Ischemia-reperfusion injury (IRI) can lead to organ dysfunction and tissue necrosis in the liver, kidney, myocardium and spinal cord, and there is currently a lack of effective treatment options. Human umbilical cord mesenchymal stem cell (HUC-MSC) and their derivatives have anti-inflammatory, anti-apoptotic, reactive oxygen species scavenging, mitochondrial and endothelial function improvement properties, and are ideal gene therapy carrier cells, providing new possibilities for the treatment of IRI in different organs. This article reviews the concept and mechanisms of IRI, the biological characteristics of HUC-MSC and their derivatives and their comparison with mesenchymal stem cells from other sources, and the mechanisms of HUC-MSC in treating IRI in different organs. It also summarizes and analyzes the advantages and disadvantages of HUC-MSC in protecting different organs from IRI, and prospects future research directions to explore more valuable research paths.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Objective To investigate the expression of serum Sestrin2 and Toll-like receptor 7(TLR7)in patients with severe pneumonia and sepsis and their predictive value for heart failure.Methods A total of 86 patients with severe pneumonia and sepsis complicated with heart failure(complicated with heart failure group)and 86 patients with severe pneumonia and sepsis(uncomplicated with heart failure group)who were diagnosed and treated in Shanxi Provincial People's Hospital from February 2022 to May 2023 were studied.Another 86 patients who underwent health examinations were included as the control group.Enzyme linked immunosorbent assay(ELISA)method was applied to measure serum levels of Sestrin2 and TLR7.Color doppler echocardiography was applied to measure cardiac function related indicators:left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDD),and left ventricular end systolic diameter(LESD).The expression of Sestrin2 and TLR7 levels and cardiac function in three groups was analyzed.Pearson correlation was applied to analyze the relationship between serum levels of Sestrin2 and TLR7 and cardiac function related indicators in patients with heart failure.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum levels of Sestrin2 and TLR7 in patients with severe pneumonia and sepsis complicated with heart failure.Results The serum levels of Sestrin2(11.59±3.31 ng/ml,16.13±3.62 ng/ml),TLR7(48.93±9.52 ng/ml,61.74±10.11 ng/ml),and cardiac function related indicators[LVEDD(53.28±5.76 mm,62.54±6.11 mm)and LESD(38.16±4.38 mm,48.15±5.02 mm)]were higher in uncomplicated heart failure group and complicated heart failure group than those in control group(7.11±2.34 ng/ml,40.12±10.16 ng/ml,44.86±5.02 mm,29.02±4.07 mm),with significant differences(qSestrin2=13.241,26.659,qTLR7=8.224,20.182,qLVEDD=13.824,29.028,qLESD=18.805,39.359,all P＜0.05),and those values in complicated with heart failure group were higher than those in uncomplicated with heart failure group,with significant differences(q=13.418,11.985,15.203,20.554,all P＜0.05).The LVEF(55.43％±6.62％,41.67％±5.84％)index in uncomplicated heart failure group and complicated heart failure group was lower than that in control group(62.75％±7.16％),with significant differences(q=10.344,29.789,all P＜0.05),and the index in complicated with heart failure group was lower than that in uncomplicated with heart failure group,with significant difference(q=19.455,P＜0.05).Pearson correlation analysis showed that serum levels of Sestrin2 and TLR7 in patients with heart failure were negatively correlated with LVEF(r=-0.419,-0.467,all P＜0.05),and positively correlated with LVEDD and LESD(r=0.456,0.419;0.402,0.437,all P＜0.05).Sestrin2 was positively correlated with TLR7(r=0.641,P＜0.05).ROC curve results showed that the area under the curve(AUC)of serum Sestrin2 combined TLR7 for predicting heart failure in severe pneumonia sepsis patients was 0.940,with sensitivity of 74.9％and specificity of 73.3％.Conclusion The serum levels of Sestrin2 and TLR7 in patients with severe pneumonia and sepsis were elevated and may have good predictive value for patients with heart failure.

Objective:To investigate the effects of intra-articular injection of exosomes derived from dental pulp stem cells from hu-man exfoliated deciduous teeth(SHED-EXO)on subchondral bone homeostasis in rat temporomandibular joint osteoarthritis(TMJ OA)process.Methods:36 male SD rats were randomly divided into 3 groups(n=12):control(CON),sodium iodoacetate(MIA)-induced TMJ OA(MIA),and SHED-EXO injection into TMJ OA(SHED-EXO)groups.At 2 and 6 weeks post-treatment,Micro-CT,Double labeling,TRAP staining,and immunohistochemical staining were employed to detect osteoclasts and osteoblasts in the subchondral bone.Additionally,the mRNA expression levels of ADAMTs5,IL-1β,OCN and OPG/RANKL were analyzed by qRT-PCR.Results:The MIA group exhibited significant bone loss and an enlarged bone marrow cavity.In comparison with the CON group,BV/TV and Tb.Th were lower(P＜0.001),while BS/BV,Tb.Sp,and Tb.N were higher(P＜0.01).Additionally,the bone formation rate within 5 days was low-er than that of the control group(P＜0.001).When compared to the MIA group,the SHED-EXO group showed a significant increase in bone morphology and bone mass.BV/TV and Tb.Th were increased(P＜0.01),while BS/BV,Tb.Sp and Tb.N were decreased(P＜0.05).The bone formation rate was higher(P＜0.01).Compared with both the control and treatment groups,the MIA group exhibited a significant increase in the number of osteoclasts in the subchondral bone(P＜0.01),along with a notable decrease in H-type blood vessels and OCN-positive areas(P＜0.01).Conclusion:Intra-articular injection of SHED-EXO can reg-ulate condylar subchondral bone homeostasis in TMJ OA of rats by promoting osteogenesis and inhibiting osteoclasts.

Objective:To explore the medication law and ideas of national TCM master Zhang Lei in the treatment of patients with "stagnant pulse" based on data mining.Methods:Medical records of Professor Zhang's diagnosis and treatment of "stagnant pulse" disease from 1 April 2021 to 1 August 2022 in the Third Affiliated Hospital of Henan University of Chinese Medicine were collected. Excel 2019 and IBM SPSS Modeler 14.1 were used for frequency statistics, attribute analysis of Chinese materia medica, and association rule analysis. Clustering analysis of drugs was conducted using IBM SPSS Statistics 21, and conclusion and summary were performed based on Professor Zhang's clinical diagnosis and treatment experience.Results:Totally 213 medical records were collected, including 332 prescriptions. The main syndromes involved in patients were liver depression and qi stagnation, wood and soil stagnation, etc. The prescriptions involves a total of 243 kinds of Chinese materia medica. The top 5 kinds of Chinese materia medica in terms of medication frequency ranking were Glycyrrhizae Radix et Rhizoma (163 times), Bupleuri Radix (117 times), Pinelliae Rhizoma Praeparatum cum Alumine (110 times), Poria (108 times), Scutellariae Radix (104 times). Professor Zhang's medication for treating patients with "stagnant pulse" was mainly cold and warm; the tastes were mainly sweet, bitter, and pungent; the main meridians were spleen, lung, liver, stomach, and heart; the common medicinal pair was Bupleuri Radix-Angelicae Sinensis Radix, and the basic prescription included Bupleuri Radix, Pinelliae Rhizoma Praeparatum cum Alumine, Glycyrrhizae Radix et Rhizoma, Poria, Paeoniae Radix alba, Scutellariae Radix, Angelicae Sinensis Radix, Citri Reticulatae Pericarpium, Cyperi Rhizoma. Clustering analysis yielded four core categories: category 1 Jujubae Fructus, Zingiberis Rhizoma Recens, Codonopsis Radix, Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, Pinelliae Rhizoma Praeparatum cum Alumine, Scutellariae Radix, Coptidis Rhizoma, Ostreae Concha; category 2 Massa Medicata Fermentata, Astrctylodis Rhizoma, Chuanxiaong Rhizoma; category 3 Cyperi Rhizoma, Gardeniae Fructus, Bupleuri Radix, Menthae Haplocalycis Herba, Moutan Cortex, Paeoniae Radix alba, Angelicae Sinensis Radix, Poria, Citri Reticulatae Pericarpium, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma; category 4 Coicis Semen and Rhei Radix et Rhizoma.Conclusion:Professor Zhang's treatment for "stagnant pulse" is mainly to relieve depression, emphasize the balance of cold and heat, and also take care of the healthy qi to help dispel pathogenic factors and prevent transmission of changes.

Pancreatic neuroendocrine neoplasm (pNEN) is highly heterogeneous, and the prognosis varies among tumors of different stages and grades. However, there is lacking high pro-gnostic predictors with sensitivity and specificity. Inflammation plays a pivotal role in the occurrence and development of different tumors, various inflammatory markers such as neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio are of great significance in the diagnosis, treat-ment, and prognosis of tumors. Several studies have demonstrated that inflammatory markers are associated with poor prognosis and can serve as predictive factors for tumor prognosis. The authors summarize recent advances in the researches focused on the prognostic value of inflamma-tory markers in pNEN, in order to provide novel insights for clinical decision-making of pNEN.

Objective:To evaluate the consistency of the Chinese three-dimensional anterior visual field analysis system (Scansys), the anterior segment analyzer (Pentacam), the frequency-domain anterior segment optical coherence tomography system (CASIA SS-1000), and a new ultra-high frequency digital ultrasound scanning system (Arcscan Insight100) to measure central vault after implantable collamer lens (ICL) implantation in myopic eyes with crystalline lenses.Methods:A diagnostic test study was conducted.Fifty-six myopic patients (56 eyes) who underwent ICL V4c implantation from June to December 2019 were included.Scansys, Pentacam, CASIA and Arcscan were used to measure the central vault after surgery.The vault measurements were compared.Correlations between the measurements of the four instruments were analyzed using Pearson correlation analysis, and consistency comparisons were analyzed using the Bland-Altman method.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2021[13]). Written informed consent was obtained from each subject.Results:The central vault measurements by Scansys, Pentacam, CASIA and Arcscan were (481.8±191.6), (476.4±190.6), (619.3±207.5) and (534.0±221.2)μm, respectively, with a statistically significant overall difference ( F=143.301, P<0.001). The vault measurements by Scansys and Pentacam were significantly lower than CASIA and Arcscan, and Arcscan was lower than CASIA, with statistically significant differences (all at P<0.001). There were strong positive correlations in vault measurements between Arcscan and CASIA, Arcscan and Pentacam, Arcscan and Scansys, CASIA and Pentacam, CASIA and Scansys, Pentacam and Scansys ( r=0.982, 0.933, 0.931, 0.942, 0.941, 0.989; all at P<0.001). Intraclass correlation coefficients of vault measurements by Scansys, Pentacam, CASIA and Arcscan were 0.985, 0.975, 0.998, 0.992, respectively.The 95% limits of agreement of vault measurements differences were -170 to 0, 0 to 280, 0 to 280, -110 to 210, -100 to 220 μm, between CASIA and Arcscan, CASIA and Scansys, CASIA and Pentacam, Arcscan and Scansys, Arcscan and Pentacam, respectively, and the maximum absolute value of the difference was beyond the clinically acceptable range, showing poor agreement.The 95% limits of agreement of vault measurement difference was -60 to 50 μm between Scansys and Pentacam, showing a good agreement. Conclusions:The repeatability of the vault after ICL V4c implantation in myopic eyes measured by the four instruments is good.Among them, the vault measurements of Scansys and Pentacam are smaller, showing good consistency, and their results could be substituted for each other.The measurement of CASIA is the largest, followed by Arcscan, which have a large difference from each other, and their results can not be substituted for each other, which should be comprehensively analyzed with the actual situation in clinical work.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.