Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P＜0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P＜0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P＜0.05)and negatively correlated with the expression of FBXL5 and FTH1(P＜0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P＜0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P＜0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P＜0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P＜0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P＜0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

OBJECTIVE: To evaluate the effect and safety of Chinese medicine (CM) Fuzheng Huazhuo Decoction (FHD) in treating patients with coronavirus disease 2019 (COVID-19) who persistently tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This retrospective cohort study was conducted at Shanghai New International Expo Center shelter hospital in China between April 1 and May 30, 2022. Patients diagnosed as COVID-19 with persistently positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results for ⩾8 days after diagnosis were enrolled. Patients in the control group received conventional Western medicine (WM) treatment, while those in the FHD group received conventional WM plus FHD for at least 3 days. The primary outcome was viral clearance time. Secondary outcomes included negative conversion rate within 14 days, length of hospital stay, cycle threshold (Ct) values of the open reading frame 1ab (ORF1ab) and nucleocapsid protein (N) genes, and incidence of new-onset symptoms during hospitalization. Adverse events (AEs) that occurred during the study period were recorded. RESULTS: A total of 1,765 eligible patients were enrolled in this study (546 in the FHD group and 1,219 in the control group). Compared with the control group, patients receiving FHD treatment showed shorter viral clearance time for nucleic acids [hazard ratio (HR): 1.500, 95% confidence interval (CI): 1.353-1.664, P<0.001] and hospital stays (HR: 1.371, 95% CI: 1.238-1.519, P<0.001), and a higher negative conversion rate within 14 days (96.2% vs. 82.6%, P<0.001). The incidence of new-onset symptoms was 59.5% in the FHD group, similar to 57.8% in the control group (P>0.05). The Ct values of ORF1ab and N genes increased more rapidly over time in the FHD group than those in the control group post-randomization (ORF1ab gene: β =0.436±0.053, P<0.001; N gene: β =0.415 ±0.053, P<0.001). The incidence of AEs in the FHD group was lower than that in the control group (24.2% vs. 35.4%, P<0.001). No serious AEs were observed. CONCLUSION FHD was effective and safe for patients with persistently positive SARS-CoV-2 PCR tests. (Registration No. ChiCTR2200063956).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/virology* ; Adult ; Aged ; Treatment Outcome

The cooccurrence of NPM1, FLT3-ITD, and DNMT3A mutations (i.e., triple mutation) is related to dismal prognosis in patients with acute myeloid leukemia (AML) receiving chemotherapy alone. In this multicenter retrospective cohort study, we aimed to identify whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut AML across four transplant centers in China. Fifty-three patients with triple-mutated AML receiving allo-HSCT in complete remission were enrolled. The 1.5-year probabilities of relapse, leukemia-free survival, and overall survival after allo-HSCT were 11.9%, 80.3%, and 81.8%, respectively. Multivariate analysis revealed that more than one course of induction chemotherapy and allo-HSCT beyond CR1 were associated with poor survival. To our knowledge, this work is the largest study to explore the up-to-date undefined role of allo-HSCT in patients with triple-mutated AML. Our real-world data suggest that allo-HSCT could overcome the poor prognosis of DNMT3A^mutNPM1^mutFLT3-ITD^mut in AML.
Humans ; Nucleophosmin ; Leukemia, Myeloid, Acute/mortality* ; Hematopoietic Stem Cell Transplantation/methods* ; Male ; Female ; DNA Methyltransferase 3A ; Adult ; China ; Retrospective Studies ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; Middle Aged ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Mutation ; Young Adult ; Transplantation, Homologous ; Nuclear Proteins/genetics* ; Adolescent ; Aged

Purpose The current study aims to elucidate the interrelationships among IREB2,FBXL5,iron ho-meostasis,and the therapeutic efficacy of neoadjuvant chemotherapy.Methods A total of 97 samples,classified into colorectal cancer neoadjuvant chemotherapy-resistant and-sensitive groups,along with their corresponding paracancer-ous normal mucosa were collected.The expression levels of FBXL5,IREB2,TFRC and FTH1 were detected by immu-nohistochemistry,Werstern blot and RT-qPCR.The contents of ferroptosis-related markers Fe2+,MDA,ROS and GSH were detected by applying the kit,and the levels of these markers were analyzed.The relationship between each factor in different colorectal cancer tissues and tumor regression rate and prognosis of neoadjuvant chemotherapy were ana-lyzed.Results(1)The expression of IREB2,FBXL5,TFRC and FTH1 in colorectal cancer was higher than that in normal intestinal mucosa(P＜0.05),and the expression of FBXL5 and FTH1 in colorectal cancer drug-resistant group was lower than that in the sensitive group,whereas the expression of IREB2 and TFRC was higher than that in the sen-sitive group(P＜0.05);(2)The correlation analysis showed a positive correlation between the expression of IREB2 and TFRC in the drug-resistant group,and a negative correlation with the expression of FBXL5 and FTH1 in the drug-resistant group.TFRC expression in the colorectal cancer resistance group were positively correlated(P＜0.05)and negatively correlated with the expression of FBXL5 and FTH1(P＜0.05);(3)the content of Fe2+and GSH was high-er than that of the sensitivity group in the colorectal cancer resistance group,and the level of ROS was lower than that of the sensitivity group(P＜0.05);(4)Fe2+was positively correlated with the expression of IREB2,TFRC,and neg-atively correlated with the expression of FBXL5 and FTH1,and was negatively correlated with the expression of FBXL5 and FTH1.FTH1 expression were both negatively correlated(P＜0.05);(5)tumor regression rate was positively cor-related with the expression of FBXL5 and FTH1,and negatively correlated with the expression of IREB2 and TFRC,as well as positively correlated with the level of ROS,and negatively correlated with Fe2+and GSH(P＜0.05);(6)The expression of IREB2 and TFRC was positively correlated with tumor diameter and lymph node metastasis,and the ex-pression of FBXL5 and FTH1 was negatively correlated with tumor diameter and lymph node metastasis,and the expres-sion of FBXL5 was also negatively correlated with the depth of tumor infiltration(P＜0.05);(7)Kaplan-Meier analy-sis showed that lymph node metastasis,FBXL5,IREB2,TFRC,FTH1,and TRG grading were closely related to the prognosis of colorectal cancer patients(P＜0.05).Cox multivariate regression analysis indicated that lymph node me-tastasis,high expression of IREB2 and TFRC,low expression of FBXL5 and FTH1,and low tumor regression grade(TRG)were risk factors for the ineffectiveness of neoadjuvant chemotherapy in colorectal cancer patients.Conclusion FBXL5 and IREB2 are not only associated with high iron homeostasis,but also closely related to the efficacy and prognosis of neoadjuvant chemotherapy for colorectal cancer.In the future,they may become new targets for the treat-ment of colorectal cancer and improve the prognosis of patients.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

To investigate the expression of serine metabolism related genes and inflammatory relat-ed genes in CD4+T cells of healthy and cows with ketosis.Firstly,CD4+T cells in peripheral blood of dairy cows were isolated by magnetic bead sorting.Second,expression of serine metabolism re-lated genes PHGDH,PAST1,PSPH,SHMT1,SHMT2,SDS,SFXN1 and inflammation related genes IL-6,IFN-γ,IL-17A,FOXP3,IL-10,TGF-β in CD4+T cells in healthy and ketosis cows was detected by fluorescence quantitative PCR.The transcription levels of PHGDH,PAST1 and PSPH in CD4+T cells of ketosis cows were significantly increased compared with healthy cows(P＜0.01),the transcription level and translation level of SDS were significantly increased(P＜0.01).The transcription levels of SHMT2 were significantly decreased(P＜0.05).Transcription and translation levels of SFXN1 were significantly decreased(P＜0.05).The transcription level of SHMT1 was decreased but not significantly.Compared with healthy cows,the transcription levels of IL-6,IFN-γ and IL-17A in CD4+T cells of ketosis cows were significantly increased(P＜0.01),the transcription levels of IL-10,TGF-β and FOXP3 were significantly decreased(P＜0.05).The results showed that the expression of genes related to serine synthesis increased,the expression of genes related to serine decomposition decreased,the expression of pro-inflammatory factors increased,and the expression of anti-inflammatory factors decreased,suggesting that serine metab-olism plays an important role in the inflammatory process of dairy cows.