecobalamin group compared to the experimental group.Immunofluorescence staining indicated reduced ROS and P62 ex-pression and increased parkin and microtubule-associated protein light chain 3(LC3)expression in the experimental group compared to the mecobalamin group.Protein analysis showed decreased JNK,c-Jun,and P62 levels,and increased parkin and LC3 levels in the mecobalamin and experimental groups compared to the model group.CONCLUSION:Celo-side I reduces ROS expression,inhibits the JNK/c-Jun pathway,enhances mitophagy,reduces apoptosis,and protects RGCs in optic nerve injury models.

Objective To observe the role of dried tangerine peel in Yigong Powder improves iron metabolism and promotes red blood cell generation in anemia of chronic disease (ACD).Methods With a two-by-two factorial design,the Yigong Powder was divided into dried tangerine peel and Chenpi absent Decoction. According to the random number table method,32 zymosan-induced generalized inflammation (ZIGI) mice were randomly divided into the model group,the dried tangerine peel group,the Chenpi absent Decoction group,and the Yigong Powder group. The dried tangerine peel group,Chenpi absent Decoction group and the Yigong Powder group were given dried tangerine peel(3.083 g/kg),Chenpi absent Decoction(12.33g/kg),and Yigong Powder(15.413g/kg)by gavage to the corresponding group of mice. The model group was given an equal amount of physiological saline by gavage,and treated continuously for 7 days. After the completion of administration,the body weight of each group of mice was recorded. The hemoglobin content of each group of mice was detected using a fully automatic cell counter,the serum iron content was detected using colorimetry,the serum ferritin content was detected using enzyme-linked immunosorbent assay (ELISA),and the spleen index was calculated. The liver tissue inflammatory factors interleukin-1β (IL-1β),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),interferon-γ (IFN-γ),interleukin-4 (IL-4),and interleukin-10 (IL-10) levels were detected using Luminex method. The mRNA expressions of liver tissue hepcidin gene (HAMP) and membrane iron transporter ( Fpn) were detected using real-time fluorescence PCR method. Results Dried tangerine peel and Chenpi absent Decoction both showed interactive effects in regulating hemoglobin,serum iron,serum ferritin content,improving spleen index,and regulating the mRNA expressions of HAMP,Fpn,as well as IL-1β and IFN-γ (P<0.05). Compared with the model group,dried tangerine peel significantly increased hemoglobin,serum iron content,and Fpn mRNA expression in ZIGI model mice,while decreasing ferritin content,spleen index,HAMP mRNA expression,and the levels of IL-1β,IL-6,TNF-α,and IFN-γ (P<0.05). Chenpi absent Decoction significantly increased serum iron content and Fpn mRNA expression in ZIGI model mice,while reducing spleen index,ferritin content,HAMP mRNA expression,and the levels of IL-1β and IFN-γ、IL-4 (P<0.05). Conclusion The effects of dried tangerine peel on inflammatory factors (IL-6 and TNF-α) and Fpn may play a key role in the improvement effects of Yigong Powder on ACD and iron metabolism.

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Objective:To explore the pathogenesis of gallbladder cholesteryl polyps (GCP) and gallbladder cholesterol calculus (GCC) by studying the different changes of mucin (MUC) expression and reverse cholesterol transporter (RCT) in gallbladder mucosa epithelium.Methods:The data of 10 GCP patients (GCP group), 10 GCC patients (GCC group) and 5 patients with normal gallbladder resection (control group) were retrospectively analyzed, who underwent cholecystectomy in the Department of General Surgery, Xuanwu Hospital, Capital Medical University from January to December 2021. Among the 10 patients in the GCP group, there were 5 males and 5 females, aged (43.40±9.59) years old. Among the 10 patients in the GCC group, 5 males and 5 female, aged (45.00±8.13) years old. Among the 5 patients in the control group, there were 3 males and 2 females, aged (43.80±6.01) years old. Immunohistochemical analysis was used to investigate the expression differences of various subtypes of MUC and RCT [ATP binding cassette transporter G1 (ABCG1) and B group type I scavenger receptor (SR-BI)] among each group.Results:Compared with the control group, the expression of MUC1 (3.40±0.70 vs. 0), MUC5AC (1.50±0.53 vs. 0), MUC6 (4.70±0.48 vs. 0), and ABCG1 (3.50±0.53 vs. 1.60±0.55) in the gallbladder mucosa of the GCP group increased, while the expression score of SR-BI decreased (1.70±0.48 vs. 3.40±0.55), with statistical significance (all P<0.001). Compared with the control group, the expression of MUC1 (4.80±0.42 vs. 0), MUC5AC (4.70±0.48 vs. 0), MUC6 (3.30±0.67 vs. 0), and ABCG1 (3.40±0.52 vs. 1.60±0.55) in the gallbladder mucosa of the GCC group increased, while the expression score of SR-BI decreased (0 vs. 3.40±0.55), with statistically significant differences (all P<0.001). Conclusion:The different expression levels of MUC1, MUC5AC, MUC6, and RCT proteins lead to the differential formation of GCP and GCC on the basis of the co-pathogenesis in high cholesterol in bile.

Objective To investigate the effect of H₂O₂-induced oxidative stress on autophagy and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs). Methods hBMSCs were isolated and cultured. The cells were divided into control group, 3-MA group, H₂O₂ group, H₂O₂ combined with 3-MA group. DCFH-DA staining was used to analyze the level of reactive oxygen species (ROS). hBMSCs were treated with 0, 50, 100, 200, 400 μmol/L H₂O₂, and then the cell viability was detected by CCK-8 assay. The level of autophagy was detected by monodansylcadaverine (MDC) staining and LysoTracker Red staining. The cell apoptosis was detected by flow cytometry. Western blotting was used to detect the expression of beclin 1, mTOR, phosphorylated mTOR (p-mTOR), cleaved caspase-3(c-caspase-3) and caspase-3 proteins. Results Compared with the control group and 3-MA group, ROS level and autophagosomes were increased and the proliferation and apoptosis were decreased in H₂O₂ group. The protein expression of beclin 1, mTOR, c-caspase-3 was up-regulated, while the p-mTOR was down-regulated. Compared with the 3-MA group, the H₂O₂ combined with 3-MA group also had an increased ROS level and autophagosomes, but not with significantly increased apoptosis rate; The protein expression of beclin 1, mTOR, c-caspase-3 was up-regulated, and the p-mTOR was down-regulated. Conclusion H₂O₂ can induce hMSCs to trigger oxidative stress response. It enhances the autophagy and inhibits the proliferation and apoptosis of hBMSCs.
Humans ; Beclin-1/metabolism* ; Caspase 3/metabolism* ; Reactive Oxygen Species/metabolism* ; Hydrogen Peroxide/pharmacology* ; Apoptosis ; TOR Serine-Threonine Kinases/metabolism* ; Oxidative Stress ; Autophagy ; Mesenchymal Stem Cells/metabolism* ; Cell Proliferation

Objective:To investigate the optimal keV value of a novel dual-layer spectral detector CT virtual monoenergetic images (VMI) for displaying esophageal cancer lesions and to evaluate its diagnostic efficacy for preoperative T staging of esophageal cancer.Methods:The data of 50 patients with esophageal carcinoma in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from October 2019 to August 2020 were retrospectively analyzed. There were 42 males and 8 females, aged 49-78(65±7) years. All patients underwent novel dual-layer spectral detector CT chest enhanced scan before treatment, the conventional CT images and 40-200 keV VMI were reconstructed. One-way ANOVA and Kruskal-Wallis H rank sum test were used to compare the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) among conventional CT images and 40-200 keV VMI.The 5-grade grading method were applied for subjective evaluation, and the Friedman test was used to compare the differences in the subjective evaluation of image quality in each group.Spearman test was used to analyze the correlation of images at different energy levels with SNR and CNR. Fisher exact test was used to compare the accuracy of conventional CT and optimal keV value images for preoperative diagnosis of T staging of esophageal cancer. Results:There were significant differences in SNR and CNR among conventional CT images and 40-200 keV VMI images ( P<0.001), and the SNR and CNR of 40 keV images were superior to those of conventional CT images and 70-200 keV VMI images ( P<0.05). The energy level of 40-200 keV VMI was negatively correlated with SNR and CNR (SNR: r=-1.000, P<0.001; CNR: r =-1.000, P<0.001). The overall difference in subjective image quality scores among conventional CT images and 40-200 keV VMI was statistically significant (χ 2=498.37, P<0.001), of which the subjective image quality of 40-60 keV VMI was superior to that of conventional CT images ( P<0.05). The accuracy of preoperative diagnosis of T-stage of esophageal cancer was 62.9% (22/35) for both 40 keV VMI and conventional CT images. Conclusion:The novel dual-layer spectral detector CT of 40 keV VMI has the best display of esophageal cancer, and the accuracy of preoperative diagnosis of T staging is similar to that of conventional CT.

Objective:To explore effects of establishing a modified Subjective Global Assessment (SGA) -based nutritional management scheme in undergoing maintenance hemodialysis (MHD) .Methods:Using the convenient sampling method, a total of 208 patients who received MHD treatment in Jinhua Hospital of Traditional Chinese Medicine from September 2019 to December 2020 were selected as the research subjects. They were divided into the control group and the observation group according to random number table method, with 104 cases in each group. The control group received routine nutrition intervention, while the observation group received nutritional management scheme based on modified SGA at basis of the control group. The nutritional indicators, anthropometric indicators, renal function indicators before and after 6 months of intervention and the total incidence of complications after 6 months of intervention were compared between the two groups.Results:After 6 months of intervention, the nutritional indexes and anthropometric indexes of the observation group were higher than those of the control group and the renal function index were lower than those of the control group, and the differences were statistically significant ( P<0.05) . The total incidence of complications in the observation group was 55.77% (58/104) , which was lower than 80.77% (84/104) in the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The establishment of the modified SGA-based nutritional management scheme in MHD patients can ensure reasonable nutritional intake, improve nutritional index levels, reduce inflammatory response, improve immune function, maintain stable renal function, and reduce the occurrence of complications.

The diagnosis and management of myocarditis in children is a major challenge for pediatric cardiologists.In 2021, the American Heart Association redefined pediatric myocarditis after summarizing existing relevant information and treatment strategies for pediatric myocarditis, which emphasized the immunopathogenesis, new and conti-nuously changed main causes, modern laboratory testing methods and advances in the use of mechanical circulatory support.In particular, innovations of cardiac magnetic resonance in children myocarditis have been highlighted.The main contents of the statement to help pediatricians understand the diagnosis and management of myocarditis in children are interpreted.

Low back pain is becoming an important factor that affects people's quality of life today, and the social losses caused by lowback pain are hugeevery year. Lumbar disc herniation (LDH) is one of the main diseases that cause low back pain. The mechanism of lumbar disc herniation in the biomedical science is still controversial. Inflammatory factor is a cytokine secreted by tissue cells and involved in mediating the inflammatory response. Studies have shown that some factors stimulated by the extrusive nucleus pulposus, like inflammatory factors, degeneration-related genes and downstream expression products, can cause the degeneration of intervertebral disc. IL-1, IL-6, TNF-α, MMPs, and TGF-β have become the hot topicin disc degeneration. Signaling pathway is the main pathway for inflammatory factors to participate in the regulation of various biochemical reactions in cells. The inflammatory factors interact with different proteins to activate or inhibit different pathways, thereby achieving regulation of the cell cycle, regulates gene expression, induces immune inflammatory response, and apoptosis. Research on the role of various inflammatory factors in the body and related molecular signaling pathways will help us understand the mechanism of LDH. Most of the experimental studies only focus on the influence of a certain cytokine or single pathway on intervertebral disc degeneration, but different inflammatory factors and their signaling pathways often crosstalk with each other through special channels, forming a complex and precise signal transduction regulation network jointly regulates various physiological or pathological processes in the body, and the occurrence of disease is often accompanied by multiple factors. Studying the effect of a single signal network on the disease cannot fully explain the cause of the disease and related clinical manifestations. Therefore, clarifying the role of various inflammatory factors in IDD and exploring and analyzing the ways in which each factor regulates each other will provide ideas for understanding the mechanism of lumbar degeneration and exploring new methods for preventing and treating LDH in the future.