ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group， ferroptosis inhibitor group （2 mg·kg^-1）， enalapril group （2.1 mg·kg^-1）， and low- and high-dose （4 g·kg^-1 and 8 g·kg^-1， respectively） Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma， with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment， echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， transforming growth factor-β （TGF-β）， and myosin heavy chain-β （MHC-β） were measured by enzyme-linked immunosorbent assay （ELISA）. Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde （MDA） and glutathione （GSH） in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E₂-related factor 2 （Nrf2） in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. ResultsCompared with the sham group， the model group showed increased left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， disarrangement of myocardial cells， inflammatory cell infiltration， severe myocardial fibrosis， increased myocardial iron deposition， and irregular mitochondrial morphology with vacuolation. Furthermore， the modeling led to increased MDA （P<0.01）， decreased GSH （P<0.01）， diminished Nrf2 fluorescence intensity in the myocardial tissue， and downregulated expression levels of Nrf2， SLC7A11， and GPX4 （P<0.01）. Compared with the model group， Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD， LVESD， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.05， P<0.01）， alleviated pathological changes such as myocardial cell disarrangement， inflammatory cell infiltration， myocardial fibrosis， and iron deposition， lowered the level of MDA （P<0.05， P<0.01）， raised the level of GSH （P<0.05， P<0.01）， improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue， enhanced Nrf2 fluorescence intensity， and upregulated the expression levels of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis， the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.

ObjectiveTo investigate the effect of Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma on ferroptosis in the rat model of myocardial infarction and further elucidate its role in myocardial remodeling. MethodsThe rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The 50 successfully modeled rats were randomly divided into model group， ferroptosis inhibitor group （2 mg·kg^-1）， enalapril group （2.1 mg·kg^-1）， and low- and high-dose （4 g·kg^-1 and 8 g·kg^-1， respectively） Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma， with 10 rats in each group. The rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. After 4 weeks of treatment， echocardiography was used to assess the cardiac structure and function. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe pathological morphology and fibrosis of the myocardial tissue. Serum levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， transforming growth factor-β （TGF-β）， and myosin heavy chain-β （MHC-β） were measured by enzyme-linked immunosorbent assay （ELISA）. Prussian blue staining was performed to detect myocardial iron deposition. The myocardial mitochondrial structure was observed by transmission electron microscopy. Levels of malondialdehyde （MDA） and glutathione （GSH） in the myocardial tissue were determined by lipid peroxidation assay kits. Immunofluorescence assay was conducted to observe the fluorescence intensity of nuclear factor E₂-related factor 2 （Nrf2） in the myocardial tissue. Western blot analysis was performed to evaluate the expression levels of proteins in the Nrf2/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. ResultsCompared with the sham group， the model group showed increased left ventricular end-diastolic diameter （LVEDD）， left ventricular end-systolic diameter （LVESD）， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.01）， decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， disarrangement of myocardial cells， inflammatory cell infiltration， severe myocardial fibrosis， increased myocardial iron deposition， and irregular mitochondrial morphology with vacuolation. Furthermore， the modeling led to increased MDA （P<0.01）， decreased GSH （P<0.01）， diminished Nrf2 fluorescence intensity in the myocardial tissue， and downregulated expression levels of Nrf2， SLC7A11， and GPX4 （P<0.01）. Compared with the model group， Gardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma reduced the LVEDD， LVESD， and serum levels of NT-proBNP， TGF-β， and MHC-β （P<0.05， P<0.01）， increased the LVEF and LVFS （P<0.05， P<0.01）， alleviated pathological changes such as myocardial cell disarrangement， inflammatory cell infiltration， myocardial fibrosis， and iron deposition， lowered the level of MDA （P<0.05， P<0.01）， raised the level of GSH （P<0.05， P<0.01）， improved the mitochondrial morphology and reduced vacuolation in the myocardial tissue， enhanced Nrf2 fluorescence intensity， and upregulated the expression levels of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the rat model of myocardial infarction. ConclusionGardeniae Fructus-Salviae Miltiorrhizae Radix et Rhizoma alleviates pathological damage and myocardial remodeling in the rat model of myocardial infarction by inhibiting ferroptosis， the mechanism of which is related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.

The recombinant human thyroid-stimulating hormone (rhTSH) can be used for differentiated thyroid cancer (DTC) preparation before ¹³¹I therapy, and follow-up. Since its approval by the American Food and Drug Administration (FDA) in 1998, rhTSH has been clinically used in European countries, the United States, and other countries for nearly 30 years. In April 2024, China’s first independently developed rhTSH agent was approved. Based on clinical experience and evidence from domestic and international studies, an expert consensus on the application of rhTSH has been developed following thorough consultations among experts. The consensus offers evidence-based recommendations to guide the appropriate use of rhTSH in clinical practice.

Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To investigate the association between fluid balance trajectories within the first 3 days of intensive care unit (ICU) admission and 28-day mortality as well as the incidence of continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis (SAP). METHODS: Clinical data of SAP patients were extracted from the Medical Information Mart of Intensive Care-IV (MIMIC-IV). Group-based trajectory modeling (GBTM) was used to analyze the daily fluid balance of patients within 3 days of ICU admission, and grouping them accordingly. Univariate and multivariate Logistic regression analyses were performed to assess the association between fluid balance trajectory and 28-day mortality and ICU CRRT in SAP patients. RESULTS: A total of 251 SAP patients were included, with 33 deaths within 28 days, and a 28-day mortality of 13.15%; 49 patients (19.52%) continued to receive bedside CRRT after 3 days of ICU admission. The fluid balance on the 3rd day, cumulative fluid balance within 3 days of ICU admission, and incidence of CRRT in the death group were significantly higher than those in the survival group. According to GBTM groups, there were 127 cases in the moderate fluid resuscitation with rapid reduction (MF group), 44 cases in the large fluid resuscitation with rapid reduction (LF group), 20 cases in the moderate fluid resuscitation with slow reduction (MS group), and 60 cases in the small fluid resuscitation with slow reduction (SS group). The cumulative fluid balance within 3 days of ICU admission of the MF group, LF group, MS group, and SS group were 8.60% (5.15%, 11.70%), 16.70% (13.00%, 21.02%), 23.40% (19.38%, 25.45%), and 0.65% (-2.35%, 2.20%), respectively, and the incidence of CRRT during ICU hospitalization were 11.02%, 29.55%, 85.00%, and 8.33%, respectively, with statistically significant differences among the groups (both P < 0.05); the 28-day mortality were 11.02%, 18.18%, 20.00%, and 11.67%, respectively, with no statistically significant difference among the groups (P > 0.05). Kaplan-Meier survival curve analysis showed there was no statistically significant difference in 28-day cumulative survival rate among groups with different fluid balance trajectories (Log-rank test: χ ² = 2.31, P = 0.509). Multivariate Logistic regression analysis showed that cumulative fluid balance within 3 days of ICU admission was an independent risk factor for 28-day mortality [odds ratio (OR) = 1.071, 95% confidence interval (95%CI) was 1.005-1.144, P = 0.040] and CRRT requirement (OR = 1.233, 95%CI was 1.125-1.372, P < 0.001); early aggressive fluid resuscitation on day 1 reduced CRRT risk (OR = 0.866, 95%CI was 0.756-0.978, P = 0.030). CONCLUSIONS Dynamic fluid management is essential in SAP patients. While early aggressive fluid resuscitation may reduce CRRT demand, excessive cumulative fluid balance is associated with increased 28-day mortality and CRRT incidence.
Humans ; Male ; Female ; Middle Aged ; Water-Electrolyte Balance ; Continuous Renal Replacement Therapy ; Intensive Care Units ; Aged ; Adult ; Pancreatitis/mortality* ; Logistic Models ; Retrospective Studies ; Renal Replacement Therapy

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

In this work,near infrared carbon quantum dots(NIR-CDs)were synthesized by hydrothermal method using biomass material Clausena lansium leaves.The synthesized NIR-CDs emitted maximum fluorescence signal at 677 nm,which was independent of excitation wavelength.The characterization results showed that there were abundant groups on the surface of NIR-CDs.Pd2+could form non-fluorescent compounds with the surface groups of NIR-CDs,resulting in fluorescence quenching(Fluorescence signal was denoted as F0).Because chlorpromazine hydrochloride(CPZ)parent nucleus contained unoxidized S atom,CPZ could form stable colored complex with Pd2+under acidic conditions.In the presence of CPZ,Pd2+dissociated from the surface of NIR-CDs and bonded with CPZ,so that the fluorescence signal could be restored(Fluorescence signal was denoted as F).An"on-off-on"fluorescence sensor was thus constructed.The fluorescence signal recovery value of NIR-CDs(△F=F-F0)showed a good linear relationship with the concentration of CPZ in the range of 5.68-28.43 μg/mL,and the detection limit(3σ)was 0.078 μg/mL.The sensor was applied to determination of CPZ in pharmaceutical preparations,and the recoveries were 94％-106％.The developed fluorescence sensor was expected to be used in quality control of actual pharmaceutical preparations.

Objective To investigate the impacts of usnea acid(UA)on the proliferation of human ovarian cancer(OC)cells.Methods Ovarian adenocarcinoma cells SKOV3 were randomly divided into control group,L-UA group,M-UA group,H-UA group(with 10,20,and 50 μmol/L UA added respectively),pcDNA3.1-NC group and pcDNA3.1-PD-1 group.RT-qPCR method was applied to detect the expression of programmed cell death 1(PD-1)and programmed cell death ligand 1(PD-L1)in SKOV3 cells.CCK-8 assay and plate method were applied to detect the effect of UA on SKOV3 cell proliferation.The effect of UA on SKOV3 cells apoptosis was examined by flow cytometry.Mouse ovarian epithelial cancer cell line ID8 cells were collected to construct an OC mouse model,and the mass and volume of OC tumors were recorded.Immuno-histochemical microscopy was applied to detect the infiltration of PD-1,PD-L1,and CD8+T cells.Results The PD-1 mRNA,PD-L1 mRNA,colony count,A450 val-ue,PCNA protein,PD-1 protein,and PD-L1 protein in the L-UA,M-UA,and H-UA groups were lower than those in the control group,the apoptosis rate and Bax protein were higher in the control group(P<0.05).Com-pared with the H-UA group and the pcDNA3.1-NC group,the PD-1 mRNA,PD-L1 mRNA,colony count,A450 value,PCNA protein,PD-1 protein,and PD-L1 protein in the pcDNA-3.1-PD-1 group increased and the apoptosis rate and Bax protein decreased(P<0.05).The quality,volume,positivity rate of PD-1and PD-L1 of OC tumors in the UA group was lower than that in the control group,the counting number of CD8+T cell infiltration was higher than control group(P<0.05).Conclusions UA may inhibit progression of OC cell line SKOV3 by regula-ting cell proliferation,apoptosis,and immune escape.

Objective To investigate the effects of galangin on the migration and invasion abilities of cervical cancer Hela cells and its potential mechanisms.Methods Hela cells were treated with different concentrations of galangin(0,5,10,20,40,60,80,100 μmol/L)for 48 hours,and CCK-8 assay was used to assess the impact of galangin on cell viability and to determine the half-maximal lethal concentration(IC50)of galangin.Hela cells were divided into a control group(0 μmol/L)and a galangin group(40 μmol/L treatment).Scratch wound healing assays and Transwell chamber assays were conducted to evaluate the migration and invasion abilities of the cells in each group.Western Blot was used to detect the protein expression of E-cadherin and N-cadherin.DIA quantitative proteomics technology was used to detect and screen the differentially expressed proteins between the two groups.Biological function enrichment analysis of the differential genes was performed using the KEGG Pathway and Gene Set Enrichment Analysis(GSEA)methods.Western Blot was used to verify the expression levels of Hippo/YAP signaling pathway-related proteins YAP and p-YAP.Results Compared to the control group,galangin(40 μmol/L)significantly inhibited the viability of Hela cells in a concentration-dependent manner(P<0.001).Compared with the control group,the scratch healing ability and invasion ability of cervical cancer Hela cells treated with galangin(40 μmol/L)were significantly reduced(P<0.001).The expression of E-cadherin protein was increased(P<0.05)and the expression of N-cadherin protein was decreased(P<0.001)in the galangin group(40 μmol/L)compared to the control group.KEGG and GSEA enrichment results indicated that the inhibition of malignant progression in cervical cancer by galangin was significantly associated with the Hippo/YAP signaling pathway.Western Blot confirmed that the expression level of the hallmark protein p-YAP in the Hippo signaling pathway was increased(P<0.01),while the expression level of YAP protein was decreased(P<0.05).Conclusion Galangin inhibits the proliferation,migration and invasion abilities of Hela cells in a dose-dependent manner.The underlying mechanism might be associated with the activation of the Hippo/YAP signaling pathway.