OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.
Dermatitis, Atopic/genetics* ; Interleukins/metabolism* ; Animals ; Methicillin-Resistant Staphylococcus aureus/immunology* ; Mice ; Keratinocytes/microbiology* ; Humans ; Interleukin-33/immunology* ; Inflammation/microbiology* ; Staphylococcal Infections/microbiology* ; Disease Models, Animal ; Hypersensitivity/microbiology* ; Mice, Inbred C57BL

Objective:To explore the feasibility of actively screening patients with chronic obstructive pulmonary disease (COPD) among inpatients in county territory-level hospitals based on the collection of comorbidity-related diseases and questionnaire surveys.Methods:This study was a cross-sectional study. From April 1, 2023, to November 30, 2023, a total of 1 392 inpatients who met the screening criteria in county territory-level hospitals within the Western Medical Group of Baiyun District, Guangzhou, were included in the study. General information, disease data, and COPD screening data of the patients were collected. A total of 1 392 questionnaires were distributed, all of which were returned and included in the analysis. Descriptive analysis, comparative analysis, and association rule mining were conducted, including the distribution of general information, distribution of common comorbidity-related diseases in COPD, distribution of questionnaire screening and pulmonary function test results, comparison of screening results based on comorbidity-related diseases grouping, comparison of screening results based on questionnaire screening results grouping, comparison of screening results based on smoking total score grouping, and association rules between screening results and pulmonary function test results and other research data.Results:Among the 1 392 study subjects, 334 cases (24.0%) had a positive self-screening questionnaire for COPD, 44 cases (13.2%) completed pulmonary function tests, and 17 cases (38.6%) were diagnosed with COPD. The positive rate of the screening questionnaire among inpatients was lowest in surgical patients without comorbidity-related diseases and highest in male patients with single/multiple comorbidity-related diseases and symptoms of chronic respiratory system diseases. The group with multiple comorbidity-related diseases had a significantly higher positive rate in the screening questionnaire than the group with single comorbidity-related diseases and the group without comorbidity-related diseases. Only 13.2% of inpatients with a positive screening questionnaire completed pulmonary function tests, with residents covered by medical insurance with multiple comorbidity-related diseases, including cardiovascular diseases, having the lowest rate, and patients with symptoms of chronic respiratory system diseases and single comorbidity-related diseases having the highest rate.Conclusions:Based on the collection of comorbidity-related diseases and questionnaire surveys, it is feasible to actively screen COPD patients among inpatients in county territory-level hospitals. However, efforts are needed to further increase the proportion of inpatients with positive screening questionnaires undergoing pulmonary function tests.

Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6％(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P＜0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P＜0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P＜0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P＜0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P＜0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.

Objective:To review the scope of related factors that affect the elderly′s participation in digital health intervention, and to provide a certain reference for the application and development of smart elderly technology.Methods:Based on the scope review guidelines issued by the Joanna Briggs Institute in Australia in 2019, the inclusion and exclusion criteria were determined according to the PCCS principles. Chinese and English literatures were searched in PubMed, Cochrane Library, JBI, CINAHL, Web of Science, Scopus, CNKI, Wanfang database and Chinese biomedical literature database. The search time limit was from the establishment of the database to November 30, 2021. Two researchers independently read, and used EndNoteX9 and Excel tables to extract relevant data from the literature for summary and analysis.Results:Totally 20 articles were selected, including 2 mixed studies, 10 cross-sectional studies, 6 qualitative studies, and 2 quasi-experimental studies. Relevant factors affecting the participation of the elderly in digital health interventions involved the developers, users and the user himself of digital health intervention systems, including the degree of system integration of system development, the degree of autonomy of the elderly, the credibility and accessibility of system equipment and ease of use; the degree of compatibility of equipment in the process of use, the degree of digital infrastructure configuration, the degree of Internet penetration, the availability and reliability of health information resources, the degree of training and education, the degree of communication with the elderly in the process of participation, financial payment, etc.; the four inherent factors of the elderly included the cost of technology use, technical anxiety, privacy and safety, and health needs.Conclusions:The elderly, medical staff, developers and other stakeholders should jointly participate in decision-making on the development and management of the digital health intervention system for the elderly, especially by inviting and empowering the elderly , and improve the training and feedback of the system application and use process, accelerate the popularization and promotion of technical resources, and increase social capital and financial payment incentives to reduce the burden on the elderly and the medical system.

Objective:To conduct quality evaluation and content analysis of adult postoperative nausea and vomiting (PONV) guidelines, so as to provide reference for management of clinical PONV.Methods:Web of Science, Embase, PubMed, UpToDate, SinoMed, Wanfang Database, China National Knowledge Infrastructure, VIP, domestic and foreign clinical practice guidelines and related professional association websites were systematically searched, and the search period was from database establishment to May 6, 2022. Four researchers independently evaluated the guidelines that met the inclusion and exclusion criteria using a clinical guideline research and evaluation system, and summarized the recommendations of the guidelines.Results:Finally, a total of 15 guidelines were included in this study. The overall quality evaluation of the guide was 3 A-level recommendations and 12 B-level recommendations. The average standardization percentages for 6 areas were 81.57% for scope and purpose, 49.91% for participants, 65.38% for rigor, 89.54% for clarity, 34.86% for applicability and 55.42% for independence. A total of 18 recommendations were summarized from five aspects, such as team and organizational management, PONV risk assessment, baseline risk reduction, multimodal prevention of PONV and effectiveness evaluation and monitoring.Conclusions:The guidelines for PONV management mainly come from foreign countries. It is recommended that clinical personnel should learn from foreign guidelines and combine them with domestic clinical situations to localize the recommended opinions and guide the development of clinical practice.

Objective:To systematically review the disease treatment and management experience of parents of children with attention deficit hyperactivity disorder (ADHD) .Methods:Qualitative or mixed studies on the treatment and management experience of parents of children with ADHD were searched in databases such as PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, Scopus, CINAHL, ProQuest, China National Knowledge Infrastructure, WanFang Data, and VIP. The search period was from database establishment to October 8, 2022. The quality of the included literature was evaluated using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. Nvivo 11 software was used to integrate the results through aggregation integration methods.Results:A total of 13 articles were included and 36 research results were extracted.The results were categorized into 10 new categories and formed into 4 integrated results, including the impact of disease cognition of parents of children with ADHD on medical seeking behavior, psychological adjustment of parents of children during treatment, disease response of parents of children, and social resource needs for treatment and management of children.Conclusions:The role and responsibility of parents in the treatment and management of ADHD children are very important. We need to strengthen the popularization of knowledge about ADHD, enhance parents' awareness of the disease, pay attention to parents' psychological status, provide multi-channel social support, meet the treatment and educational needs of children, and promote the construction of an individualized and multidisciplinary comprehensive management system to improve the short-term and long-term outcomes of ADHD children.

Objective:To evaluate the efficacy of ultrasound-guided adductor canal approach to nerve block using one-puncture four-point technique for analgesia after total knee arthroplasty (TKA).Methods:Sixty patients of both sexes, aged 65-80 yr, with body mass index of 18-27 kg/m 2, of American Society of Anesthesiologists physical status Ⅱor Ⅲ, scheduled for elective unilateral TKA under general anesthesia, were enrolled in this study.Peripheral nerve block was performed for postoperative analgesia under ultrasound guidance.All the patients were allocated into 2 groups ( n=30 each) using a random number table method: adductor canal block combined with posterior approach to sciatic nerve block group (group ASB) and adductor canal approach to nerve block using one-puncture four-point technique including sciatic nerve, medial vastus muscle nerve, saphenous nerve, anterior femoral cutaneous nerve at adductor canal level group (group ANSB). When visual analogue scale score ≥4 during postoperative movement, ketorolac tromethamine 0.6 mg/kg was intravenously injected as rescue analgesic. The muscle strength of quadriceps on the affected side, range of knee joint motion and rate of the ability to walk for 10 m using the walker were recorded at 2, 8, 24 and 48 h after surgery.The consumption of analgesics for rescue analgesia, manipulation completion time, length of hospital stay and patients′ satisfaction score were recorded within 48 h after surgery. Results:Compared with group ASB, the consumption of ketorolac tromethamine was significantly reduced, manipulation completion time and length of hospital stay were shortened, patients′ satisfaction scores were increased, and the range of knee joint motion and rate of the ability to walk for 10 m using the walker were increased at 2, 8, 24 and 48 h after surgery in group ANSB ( P<0.05). There was no significant difference in muscle strength of quadriceps between two groups ( P>0.05). Conclusion:Ultrasound-guided adductor canal approach to nerve block using one-puncture four-point technique provides better efficacy than adductor canal block combined with posterior approach to sciatic nerve block when used for analgesia after TKA.

Objective:To explore the effect of smoking on the wound healing of stage 4 pressure ulcers in rats.Methods:Fifty male Sprague-Dawley rats aged 6-8 weeks were divided into simple pressure ulcer group and smoking+ pressure ulcer group according to the random number table, with 25 rats in each group. After the rats in the smoking+ pressure ulcer group received passive smoking intervention for 12 weeks, an iron plate was placed in the back muscle of each rat in 2 groups, and a magnet was placed outside the skin at the corresponding position of the iron plate for 2 h at each time, with 5 times a day and continuously for 6 days to reproduce stage 4 pressure ulcer model. Immediately after establishing the model, 3 rats in each group were sacrificed and wound tissue was collected, and hematoxylin-eosin staining was applied to observe the pathological changes of the wounds. On 1, 3, 7, and 14 day (s) after establishing the model, 3 rats in each group were collected to measure the pressure ulcer wound area by the paper jam method. After measurement of the wound area, the rats were sacrificed and the wound tissue was collected, and the protein expression levels of matrix metalloproteinases 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in wound tissue were detected by immunohistochemical method, and the ratio of MMP-9/TIMP-1 was calculated.The wound healing time of the remaining 10 rats in each group was recorded. Data were statistically analyzed with analysis of variance for factorial design, two independent sample t test, and Bonferroni correction. Results:(1) Immediately after establishing the model, muscle fiber necrosis and dissolution with large areas were seen on the wound, the myofibrils arranged loosely, and more lymphocytes and monocytes infiltration were seen around the wound of rats in simple pressure ulcer group. A large number of necrotic myofibers were dissolved and gradually disappeared, the myofibrils arranged loosely, and the number of diffuse lymphocytes and monocyte infiltration in wound of rats in smoking+ pressure ulcer group were significantly higher than those in simple pressure ulcer group. (2) The wound areas of rats in smoking+ pressure ulcer group were significantly larger than those in simple pressure ulcer group on 1, 3, 7, and 14 day (s) after establishing the model ( t=3.019, 2.549, 2.181, 3.674, P<0.05 or P<0.01). (3) On 1 to 14 days after establishing the model, the protein expression levels of MMP-9 and TIMP-1 in the wound tissue and the ratio of MMP-9/TIMP-1 of rats in the two groups increased first and then decreased. On 1, 3, 7, and 14 day (s) after establishing the model, the protein expression levels of MMP-9 in the wound tissue and the ratio of MMP-9/TIMP-1 of rats in smoking+ pressure ulcer group were significantly higher than those in simple pressure ulcer group ( t=4.783, 4.508, 6.325, 7.204, 3.078, 2.989, 4.081, 4.696, P<0.05 or P<0.01), and the protein expression levels of TIMP-1 in wound tissue of rats in the two groups were similar. (4) The wound healing time of rats in smoking+ pressure ulcer group was (48.9±2.6) d, which was significantly longer than (35.2±2.3) d of simple pressure ulcer group ( t=12.477, P<0.05). Conclusions:Smoking can up-regulate the expression of MMP-9 in pressure ulcer wound and result in an imbalance of MMP-9/TIMP-1, thereby affecting the wound healing of stage 4 pressure ulcers in rats.

OBJECTIVE: To explore the histological structure of the deciduous teeth and the tooth germs of Tibetan miniature pigs for studies of dental tissue diseases and tooth regeneration. METHODS: The structure of the deciduous teeth of Tibetan miniature pigs was observed by X-ray. The ultrastructure of the enamel and dentin of deciduous teeth was characterized by scanning electron microscopy. The jaws and teeth were three-dimensionally reconstructed using Mimics software based on Micro-CT scanning of the deciduous teeth. Image J software was used to calculate the gray value and the mineralization density of the deciduous teeth. Hisotological structure of the tooth germ and the pulp tissue of Tibetan miniature pigs was observed using HE staining. RESULTS: The deciduous teeth of Tibetan miniature pigs were composed of enamel, dentin and medullary pulp tissue. The permanent tooth germ were formed during the deciduous dentition. The enamel and dentin ultrastructure of deciduous teeth were consistent with that of human deciduous teeth. The enamel and dentin mineralization densities were 2.47±0.09 g/cm and 1.72±0.07 g/cm, respectively. The pathological structures of tooth germ and pulp tissue were similar to those of human teeth, and the pulp tissue of the deciduous teeth was in an undifferentiated state. CONCLUSIONS The deciduous teeth of Tibetan miniature pig have similar anatomy, ultrastructure and histopathological structure to human teeth and can serve as a good animal model for studying human dental tissue diseases and the mechanisms of tooth regeneration.
Animals ; Dental Enamel ; ultrastructure ; Dental Pulp ; Dentin ; ultrastructure ; Swine ; Swine, Miniature ; Tibet ; Tooth Germ ; Tooth, Deciduous ; anatomy & histology