Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

The rising incidence of overweight and obesity among children and adolescents has become a significant public health issue both domestically and globally.In South China,the rates of overweight and obesity among children and adolescents are relatively low compared with the national average,thanks to the unique regional climate,culture,and dietary habits,which are conducive to the prevention and control of childhood and adolescent overweight and obesity.This consensus,based on practical experiences in weight management for overweight and obese children and adolescents in South China,in combination with evidence-based medical research,systematically establishes a standardized diagnosis and treatment framework for childhood and adolescent overweight and obesity.It covers core aspects such as diagnosis and assessment,lifestyle interventions,behavioral interventions,pharmacological treatment and traditional Chinese medical therapies.This consensus incorporates regional characteristics into the management framework for childhood and adolescent overweight and obesity,aiming to provide clinicians with scientifically sound and practical guidance,and to offer a regional model for curbing the growing trend of childhood obesity.

Objective:To analyze the physical activity level of patients treated with a percutaneous coronary intervention (PCI) for coronary artery disease in the early out-of-hospital recovery phase, and the factors influencing it.Methods:Patients who had been discharged within the previous 6 months after their first PCI treatment were surveyed using a general information questionnaire, the long form of the International Physical Activity Questionnaire (IPAQ), the Chinese version of the Tilburg Frailty Scale, the Social Support Rating Scale, and for their ability in the activities of daily living. Epidemiological descriptive methods were used to analyze the reported physical activity levels, and multifactoral logistic regression was applied to explore the influencing factors. The receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of the risk factors.Results:A total of 394 former patients were surveyed, including 117 (30%) reporting a low level of physical activity, 202 (51%) describing a moderate level and 75 (19%) claiming a high level. The univariate analysis revealed significant differences in physical activity levels among those of different ages, with different chronic co-morbidities, and with different frailty and self-care ability. Multifactoral logistic regression analysis showed that advanced age, chronic co-morbidities, frailty and little self-care ability are significant predictors of a low level of physical activity. The area under the ROC curve for predicting the physical activity level by combining those four factors was 0.89 (95% CI 0.84-0.94), with a sensitivity of 0.89 and a specificity of 0.80. Conclusions:The physical activity level of patients treated with PCI for coronary disease is moderately low early after their release from the hospital. Targeted intervention to increase it is called for.

Objective:To explore the characteristics of the brain functional networks in children with spastic cerebral palsy (SCP) while at rest and to correlate them with motor functioning.Methods:Thirty-six children with SCP were enrolled as the SCP group, while thirty-four age-matched healthy children were recruited as the control group (the HC group). Functional near-infrared spectroscopy was used to detect changes in the concentration of oxygenated hemoglobin in the children′s cerebral cortex while at rest. The left prefrontal cortex (LPFC), right prefrontal cortex (RPFC), left motor cortex (LMC), and right motor cortex (RMC) were selected as regions of interest. Phase locking values (PLVs) were used to evaluate the strength of functional connectivity (FC) among these brain regions, and graph theory methods were applied to analyze the topological properties of the brain networks. Motor functioning was assessed using the gross motor function measure (GMFM).Results:The analyses of FC strength revealed that the SCP group had significantly weaker FC among all of the regions of interest while at rest compared to the HC group. Their PLVs for LPFC-RPFC, LPFC-RMC, RPFC-RMC and LMC-RMC connectivity were all significantly smaller. Graph theory analysis showed that the SCP group had significantly lower global efficiency (GE) and smaller clustering coefficients (CCs) and network density (D), while their characteristic path lengths were significantly longer. According to the correlation analysis, the PLVs for LMC-RMC connections in the SCP group were positively correlated with their scores on dimensions D and E of the GMFM ( r=0.496 and r=0.579 respectively). GE ( r=0.587 and r=0.642) and CC ( r=0.318 and r=0.759) showed similar significant positive correlations with GMFM dimensions D and E. Conclusions:At rest, the functional networks in the brains of children with SCP exhibit abnormalities closely associated with their motor dysfunction.

Objective:To investigate the cytopathological features of thyroid tumor with DICER1 mutation.Methods:A retrospective study on the preoperative cell smear was conducted on thyroid tumors with DICER1 gene mutations detected by Sanger sequencing in the Department of Pathology Shanghai Sixth People′s Hospital affiliated to Shanghai Jiaotong University School of Medicine from May 2022 to November 2024.Results:Totally 163 cases with histological features indicating DICER1 mutation related thyroid tumor underwent Sanger sequencing. Fifteen cases were confirmed to harbor DICER1 mutation (15/163,9.2%). Fourteen of 15 patients were female, and only 1 was male; average age 42(31,47) years. Eight cases presented with D1709 hotspot mutation (8/15) and 7 cases with the E1813 hotspot mutation (7/15) and there was no statistical significant difference between mutation rate of different hotspot ( F=0.620， P=0.438). All specimens were stained with hematoxylin-eosin staining. A moderate number of cells were observed for all cases, predominantly with macrofollicular pattern and rare small papillae. The cell nuclei were mainly uniform, small, round and dark, slightly enlarged or medium-sized. Several cases could also present RAS-like nuclear features: 3 cases showed visible nuclear grooves. According to the expert consensus on the cytopathological diagnosis of thyroid fine needle aspiration (version 2023),the cytopathological diagnostic categories were: Ⅱ, 6 cases; Ⅲ, 2 cases; Ⅳ, 6 cases; and Ⅴ, 1 case. Postoperative histological diagnoses included follicular thyroid carcinoma in 2 cases, high-grade differentiated thyroid carcinoma in 1 case, follicular thyroid adenoma in 3 cases, follicular thyroid tumor of undetermined malignant potential in 4 case, and thyroid follicular nodular disease in 5 cases. Conclusions:The morphological features of DICER1-mutated thyroid tumors are predominant macrofollicles, with uniformly small round and dark nuclei. It is difficult to identify typically diagnostic atrophic follicles on cell smear, leading to a preoperative diagnosis of benign non-neoplastic or indeterminate category. Therefore, it is necessary to carefully observe the macro-follicles and small round dark nuclear features, which is necessary to suggest a genetic test of DICER1 gene and to confirm the diagnosis before surgery.

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

OBJECTIVES: To investigate the role and mechanism of copper overload-mediated endoplasmic reticulum stress (ERS) in vascular endothelial injury in Kawasaki disease (KD). METHODS: Four-week-old male C57BL/6 mice were randomly divided into four groups: control, KD, KD plus copper chelator tetrathiomolybdate (TTM), and KD plus ERS inhibitor AMG PERK 44 (AMG) (n=20 per group). A KD mouse model was established using Candida albicans extract. Human umbilical vein endothelial cells (HUVECs) were divided into control (intervention with healthy children's serum), KD (intervention with KD patients' serum), and KD+TTM (intervention with KD patients' serum plus 20 µmol/L TTM). Copper deposition in mouse heart tissue was assessed using rubeanic acid staining. Vascular pathological changes were observed using hematoxylin-eosin staining and measurement of abdominal aortic diameter and area. ERS activation was detected by transmission electron microscopy and immunofluorescence. HUVEC viability, apoptosis, and functional changes were evaluated using CCK8, flow cytometry, cell scratch assay, and angiogenesis experiments. ERS marker protein expression levels were measured by Western blot. RESULTS: Compared to the KD group, the KD+TTM and KD+AMG groups showed reduced copper deposition in the vascular wall, decreased swelling of coronary endothelial cells and endoplasmic reticulum, reduced inflammatory cell infiltration, and less abdominal aortic lesion expansion. The abdominal aortic diameter and area, and the fluorescence intensity of ERS marker proteins (GRP78 and CHOP) were significantly lower (P<0.05). Compared to the KD group, the KD+TTM group exhibited increased cell viability, tube number, and scratch healing rate, along with decreased apoptosis rate and expression of ERS marker proteins (GRP78, CHOP, ATF6, and p-PERK) (P<0.05). CONCLUSIONS Copper overload aggravates vascular endothelial injury in KD by activating the ERS pathway. TTM can exert protective effects on the endothelium by regulating copper metabolism and inhibiting the ERS pathway.
Endoplasmic Reticulum Stress ; Copper/toxicity* ; Male ; Mucocutaneous Lymph Node Syndrome/metabolism* ; Animals ; Humans ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Mice ; Human Umbilical Vein Endothelial Cells ; Apoptosis ; Endothelium, Vascular/injuries*

An 11-year-old boy presented with erythematous plaques over the bilateral mandibular and mental regions for 2 years, accompanied by cough and dyspnea for more than 2 months. Chest computed tomography angiography revealed marked stenosis of the right pulmonary artery, irregular aortic caliber, and aortic wall thickening. Histopathological examination of the skin lesion, including immunohistochemistry and special stains, confirmed a chronic suppurative inflammation. Whole-exome sequencing was negative. A final diagnosis of granuloma faciale and Takayasu arteritis was established. Combination therapy with systemic tocilizumab, prednisone, and methotrexate, along with topical 0.1% tacrolimus ointment, resulted in a favorable clinical response. This report summarizes the clinical features of a pediatric case of granuloma faciale and Takayasu arteritis and reviews the etiology, diagnostic approach, and current treatment strategies for the disorders, aiming to enhance clinicians' understanding of these conditions.
Humans ; Male ; Child ; Takayasu Arteritis/diagnosis* ; Facial Dermatoses/diagnosis*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.