Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection,with a high mortality rate.Sirtuin 3,a deacetylase within mitochondria,plays an important regulatory role in cellular metabolism,oxidative stress,and inflammatory responses.In recent years,significant progress has been made in the study of the function and regulatory role of sirtuin 3 in sepsis-related diseases.Research has shown that sirtuin 3 can alleviate organ damage caused by sepsis by regulating mitochondrial function,reducing oxidative stress,and inhibiting inflammatory responses.The specific mechanisms include the regulation of mitochondrial bioenergetics,activation of antioxidant enzyme systems,and inhibition of inflammatory mediator expression.In addition,sirtuin 3 plays a protective role in the pathological process of sepsis by interacting with multiple signaling pathways.This article summarizes the functions and regulatory mechanisms of sirtuin 3 in various sepsis-related diseases,aiming to provide new targets and strategies for the prevention and treatment of sepsis in the future.
Sepsis/metabolism* ; Sirtuin 3/physiology* ; Humans ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the susceptibility of venetoclax-resistant acute myeloid leukemia (AML) cell lines to ferroptosis and to uncover the underlying molecular mechanisms using transcriptomic and metabolomic analysis methods. METHODS: Venetoclax-resistant AML cell lines were constructed using a low-dose concentration escalation method. The sensitivity of cells to chemotherapeutic drugs was detected by CCK-8 assay. The susceptibility of drug-resistant cell lines to ferroptosis was assessed using transcriptomic and metabolomic analysis methods. The expression of cellular GPX4 and SLC7A11 protein was detected by Western blot, and cell death and lipid peroxidation levels were measured by flow cytometry. Depmap database and TCGA cohort were applied to explore the effect of ferroptosis-related genes expression on prognosis. RESULTS: Venetoclax-resistant cell lines exhibited sensitivity to ferroptosis inducers RSL3, APR246, and sorafenib. The ferroptosis inhibitor Fer-1 partially inhibited cell death induced by these inducers. Compared with the parental cells, significant changes in metabolites and gene expression levels related to ferroptosis were observed in the resistant cell lines. In particular, deregulated expression of SLC7A11 and GPX4 may play critical role in ferroptosis susceptibility. Besides, GPX4 was identified as more important for AML cell survival and higher GPX4 expression may predict shortened overall survival, NPM1 mutant and IDH1 R132 mutation positive patients may prone to possess higher GPX4 expression. CONCLUSION Venetoclax-resistant AML cell lines remain susceptible to ferroptosis, higher GPX4 expression maybe a critical marker for poor prognosis. Regulating the expression of ferroptosis-related genes and metabolites may enhance the efficacy of venetoclax and provide new treatment options for AML patients.
Humans ; Ferroptosis ; Leukemia, Myeloid, Acute/metabolism* ; Sulfonamides/pharmacology* ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology* ; Drug Resistance, Neoplasm ; Metabolomics ; Cell Line, Tumor ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Amino Acid Transport System y+/metabolism* ; Transcriptome

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy