BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.

Ovarian cancer is a common gynecologic malignancy.In clinical practice,recurrent ovarian cancer is mainly classified into two categories on the basis of platinum-free interval,platinum-resistant and platinum-sensitive,corresponding to different treatment modalities and prognoses.The treatment of platinum-resistant ovarian cancer is challenging.Some scholars have pointed out limitations in the binary classification of platinum-free interval.In this article,the classification of recurrent ovarian cancer,the treatment challenges of platinum-resistant ovarian cancer,the limitations of the platinum-free interval binary classification,and new classification perspectives were reviewed to help physicians enhance their understanding on the research progress in ovarian cancer classification and develop more effective treatment strategies.

Performance appraisal of public hospitals have given a guidance for the development of public hospitals at all levels.A Class A tertiary hospital reviewed the problems in the development of the hospital at the present stage and focused on the following four aspects:①insufficient fine management;②No clear orientation of discipline development;③The bottleneck of the improvement of medical operation efficiency;④New challenges in the reform of payment mode.The tertiary hospital launched a fine management practice in May 2022,in order to solve the problems by taking the Department of Surgery as a pilot area,laying the foundation for fine management through information system construction,improving the efficiency of medical operation through management process optimization,improving the overall competitiveness of disciplines through the construction of sub-specialty and Discipline Alliance and adjusting the performance appraisal index system to play the role of performance incentives.The measures effectively improve the overall capacity and efficiency of hospital medical services and help the hospital to achieve high-quality development.

Objective:To evaluate the curative effect of Sun's procedure using sutureless artificial blood vessel replacement technique on acute type A aortic dissection.Methods:Retrospective analysis was performed on 40 patients with acute type A aortic dissection who underwent Sun's procedure in The First People's Hospital of Nanning from May 2019 to April 2023. According to the surgical method, the patients were divided into sutureless group (20 cases) and traditional group (20 cases).The time of stopping circulation, cardiopulmonary bypass, recovery time, intubation time, blood loss 12 h after operation, cerebral infarction and acute renal failure were compared between the two groups.Patients older than 70 years, patients with preoperative malperfusion syndrome, or patients who did not undergo Sun's procedure were excluded.Results:The time of stopping circulation[( 13.6±3.3)min vs. ( 28.2±5.6)min, P<0.001] and the time of cardiopulmonary bypass[(116.0±34.8)min vs.(219.1±46.3 )min, P<0.001]and blood loss at 12 h after operation[( 474.5±301.0)ml vs. (422.7±389.8)ml, P<0.001] in the sutureless group were significantly lower than those in the traditional group.All patients survived and were discharged from hospital. There were no significant differences in recovery time, intubation time, cerebral infarction and acute renal failure between the two groups. Conclusion:Sutureless artificial blood vessel replacement technique can significantly shorten the time of stopping circulation and cardiopulmonary bypass, effectively protect the function of the whole body organs, and reduce the occurrence of postoperative complications.Moreover, it is easy to carry out in primary hospitals, and it is a safe and effective new surgical strategy for treating acute type A aortic dissection with Sun's surgery.

Objective: To examine the developmental trajectory of fine motor ability in schoolage children with attention deficit hyperactivity disorder (ADHD) for two years, so as to provide scientific evidence to promote motor development in ADHD children. Methods: From April to June 2019, 31 children aged 6-8 years old were selected from a public elementary school. They were diagnosed with ADHD by two psychiatric professionals according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Additionally, 31 typical developmental children, matched for age, sex and IQ with the ADHD group, were recruited as the control group. Fine motor ability was assessed with tasks of hand manual dexterity in Movement Assessment Battery for Children-2 (MACB-2), and a followup assessment was conducted from April to June 2021. The development changes of fine motor ability between two groups of children were compared by using t test and repeated measures analysis of variance. Results: Between baseline and followup periods after two years, the total score of hand fine motor in the ADHD group did not show significant improvement (7.4±3.0, 8.0±3.4; t=-1.05, P>0.05), while there was a small effect size improvement in typically developing control group (9.5±2.1, 10.5±2.4; t=-2.12, effect size=0.38, P<0.05). Followup after two years, coin/peg throwing scores with dominant hand improved between ADHD group and control group (7.0±3.3, 9.5±3.2; 8.4±2.8, 11.6±1.6) (t=-3.74, -6.33, P<0.01; effect size=0.67, 1.14), with a smaller improvement in the ADHD group. The score for threading beads/threads decreased in between ADHD group and control group (7.9±2.4, 5.8±3.1; 9.2±1.1, 8.2±1.9) (t=3.89, 2.78, P<0.01; effect size=0.70, 0.50), with a greater decrease in the ADHD group. Conclusions The development speed of fine motor ability in children with ADHD aged 6-8 is slow and continues to lag behind normal developmental children. Fine motor development in children with ADHD should be closely monitored, and targeted interventions should be implemented when necessary.

Objective:To investigate the clinical value of Tyro3/Axl/Mertk (TAM) receptor tyrosine kinase and ligands in severity evaluation for acute pancreatitis (AP).Methods:The peripheral blood and clinical data of 27 patients with AP admitted in the Department of Gastroenterology of Shanghai General Hospital from February 2020 to July 2022 were prospectively selected. The patients were divided in to mild AP group (MAP, n=13), moderately severe AP (MSAP, n=10) and severe AP group (SAP, n=4) according to the 2012-revised Atlanta classification for AP. Another 10 healthy normal subjects were selected as the control group. The general information, biochemical indicators and blood cell analysis of the patients were recorded, and the levels of serum Gas6, protein S and soluble Axl (sAxl) were measured by ELISA. Linear regression equations were used to analyze the correlation of serum Gas6, protein S and sAxl levels with the white blood cell (WBC) counts, neutrophil percentages, lymphocyte percentages, and monocyte percentages of each group, and to assess the clinical value of Gas6, protein S and sAxl in predicting the severity of AP patients. Results:Compared with the control group, the serum Gas6 level [(31.3±13.0)ng/ml vs (21.2±2.6)ng/ml], protein S level [(24.4±11.3)μg/ml vs (17.7±3.4)μg/ml], and sAxl level [(9.0±4.4)ng/ml vs (6.6±1.3)ng/ml] were significantly higher in the AP group. The Gas6 level was significantly higher in the SAP group (54.1±13.7 ng/ml) than in the MAP group (31.0±9.4 ng/ml) and the MSAP group (25.2±8.9 ng/ml), and the differences were statistically significant (all P value <0.05). The Gas6 level was significantly positively correlated with the WBC count ( r=0.1733) and neutrophils percentage ( r=0.4424), and negatively correlated with lymphocyte percentage(r=-0.363), with statistically significant differences (all P value <0.05). The levels of protein S and sAXL were positively correlated WBC count and neutrophil percentage, and negatively correlated with monocyte percentage and lymphocyte percentage, but the differences were not statistically significant. Conclusions:The serum levels of Gas6 increase significantly with the severity grading of AP, which may serve as a relatively good predictor for the early severity assessment of AP.

Guided by the theory of "kidney generates marrow"， the study elaborates the viewpoint that the route of Yin Heel Channel （阴跷脉） is consistent with the "kidney-marrow-brain" axis from the perspective of the circulation of the meridians and the relationship between the zang-fu organs. Accordingly， it is believed that disease of Yin Heel Channel and dysfunction of the "kidney-marrow-brain" axis are the core pathogenesis of children enuresis， and it is elaborated from the following three major aspects， firstly， insufficient kidney essence， dysfunction of the "kidney-marrow-brain" axis， secondly， disease of Yin Heel Channel and deficiency and cold in lower jiao， and thirdly， disease of Yin Heel Channel and loss of nourishment of Chong Vessel. It is proposed to use the mode of "firstly needle， secondly moxibustion， and lastly consolidation" to treat children enuresis. Needle is to adjust yin and yang， warm yang and tonify kidney， and wake up the brain and open the orifices. The acupoints in Yin Heel Channel such as Zhaohai （KI 6）， Jiaoxin （KI 8） and confluence points of the eight extraordinary vessels such as Waiguan （TE 5）， Zulinqi （GB 41） are used， together with Baihui （GV 20）， Yintang （EX-HN 3）， Guanyuan （CV 4）， Qixue （KI 13）， Dazhong （KI 4）. Moxibustion is to reinforce healthy qi and warm yang， bank up the root and consolidate the original qi by moxibustion at Shenque （CV 8）， Mingmen （GV 4）， and Xuanshu （GV 5）. Consolidation is to use acupoints application to consolidate the therapeutic effect， and Guanyuan （CV 4） & Pangguangshu （BL 28）， Qihai （CV 6） & Zhishi （BL 52）， and Shenque （CV 8） & Ciliao （BL 32） are commonly used as the three groups of acupoints to warm the kidney and stop collapse， regulate and tonify the qi and blood.