OBJECTIVE: To analyze the efficacy and access safety of extracorporeal membrane oxygenation (ECMO) in series with continuous renal replacement therapy (CRRT) access for critically ill patients using propensity score matching analysis, and to explore the potential influencing factors of infection. METHODS: A total of 200 critically ill patients who received both ECMO and CRRT treatment in the intensive care unit (ICU) of Huai'an Second People's Hospital from December 2020 to December 2024 were retrospectively selected as the research subjects. They were divided into the independent operation group (72 cases) and the series system group (128 cases) according to the access connection mode of ECMO and CRRT. Propensity score matching analysis was used to perform 1 : 1 matching for patients of the two groups. The general data [age, gender, body mass index (BMI), clinical diagnosis, underlying disease, intubation method, intubation position, disease severity, ECMO support duration, catheter indwelling duration, oxygenation index (PaO₂/FiO₂) at 48 hours after ECMO initiation, serum creatinine (SCr), procalcitonin (PCT), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT)], treatment status [ECMO initiation duration, ECMO operation duration, ECMO flow, left ventricular ejection fraction (LVEF), CRRT initiation duration, CRRT catheter indwelling duration, inflow and outflow volume of replacement fluid], clinical outcome indicators (28-day survival rate, length of ICU stay, renal function recovery, fluid balance compliance rate), and access safety indicators (incidence of ECMO access thrombosis, incidence of infection, and incidence of bleeding events) of all the patients were collected. Subgroup analysis was conducted based on the occurrence of infection, and multivariate Logistic regression analysis was used to screen the potential risk factors for infection in critically ill patients receiving both ECMO and CRRT treatment. RESULTS: Finally, a total of 120 patients were successfully matched, with 60 patients in both the independent operation group and the series system group. No statistically significant differences were observed in the general data between the two groups, indicating comparability. Compared with the independent operation group, the ECMO flow at 48 hours after ECMO initiation, SCr, and alanine transaminase (ALT) of the patients in the series system group were significantly decreased, while the LVEF at 48 hours after ECMO initiation was significantly increased, additionally, the CRRT initiation duration, CRRT catheter indwelling duration, and the length of ICU stay were significantly shortened, and the inflow and outflow volume of replacement fluid were significantly increased. The incidence of infection and bleeding events in the series system group was significantly lower than that in the independent operation group [infection incidence: 11.67% (7/60) vs. 36.67% (22/60), bleeding event incidence: 8.33% (5/60) vs. 48.33% (29/60), both P < 0.05]. No significant difference was found in the other general data, treatment status, clinical outcome indicators, or access safety indicators between the two groups. Among the 120 patients, 29 cases developed infection (accounting for 24.17%), and 91 cases had no infection (accounting for 75.83%). Compared with the non-infection group, the catheter indwelling duration was significantly prolonged and PCT was significantly increased in the infection group, while the PLT and the proportion of patients with ECMO and CRRT access connected via the series system were significantly decreased. Multivariate Logistic regression analysis showed that catheter indwelling duration [odds ratio (OR) = 1.277, 95% confidence interval (95%CI) was 1.001-1.629, P = 0.049], PCT (OR = 1.529, 95%CI was 1.222-1.914, P < 0.001], PLT (OR = 0.953, 95%CI was 0.926-0.981, P = 0.001), and access connection mode (OR = 0.289, 95%CI was 0.090-0.930, P = 0.037) were potential risk factors for infection in critically ill patients. CONCLUSIONS The ECMO-in-series CRRT access can accelerate the initiation of CRRT, avoid local bleeding, stabilize patients' cardiac, hepatic and renal functions, reduce potential infection risks, and improve the prognosis of patients.
Humans ; Extracorporeal Membrane Oxygenation/adverse effects* ; Critical Illness/therapy* ; Retrospective Studies ; Continuous Renal Replacement Therapy ; Male ; Female ; Intensive Care Units ; Propensity Score ; Middle Aged ; Renal Replacement Therapy ; Adult ; Aged ; Risk Factors

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Xiaohuang Qudan decoction (XHQDD) is a classical traditional Chinese medicine (TCM) formula widely used in the treatment of cholestatic liver injury. Despite its widespread use, the protective mechanism of XHQDD against cholestatic liver injury remains incompletely understood. The aim of this study was to investigate whether XHQDD mediates its beneficial effects by inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway and regulating TH17/Treg balance. To this end, the researchers used Sprague-Dawley (SD) rats and established a cholestatic liver injury model by oral administration of alpha-naphthylisothiocyanate (ANIT). The experimental group was divided into six groups: Control (CON), ANIT, ursodeoxycholic acid (UDCA), XHQDD-low dose (XHQDD-L) group, XHQDD-medium dose (XHQDD-M) group, and XHQDD-high dose (XHQDD-H) groups. Then, after 7 d of treatment, various tests were performed to verify the results. Firstly, XHQDD and its drug-containing serum were analyzed by ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS), and 14 blood-entry components were identified. Then, bile flow was monitored and found to be significantly reduced in the model group, which was significantly reversed in the UDCA and XHQDD groups. To further assess ANIT-induced liver injury, hematoxylin and eosin (H&E) and Sirius red staining, alongside transmission electron microscopy (TEM), were employed to observe liver tissues, revealing hepatocellular injury, cholestasis, and hepatic fibrotic changes. Serum inflammatory factors and liver injury indicators were assessed using enzyme-linked immunosorbent assay (ELISA), indicating an inflammatory state in ANIT-induced liver injury rats. The expression levels of JAK2/STAT3-related genes and proteins in liver and intestinal tissues were measured via quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunohistochemistry, immunofluorescence (IF) staining, and Western blottting (WB) assays. These studies revealed that the inflammatory state of liver-injured rats was inextricably linked to the inflammatory cascade associated with the JAK2/STAT3 pathway and that XHQDD may exert anti-inflammatory efficacy by inhibiting the JAK2/STAT3 pathway. Flow cytometry was used to determine the percentage of T helper 17 (Th17)/regulatory T (Treg) cells in serum and hepatocytes, and it was further found that XHQDD was able to regulate Th17/Treg immune homeostasis in liver-injured rats. The findings suggest that XHQDD markedly alleviates inflammation in ANIT rats, potentially treating cholestasis and liver injury through JAK2/STAT3 inhibition and Th17/Treg balance regulation.
Animals ; STAT3 Transcription Factor/immunology* ; Janus Kinase 2/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Rats, Sprague-Dawley ; 1-Naphthylisothiocyanate/adverse effects* ; Male ; Rats ; Th17 Cells/immunology* ; Cholestasis/immunology* ; Signal Transduction/drug effects* ; T-Lymphocytes, Regulatory/immunology* ; Chemical and Drug Induced Liver Injury/immunology* ; Liver/drug effects*

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

OBJECTIVE: Exposure to polycyclic aromatic hydrocarbons (PAHs) or metal(loid)s individually has been associated with neural tube defects (NTDs). However, the impacts of PAH and metal(loid) co-exposure and potential interaction effects on NTD risk remain unclear. We conducted a case-control study in China among population with a high prevalence of NTDs to investigate the combined effects of PAH and metal(loid) exposures on the risk of NTD. METHODS: Cases included 80 women who gave birth to offspring with NTDs, whereas controls were 50 women who delivered infants with no congenital malformations. We analyzed the levels of placental PAHs using gas chromatography and mass spectrometry, PAH-DNA adducts with ³²P-post-labeling method, and metal(loid)s with an inductively coupled plasma mass spectrometer. Unconditional logistic regression was employed to estimate the associations between individual exposures and NTDs. Least absolute shrinkage and selection operator (LASSO) penalized regression models were used to select a subset of exposures, while additive interaction models were used to identify interaction effects. RESULTS: In the single-exposure models, we found that eight PAHs, PAH-DNA adducts, and 28 metal(loid)s were associated with NTDs. Pyrene, selenium, molybdenum, cadmium, uranium, and rubidium were selected through LASSO regression and were statistically associated with NTDs in the multiple-exposure models. Women with high levels of pyrene and molybdenum or pyrene and selenium exhibited significantly increased risk of having offspring with NTDs, indicating that these combinations may have synergistic effects on the risk of NTDs. CONCLUSION Our findings suggest that individual PAHs and metal(loid)s, as well as their interactions, may be associated with the risk of NTDs, which warrants further investigation.
Humans ; Neural Tube Defects/chemically induced* ; Polycyclic Aromatic Hydrocarbons/adverse effects* ; Female ; Case-Control Studies ; China/epidemiology* ; Adult ; Pregnancy ; Environmental Pollutants ; Maternal Exposure/adverse effects* ; Metals/toxicity* ; Young Adult ; Risk Factors

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line