Objective To explore the effects of Ginkgo biloba extract (GBE) on cardiac microvascular endothelial cells (CMECs) under oxygen and glucose deprivation/reperfusion (OGD/R) condition and its molecular mechanisms. Methods An OGD/R-induced injury model was established in CMECs. According to different intervention, CMECs were divided into four groups: normoxia blank control group (WT group), WT + GBE group, OGD/R group, and OGD/R + GBE group. Cell apoptosis was detected by flow cytometry technology in each group. The oxidative stress was examined by MitoSox staining. The migration abilities were measured by scratch assay. The expressions of PERK/eIF2α/CHOP, nuclear factor kappa B (NF-κB), and endothelial cell function markers were detected by Western blotting. Results Compared with the WT group, the endothelial cell apoptosis level in the OGD/R group significantly increased, with markedly aggravated cellular dysfunction. The expressions of p-NF-κB, vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were significantly upregulated (P＜0.05), and the activation of the CHOP signaling pathway was notably enhanced (P＜0.05). After intervention with GBE, endothelial cell apoptosis caused by OGD/R injury was significantly reduced, oxidative stress and inflammation levels were markedly downregulated, and the expression of p-NF-κB was considerably decreased (P＜0.05), while the CHOP signaling pathway was notably inhibited (P＜0.05). Furthermore, it was found that GBE could promote expression of SIRT6 to regulate the above molecules, thereby alleviating cardiac microvascular endothelial cell injury under OGD/R condition. On the contrary, when SIRT6 was knocked down, the protective effects were significantly reduced. Conclusions GBE improves endothelial cell dysfunction, endoplasmic reticulum stress, and endothelial cell apoptosis caused by OGD/R injury by promoting the expression of SIRT6 protein, thus regulating the NF-κB inflammatory pathway and CHOP signaling pathway.

Recently, significant progress has been made in the field of endovascular repair of complex aortic disease involving the major branches (aortic arch disease and complex abdominal aortic aneurysms). Open surgery was considered the “gold standard” for the treatment of these complicated aortic diseases, but was challenged by the huge surgical trauma and high risk of post-operative complications. However, the rapid development of branched and fenestrated endografts has provided an alternative safe and effective minimally invasive treatment for patients who cannot tolerate open surgery. Preliminary evidence has also shown that branched and fenestrated endografts have achieved significant technical success rates and clinical outcomes and have gradually become an important direction of innovation and development for endovascular repair of complex aortic disease. Nevertheless, both branched and fenestrated endografts are currently in the early stages of experience and a series of high-quality research studies are needed in the future to further compare them with open surgery and within different endovascular techniques.

Objective: To understand the growth and development levels of four physical measurements in children aged 3-6 years in China, so as to provide a reference for child nutrition improvement and health promotion. Methods: A stratified random sampling method was used to collect physical measurement data from 120 kindergartens 25 842 children aged 3-6 years across 24 provinces and cities in seven natural geographical regions of North China, Northeast China, East China, Central China, South China, Southwest China and Northwest China from 2020 to 2023. The development levels of head circumference, chest circumference, waist circumference, and hip circumference were evaluated using a grading method. The analysis of gender and age differences was conducted using Mann-Whitney U- test and Kruskal-Wallis test, and the comparison of abnormal detection rates for different genders was conducted using Chi square test. Results: The distribution range of children aged 3-6 was 51.74(50.08, 53.33) cm in terms of head circumference, 55.73(52.09, 59.04) cm in terms of chest circumference, 53.04(48.92, 56.40) cm in terms of waist circumference, and 59.36(56.30, 62.32) cm in terms of hip circumference. The detection rate of abnormal head circumference in boys and girls aged 3-6 years old was relatively high (19.71%-42.02%), and the detection rate of abnormal physical circumference development levels in boys was higher than that in girls of all ages ( χ 2=5.63-83.35, P <0.05). The detection rate of abnormal hip circumference (4.89%-6.53%) and chest circumference (4.51%-6.38%) in boys and girls aged 3-6 was relatively low, and there was no statistically significant difference in the abnormal rate between different ages and genders ( χ 2=0.00-1.61, 0.00-3.71, P >0.05). The detection rate of abnormal waist circumference in boys and girls aged 3-6 was relatively high (13.70%-42.45%), and the detection rate of abnormal waist circumference in girls was higher than that in boys aged 4-6 groups ( χ 2=10.49-58.18, P < 0.05). Conclusions The overall physical development of children aged 3-6 years in China is improving, but the abnormal detection rates for head circumference and waist circumference are relatively high. Child healthcare should focus on preventing and treating abdominal obesity, with differentiated health intervention strategies based on different age groups and genders.

OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury （CIRI） in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group， model group， Xinnao shutong low-dose， high-dose group （220， 440 mg/kg）， Ginkgo biloba leaves extract group （positive control， 150 mg/kg）. Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days. Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model； the samples were taken 24 h after the operation； the cerebral infarction area of rats was detected， and the cerebral infarction rate was calculated. The pathological changes of brain tissues were observed， and the levels of lipid peroxide （LPO）， malondialdehyde （MDA） and glutathione （GSH） in cerebral tissue were detected； mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase 1（HO-1） and glutathione peroxidase 4 （GPX4） were all detected in cerebral tissue of rats. RESULTS Compared with model group， the cerebral infarction rate， the content of total iron in cerebral tissue and serum level of LPO （except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group） were all decreased significantly in G. biloba leaves extract group and Xinnao shutong groups （P＜0.05 or P＜0.01）； the serum level of GSH， the protein and mRNA expressions of Nrf2， HO-1 and GPX4 were all increased significantly （P＜0.05 or P＜0.01）. The pathological damage to brain tissue was reduced， the number of nerve cells increased， the edema was alleviated， and the nuclear membrane was flattened. CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI， the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.

Recently, significant progress has been made in the field of endovascular repair of complex aortic disease involving the major branches (aortic arch disease and complex abdominal aortic aneurysms). Open surgery was considered the “gold standard” for the treatment of these complicated aortic diseases, but was challenged by the huge surgical trauma and high risk of post-operative complications. However, the rapid development of branched and fenestrated endografts has provided an alternative safe and effective minimally invasive treatment for patients who cannot tolerate open surgery. Preliminary evidence has also shown that branched and fenestrated endografts have achieved significant technical success rates and clinical outcomes and have gradually become an important direction of innovation and development for endovascular repair of complex aortic disease. Nevertheless, both branched and fenestrated endografts are currently in the early stages of experience and a series of high-quality research studies are needed in the future to further compare them with open surgery and within different endovascular techniques.

Objective: To investigate the mechanism by which serum amyloid P component (SAP) alleviates periodontitis in mice, providing an experimental basis to establish SAP as a novel therapeutic agent for periodontitis. Methods: Ethical approval was obtained from the Institutional Animal Ethics Committee. Periodontitis models were established in wild-type (WT) mice and SAP-transgenic (SAP-Tg) mice, divided into four groups: WT control (WT group), WT periodontitis (WT+P group), SAP-Tg control (Tg group), and SAP-Tg periodontitis (Tg+P group). On day 7, the mice were euthanized, and periodontal tissues, teeth, and alveolar bone were collected. SAP protein expression was detected by enzyme-linked immunosorbent assay (ELISA). Micro-CT and HE staining were used to measure alveolar bone resorption (distance from the cementoenamel junction to the alveolar bone crest). Tartrate-resistant acid phosphatase (TRAP) staining was performed to assess osteoclast number, and immunohistochemistry (IHC) was employed to evaluate macrophage infiltration. The expression levels of inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by qRT-PCR. Oral microorganism composition was analyzed using 16S ribosomal RNA (16S rRNA) gene sequencing. Additionally, macrophages from WT and SAP-Tg mice were isolated to establish an in vitro inflammation model, divided into WT+LPS and Tg+LPS groups. The expression of macrophage polarization-related genes including inducible nitric oxide synthase (iNOS), CD86, CD163, and CD206) were assessed by qRT-PCR. After the induction of osteoclast differentiation, TRAP staining was performed. Results: ELISA results demonstrated that periodontal tissues from Tg+P group mice exhibited higher levels of SAP expression compared to the WT+P group. Micro-CT and HE staining analyses revealed that the Tg+P group showed reduced alveolar bone resorption, indicated by a shorter distance between the cementoenamel junction and alveolar bone crest, compared to the WT+P group. Furthermore, TRAP staining results indicated a decrease in osteoclast numbers in the Tg+P group compared to the WT+P group. IHC and qRT-PCR results indicated reduced macrophage infiltration and decreased expression of IL-1β, IL-6, and TNF-α in the Tg+P group. Oral microorganism sequencing showed no significant difference in periodontitis-associated pathogenic bacteria between WT+P and Tg+P groups. In vitro experiments demonstrated that compared to the WT+LPS group, the Tg+LPS group exhibited downregulated M1 macrophage markers (iNOS and CD86) and upregulated M2 macrophage markers (CD163 and CD206). TRAP staining confirmed fewer osteoclasts in the Tg+LPS group. Conclusion SAP overexpression effectively alleviates periodontitis severity in mice by inhibiting M1 macrophage polarization, reducing pro-inflammatory cytokine expression, and suppressing osteoclast differentiation, thereby attenuating alveolar bone resorption.

This paper analyzed the traditional Chinese medicine （TCM） and western medical understanding of coronary microvascular disease （CMVD） from the three dimensions of "disease-syndrome-symptom". In western medicine， by summarizing the suspected diagnosis and understanding of CMVD， it is believed that inflammatory responses and vascular endothelial damage are the key mechanisms of the pathogenesis. From the perspective of TCM， the disease location is at blood， vessels and heart， and the fundamental cause is spleen and kidney depletion， closely realted to phlegm， stasis， toxin， wind and qi. Integrating the understanding of both TCM and western medicine， clinical treatment advocates taking the CMVD pathology as the base， and the TCM understanding of pathogenesis as the main focus. The properties of Chinese herbal medicinals is used as the guidance for medication， and the pharmacological understanding as the assisstance of treatment， with the medical history and the severity of the condition are additionally considered. It is finally proposed that during the acute phase， the methods of nourishing yin and resolving toxins， softening hardness and dissipating masses， dispelling wind and unblocking collaterals should be applied to alleviate the emergency. In the subacute phase， the focus should be on raising and lifting qi promote its movement， with flexible use of medicinals that can unblock yang. In the remission phase， the method of tonifying spleen and fortifying kidney should be used to maintain the stability of the condition.

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON₃ group), 7-day control group (CON₇ group), 3-day oil fume exposure group (COF₃ group), and 7-day oil fume exposure group (COF₇ group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4⁺ and CD8⁺T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF₃ group and the COF₇ group were significantly increased (P<0.05) except IL-6 in the COF₃ group, and the levels in the COF₇ group were significantly higher than those in the COF₃ group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF₇ group after HE staining. The flow cytometry results showed that the proportions of CD4⁺ and CD8⁺T cells in adipocytes of the COF₃ group and the COF₇ group were increased compared to the corresponding control group, with a significant increase in the COF₇ group (P<0.05), and the CD4⁺/CD8⁺T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF₃ group and the COF₇ group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF₃ group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF₇ group were significantly higher than those in the CON₇ group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

Background It is unclear if there is any combined effect of air pollutants and non-optimal temperature on metabolic syndrome, or any molecular mechanisms of related signaling pathways in the process, which requires urgent systematic research. Objective To observe the effects of combined exposure to PM_2.5 and non-optimal temperature on metabolic damage at gene and protein levels in mice, and elucidate the role of related signaling pathway in crucial organs. Methods A total of 60 six-week-old male C57BL/6J mice were randomly divided into six groups: a normal temperature-filter air group (T_N-FA), a normal temperature-concentrated PM_2.5 group (T_N-PM), a heat-filter air group (T_H-FA), a heat-concentrated PM_2.5 group (T_H-PM), a cold-filter air group (T_C-FA), and a cold-concentrated PM_2.5 group (T_C-PM). The Shanghai Meteorological and Environmental Animal Exposure System (Shanghai-METAS) was used to provide combined exposure settings of air types [concentrated PM_2.5 and filter air (FA)] and temperatures [normal (22°C), cold (4°C), and heat (30°C)] for 4 weeks. Skeletal muscle and white adipose tissue (WAT) of the mice were sampled at the end of exposure, and transcriptomics and Western blot (WB) assay were adopted to observe selected gene and protein expression levels in the samples respectively. Results The transcriptomics results indicated that the PM_2.5 exposure enhanced the number of differentially expressed genes. Specifically, 4820 genes were differentially expressed in the T_N-PM mice compared to the T_N-FA mice at normal temperature, and 1143 genes were differentially expressed in the Tc-PM mice compared to the Tc-FA mice in the cold environment. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway and the endoplasmic reticulum protein processing pathway were identified as the most significant pathways in metabolic injury resulting from combined exposure to PM_2.5 and non-optimal temperature exposure. The WB results showed that exposure to PM_2.5 in the normal temperature and the cold environments led to a significant increase in the expression of p-AKT in WAT (P<0.01, P<0.05) and a significant decrease in the expression of GLUT4 (P<0.05, P<0.01). In skeletal muscle, exposure to PM_2.5 led to a significant decrease in GLUT4 (P<0.05) in all environments, with a consistent trend of change as observed in WAT. Conclusion Cold/heat exposure might promote PM_2.5-induced metabolic disorder through suppression of the AKT/GLUT4 pathway, aggravating metabolic damage.

Objective:To analyze and summarize the efficacy and safety of thalidomide in the treatment of refractory systemic juvenile idiopathic arthritis（sJIA）.Methods:The clinical data of ten patients with refractory sJIA admitted to Department of Nephrology and Immunology in Children's Hospital of Hebei Province from January 2015 to March 2022 were collected，and the clinical manifestations，efficacy and safety of thalidomide in the treatment of refractory sJIA were analyzed retrospectively. Systemic juvenile arthritis disease activity score（sJADAS）was used to evaluate the efficacy of the treatment. Statistical analysis was performed by repeated measurements using general linear models.Results:Among the 10 children（4 males and 6 females）with refractory sJIA，the average age of onset was（7.5±3.3）years. Seven patients were complicated with macrophage activation syndrome at an early stage of disease.The average course of disease was（4.4±1.7）years，and the longest course of disease was 8.3 years. Before the application of thalidomide，all the 10 children experienced relapses（ranging from 2 to 10 times）. The indices of 10 children treated with thalidomide at 6 months and 12 months were compared with those before treatment. Peripheral blood leukocytes［（10.19±3.67）×10 9/L，（8.53±2.83）×10 9/L vs.（16.11±7.81）×10 9/L， F=7.918，11.084， P=0.020，0.009］，C-reactive protein［19.13（0.38，35.21）mg/L，8.05（0.10，18.00）mg/L vs. 59.34（24.20，131.90）mg/L， F=7.030，12.731， P=0.026，0.006］，sJADAS scores［6.00（1.50，12.50）scores，3.00（0，12.50）scores vs. 20.00（11.50，28.00）scores， F=14.710，17.870， P=0.004，0.002］were decreased significantly. The doses of prednisone［0.13（0，0.45）mg/（kg·d），0.02（0，0.06）mg/（kg·d）vs. 0.42（0.16，1.47）mg/（kg·d）， F=5.890，7.623， P=0.041，0.022］were significantly decreased.All the differences were statistically significant. Prednisone was successfully discontinued in 7 cases. Tocilizumab was gradually withdrawn in 3 cases，and tocilizumab administration interval was prolonged in 1 case. None of the 10 children had serious adverse reactions. Conclusion:Thalidomide is clinically effective in the treatment of sJIA，and can reduce the required dose of prednisone and prolong the tocilizumab free remission.