Based on advancements in modern medical research regarding the intricate connection between the endocrine and exocrine functions of the pancreas， as well as the relationship between pancreatic functions and traditional Chinese medicine （TCM） spleen system， this paper discussed the categorization of the pancreas. It is proposed that the pancreas is neither a true zang organ nor a fu organ， but possessed the attributes of an extraordinary fu-organ and can be classified under the spleen. The spleen governs transportation and transformation， ascent of the clear and dispersion of essence， which encompasses the endocrine and exocrine functions， and pancreatic enzymes and glucose-regulating hormones form the material basis for the spleen's function of dispersing essence. Diseases of the pancreas exhibit characteristics of both zang-organ deficiency and fu-organ excess， so treatment should simultaneously supplement zang-organ disease and regulate fu-organ disease when pancreas showing endocrine and exocrine co-morbidities， with focus on restoring the pancreas （spleen）'s dispersing essence function. Therapeutic strategies include supplementing spleen qi， nourishing spleen yin to strengthen spleen earth， unblocking spleen collaterals， raising spleen yang， and removing spleen turbidity to support the spleen's dispersing essence function， so as to replenish the essential qi of zang-fu organs， ensure their distribution throughout the body， and improve the endocrine and exocrine functions of the pancreas.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome

Objective:To compare the effect of high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV) in the treatment of pediatric acute respiratory distress syndrome (ARDS).Methods:A prospective randomized controlled study was conducted on ARDS children treated with mechanical ventilation in the Intensive Care Unit (ICU) of Children′s Hospital, Capital Institute of Pediatric from January 2017 to December 2018.They were randomly (computer digital method) divided into HFOV group and CMV group.The basic data and clinical indicators, such as pediatric critical illness scores, oxygenation index (OI), blood gas, mechanical ventilation time, ventilator parameters, ICU hospitalization time, complications, prognosis, dynamic changes of inflammatory factors, use of sedative muscle relaxants and vasoactive drugs, were recorded.SPSS 22.0 software was used to analyze the data.The Mann Whitney U test was used for inter-group comparison.The χ2 test was adopted for the comparison of counting data. Results:A total of 45 children were included in the analysis.There were 21 cases in the HFOV group and 24 cases in the CMV group.Moderate and severe ARDS was detected in 34 cases, including 16 cases in the HFOV group and 18 cases in the CMV group.Compared with those in the CMV group, the levels of OI-24 h and OI-48 h in the HFOV group were significantly lower [7.4 (5.9, 8.6) vs.9.0 (6.7, 13.6), P=0.018] and [5.9 (5.2, 8.5) vs.9.2 (7.4, 12.4), P=0.001].The levels of OI-6 h [8.2(6.5, 10.0) vs.10.5(8.2, 13.0), P=0.037], OI-12 h[7.8(6.5, 9.0) vs.9.8(8.0, 12.8), P=0.009], OI-24 h [7.7(6.4, 8.6) vs.10.1(8.7, 15.5), P<0.001], OI-48 h [6.0(5.3, 8.6) vs.10.7(8.8, 13.1), P<0.001] and OI-72 h [5.8(5.0, 8.6) vs. 8.0(6.6, 10.6), P=0.031] in children with moderate to severe ARDS of the HFOV group were significantly lower than those of the CMV group.There were no significant differences in ICU hospitalization time, invasive mechanical ventilation time, total mechanical ventilation time, 28-day prognosis, vasoactive drugs, muscle relaxants, blood purification, fluid balance, inflammatory factors, intracranial hemorrhage and pneumothorax between the 2 groups. Conclusions:This study confirms that HFOV can improve the oxygenation level in pediatric patients with ARDS more rapidly than CMV.HFOV does not increase the incidence of complications such as pneumothorax and intracranial hemorrhage, and the use of vasoactive drugs and muscle relaxants, showing safety in clinical application.

Objective To develop a data-driven model for estimating tangential ground reaction force(GRFt)from lower limb kinematic data and select the most suitable input based on a balance between input quantity and estimation accuracy,with the aim of measuring GRFt in outdoor gait experiments.Methods Gait data from ten subjects walking at five different inclines(-10°,-5°,0°,5°,10°)were used to train two data-driven models,namely a backpropagation neural network(BPNN)-based model and a polynomial sparse identification(PSI)-based model.The performance of these models was evaluated using eight kinematic data combinations and the normal ground reaction force(GRFn)as inputs to determine the optimal model and input combination.Results Under the same input dimensionality,the combination of hip-knee joint angles proved more accurate in estimating GRF,than the knee-ankle joint angle combination.Specifically,the BPNN and PSI models based on the former combination predicted GRF,with errors of 1.61％BW(body weight)and 1.84％BW,respectively,while the latter combination resulted in errors of 2.82％BW and 3.15％BW.When GRFn and all joint angles were used as inputs,the model's prediction error was only 1.46％BW.Conclusions The combination of GRFn and hip-knee joint angles achieves an optimal balance between computational complexity and estimation accuracy.This study supports the accurate estimation of GRF,in outdoor gait testing.

BACKGROUND:The liver,as the main target organ for arsenic toxicity,has become the focus of studies related to the mechanism of action of arsenic toxicity.OBJECTIVE:To investigate the effects of sodium arsenite(NaAsO2)on lipid metabolism,cell proliferation,apoptosis,and expression of related regulatory factors in human normal hepatocytes.METHODS:MIHA normal human hepatocyte cell lines were exposed to 0,10,20,and 30 μmol/L NaAsO2 for 48 hours.Cell morphology changes were observed by light microscopy.Cell viability was detected by CCK-8 assay.The cell serum total cholesterol,triacylglycerol,and total bile acids were detected by single-agent COD-PAP assay,single-agent GPO-PAP assay,and enzyme microplate assay.The intracellular lipid content was detected by oil red O staining.Cell proliferation was detected by Edu-488 infiltration.Cell cycle and apoptosis were detected by PI staining and Annexin V-FITC/PI dual-labeling combined with flow cytometry.The mRNA and protein expression levels of hepatocyte nuclear factor 4 alpha,cholesterol 7α-hydroxylase,and farnesoid X receptor were detected by real-time fluorescence quantitative PCR and western blot assay,respectively.RESULTS AND CONCLUSION:(1)Compared with the control group(0 μmol/L NaAsO2),with the increase of NaAsO2 concentration:MIHA cell viability decreased gradually.The content of total cholesterol and triacylglycerol in cell supernatant increased gradually,while the contents of total bile acids decreased gradually.The content of intracellular lipid increased gradually.The proportion of cells stagnating in S phase and G2/M phase gradually increased,and the apoptosis rate gradually increased.The expression level of hepatocyte nuclear factor 4 alpha mRNA did not show significant changes,while cholesterol 7α-hydroxylase and farnesoid X receptor mRNA expression levels decreased.The protein expression levels of hepatocyte nuclear factor 4 alpha,cholesterol 7α-hydroxylase,and farnesoid X receptor decreased gradually.(2)NaAsO2 has cytotoxicity,significantly reduces MIHA cell viability,induces cell steatosis,inhibits cell proliferation,and induces cell apoptosis.NaAsO2 down-regulates hepatocyte nuclear factor 4 alpha protein expression and the transcription and expression of cholesterol 7α-hydroxylase and farnesoid X receptor,which further induces lipid metabolism disorders in hepatocytes.

Grounded theory, as a flexible and systematic research method, serves as an important tool for gaining an in-depth understanding of clinical phenomena and nursing practice. This paper reviews the origin and development of grounded theory, its concepts and classifications, methodological procedures, and the necessity, significance, and current status of its application in the field of hospice care. The aim is to enhance the scientific application of grounded theory in hospice care research in China.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective To systematically evaluate the psychometric properties of specific self-reported outcome assessment tools for patients undergoing Endoscopic Transnasal Transsphenoidal Surgery(ETTS),with the aim of pro-viding clinical healthcare professionals with evidence to guide the selection of appropriate assessment tools.Methods A systematic search was performed across multiple databases,including the North American Skull Base Society,PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,VIP database,Wanfang database,and the China Biomedical Literature Database,for studies published from the inception of each database to January 9,2025,that are related to ETTS-specific symptom assessment tools.Totally 2 independent researchers screened the literature and extracted relevant data.The consensus-based health measurement tool selection bias risk checklist and quality standards were used to evaluate the methodological quality and psychometric properties of the included studies,which helped to form the development of recommendations.Results A total of 11 articles were included,covering 8 specific self-reported outcome assessment tools for patients undergoing endonasal transsphenoidal pituitary tumor resection.Of these,the Pituitary Outcome Score and the Leiden Bother and Needs Questionnaire for patients with pituitary disease 2 tools were rated as Grade A recommendations,and 6 tools were rated as Grade B recommendations.Conclusion POS and LBNQ-Pituitary are recommended due to their relatively strong overall methodological quality and psychometric properties.However,further validation with larger sample sizes is necessary.