ObjectiveTo investigate the effects and mechanism of the combination of arsenic trioxide （ATO） and its dimethylarsinic acid （DMAV） metabolite on apoptosis of human acute promyelocytic leukemia NB4 cells by affecting the balance of metabolic reaction. MethodsThe rats were injected with the same amount of sterile normal saline， ATO（1.6 mg·kg^-1）， and DMAV（4， 8， 16， and 32 mg·kg^-1） combined with ATO（1.6 mg·kg^-1）， respectively， to obtain the corresponding drug-containing serum. The effect of drug-containing serum on the proliferation of NB4 cells was detected by the cell counting kit-8 （CCK-8 ）method. Apoptosis was detected by flow cytometry with Annexin-V-FITC/PI double staining. Intracellular reactive oxygen species （ROS） accumulation was detected by flow cytometry using fluorescent probe DCFH-DA. The changes of mitochondrial membrane potential （Δψm） were detected by the fluorescence probe JC-1. Western blot detected the expression of apoptosis-related proteins， namely B-cell lymphoma-2（Bcl-2）-associated X protein（Bax）/Bcl-2， Cytochrome C， cleaved Caspase-9， and cleaved Caspase-3， as well as c-Jun N-terminal kinase（JNK） phosphorylation levels. Results①The Combination of the two drugs had a higher proliferation inhibition rate and more apoptosis than ATO alone. ②The combination of two drugs can significantly increase the production of ROS compared with any single treatment group. ③The Δψm was significantly reduced in the two-drug combination group compared with any single treatment group. ④Compared with either group， the combination group significantly released Cytochrome C， significantly down-regulated the expression of Bcl-2， and up-regulated the expression of Bax， cleaved Caspase-3， and cleaved Caspase-9. ⑤The phosphorylation level of JNK was significantly up-regulated in the two-drug combination group compared with any single treatment group. ConclusionThe combination of DMAV and ATO may synergistically induce mitochondrial apoptosis through ROS-mediated oxidative stress， triggering Δψm dissipation and Cytochrome C release. By activating Caspase-9/Caspase-3 and the phosphorylation level of JNK， the Bcl-2 family protein （Bax/Bcl-2） was regulated to promote the apoptosis of NB4 cells.

Objective To provide data base for the development of X-ray computed tomography (CT) diagnostic reference levels suitable for the physical characteristics of residents in Qingdao City, China. Methods A total of 3351 cases of adult CT scan data derived from 14 devices were randomly selected from three tertiary hospitals and one primary hospital from January 1 to December 31, 2022. CT examination was performed on the brain, paranasal sinus, neck, chest, abdomen, cervical vertebrae, and lumbar vertebrae. The cases also included CT angiography (CTA) data on the brain, neck artery, pulmonary artery, and aorta. The data types included tube voltage (kV), effective tube current (mAs), computed tomography dose index volume (CTDI_vol), and dose length product (DLP). The 1st, 2nd, 3rd quartile values of CTDI_vol and DLP were calculated. Results Large differences were observed in DLP among different body parts of adults. The DLP value showed a descending order of craniocerebral CTA, craniocerebral CT, abdomen CT, lumbar vertebral spiral CT, aorta CTA, pulmonary artery CTA, paranasal sinus CT, chest CT, cervical vertebral spiral CT, and neck CT. The 3rd quartile DLP values of the brain and neck were 657.9 and 228.1 mGy·cm, respectively. The CTDI_vol of the brain was largest (3rd quartile, 52.0 mGy) and the CTDI_vol of the chest was smallest (3rd quartile, 8.2 mGy). Conclusion There are significant differences in CTDI_vol and DLP between different body parts of adults in Qingdao City, and CT radiation dose levels are relatively low compared to other regions in China and other countries.

Objective:This study is to investigate the relationship of parental anger expression and symptoms in children with oppositional defiant disorder(ODD).Methods:Forty-six children with ODD and 46 age-gender-matched normal children participated.The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),guided the diagnoses.Parental anger expression and children's anger management were assessed using the State-Trait Anger Expression Inventory-2 and Children Emotion Management Scales.Results:ODD symptoms were directly predicted by maternal anger index(AI)(β=0.13,P＜0.05)and anger expression-out(AX-O)(β=0.25,P＜0.05).Children's anger cope(AC)played a mediating function to maternal AI through ODD symptoms,occupying 13％of the total effect;their AC and anger dysregulation(AD)played a mediating function to maternal AX-Othrough ODD symptoms,accounting for 29％and 18％of the total effect,respectively.Conclusion:It sug-gests that anger cope and anger dysregulation in children with oppositional defiant disordermay may play a media-ting role between maternal anger expression and oppositional defiant disorder symptoms.

OBJECTIVE To explore the effect of paeoniflorin on glucose metabolism， inflammation and oxidative stress in rats with gestational diabetes mellitus （GDM） and its potential mechanism based on nuclear factor-erythroid 2-related factor 2 （Nrf2）/ heme oxygenase-1 （HO-1）/nicotinamide adenine dinucleotide phosphate：quinone oxidoreductase 1 （NQO1） signaling pathway. METHODS The female rats fed with high fat and high sugar diet and the male rats fed with an ordinary diet were caged， the successfully conceived rats were collected， and streptozotocin was injected intraperitoneally once to induce the GDM model. The successfully modeled rats were randomly divided into the model group， metformin hydrochloride group （200 mg/kg metformin by gavage）， paeoniflorin low-， high-dose groups （45， 90 mg/kg paeoniflorin by gavage， respectively）， paeoniflorin+ML385 group （90 mg/kg paeoniflorin by gavage and intraperitoneal injection of 30 mg/kg Nrf2 inhibitor ML385）， with 12 rats in each group； in addition， another 12 conceived rats fed with an ordinary diet were selected as the control group. The rats in each drug group were given the corresponding drug/normal saline， once a day， for 2 consecutive weeks. Glucose metabolism indexes [fasting blood glucose （FBG）， fasting insulin （FINS）， insulin resistance index （HOMA-IR）]， serum inflammatory factors [interleukin-6 （IL-6）， tumor necrosis factor- α （TNF- α）] and renal tissue oxidative stress indexes [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）] were detected； the pathological changes of renal tissue were observed， and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were detected. RESULTS Compared with the control group， the renal tissue lesions of the model group were obvious， including glomerular atrophy， edema degeneration of renal tubular epithelial cells and a large number of inflammatory cell infiltration； the levels of FBG and FINS， HOMA-IR， the levels of IL-6 and TNF-α in serum， and the level of MDA in renal tissue were significantly increased （P＜0.05）， while the levels of SOD and GSH-Px and the protein expressions of Nrf2， HO-1 and NQO1 in renal tissue were significantly decreased （P＜0.05）. Compared with the model group， the renal tissue lesions of rats in paeoniflorin low-dose and high-dose groups were reduced， the above quantitative indexes were significantly improved， and the improvement effect was better in high-dose group （P＜0.05）， while ML385 could significantly reverse the improvement effect of paeoniflorin on the above indexes （P＜0.05）. CONCLUSIONS Paeoniflorin can improve the abnormal glucose metabolism， inflammation and oxidative stress damage of renal tissue in GDM rats， which may be related to the activation of Nrf2/HO-1/NOQ1 signaling pathway.

Objective To explore the changes in cerebral blood flow caused by mandibular retrusion,as well as the impact and potential mechanisms on stroke recovery.Methods 6-week-old SD male rats were selected as experi-mental subjects.The metal cannula was bonded to the rat maxillary incisor for one week,forcing mandibular retru-sion(MR).Cerebral blood flow was detected by laser speckle imaging.Cognitive function was detected by the Morris water.Then,the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO)method for one week.Meanwhile,metal cannulae were then removed in rats to restore the lower jaw's position(MCAO RO),serving as a positive control group.Consequently,rats were randomly divided into the fol-lowing groups:Sham groups,MCAO groups,MCAO MR groups,and MCAO RO groups.Neurological recovery was assessed through the modified neurological severity score(mNSS).The area of cerebral infarction was evalua-ted by using triphenyltetrazolium(TTC)staining.The changes in nerve cells were observed by using hematoxylin eosin(HE)staining.The protein expression level of vascular endothelial growth factor(VEGF)was detected by immunohistochemistry.The protein expression levels of platelet-endothelial cell adhesion molecule(CD31),sirtuin 6(SIRT6),and thioredoxin interaction protein(TXNIP)were detected by Western blot.The mRNA expression levels of SIRT6,TXNIP,and VEGF were determined by qRT-PCR.Microglia activation marker molecule 1(IBA-1)was detected by immunofluorescence.Resluts Because of mandibular retrusion,laser speckle showed de-creased cerebral blood flow,and the water maze showed decreased cognitive function.Compared to other groups,MCAO MR showed a larger ischemic area in TTC staining,while HE staining and neurological scoring showed poo-rer neurological function recovery.Western blot and qRT-PCR showed that the MCAO MR group inhibited the mR-NA and protein expression levels of SIRT6,upregulated the mRNA and protein expression levels of TXNIP,and in-creased the activation of microglia.Conclusion Mandibular retrusion reduces cerebral blood flow and alters cogni-tive function in rats.Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Objective:To analyze the clinical characteristics of eosinophilic lung diseases(ELD) in children to enhance pediatricians′ understanding of ELD.Methods:In this retrospective cross-sectional study, a total of 149 children with ELD were recruited from Beijing Children′s Hospital, Capital Medical University between April 1, 2007 and March 31, 2022.Chi-square test, Fisher′s exact test, Mann-Whitney U test and Kruskal-Wallis test were used to analyze data and conclude clinical characteristics.Spearman correlation was used to analyze the correlation between eosinophils in peripheral blood and bronchoalveolar lavage fluid.Chi-square test and Kappa consistency test were used to compare the differences and consistency in diagnostic results between bronchoalveolar lavage fluid or lung biopsy and eosinophil elevation with chest imaging abnormalities. Results:(1)The isolated lung involvement was mostly caused by allergic bronchopulmonary aspergillosis(9 patients), and other system involvement by idiopathic hypereosinophilic syndrome(89 patients).(2)The main respiratory manifestations included coughing(90 cases, 60.4%) and expectoration(41 cases, 27.5%), while 23.5%(35 cases) of patients had no respiratory symptoms; 50.3% had digestive system involvement, and 40.9% had skin involvement.These were the two most commonly affected organs.(3)Spearman correlation was performed between eosinophils in peripheral blood and bronchoalveolar lavage fluid( r=0.3, P<0.05).Chi-square test was performed to compare ELD diagnosed by bronchoalveolar lavage fluid or lung biopsy with peripheral blood eosinophilia accompanied by abnormal chest imaging( P<0.05).Kappa consistency test(Kappa<0.2) showed poor consistency between the two diagnostic methods. Conclusions:ELD are present in children, and multiple etiologies may be pathogenic.Among children with ELD, the isolated lung involvement is mainly caused by allergic bronchopulmonary aspergillosis.The digestive system and skin are the most commonly affected organs, except for lungs.The correlation between eosinophil levels in peripheral blood and bronchoalveolar lavage fluid is poor.

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

Breast cancer is one of the most prevalent malignant tumors.Bone metastasis is a common complication during the entire course of breast cancer.The vicious cycle of"tumor-bone microenvironment"was easily formed,which led to the occurrence of bone-related events such as bone pain,pathological fractures,and hypercalcemia,etc.Studies have found that active ingredients of Tripterygium wilfordii exhibit the effect of anti-breast cancer and regulation of bone microenvironment,including inhibition of tumor cell proliferation and migration,inhibition of tumor angiogenesis,induction of autophagy in tumor cells,regulation of bone formation in osteoblast cell,inhibition of bone resorption in osteoclast cell,promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts,and regulation of immune microenvironment,which may be helpful to inhibit breast cancer and bone metastasis.This article systematically reviewed the research progress on pharmacological effects of Tripterygium wilfordii in preventing breast cancer and bone metastasis,analyzed the limitations and application prospects of the current research.

Objective:To establish an animal model of acute systemic cold injury in mice.Methods:There were 98 C57BL/6 mice, half male and half female, with body weight of 22-27 g and age of 10 weeks. The mice were randomly divided into 7 groups ( n=14) according to the changes of anal temperature in cold environment, namely, group A (38.5 ± 1) ℃, group B (35 ± 1) ℃, group C (30 ± 1) ℃, group D (25 ± 1) ℃, group E (20 ± 1) ℃, group F (15 ± 1) ℃, and group G (10 ± 1) ℃, among which, group A was the blank control group, and the rest groups were the experimental group. The mice in the blank control group were placed in the normal environment (20 ± 5) ℃, and the mice in the experimental group were placed in the low temperature artificial climate box at - 20℃. The anal temperature of the mice was measured intermittently (as the core temperature), and the time required for the core temperature of the mice to drop to groups B, C, D, E, F and G was recorded. The righting reflex was used to evaluate the consciousness state, the action ability and the general state of each organ of mice were observed, and the blood routine and HE staining of each organ were detected. Results:The lower the core temperature of the experimental group, the longer the time required. The consciousness state, action ability, general state of organs, blood routine, and HE staining of organs in groups B, C, and D were basically the same as those in group A, and there was no acute systemic cold injury. Therefore, the blood routine, general observation of organs, and HE staining of organs in groups B, C, and D were no longer displayed compared with those in group A. Compared with group A, mice in group E began to suffer from disturbance of consciousness and action ability. With the decrease of core body temperature, the damage was aggravated, and mice in group G died. Compared with group A, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group E began to decrease, and the univariate variance calculation showed that only WBC changes had statistical significance ( P<0.05). Compared with groups A and E, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group F were further reduced, and the changes of each index in univariate variance calculation were statistically significant ( P<0.05). The general observation results showed that compared with group A, the lung, liver and spleen surfaces of mice in group E began to darken, and compared with groups A and E, the lung, liver, spleen, kidney and heart of mice in group F were further deepened and darkened, with irregular edges. HE staining results of various organs showed that compared with group A, the mice in group E began to have partial alveolar structure destruction and a small amount of inflammatory cell infiltration, the central vein of the liver was slightly congested, and the red and white pulp of the spleen were indistinct. Compared with groups A and E, the pathological structure damage of the lung, liver, spleen, kidney, heart and brain tissues of the mice in group F was further aggravated. Conclusions:Detection of consciousness state, action ability, general state of organs, blood routine and HE staining indices of organs in mice under low temperature can simulate the progress of clinical acute cold injury, and the animal model of acute systemic cold injury was successfully prepared.