The decrease in blood glucose in perinatal dairy cows affects the energy supply and im-mune function of peripheral blood neutrophils(PMN).Fibroblast growth factor 21(FGF21)is an important regulator of glucose metabolism,and serum FGF21 levels in some perinatal cows are significantly elevated after farrowing.In order to explore the effect of FGF21 on PMN glucose ho-meostasis in perinatal dairy cows,the cows were divided into high FGF21 group(high FGF21,n=8,FGF21＞800 ng/L)and low FGF21 group(low FGF21,n=8,FGF21＜200 ng/L)within 3 weeks postpartum.The results showed that compared with the low FGF21 group,the glucose up-take of PMN and the mRNA expression of glucose transporters SLC2A1 and SLC2A3 were signifi-cantly increased in the high FGF21 group.The activities of phosphofructokinase 1(PFK1)and glu-cose-6-phosphate dehydrogenase(G6PDH)were significantly increased,and the activity of glyco-gen synthase(GCS)was significantly decreased in PMN in the high FGF21 group.The lactate con-tent and ATP content of PMN were significantly increased,and the mRNA and protein expressions of hexokinase(HK2)and PFK1 were significantly increased in the high FGF21 group.These re-sults indicated that the uptake and utilization of glucose by PMN in perinatal peripheral blood FGF21 increased to ensure the ATP supply of PMN,which provided a theoretical basis for the pro-posal of a new strategy to alleviate immunosuppression in perinatal dairy cows.

Objective To explore the role of Erianin in atopic dermatitis(AD)and its regulatory mechanism involving the high-mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)-Ras homolog gene family member A(RhoA)/Rho-associated protein kinase 1(ROCK1)signaling pathway.Methods An AD model was induced in BALB/c mice using 1-chloro-2,4-dinitrobenzene(DNCB).Skin thickness and spleen and lymph node weight were measured and pathological changes in the back skin and ears were detected using methylamine blue and hematoxylin and eosin staining.Inflammatory factors were detected by enzyme-linked immunosorbent assay.An in vitro model of AD was established in HaCaT cells stimulated by tumor necrosis factor(TNF)-α.Cellular reactive oxygen species(ROS)were detected by flow cytometry and mitochondrial ROS(mtROS)were detected by immunofluorescence assay.Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling.HMGB1,RAGE,RhoA,and ROCK1 proteins were detected by Western blot.Results Erianin inhibited the increase in skin thickness,reduced the spleen and lymph node weights,improved the infiltration of inflammatory cells and the degranulation of mast cells,and reduced the levels of inflammatory factors(P＜0.05).Erianin also reduced the production of cellular ROS and mtROS induced by TNF-α in vitro(P＜0.01),and decreased the protein expression of HMGB1,RAGE,RhoA,and ROCK1(P＜0.01).Treatment of HMGB1-stimulated HaCaT cells with a RAGE-specific blocker(TFA)had no effect on HMGB1 expression,while expression levels of RAGE,RhoA,and ROCK1 were decreased(P＜0.01).Cells treated with the Rho kinase inhibitor Y-27632+r-HMGB1 group showed similar result to the TFA+r-HMGB1 group,except for RAGE.Conclusions Erianin relieves AD by regulating the HMGB1/RAGE-RhoA/ROCK signaling pathway.

Objective To develop the Children's Screen Interaction Quality Questionnaire(CSIQ)suit-able for measuring Chinese children aged 0 to 4 years,and to test its reliability and validity.Methods The purposive sampling method was used,and the guardians of 30 normal children aged 0 to 4 years undergoing physical examinations in the Department of Child Health Care of Guiyang Maternal and Child Health Care Hospital from February to April 2023 were selected as the interview objects.25 initial items were constructed through literature review,semi-structured interviews,and the Delphi expert consultation method.With the convenience sampling method,2 242 guardians of children aged 0 to 4 years old in the small and middle classes of 9 kindergartens in Guiyang City,Zunyi City,and Renhuai City were surveyed for item analysis,exploratory factor analysis,confirmatory factor analysis,and reliability and validity analysis.Results Exploratory factor a-nalysis extracted three factors,namely screen content interaction,reality interaction,and media interaction,with a total of 12 items.The cumulative variance explained rate of the 3-factor model was 69.829％.Confirma-tory factor analysis supported the three-factor model of CSIQ:x2/df=4.424,root mean square error of ap-proximation(RMSEA)=0.066,normed fit index(NFI)=0.955,comparative fit index(CFI)=0.965,incre-mental fit index(IFI)=0.965,Tucker-Lewis index(TLI)=0.955,goodness-of-fit index(GFI)=0.955,and the CSIQ had good convergent validity and discriminant validity.Conclusion The CSIQ has good reliability and validity.

OBJECTIVES: This study explores the differences in fluid flow within alveolar cancellous bone at various sites under orthodontic forces and elucidates the relationship between fluid shear stress and bone remodeling. These fin-dings lay the groundwork for understanding the biomechanical mechanisms of orthodontic tooth movement. METHODS: Stress relaxation tests were performed on human alveolar bone samples to determine material parameters by using the Prony series. An inverse model of alveolar bone was then developed for numerical simulations of fluid-structure interactions to calculate fluid flow within cancellous bone. Meanwhile, a rat model of tooth movement was established to investigate variations in bone remodeling speeds across different regions. RESULTS: The microstructural distribution of cancellous alveolar bone was similar in humans and rats. The bone volume fraction and trabecular thickness gradually decreased from root cervical region to root apical region, while the trabecular space gradually increased. Under the influence of orthodontic forces, fluid shear stress within cancellous bone showed spatial variability across different levels, with the highest shear stress occurring at the root apical region, ranging from 0 to 0.936 6 Pa. Additionally, the rat model of tooth movement indicated that bone remodeling occurred more rapidly at the root apical region. CONCLUSIONS Fluid stimulation has a remarkable effect on al-veolar bone remodeling, causing changes in the structure of alveolar bone and ultimately regulating the speed of structu-ral remodeling.
Bone Remodeling ; Animals ; Tooth Movement Techniques ; Rats ; Alveolar Process/physiology* ; Stress, Mechanical ; Humans ; Biomechanical Phenomena ; Cancellous Bone/physiology* ; Shear Strength

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objective:To investigate the differences in prognosis between different surgical approaches in elderly patients with advanced ovarian cancer.Methods:Based on the Surveillance, Epidemiology and End Results (SEER) database, a cohort of elderly patients with advanced ovarian cancer from 2000 to 2020 was established. Through propensity score matching, 2 094 patients were selected from those who underwent two different surgical approaches to form a matched cohort (SEER database cohort), including 1 039 patients who received cytoreductive surgery and 1 055 patients who underwent local resection. Meanwhile, 148 elderly patients with advanced ovarian cancer who were treated at the First Affiliated Hospital of Shandong First Medical University from January 2012 to January 2024 were selected (hospital cohort), among whom 85 underwent cytoreductive surgery and 63 underwent local resection. The prognostic differences among patients who underwent cytoreductive surgery and local resection in two cohorts and stratified by the International Federation of Gynecology and Obstetrics (FIGO) staging were evaluated, respectively. The relationship between the causes of death and surgical approaches in elderly patients with advanced ovarian cancer was analyzed.Results:In the SEER database cohort, the median overall survival (OS) for patients who underwent cytoreductive surgery and local resection was 37 and 40 months, respectively, with 5-year OS rates of 31.47% and 33.74%, with no statistically significant difference ( χ2=0.78, P=0.378). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC who underwent cytoreductive surgery ( n=998) and local resection ( n=962) was 38 and 40 months, respectively, with no statistically significant difference ( χ2=0.20, P=0.659). For patients with stage Ⅳ, the median OS for those who underwent cytoreductive surgery ( n=41) and local resection ( n=93) was 17 and 36 months, respectively, with a statistically significant difference ( χ2=9.37, P=0.002). Among 2 094 elderly patients with advanced ovarian cancer, 1 581 had clearly identified causes of death. In patients who underwent cytoreductive surgery, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 94.52% (742/785) and 5.48% (43/785), respectively. In patients who underwent local resection, the proportions of deaths due to ovarian cancer and non-ovarian cancer were 91.46% (728/796) and 8.54% (68/796), respectively. There was a statistically significant difference in the distribution of causes of death between the two surgical approaches ( χ2=5.69, P=0.017). In the hospital cohort, the median OS for patients undergoing cytoreductive surgery and local resection was 39 and 51 months, respectively, with 5-year OS rates of 22.85% and 23.81%, with a statistically significant difference ( χ2=6.71, P=0.010). After stratification by FIGO staging, the median OS for patients with stage ⅢB-ⅢC undergoing cytoreductive surgery ( n=29) and local resection ( n=26) was 50 and 51 months, respectively, with no statistically significant difference ( χ2=0.15, P=0.699) ; for patients with stage Ⅳ undergoing cytoreductive surgery ( n=56) and local resection ( n=37), the median OS was 35 and 47 months, respectively, with a statistically significant difference ( χ2=6.55, P=0.011) . Conclusions:The survival outcomes of local resection in elderly patients with advanced ovarian cancer are not inferior to those of cytoreductive surgery. For FIGO stage Ⅳ patients, the survival period following local resection is superior to that of cytoreductive surgery.

This study aims to investigate the anti-inflammatory and anti-apoptotic effects of total flavonoids of hawthorn leaves(TFHL)on lipopolysaccharide(LPS)-induced inflammatory injury in rat intestinal epithelial(IEC-6)cells,as well as the underlying mechanisms.An in vitro inflam-mation model was first established by treating IEC-6 cells with lipopolysaccharide(LPS).IEC-6 cells were then incubated with three concentrations of TFHL for 24 h prior to a further 24 h LPS treatment.RT-qPCR was used to quantify mRNA levels of the inflammatory genes COX-2 and iN-OS,while Western blotting was used to assess protein levels of the apoptotic markers Bax,cleaved Caspase-3,Bcl-2,and the JNK/p-JNK signaling pathway.Finally,cells were pretreated with TFHL and/or the JNK inhibitor SP600125 for 24 h before LPS exposure for 24 h,in order to evaluate the combined effects of TFHL and SP600125 on LPS-induced inflammatory cytokine expression and apoptotic protein levels in IEC-6 cells.The results showed that,compared with the LPS group,the mRNA level of COX-2 and iNOS in the 2.5,5.0,10.0 mg/L TFHL group and the Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and the Bcl-2 protein level was significantly higher(P＜0.01),p-JNK protein level and p-JNK/JNK ratio decreased significantly(P＜0.01);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+LPS group de-creased significantly(P＜0.01),Bax,and Caspase-3 protein levels decreased significantly(P＜0.01),and the level of Bcl-2 protein increased significantly(P＜0.05);compared with the LPS group,the COX-2 and iNOS mRNA levels of the TFHL+SP600125 group decreased significantly(P＜0.01),Bax and Caspase-3 protein levels decreased significantly(P＜0.01),and Bcl-2 protein level increased significantly(P＜0.01).These findings indicate that TFHL exerts anti-inflammato-ry and anti-apoptotic effects in LPS-challenged IEC-6 cells by inhibiting the JNK signaling path-way.

The decrease in blood glucose in perinatal dairy cows affects the energy supply and im-mune function of peripheral blood neutrophils(PMN).Fibroblast growth factor 21(FGF21)is an important regulator of glucose metabolism,and serum FGF21 levels in some perinatal cows are significantly elevated after farrowing.In order to explore the effect of FGF21 on PMN glucose ho-meostasis in perinatal dairy cows,the cows were divided into high FGF21 group(high FGF21,n=8,FGF21＞800 ng/L)and low FGF21 group(low FGF21,n=8,FGF21＜200 ng/L)within 3 weeks postpartum.The results showed that compared with the low FGF21 group,the glucose up-take of PMN and the mRNA expression of glucose transporters SLC2A1 and SLC2A3 were signifi-cantly increased in the high FGF21 group.The activities of phosphofructokinase 1(PFK1)and glu-cose-6-phosphate dehydrogenase(G6PDH)were significantly increased,and the activity of glyco-gen synthase(GCS)was significantly decreased in PMN in the high FGF21 group.The lactate con-tent and ATP content of PMN were significantly increased,and the mRNA and protein expressions of hexokinase(HK2)and PFK1 were significantly increased in the high FGF21 group.These re-sults indicated that the uptake and utilization of glucose by PMN in perinatal peripheral blood FGF21 increased to ensure the ATP supply of PMN,which provided a theoretical basis for the pro-posal of a new strategy to alleviate immunosuppression in perinatal dairy cows.

Objective To explore the role of Erianin in atopic dermatitis(AD)and its regulatory mechanism involving the high-mobility group box 1(HMGB1)/receptor for advanced glycation end products(RAGE)-Ras homolog gene family member A(RhoA)/Rho-associated protein kinase 1(ROCK1)signaling pathway.Methods An AD model was induced in BALB/c mice using 1-chloro-2,4-dinitrobenzene(DNCB).Skin thickness and spleen and lymph node weight were measured and pathological changes in the back skin and ears were detected using methylamine blue and hematoxylin and eosin staining.Inflammatory factors were detected by enzyme-linked immunosorbent assay.An in vitro model of AD was established in HaCaT cells stimulated by tumor necrosis factor(TNF)-α.Cellular reactive oxygen species(ROS)were detected by flow cytometry and mitochondrial ROS(mtROS)were detected by immunofluorescence assay.Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling.HMGB1,RAGE,RhoA,and ROCK1 proteins were detected by Western blot.Results Erianin inhibited the increase in skin thickness,reduced the spleen and lymph node weights,improved the infiltration of inflammatory cells and the degranulation of mast cells,and reduced the levels of inflammatory factors(P＜0.05).Erianin also reduced the production of cellular ROS and mtROS induced by TNF-α in vitro(P＜0.01),and decreased the protein expression of HMGB1,RAGE,RhoA,and ROCK1(P＜0.01).Treatment of HMGB1-stimulated HaCaT cells with a RAGE-specific blocker(TFA)had no effect on HMGB1 expression,while expression levels of RAGE,RhoA,and ROCK1 were decreased(P＜0.01).Cells treated with the Rho kinase inhibitor Y-27632+r-HMGB1 group showed similar result to the TFA+r-HMGB1 group,except for RAGE.Conclusions Erianin relieves AD by regulating the HMGB1/RAGE-RhoA/ROCK signaling pathway.