OBJECTIVE To study the improvement effects and potential mechanisms of water extract from Chrysanthemum morifolium on skeletal muscle atrophy in rats after ischemic stroke. METHODS Sprague-Dawley rats were randomly divided into sham operation group， model group， ATP group （10 mg/kg）， C. morifolium water extract high-dose and low-dose groups （1.08， 0.54 g/kg）. Except for sham operation group， ischemic stroke models were induced in rats from the other groups using middle cerebral artery occlusion. Starting from the first day after surgery， rats in each group were given corresponding drug/normal saline intragastrically， once a day， for consecutive 7 days. On the 7th day post-surgery， the rats’ body weights were measured， and their motor functions were evaluated， including Longa scores， exercise distance， grip strength； the electrophysiological signals of the skeletal muscles in rats were measured； the pathological morphology of the soleus muscle in rats was observed； the levels of tumor necrosis factor-α （TNF-α） in serum and soleus muscle were measured； the expressions of proteins related to TNF-α/c-Jun N- terminal kinase （JNK）/mitogen-activated protein kinase （MAPK） signaling pathway in the soleus muscle were determined. RESULTS Compared with sham operation group， the body weight， grip strength and exercise distance of rats were decreased/ shortened significantly （P＜0.01）； additionally， there was a notable reduction in the interpeak value of skeletal muscle electrophysiology （P＜0.05 or P＜0.01）. Longa score， as well as the levels of TNF-α in serum and soleus muscle， and the expression levels of TNF-α， phosphorylated JNK， phosphorylated MAPK， muscle ring-finger protein-1， and muscle atrophy Fbox- 1 protein in the soleus muscle， were all significantly elevated （P＜0.01）. The skeletal muscle cells of the soleus muscle in the model group showed significant atrophy， with a markedly decreased cross-sectional area （P＜0.01）. Compared with the model group， the levels of the aforementioned indicators were significantly reversed in C. morifolium water extract groups （P＜0.05 or P＜ 0.01）， and the skeletal muscle cells of the soleus muscle were markedly enlarged. CONCLUSIONS C. morifolium water extract can improve skeletal muscle atrophy in rats after ischemic stroke， the mechanism of which may be associated with suppressing the activation of the TNF- α/JNK/MAPK E-mail：19932015@cdutcm.edu.cn signaling pathway.

The European Society of Cardiology (ESC) released the "2024 ESC guidelines for the management of elevated blood pressure and hypertension" on August 30, 2024. This guideline updates the 2018 "Guidelines for the management of arterial hypertension." One notable update is the introduction of the concept of "elevated blood pressure" (120-139/70-89 mm Hg). Additionally, a new systolic blood pressure target range of 120-129 mm Hg has been proposed for most patients receiving antihypertensive treatment. The guideline also includes numerous additions or revisions in areas such as non-pharmacological interventions and device-based treatments for hypertension. This article interprets the guideline's recommendations on definition and classification of elevated blood pressure and hypertension, and cardiovascular disease risk assessment, diagnosing hypertension and investigating underlying causes, preventing and treating elevated blood pressure and hypertension. We provide a comparison interpretation with the 2018 "Guidelines for the management of arterial hypertension" and the "2017 ACC/AHA guideline on the prevention, detection, evaluation, and management of high blood pressure in adults."

To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

BACKGROUND: The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS). METHODS: Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis. RESULTS: The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls ( P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS ( P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity. CONCLUSIONS Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Humans ; Female ; Polycystic Ovary Syndrome/metabolism* ; Endometrium/metabolism* ; Sirtuin 3/genetics* ; Oxidative Stress/genetics* ; Adult ; Animals ; Mice ; Apoptosis/physiology* ; Immunohistochemistry ; Cell Proliferation/physiology*

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Based on systematic review and consensus meetings of international multidisciplinary experts, the Transfusion and Anemia Expert Initiative—Control/Avoidance of Bleeding (TAXI-CAB) project team developed management strategies for platelet and plasma transfusion in critically ill children. This consensus presents five expert consensus statements and two recommendations addressing two key questions: 1) What Laboratory Tests and Physiologic Triggers Should Guide the Decision to Administer a Platelet or Plasma Transfusion in Critically ill Children? 2) What Product Attributes Are Optimal to Guide Specific Product Selection? This consensus provides guidance for decision-making regarding plasma and platelet transfusion in critically ill children in two aspects: relevant laboratory testing indicators and additional special properties of blood components. This article explains the rationale behind the recommendations in this part of the guideline, aiming to emphasize the need for clinicians to develop transfusion strategies based on multidimensional assessment, while calling for enhanced interdisciplinary collaboration and evidence-based research to optimize blood management in critically ill children, reducing the risk of over-transfusion and improving treatment outcomes. Furthermore, there remains an urgent need for further research to explore laboratory indicators associated with bleeding risk to guide transfusion therapy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

ObjectiveTo investigate the antidepressant effect of Sinisan （SNS） by regulating glycogen aynthase kinase-3β （GSK-3β）/tumor necrosis factor alpha-induced protein 3（A20）/CCAAT enhancer binding protein β（C/EBPβ） to inhibit the activation of microglia. MethodA total of 72 male C57/6J mice were randomly divided into the normal group， model group， fluoxetine group （5.0 mg·kg^-1）， low-dose Sinisan group （4.9 g·kg^-1）， medium-dose Sinisan group （9.8 g·kg^-1）， and high-dose Sinisan group （19.6 g·kg^-1）， with 12 mice in each group. After one week of adaptive feeding， chronic unpredictable mild stress （CUMS） was performed to establish the depression model. In the fifth week， drug treatment was conducted for four weeks. In the ninth week， behavioral tests were performed， including sucrose preference test （SPT）， open field test （OPT）， elevated plus maze （EPM） test， and forced swimming test （FST）. Western blot was used to detect the expression levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， nitric oxide synthase （iNOS）， GSK-3β， A20， and C/EBPβ in the cortex. The expression of M1-polarized ionized calcium-binding adapter molecule 1 （Iba1） and cluster of differentiation 68 （CD68） in microglia was detected by immunofluorescence. ResultAfter eight weeks of CUMS， compared with the normal group， the mice in the model group had a significantly reduced sucrose preference rate （P<0.01）， and the activity in the central area of the OPT was significantly reduced （P<0.01）. The activity in the open arm area of the EPM test was significantly reduced （P<0.05）， and the immobility time of FST was increased （P<0.01）. The expression levels of inflammatory proteins IL-1β， IL-6， and iNOS were increased （P<0.01）， and the fluorescence co-localization index of Iba1 and CD68 was increased （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ were significantly increased （P<0.05， P<0.01）. After four weeks of SNS intervention， compared with the model group， the mice in the SNS group had significantly increased sucrose preference rate （P<0.01）， significantly increased activities in the central area and the open arm area in the OPT and the EPM test （P<0.05）， and significantly reduced immobility time in the FST （P< 0.01）. The protein expression levels of IL-1β， IL-6， and iNOS were significantly decreased （P<0.05）， and the fluorescence co-localization index of Iba1 and CD68 was decreased in the high-dose SNS group （P<0.05）. The protein expression levels of GSK-3β and C/EBPβ in the medium-dose and high-dose SNS groups were significantly decreased （P<0.01）， and that of A20 was significantly increased （P<0.01）. ConclusionThe antidepressant effect of SNS is related to the regulation of GSK-3β/A20/C/EBPβ protein expression and the inhibition of M1-type activation of microglia.