This study aims to explore the intervention effects of isorhamnetin(Isor) on acute lung injury(ALI) and its regulatory effects on pyroptosis mediated by the NOD-like receptor family pyrin domain containing 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteine aspartate-specific protease-1(caspase-1) axis. In the in vivo experiments, 60 BALB/c mice were divided into five groups. Except for the control group, the other groups were administered Isor by gavage 1 hour before intratracheal instillation of LPS to induce ALI, and tissues were collected after 12 hours. In the in vitro experiments, RAW264.7 cells were divided into five groups. Except for the control group, the other groups were pretreated with Isor for 2 hours before LPS stimulation and subsequent assessments. Hematoxylin-eosin(HE) staining was used to observe pathological changes in lung tissue, while lung swelling, protein levels in bronchoalveolar lavage fluid(BALF), and myeloperoxidase(MPO) levels in lung tissue were measured. Cell proliferation toxicity and viability were assessed using the cell counting kit-8(CCK-8) method. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of interleukin-1β(IL-1β), IL-6, IL-18, and tumor necrosis factor-α(TNF-α). Protein levels of NLRP3, ASC, cleaved caspase-1, and the N-terminal fragment of gasdermin D(GSDMD-N) were evaluated using immunohistochemistry, immunofluorescence, and Western blot. The results showed that in the in vivo experiments, Isor significantly improved pathological damage in lung tissue, reduced lung swelling, protein levels in BALF, MPO levels in lung tissue, and levels of inflammatory cytokines such as IL-1β, IL-6, IL-18, and TNF-α, and inhibited the high expression of the NLRP3/ASC/caspase-1 axis and the pyroptosis core gene GSDMD-N. In the in vitro experiments, the safe dose of Isor was determined through cell proliferation toxicity assays. Isor reduced cell death and inhibited the expression levels of the NLRP3/ASC/caspase-1 axis, GSDMD-N, and inflammatory cytokines. In conclusion, Isor may alleviate ALI by modulating pyroptosis mediated by the NLRP3/ASC/caspase-1 axis.
Animals ; Pyroptosis/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Acute Lung Injury/physiopathology* ; Mice ; Mice, Inbred BALB C ; Quercetin/pharmacology* ; Caspase 1/genetics* ; CARD Signaling Adaptor Proteins/genetics* ; Male ; RAW 264.7 Cells ; Humans ; Lung/metabolism*

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

This paper briefly introduced the varying coefficient model and used the varying coefficient Cox model as an example to demonstrate its application in the fields of medicine and public health through real data analysis,thereby provided methodological references for related research.The example was based on chronic disease management data from a Center for Disease Control and Prevention,fitting a varying coefficient Cox model to explore the time-varying association between body mass index(BMI)and mortality risk among a hypertensive population.The results showed that being underweight(BMI＜18.5 kg/m2)was associated with a higher risk of mortality,but this association weakened over time;being overweight(23 kg/m2≤BMI＜25 kg/m2)was associated with a lower risk of mortality,and this association also weakened over time.The varying coefficient model captured how the impact of exposure factors on outcomes changed with other variables,helping to comprehensively understand the complex relationships between variables,and had significant application and promotion value in medical and public health research.

Objective To compare the effect of three-dimensional visual (3DV) model, three-dimensional printing (3DP) model and computer-aided design (CAD) modified 3DP model in video-assisted thoracoscopic surgery (VATS) sublobular resection. Methods The clinical data of patients who underwent VATS sublobular resection in the Affiliated Hospital of Hebei University from November 2021 to August 2022 were retrospectively analyzed. The patients were divided into 3 groups including a 3DV group, a 3DP group and a CAD-3DP group according to the tools used. The perioperative indexes and subjective evaluation of operators, patients and their families were compared. Results A total of 22 patients were included. There were 5 males and 17 females aged 32-77 (56.95±12.50) years. There were 9 patients in the 3DV group, 6 patients in the 3DP group, and 7 patients in the CAD-3DP group. There was no statistical difference in the operation time, intraoperative blood loss, drainage volume, hospital stay time or postoperative complications among the groups (P>0.05). Based on the subjective evaluations of 4 surgeons, the CAD-3DP group was better than the 3DV group in the preoperative planning efficiency (P=0.025), intuitiveness (P=0.045) and doctor-patient communication difficulty (P=0.034); the CAD-3DP group was also better than the 3DP group in the overall satisfaction (P=0.023), preoperative planning difficulty (P=0.046) and efficiency (P=0.014). Based on the subjective evaluations of patients and their families, the CAD-3DP group was better than the 3DP group in helping understand the vessel around the tumor (P=0.016), surgical procedure (P=0.020), procedure selection (P=0.029), and overall satisfaction (P=0.048); the CAD-3DP group was better than the 3DV group in helping understand the tumor size (P=0.038). Conclusion CAD-modified 3DP model has certain advantages in pre-planning, intraoperative navigation and doctor-patient communication in the VATS sublobectomy.

Aortic valve stenosis,as a common heart valve disease,progresses rapidly and has a poor clinical prognosis.In the case of combined acute heart failure,the pumping function of the heart is severely impaired,which may lead to a significant decrease in cardiac output,resulting in a state of shock.Transcatheter aortic valve replacement(TAVR)has become a first-line treatment for elderly patients with aortic valve stenosis since its first successful case in 2002.In China,with the advancement of technology and the strengthening of physician training,the capacity of grassroots hospitals in TAVR treatment is increasing.This case reports a patient with severe aortic valve stenosis accompanied by acute heart failure and shock status who received emergency TAVR treatment at a grassroots hospital.Due to limitations in conditions,TAVR was urgently implemented without extracorporeal circulation and extracorporeal membrane oxygenation support.The patient's blood pressure immediately rose to 105/65 mmHg after valve dilation during surgery,and the postoperative symptoms were significantly relieved.Follow up color Doppler ultrasound showed that the stenosis was relieved and the heart function was significantly improved.The success of this surgery provides a reference for emergency TAVR treatment in patients with severe aortic valve stenosis and heart failure in grassroots hospitals.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

A new alkaloid (1) and six known compounds (2-7) were isolated from the solid fermentation extract of the endophytic fungus Alternaria tenuissima Pas85 of Phragmites australis by silica gel column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and other chromatographic techniques. The structures of these compounds were determined by HREIMS, NMR, IR spectroscopy, and literature comparison, and the anti MRSA (methicillin-resistant Staphylococcus aureus) activity of 1-5 were tested. Compounds 1, 2, 3 and 4 exhibited certain inhibitory activity with MIC values of 64, 4, 32 and 32 μg·mL^-1, respectively, and compound 5 showed no significant inhibitory activity.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters.