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.

Objective To understand the current status of low-density lipoprotein cholesterol (LDL-C) control in patients after coronary artery bypass grafting (CABG). Methods Clinical data of patients who underwent isolated CABG in Beijing Anzhen Hospital in 2023 were collected. All patients returned to our hospital approximately one year after surgery (10-13 months) for a lipid level recheck. We analyzed their LDL-C attainment status and influencing factors. Patients were categorized into two groups based on whether their LDL-C met the target: a LDL-C attainment group and a LDL-C non-attainment group. Results This study included 1456 patients who underwent CABG, including 320 females and 1136 males, with an average age of (61.41±9.12) years. One year post-surgery, 234 patients achieved the LDL-C target, with an attainment rate of 16.07%. The proportion of patients in the LDL-C attainment group who were ultra-high risk (77.35% vs. 92.06%, P＜0.001), female (16.24% vs. 23.08%, P=0.021), and those with comorbid hypertension (55.98% vs. 63.18%, P=0.038) was significantly lower than those in the LDL-C non-attainment group. Additionally, the baseline body mass index (BMI) [(25.37±3.24) kg/m2 vs. (26.03±3.56) kg/m2, P=0.017], total cholesterol levels [(3.30±0.84) mmol/L vs. (4.01±1.03) mmol/L, P＜0.001], LDL-C [(1.62±0.63) mmol/L vs. (2.25±0.85) mmol/L, P＜0.001], and high-density lipoprotein cholesterol [(0.98±0.26) mmol/L vs. (1.02±0.24) mmol/L, P=0.049] upon admission in the attainment group were all lower than those in the non-attainment group. Moreover, the lipid-lowering drug usage rate in the attainment group (100.00% vs. 96.24%, P=0.003) and the proportion using two types of drugs together (25.21% vs. 10.72%, P＜0.001) were both higher than those in the non-attainment group, while the statin monotherapy rate was lower than that in the non-attainment group (74.79% vs. 85.19%, P＜0.001). Logistic regression analysis showed that baseline BMI (OR=0.928, P=0.012) and baseline LDL-C levels (OR=0.207, P<0.001), patient cardiovascular risk stratification (OR=0.155, P<0.001) and lipid-lowering drug treatment regimen (OR=3.758, P<0.001) are significant factors affecting the LDL-C control status. Conclusion The LDL-C compliance rate of patients undergoing CABG is at a relatively low level 1 year after surgery. Patients with very high risk of atherosclerotic cardiovascular disease, high baseline LDL-C levels, and overweight or obesity should be strengthened lipid management. For these patients, the intensity of lipid-lowering drug use or combination medication should be increased upon discharge.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Primary cilia—those solitary, microtubule-based projections extending from the surface of most eukaryotic cells—are increasingly recognized not merely as cellular appendages, but as sophisticated signaling hubs. By compartmentalizing specific receptors (e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.

Malignant tumors remain one of the most critical global public threats to human health. The early diagnosis and precise therapeutic interventions are pivotal for improving patient survival rates and prognosis. Gold nanoclusters (Au NCs), distinguished by their ultra-small size (<3 nm), tunable optical properties, and exceptional biocompatibility, have emerged as transformative agents in precision oncology. This comprehensive review systematically summarizes the multifaceted applications of Au NCs in malignant tumor treatment. We discuss their roles as follows. (1) Intelligent delivery vehicles for targeted chemotherapy and controlled release through surface functionalization. (2) Therapeutic agents for chemodynamic therapy (CDT). This capability stems from their intrinsic enzyme-like catalytic activity or potent thioredoxin reductase (TrxR) inhibitory function, which disrupts the intracellular redox homeostasis and effectively activates downstream apoptotic pathways.(3) Direct therapeutic agents are characterized by their energy conversion capabilities: they can either convert absorbed light into heat to directly kill cancer cells, or transfer that photon energy to surrounding oxygen molecules to generate cytotoxic reactive oxygen species (ROS), leading to cell apoptosis or necrosis. (4) Potent radiosensitizers that enhance radiotherapy efficacy by enhancing localized radiation dose and promoting ROS generation. This review systematically summarizes the recent advances in Au NCs as intelligent delivery systems, direct chemotherapeutic agents, phototherapeutic agents, and efficient radiosensitizers in tumor treatment, elucidating how Au NCs overcome traditional therapeutic limitations through synergistic strategy. It establishes a robust theoretical foundation for next-generation nanotheranostic platforms. However, the translation of laboratory findings into functional clinical technologies confronts three significant challenges. First, although researchers can synthesize atomically precise Au NCs, achieving large-scale production of batches with completely consistent structure, size, and surface chemistry remains extremely challenging. To effectively control the final synthetic product, a deep understanding of the characteristics and formation mechanisms of Au NCs is essential. The traditional “trial-and-error” experimental approach faces inherent limitations when dealing with vast combinations of variables, which is time-consuming, labor-intensive, and struggles with systematic exploration and reproducibility. Machine learning has emerged as a powerful tool to bridge fundamental research and clinical application, which can guide experiments in reverse by predicting synthesis success through data mining and multi-variable analysis. In the future, we anticipate to achieve precise prediction and on-demand design of Au NCs’ structure and properties. Secondly, a systematic framework for evaluating the in vivo pharmacokinetics and long-term toxicity of Au NCs is absent. To address this gap, it is crucial to develop advanced imaging methodologies and integrated theranostic platforms. Au NCs, serving as both a therapeutic core and a highly promising photoluminescent material, are key to constructing such platforms through integration with other agents. These multifunctional systems are designed to achieve optimal synergistic therapy by combining multiple treatment modalities. Finally, the investigation of Au NCs is still largely confined to preclinical cellular and animal studies. Progress necessitates comprehensive clinical research to rigorously assess their safety and efficacy across a range of human cancer models, thereby ensuring broad clinical applicability. In summary, Au NCs-based platforms hold immense promise for translation into clinical anticancer therapy.

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

Gastric cancer is one of the most common malignant tumors in the digestive tract, which has the characteristics of high morbidity and mortality. However, gastric cancer is not achieved overnight but is gradually developing through the interaction of many factors. Therefore, actively delaying or blocking the "inflammation-cancer" transformation in gastric mucosa is the key to treatment. Nod-like receptor protein 3(NLRP3) inflammasome is a multi-protein signal complex and one of the important innate immune signal receptors. Inflammation plays an important role in the occurrence and development of gastric cancer, and continuous inflammation mediation will trigger the transformation from inflammation to cancer. Therefore, the significance of NLRP3 inflammasome to gastric mucosa lies in the transformation between inflammation and cancer. Traditional Chinese medicine(TCM) has the functions of multi-components, multi-targets, and few adverse reactions. A large number of studies show that TCM and related monomers have significant effects in treating liver, kidney, and immune diseases through mediating NLRP3 inflammasome, but there is less research on the "inflammation-cancer" transformation in gastric mucosa. By combing the NLRP3-related nuclear factor-κB transcription factor(NF-κB), hypoxia inducible factor-1α(HIF-1α), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), and other signal pathways, this paper clarified their mechanisms in the "inflammation-cancer" transformation in gastric mucosa, delayed the process of "inflammation-cancer" transformation in gastric mucosa through four aspects: energy metabolism, pyroptosis, immune response, and vascular endothelial growth factor, and prevented and treated "inflammation-cancer" transformation in gastric mucosa from three aspects: TCM monomer, TCM compound prescription, and other therapies, so as to provide ideas for the subsequent treatment of "inflammation-cancer" transformation in gastric mucosa with TCM.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/pathology* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Inflammation/drug therapy* ; Signal Transduction/drug effects*

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats