OBJECTIVE To evaluate the efficacy and safety of total glucosides of paeonia （TGP） in the treatment of systemic lupus erythematosus （SLE）. METHODS Randomized controlled trial （RCT） about TGP combined with western medicine versus western medicine alone for SLE treatment were retrieved from PubMed， Embase， Cochrane Library， Web of Science， CNKI， VIP， Wanfang Data， and CBM. The search period spanned from the inception of each database to June 1， 2025. After literature screening， data extraction， and quality assessment of the included studies， Meta-analysis was performed using RevMan 5.4 software. RESULTS Fifteen RCTs， involving 1 318 patients， were included. Meta-analysis results showed that compared with western medicine alone， TGP combined with western medicine significantly improved clinical efficacy [OR＝4.96， 95%CI（3.41， 7.23）， P＜0.000 01]， complement 3 [MD＝0.18， 95%CI （0.13， 0.23）， P＜0.000 01] and complement 4[MD＝0.08， 般021） 95%CI （0.04， 0.11）， P＜0.000 01]， and reduced the levels of immunoglobulin G （IgG） [MD＝－3.10， 95%CI （－3.59，－2.62）， P＜0.000 01]， IgA [MD＝－0.68， 95%CI （－0.78， －0.58）， P＜0.000 01]， IgM [MD＝－0.43， 95%CI （－0.53，－0.34）， P＜0.000 01]， systemic lupus erythematosus disease activity index （SLEDAI） [MD＝－1.59， 95%CI （－2.20， －0.99）， P＜0.000 01]， recurrence rate [OR＝0.23， 95%CI （0.13， 0.42）， P＜0.000 01] and the incidence of adverse drug reactions [OR＝ 0.54， 95%CI （0.36， 0.82）， P＝0.004]. CONCLUSIONS TGP therapy can improve clinical efficacy of SLE patients， promote the restoration of immunoglobulins and complements， reduce SLEDAI and recurrence rate and has good safety.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.

Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Objective To clarify the risk factors of diaphragmatic dysfunction (DD) after cardiac surgery with extracorporeal circulation. Methods A retrospective analysis was conducted on the data of patients who underwent cardiac surgery with extracorporeal circulation in the Department of Cardiovascular Surgery of Peking University People's Hospital from January 2023 to March 2024. Patients were divided into two groups according to the results of bedside diaphragm ultrasound: a DD group and a control group. The preoperative, intraoperative, and postoperative indicators of the patients were compared and analyzed, and independent risk factors for DD were screened using multivariate logistic regression analysis. Results A total of 281 patients were included, with 32 patients in the DD group, including 23 males and 9 females, with an average age of (64.0±13.5) years. There were 249 patients in the control group, including 189 males and 60 females, with an average age of (58.0±11.2) years. The body mass index of the DD group was lower than that of the control group [(18.4±1.5) kg/m2 vs. (21.9±1.8) kg/m2, P=0.004], and the prevalence of hypertension, chronic obstructive pulmonary disease, heart failure, and renal insufficiency was higher in the DD group (P<0.05). There was no statistical difference in intraoperative indicators (operation method, extracorporeal circulation time, aortic clamping time, and intraoperative nasopharyngeal temperature) between the two groups (P>0.05). In terms of postoperative aspects, the peak postoperative blood glucose in the DD group was significantly higher than that in the control group (P=0.001), and the proportion of patients requiring continuous renal replacement therapy was significantly higher than that in the control group (P=0.001). The postoperative reintubation rate, tracheotomy rate, mechanical ventilation time, and intensive care unit stay time in the DD group were higher or longer than those in the control group (P<0.05). Multivariate logistic regression analysis showed that low body mass index [OR=0.72, 95%CI (0.41, 0.88), P=0.011], preoperative dialysis [OR=2.51, 95%CI (1.89, 4.14), P=0.027], low left ventricular ejection fraction [OR=0.88, 95%CI (0.71, 0.93), P=0.046], and postoperative hyperglycemia [OR=3.27, 95%CI (2.58, 5.32), P=0.009] were independent risk factors for DD. Conclusion The incidence of DD is relatively high after cardiac surgery, and low body mass index, preoperative renal insufficiency requiring dialysis, low left ventricular ejection fraction, and postoperative hyperglycemia are risk factors for DD.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

Objective To evaluate the accuracy of multiparametric imaging on the dual-source CT through acceptance and commissioning testing, and to provide a reference for standardized clinical application. Methods Both the adult and pediatric dual-source CT scanning modes were used to scan the electron density phantom, and identical multiparametric image reconstruction tasks were performed, including the conventional CT images, the mixed CT images, the virtual monoenergetic images, the iodine images, the electron density images, and the effective atomic number images. Results In the adult scanning mode, the virtual monoenergetic CT numbers showed the greatest difference for the cortical bone (1722 HU at 40 keV vs. 30 HU at 80 keV), with smaller differences observed for other materials as their atomic numbers decreased. The pediatric scanning mode exhibited a similar trend, with the largest difference occurring at 40 keV (1393 HU). In the adult scanning mode, the deviations between the theoretical and measured iodine concentration values were all within 5%, whereas in the pediatric scanning mode, the largest deviation was 15% for an iodine concentration of 2.0 mg/mL. For the electron density, the largest deviation between the theoretical and measured values occurred in the LN450 lung (9.18% in the adult scanning mode and 8.96% in the pediatric scanning mode); the deviations for the LN300 lung were all below 7.2%, for aluminum below 6.3%, and for other tissues within 3%. For the effective atomic number, the deviations between the theoretical and measured values were all within 5% in both scanning modes. Conclusion To ensure the accuracy and reproducibility of the dual-source CT applications, a comprehensive acceptance testing protocol should be established to guarantee the safety and precision of the CT localization process.

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.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L^-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
Withanolides/isolation & purification* ; Physalis/chemistry* ; Humans ; Molecular Structure ; Cell Line, Tumor ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Cell Proliferation/drug effects* ; Plant Leaves/chemistry* ; Plant Extracts/pharmacology*