Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

Objective:To investigate the role of insulin-like growth factor binding protein 5 (IGFBP5) in cardiac remodeling following acute myocardial infarction (AMI).Methods:In vivo experiments, a mouse model of AMI was established and randomly divided into three groups: sham-operation group, early AMI group (day 3), and late AMI group (day 28). Western blotting was used to detect the expression of fibrosis-related proteins and IGFBP5 in myocardial tissue. Immunofluorescence staining was performed to assess changes in IGFBP5 expression in the infarcted area at days 3 and 28. Serum IGFBP5 levels were measured using ELISA. In vivo experiments, IGFBP5 expression was silenced in mouse cardiac fibroblasts using siRNA, and the effect on transforming growth factor-β (TGF-β)-induced myofibroblast transdifferentiation was evaluated. One-way ANOVA was used for statistical comparisons among multiple groups.Results:On day 28 after AMI, IGFBP5 expression in myocardial tissue and serum was significantly elevated and positively correlated with the expression of fibrosis markers, including Fibronectin, Periostin, and α-SMA ( P<0.01). Both mouse serum analysis and immunofluorescence staining of heart tissue sections showed that the expression level of IGFBP5 was significantly increased in the late stage of AMI compared to baseline( P<0.001), indicating its potential as a prognostic marker for myocardial infarctionIn vitro, silencing IGFBP5 expression inhibited TGF β-induced fibroblast transdifferentiation and reduced the expression of fibrosis-related proteins ( P<0.05). Conclusion:IGFBP5 may play a role in the progression of AMI and serve as both a potential therapeutic target and a prognostic biomarker.

Shewanella oneidensis MR-1, a Gram-negative bacterium with a significant role in the adsorption and reduction of uranium in wastewater and a quorum-sensing effect, can be used to remove uranium from wastewater. Exogenous signaling molecules (acyl-homoserine lactones, AHLs) can be added to induce the quorum sensing behavior for rapid biofilm formation, thereby improving the removal efficiency of this bacterium for uranium. Extracellular polymeric substances (EPS), as the significant components of biofilm, play a key role in biofilm formation. To investigate the quorum sensing behavior induced by AHLs, we systematically investigated the effects of AHLs on the EPS secretion and biofilm properties of S. oneidensis MR-1 by regulating parameters such as AHL species, concentration, addition time point, and contact time. The results showed that the addition of 10 μmol/L N-butyryl-l-homoserine lactone (C4-HSL) after 6 h of culture and continued incubation to reach the time point of 72 h significantly promoted the secretion of EPSs, in which the content of extracellular proteins and extracellular polysaccharides was increased by 15.2% and 28.2%, respectively, compared with that of the control group. The biofilm electrodes induced by signaling molecules showed superior properties, which were evidenced by an increase of exceeding 20 μm in biofilm thickness, an increase of 33.9% in the proportion of living cells, enhanced electroactivity, and an increase of 10.7% in the uranium removal rate. The biofilm electrode was confirmed to immobilize uranium in wastewater mainly by electrosorption, physicochemical adsorption, and electro-reduction through characterization means such as X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). This study provides a new technical idea for the efficient recovery of uranium in wastewater and enriches the theoretical system of quorum sensing regulation of electroactive biofilms.
Biofilms/drug effects* ; Acyl-Butyrolactones/pharmacology* ; Quorum Sensing/drug effects* ; Uranium/metabolism* ; Shewanella/metabolism* ; Adsorption ; Uranium Compounds/metabolism* ; Wastewater/chemistry* ; Biodegradation, Environmental ; Extracellular Polymeric Substance Matrix/metabolism*

The inference of tissue origin of body fluid stains is crucial for case investigation and court proceedings.However,traditional methods for identification of body fluid stains,such as morpho-logical,chemical,and immunoassay identifications have certain limitations,and there is an urgent need for more efficient methods for confirmatory experiments.In recent years,the rapid development of tran-scriptomics technology has provided new means for the identification of tissue origin of body fluid stains.Different types of RNA in the transcriptome have their own advantages.This paper elaborates in detail on the application of different types of RNA,such as mRNA,miRNA,circRNA,lncRNA,piRNA and microbial transcriptomics in body fluid identification,and summarizes their respective ad-vantages and limitations,in order to provide a reference for related research.

Objective:To investigate the differences in clinical characteristics and antibiotic resistance of neonatal sepsis（NS）caused by different Gram-staining pathogens.Methods:A retrospective study was conducted on confirmed NS cases admitted to the Neonatal Ward of the Pediatric Department at The First Affiliated Hospital of Dali University，from June 1，2014，to May 31，2024.Patients were divided into Gram-positive and Gram-negative groups based on blood or cerebrospinal fluid（CSF）culture results.Clinical characteristics，pathogen distribution，and antibiotic resistance were compared between the two groups.Results:A total of 98 cases were included，with 81 in the Gram-positive group and 17 in the Gram-negative group.Multivariate logistic regression analysis revealed that NS cases with a high neutrophil percentage（ OR=0.933，95% CI：0.899-0.969）or hemorrhagic symptoms/signs（ OR=0.059，95% CI：0.008-0.458）were less likely to have Gram-positive pathogens detected in blood or CSF cultures（ P<0.05）.Common Gram-positive pathogens included Staphylococcus epidermidis with 35 strains（33.65%）and Staphylococcus hominis with 22 strains（21.15%）.The predominant Gram-negative pathogen was Escherichia coli with 14 strains（13.46%）.Gram-positive pathogens exhibited high resistance to oxacillin（91.30%），erythromycin（90.91%），and penicillin G（90.00%），but low resistance to tigecycline（0），linezolid（0），and vancomycin（0）.Gram-negative pathogens showed high resistance to ampicillin（92.31%），cefazolin（90.00%），and ampicillin/sulbactam（75.00%），but low resistance to amikacin（6.25%），latamoxef（0），and ertapenem（0）.The incidence of concurrent purulent meningitis was lower in the Gram-positive group than in the Gram-negative group（9.88% vs.47.06%， χ2=11.628， P<0.05），and there was significant difference. Conclusion:NS cases with high neutrophil percentages or hemorrhagic symptoms/signs are less likely to be caused by Gram-positive pathogens.Staphylococcus epidermidis and Staphylococcus hominis are common Gram-positive pathogens，while Escherichia coli is the predominant Gram-negative pathogen in NS.Both Gram-positive and Gram-negative pathogens exhibit resistance to specific antibiotics.NS caused by Gram-positive pathogens is less likely to be complicated by purulent meningitis compared to those caused by Gram-negative pathogens.

Objective:To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods:Thirty-six adult New Zealand White rabbits were randomly divided into control group, intravitreal injection group, and intracameral injection group, with 12 rabbits in each group.In the control group, 0.1 ml of balanced salt solution (BSS) was injected into the vitreous cavity of one eye, and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group, 0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye, respectively.Slit-lamp microscopy, ophthalmoscope, optical coherence tomography (OCT), and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1, 7, 14, and 28 after injection.After sacrifice, both eyeballs were removed, and the corneas and retinas were examined using optical microscopy, scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital (No.IRB00006761-2015197). Results:Slit-lamp microscopy and OCT showed no corneal edema, intraocular inflammation, or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection, which resolved 7 days after injection. In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1, 7, and 14 days after injection among the three groups ( Fgroup=1.21, P=0.32; Ftime=1.21, P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection, retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group, inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer, and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group, a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group, 1 day after injection swelling of corneal endothelial cells, dilatation of the endoplasmic reticulum, and partial mitochondrial swelling were observed, which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group, swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However, structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection. Conclusions:Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina, which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.

Objective:To explore the risk factors of suicidal ideation in bereavement callers of Beijing psy-chological support hotline.Methods:Bereavement callers from 2022-2023 hotline callers who were assessed for grief reactions were included in this study.Callers were assessed for current suicidal ideation by asking them if they had suicidal ideation within two weeks.The general demographic data of bereavement callers were collected,and the distress,hope and suicide risk factors of bereavement callers were assessed by hotline interview.The depression de-gree of bereavement callers was assessed by diagnostic screening scale for depression.Logistic regression analysis was used to explore the risk factors of suicidal ideation.Results:Seventy-seven point two percent(1 028/1 332)of callers reported suicidal ideation.Those who were over 25 years old(OR=0.50),with 10-16 years of education(OR=0.59),with over 16 years of education(OR=0.28),and had a high sense of hope(OR=0.41)were less likely to have suicidal ideation.Those with previous suicide history(OR=2.70),high levels of distress(OR=1.72),and high levels of depression(OR=2.86)were more likely to have suicidal ideation.Conclusion:A history of previous suicide,high levels of distress,and high levels of depression among bereavement callers were risk fac-tors for suicidal ideation.

OBJECTIVE: To study incident and clinical characteristics of the coronary microcirculation dysfunction (CMD) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI) by myocardial contrast echocardiography (MCE) and to explore the predictive value of CMD for in-hospital acute heart failure event. METHODS: One hundred and forty five patients with AMI who had received PCI and completed MCE during hospitalization in Peking University People' s Hospital from November 2015 to July 2021 were enrolled in our study. The patients were divided into CMD group and normal group according to the coronary microcirculation status detected by MCE. Clinical data and MCE data of the two groups were collected and analyzed. The acute heart failure event during hospitalization was described. A multivariate Logistic regression model was built to analyze the risk of acute heart failure in patients with CMD. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of CMD in predicting acute heart failure event. RESULTS: CMD detected by MCE occurred in 87 patients (60%). Compared with normal group, patients with CMD had higher troponin I (TnI) peak level [52.8 (8.1, 84.0) μg/L vs. 18.9 (5.7, 56.1) μg/L, P=0.005], poorer Killip grade on admission (P=0.030), different culprit vessel (P < 0.001) and more patients had thrombolysis in myocardial infarction (TIMI) flow pre-PCI less than grade 3 in culprit vessel (65.1% vs. 43.1%, P=0.025). Meanwhile, patients with CMD had poorer left ventricular ejection fraction (LVEF) [52% (43%, 58%) vs. 61% (54%, 66%)], poorer global longitudinal strain (GLS) [-11.2% (-8.7%, -14.0%) vs.-13.9% (-10.8%, -17.0%)] and worse wall motion score index (WMSI) (1.58±0.36 vs. 1.25± 0.24) (P all < 0.001). Acute left heart failure happened in 13.8% of the CMD patients, which were significant higher than that in the patients with normal coronary microcirculation perfusion (1.7%, P=0.013). After correcting for the culprit vessel, the TIMI flow pre-PCI in the culprit vessel and the peak TnI value, the risk of acute left heart failure in the patients with CMD was still high (OR=9.120, 95%CI: 1.152-72.192, P=0.036). The area under ROC curve (AUC) was 0.677 (95%CI: 0.551-0.804, P=0.035). CONCLUSION The incidence of CMD detected by MCE in patients with AMI post-PCI was 60%. Patients with CMD have a higher risk of acute left heart failure during hospitalization.
Humans ; Heart Failure/physiopathology* ; Microcirculation ; Percutaneous Coronary Intervention/adverse effects* ; Myocardial Infarction/complications* ; Male ; Female ; Hospitalization ; Middle Aged ; Aged ; Echocardiography ; Coronary Circulation ; Predictive Value of Tests ; Troponin I/blood*

Traditional Chinese medicine formula (TCMF) represents a fundamental component of Chinese medical practice, incorporating medical knowledge and practices from both Han Chinese and various ethnic minorities, while providing comprehensive insights into health and disease. The foundation of TCMF lies in its holistic approach, manifested through herbal compatibility theory, which has emerged from extensive clinical experience and evolved into a highly refined knowledge system. Within this framework, Chinese herbal medicines exhibit intricated characteristics, including multi-component interactions, diverse target sites, and varied biological pathways. These complexities pose significant challenges for understanding their molecular mechanisms. Contemporary advances in artificial intelligence (AI) are reshaping research in traditional Chinese medicine (TCM), offering immense potential to transform our understanding of the molecular mechanisms underlying TCMFs. This review explores the application of AI in uncovering these mechanisms, highlighting its role in compound absorption, distribution, metabolism, and excretion (ADME) prediction, molecular target identification, compound and target synergy recognition, pharmacological mechanisms exploration, and herbal formula optimization. Furthermore, the review discusses the challenges and opportunities in AI-assisted research on TCMF molecular mechanisms, promoting the modernization and globalization of TCM.
Artificial Intelligence ; Drugs, Chinese Herbal/pharmacokinetics* ; Humans ; Medicine, Chinese Traditional ; Animals