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

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 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 compare the impact of continuous profound neuromuscular blockade versus con-ventional neuromuscular blockade on postoperative shoulder pain in patients undergoing robot-assisted laparoscopic surgery during steep Trendelenburg position.Methods This study was a single-center,randomized,double-blind clinical trial.The inclusion criteria encompassed individuals aged between 18 and 80 years,with an American Society of Anesthesiologists status of Ⅰ or Ⅱ,and a body mass index ranging from 18 kg/m2 to 30 kg/m2.A total of one hundred patients were randomly assigned to either the deep neuromuscular blockade group(D group)or the conventional neuromuscular blockade group(C group),with equal distribution of fifty cases in each group.Rocuronium dosage was titrated to achieve post-tetanic count values of 1～2 and train-of-four stimulation levels of 1～2 during surgery for D and C groups respectively.At the end of surgery,sugammadex was administered for reversal of neuromuscular blockade.The primary endpoint assessed the incidence of postoperative shoulder pain within three days after surgery.Secondary endpoints included Leiden score evaluation during intraoperative period,number of additional neuromus-cular blockers required by the surgeon,recovery time for muscle relaxation postoperatively,nausea and vomiting scores during recovery phase,visual analog scale(VAS)scores in Post-Anesthesia Care Unit(PACU)as well as within three days after surgery,incidence rate for postoperative pulmonary complications,length of hospital stay duration and patient satisfaction score.Results The incidence of postoperative shoulder pain was significantly lower in group D compared to group C(D group 32%vs.C group 56%;P<0.05).However,there were no significant differences in postoperative shoulder pain VAS scores between the two groups(P>0.05).No significant differences were observed between the groups in terms of Leiden score,surgeon's requirement for additional neuromuscular blockers,nausea and vomiting in PACU,and VAS score(P>0.05).Group D exhibited better early postoperative activity pain scores than group C(P<0.05).There were no significant differences in VAS scores between the groups at other time points(P>0.05).Furthermore,there were no significant differences in the incidence of postoperative pulmonary complications,length of stay,and satisfaction scores between the two groups.Conclusion The imple-mentation of continuous deep neuromuscular blockade in patients undergoing robot-assisted laparoscopic surgery with steep Trendelenburg position can effectively mitigate the occurrence of postoperative shoulder pain.

Objective To explore the predictive value of serum fibrinogen(Fbg)and pentaxin-3(PTX3)levels for perioperative major adverse cardiovascular events(MACE)in elderly patients undergoing hip re-placement surgery.Methods A total of 201 patients who underwent hip replacement surgery in the Qilu Hos-pital of Shandong University,Dezhou Hospital(the hospital)from January 2022 to December 2022 were re-garded as the study group,and based on the presence or absence of MACE during the perioperative period,pa-tients were separated into the non MACE group(183 cases)and the MACE group(18 cases).Another 150 healthy examinees from the hospital were selected as the control group.Fully automated biochemical analyzer and enzyme linked immunosorbent assay(ELISA)were applied to detect serum Fbg and PTX3 levels in re-search objects.Multivariate Logistic regression was applied to analyze the influencing factors of perioperative MACE in elderly patients undergoing hip replacement surgery.Receiver operating characteristic(ROC)curve was applied to evaluate the predictive value of serum indicators for perioperative MACE in elderly patients un-dergoing hip replacement surgery.Results Compared with the control group,the serum Fbg and PTX3 levels in the study group were obviously increased,and the differences were statistically significant(P＜0.05).There were 18 cases who had MACE in elderly patients undergoing hip replacement surgery,with an incidence rate of 8.95％.Compared with the non MACE group,the serum Fbg and PTX3 levels in the MACE group were obviously increased,and the differences were statistically significant(P＜0.05).Elevated serum Fbg,PTX3,cardiac troponin I(cTnI),brain natriuretic peptide(BNP)levels,and decreased left ventricular ejection fraction were independent risk factors for perioperative MACE in elderly patients undergoing hip arthroplasty(P＜0.05).The area under the curve(AUC)of single and combined detection of serum Fbg and PTX3 levels for predicting the occurrence of perioperative MACE in elderly patients undergoing hip arthroplasty was 0.824,0.809,and 0.917,respectively.The combined prediction value of the two was higher than that of indi-vidual prediction(Z combination-Fbg=2.333,P=0.019;Z combination-PTX3=3.110,P=0.001).Conclusion The periop-erative serum Fbg and PTX3 levels in elderly patients undergoing hip replacement surgery are elevated,and the combination of the two has good predictive value for the occurrence of perioperative MACE.

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.

OBJECTIVE: Angelicae Sinensis Radix (ASR, Danggui in Chinese), Cistanches Herba (CH, Roucongrong in Chinese), Ginseng Radix et Rhizoma (PG, Renshen in Chinese), and Panacis Quinquefolii Radix (PQ, Xiyangshen in Chinese), widely used as medicine and dietary supplement around the world, are susceptible to fungal and mycotoxin contamination. In this study, we aim to analyze their fungal community by DNA metabarcoding. METHODS: A total of 12 root samples were collected from three main production areas in China. The samples were divided into four groups based on herb species, including ASR, CH, PG, and PQ groups. The fungal community on the surface of four root groups was investigated through DNA metabarcoding via targeting the internal transcribed spacer 2 region (ITS2). RESULTS: All the 12 samples were detected with fungal contamination. Rhizopus (13.04%-74.03%), Aspergillus (1.76%-23.92%), and Fusarium (0.26%-15.27%) were the predominant genera. Ten important fungi were identified at the species level, including two potential toxigenic fungi (Penicillium citrinum and P. oxalicum) and eight human pathogenic fungi (Alternaria infectoria, Candida sake, Hyphopichia burtonii, Malassezia globosa, M. restricta, Rhizopus arrhizus, Rhodotorula mucilaginosa, and Ochroconis tshawytschae). Fungal community in ASR and CH groups was significantly different from other groups, while fungal community in PG and PQ groups was relatively similar. CONCLUSION DNA metabarcoding revealed the fungal community in four important root herbs. This study provided an important reference for preventing root herbs against fungal and mycotoxin contamination.