[The predictive value of central venous-arterial CO2 difference/arterial-central venous O2 difference ratio for progressive organ dysfunction in patients with septic shock after resuscitation].

Objective: To study the predictive value of central venous-arterial CO2 difference (Pv-aCO2)/arterial-central venous O2 difference (Ca-vO2) ratio for progressive organ dysfunction in patients with septic shock after resuscitation. Methods: Septic shock patients receiving resuscitation in ICU were retrospectively enrolled from July 2018 to June 2019 at the First Affiliated Hospital Anhui Medical University. Hemodynamic and laboratory data were collected. Single and multivariate logistic regression model was constructed to explore the independent risk factors of progressive organ dysfunction. The predictive value of hemodynamic parameters to progression of organ dysfunction was determined using receiver operating characteristic (ROC)curve analysis. Results: A total of 99 patients were enrolled with 25 patients (25.25%) progressing to organ dysfunction. The norepinephrine dose [0.61 (0.27,1.42) µg·kg-1·min-1 vs. 0.91 (0.47,2.87) µg·kg-1·min-1], blood lactic acid [2.93 (1.77,5.88) mmol/L vs. 6.15 (2.56,8.59) mmol/L], Pv-aCO2 [5.00 (3.98,7.85) mmHg(1 mmHg=0.133 kPa) vs. 7.00 (5.00,8.35) mmHg] and Pv-aCO2/Ca-vO2 [1.36(1.17,1.69) vs. 2.23 (1.83,2.78)] in patients with progressive organ dysfunction were significantly higher than those in patients without(P<0.05). Multivariate logistic regression analysis suggested that Pv-aCO2/Ca-vO2 (OR=20.48,95%CI 5.25-79.93,P<0.001) was independent risk factors for predicting organ dysfunction. The cutoff value of Pv-aCO2/Ca-vO2 was equal or more than 1.77 with a sensitivity of 80.00% and a specificity of 79.73%. Compared with those with Pv-aCO2/Ca-vO2<1.77, patients with Pv-aCO2/Ca-vO2≥1.77 had a greater probability of progressive organ dysfunction (47.37% vs. 8.20%, P<0.001). Conclusion: The progression of organ dysfunction in septic patients after resuscitation is associated with poor prognosis. Pv-aCO2/Ca-vO2 is a good indicator to evaluate oxygen metabolism and predict the progression of organ dysfunction.

Myocardial susceptibility to ischaemia/reperfusion in obesity: a re-evaluation of the effects of age.

BACKGROUND: Reports on the effect of age and obesity on myocardial ischaemia/reperfusion (I/R) injury and ischaemic preconditioning are contradictory. The aim of this study was to re-evaluate the effects of age and diet-induced obesity (DIO) on myocardial I/R injury and preconditioning potential. METHODS: Four groups of Wistar male rats were used: age-matched controls (AMC) receiving standard rat chow for (i) 16 weeks and (ii) 16 months respectively; DIO rats receiving a sucrose-supplemented diet for (iii) 16 weeks and (iv) 16 months respectively. The ages of groups (i) and (iii) were 22 weeks ("young") and groups (ii) and (iv) 17 months ("middle-aged") at time of experimentation. Isolated perfused working hearts were subjected to 35 min regional ischaemia/1 h reperfusion. Endpoints were infarct size (tetrazolium staining) and functional recovery. Hearts were preconditioned by 3 × 5 min ischaemia/5 min reperfusion. Results were processed using GraphPad Prism statistical software. RESULTS: Age did not affect baseline heart function before induction of ischaemia and I/R damage as indicated by infarct size and similar values were obtained in hearts from both age groups. Age also had no effect on functional recovery of hearts during reperfusion after regional ischaemia in AMC rats, but cardiac output during reperfusion was better in hearts from middle-aged than young DIO rats. The diet reduced infarct size in hearts from young rats (% of area at risk: AMC: 32.4 ± 3.6; DIO: 20.7 ± 2.9, p < 0.05), with no differences in hearts from middle-aged rats (AMC: 24.6 ± 4.6; DIO: 28.3 ± 13.5, p = NS). Compared to their respective AMC, diet-induced obesity had no significant effect on functional recovery of hearts from both age groups after exposure to regional ischaemia. When exposed to the more severe stress of global ischaemia, the functional recovery potential of middle-aged DIO rats appeared to be impeded compared to hearts of young DIO rats, while age had no effect on the functional recovery of AMC hearts. Preconditioning reduced infarct size in hearts from young control rats and both middle-aged groups, but not from young DIO rats. Age had a significant effect on functional recovery in preconditioning: it was improved in hearts from young control and DIO rats, but depressed in both middle-aged groups. CONCLUSIONS: The data showed that middle-age and obesity had no effect on baseline myocardial function and did not increase susceptibility to I/R damage upon exposure to regional ischaemia. On the contrary, obesity reduced I/R damage in young rats. Preconditioned aging hearts showed a decreased infarct size, but a reduction in functional recovery.

[The efficacy and safety of testa triticum tricum purif in treatment of functional constipation in the late middle-aged and elderly patients: a multicenter randomized controlled clinical trial].

Objective: To evaluate the efficacy and safety of testa triticum tricum purif for the treatment of functional constipation(FC) in the late middle-aged and elderly patients. Methods: This study was designed as a multicenter randomized controlled trial. Patients who met Rome Ⅲ diagnostic criteria of FC were enrolled, with age between 55-85 years old. Those with organic diseases were excluded. The patients were randomly allocated to receive testa triticum tricum purif (3.5 g bid) or polyethylene glycol 4000 powder (PEG4000, 10g bid) for 8 weeks, followed by single dose of maintenance therapy for 4 weeks. Follow-up visits were at 4 and 12 weeks after treatment discontinuation. The independent investigators in each center evaluated the constipation symptoms scores. The primary endpoints included rates of significant improvement, improvement and overall improvement at the end of 2, 4 and 8 weeks of therapy, which were calculated by the reduction of symptom scores ≥75%, 50%-74%, ≥25% respectively. Results: A total of 127 FC subjects were enrolled from 3 centers, and 122 cases valid for final analysis. The mean age was (69.4±6.9) years old, including 62 cases in testa triticum tricum purif group and 60 cases in PEG4000 group. The demographic data, constipated symptoms scores and proportion of FC subtypes at baseline were comparable. The rates of significant improvement, improvement and overall improvement in testa triticum tricum purif and PEG4000 groups at the end of 2, 4 and 8 weeks were 37.70% (23/61) vs 59.32% (35/59) (P=0.018), 57.38% (35/61) vs 74.14% (43/58) (P=0.054), and 64.41% (38/59) vs 79.31% (46/58) (P=0.073) respectively. Testa triticum tricum purif therapy significantly improved the proportion of spontaneous bowel movement(SBM) ≥3 times/week from 43.55% (27/62) to 80.33% (49/61), 83.61% (51/61) and 93.22% (55/59) at 2, 4, and 8 weeks respectively (all P<0.01), which were comparable with PEG4000 group (all P>0.05). The proportion of normalized stool forms in study group was significant higher than that of control group at the end of 8 weeks [86.44% (51/59) vs 67.24% (39/58), P=0.014]. Only one patient complained mild abdominal distension during testa triticum tricum purif therapy. Conclusions: The efficacy of testa triticum tricum purif for the treatment of FC in late middle-aged and older patients is comparable with osmotic laxatives PEG4000, which has significant effect on normalization of fecal forms and reliable safety.

Icariin induces S-phase arrest and apoptosis in medulloblastoma cells.

Medulloblastoma is the most common type of malignant brain tumor in children. Despite a relatively high long-term survival rate, complications still represent great burden for the majority of patients receiving traditional therapy. Therefore, the development of new effective treatments and drugs is urgently needed. A cell counting kit-8 (CCK-8) and colony formation assay were used to evaluate medulloblastoma cell proliferation and colony formation, respectively. Cell cycles and apoptosis were assessed by flow cytometry. A western blot was performed to determine the levels of protein expression. Axenograft model of medulloblastoma was established to evaluate the in vivo anticancer effects of icariin. The CCK-8 assay showed that icariin decreased cell viability in a dose- and time-dependent manner. The colony formation assay indicated that icariin potently inhibited the colony formation ability of Daoy and D341 cells. Icariin-induced proliferation inhibition may be due to S-phase arrest in medulloblastoma cells. In addition, icariin induced apoptosis in a dose-dependent manner, as shown by the results of annexin V/propidium iodide (PI) double staining and Hoechst 33342 staining. Icariin progressively inhibited tumor growth and induced apoptosis in a mouse model. Moreover, cell cycle regulators Cyclin A, CDK2, and Cyclin B1, and apoptosis-related proteins caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP), and Bcl-2 were modulated in response to treatment with icariin in vitro and in vivo. Our results suggest that icariin may exert anticancer effects. Thus, it is a promising drug for medulloblastoma treatment.

[Experimental study of dopamine ameliorating the inflammatory damage of olfactory bulb in mice with allergic rhinitis].

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.

[A case of spontaneous remission of acute myeloid leukemia with MLL-AF9 rearrangement and abnormal liver function].

Objective: To explore the clinical features and possible pathogenesis of spontaneous remission of acute myeloid leukemia (AML) . Methods: We retrospectively analyzed the clinical data of a patient with spontaneous remission of AML, MLL-AF9 rearrangement, and abnormal liver function in the First Affiliated Hospital of Zhengzhou University, and the relevant pieces of literature were summarized. Results: The patient experienced lung infection, fever, and liver dysfunction and was treated with anti-infection and blood transfusion. After complete response (CR) , the patient remained in CR with mild, indirect bilirubin elevation at 35 months of follow-up. Additionally, 56 cases of adult AML (non-acute promyelocytic leukemia) were reported in the literature from 1990 to June 2021. The cases were checked by bone marrow aspiration, and our patients were summarized and analyzed. Furthermore, 57 patients, including 37 males and 20 females, with a median age of 51 (20-83) years and a median remission time of five months; 52 patients achieved complete remission. In addition, there were five cases with long-term remission and a chromosomal record, with no recurrence so far, three with normal karyotype and two with t (9;11) (q21;q23) . Conclusion: The spontaneous remission of leukemia is rare and may be related to immunosuppression and genes.

[Gadolinium angiography of inner ear in patients with sudden deafness and its clinical analysis].

Objective: To observe the gadolinium imaging findings of inner ear in patients with sudden deafness and to analyze its clinical features. Methods: From November 2017 to July 2020, 21 patients with sudden deafness in the People's Hospital of Dongsheng District, Ordos City were selected as the research objects, including 14 males and 7 females, aged 36-76 years, with a median age of 50 years. The course of disease was 1-19 days, with an average of 5.5 days. The patients received audiology tests, laboratory examination, and intravenous gadolinium angiography, each of whom was scanned twice by 3D-FLAIR sequence: once before intravenous gadolinium injection, and once again 4.5-6.0 h after intravenous gadolinium injection. The following corresponding clinical treatment was given. The imaging manifestations and clinical features were observed. Results: Among 21 cases of sudden deafness in acute stage, the signal intensity of 11 cases was significantly higher than that of the contralateral ear, and 2 cases had vestibular labyrinthine hydrops. In laboratory examination, only 2 cases of total deafness had increased WBC count and faster erythrocyte sedimentation rate, and the rest had no abnormality. The hearing types of 21 patients with sudden deafness were: total deafness in 8 cases, flat decline in 10 cases, low frequency decline in 1 case, high frequency decline in 2 cases. The total effective rate was 57% (12/21). The hearing types of 11 patients with abnormal gadolinium angiography were total deafness in 5 cases, flat decline in 5 cases and high frequency decline in 1 case. The total effective rate was 64% (7/11). Conclusion: Gadolinium angiography is abnormal in some patients with sudden deafness, and the permeability of blood labyrinth barrier may be increased, which is worthy of further study.

Kinases and phosphatases in ischaemic preconditioning: a re-evaluation.

Activation of several protein kinases occurs during myocardial ischaemia and during subsequent reperfusion. In contrast to the intensive investigation into the significance of kinase activation in cardioprotection, relatively little is known about the role of the phosphatases in this regard. The aim of this study was to re-evaluate the putative roles of PP1 and PP2A in ischaemia/reperfusion and in triggering ischaemic preconditioning. Isolated perfused working rat hearts were subjected to sustained global (15 or 20 min) or regional ischaemia (35 min), followed by reperfusion. Hearts were preconditioned using global ischaemia (1 x 5 or 3 x 5 min, alternated with 5 min reperfusion). To inhibit both PP1 and PP2A cantharidin (5 muM) was used. To inhibit PP2A only, okadaic acid (7.5 nM) was used. The drugs were administered during the preconditioning protocol, before onset of sustained ischaemia (pretreatment) or during reperfusion. Endpoints were mechanical recovery during reperfusion, infarct size and activation of PKB/Akt, p38 MAPK and ERK p42/p44, as determined by Western blot. Pretreatment of hearts with okadaic acid or cantharidin caused a significant reduction in mechanical recovery after 15 or 20 min global ischaemia. Administration of the drugs during an ischaemic preconditioning protocol abolished functional recovery during reperfusion and significantly increased infarct size. Administration of the drugs during reperfusion had no deleterious effects and increased functional recovery in 3 x PC hearts. To find an explanation for the differential effects of the inhibitors depending on the time of administration, hearts were freeze-clamped at different time points during the perfusion protocol. Administration of cantharidin before 5 min ischaemia activated all kinases. Subsequent reperfusion for 5 min without the drug maintained activation of the kinases until the onset of sustained ischaemia. Cantharidin given during preconditioning was associated with activation of p38MAPK and PKB/Akt during reperfusion after sustained ischaemia. However, administration of the drug during reperfusion only after sustained ischaemia caused activation of both PKB/Akt and ERK p42/p44. Phosphatase inhibition immediately prior to the onset of sustained ischaemia or during preconditioning abolishes protection during reperfusion, while inhibition of these enzymes during reperfusion either had no effect or enhanced the cardioprotective effects of preconditioning. It is proposed that inhibition of phosphatases during reperfusion may prolong the period of RISK activation and hence protect the heart.

LncRNA PCAT-1 regulated cell proliferation, invasion, migration and apoptosis in colorectal cancer through targeting miR-149-5p.

OBJECTIVE: Emerging studies suggested that lncRNA plays an important role in cell progression of multiple cancers. In CRC, the function of some lncRNAs has been verified to be related to cell proliferation, apoptosis, migration and invasion, providing a crucial theoretical basis for the treatment of colorectal cancer. Due to the complexity of the regulation mechanism of cell growth, the regulation mechanism related to lncRNA still needs to be further studied in CRC. PATIENTS AND METHODS: The qRT-PCR assay was used to carry out the expression of prostate cancer-associated ncRNA transcripts 1 (PCAT-1) and miR-149-5p. The Western blots were used to measure the protein expression of CDK4, Cyclin D1, MMP-2, MMP-9, Bcl-2, Bax and ß-actin. Additionally, flow cytometry and MTT assay were used to assess cell apoptosis and cell proliferation, respectively. Moreover, transwell assay was applied to measure the ability of cells migrated and invasion in CRC. Luciferase reporter assay was performed to detect luciferase activities. RESULTS: In this study, lncRNA PCAT-1 expression was significantly upregulated in CRC cells and tissues. More than that, knockdown of lncRNA PCAT-1 inhibited cell proliferation, migration and invasion while promoted cell apoptosis in CRC cells. Of note, lncRNA PCAT-1 directly targeted miR-149-5p and miR-149-5p expression was significantly downregulated in CRC cells and tissues. Moreover, miR-149-3p reversed the suppressive effects of PCAT-1 on the cell growth of CRC cells. CONCLUSIONS: Our study demonstrated that LncRNA PCAT-1 regulated cell proliferation, invasion, migration and apoptosis in colorectal cancer through targeting miR-149-5p and provided a new regulatory mechanism of CRC.

Twist1/2 activates MMP2 expression via binding to its promoter in colorectal cancer.

OBJECTIVE: This study aimed to characterize the effect of Twist2 on epithelial-to-mesenchymal transition (EMT) and the invasive potential of colorectal cancer (CRC) cells and to explore the mechanisms underlying the regulative effect of Twist1 and Twist2 on matrix metalloproteinase 2 (MMP2) expression in CRC. PATIENTS AND METHODS: Data mining was performed in colorectal cancer cohort (COADREAD) in the Cancer Genome Atlas (TCGA-COADREAD). CRC LoVo and HCT116 cells were used as in vitro cell models. RESULTS: CRC tumors with lymphatic invasion (N = 102) had a significantly higher expression of TWIST1 (p = 0.01) and TWIST2 (p = 0.02) than the lymphatic invasion negative cases (N = 228). TWIST2 overexpression enhanced EMT and the invasive potential of the CRC LoVo and HCT116 cells, while TWIST2 knockdown reversed the EMT process and weakened the invasive potential of the cells. TWIST1 and TWIST2 were co-upregulated with MMP2 and MMP9 in COADREAD cohort. TWIST1 or TWIST2 overexpression significantly elevated nuclear ß-catenin accumulation, which is a known signaling pathway elevating MMP2 and MMP9 expression. More importantly, we found that both Twist1 and Twist2 could transcriptionally activate MMP2 via directly binding to its promoter. However, this mechanism was not observed in the MMP9 promoter. CONCLUSIONS: TWIST1/2 is associated with lymphatic invasion in CRC. TWIST2 upregulation enhances EMT and the invasive potential of CRC cells. TWIST1/2 can enhance the Wnt/ß-catenin signaling pathway in CRC cells. In addition, Twist1/2 can bind to the MMP2 promoter and promote its transcription.

Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia.

Glycolysis is critical for cancer stem cell reprogramming; however, the underlying regulatory mechanisms remain elusive. Here, we show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH+ subpopulations, decreases stemness-related transcriptional factor expression, and inhibits sphere-formation ability and tumor growth. Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poor overall survival. In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates glycolysis to promote stem-like traits. Moreover, through screening hypoxia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is responsible for glycolysis and BCSC maintenance. Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewal ability in vitro and in vivo. Accordingly, H19 and PDK1 expression exhibits strong correlations in primary breast carcinomas. H19 acting as a competitive endogenous RNA sequesters miRNA let-7 to release Hypoxia-inducible factor 1α, leading to an increase in PDK1 expression. Lastly, aspirin markedly attenuates glycolysis and cancer stem-like characteristics by suppressing both H19 and PDK1. Thus, these novel findings demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provides a potential therapeutic strategy for breast malignancy.

Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia.

This corrects the article DOI: 10.1038/onc.2017.368.

microRNA-126 expression and its mechanism of action in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of the present study is to investigate the expression level of microRNA-126 (miRNA-126) in the plasma of patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Thirty SLE patients admitted at our institution were recruited in study group and 30 normal subjects seeking health check-up at our institution during the same period were included in control group. Plasma levels of miRNA-126 were determined using fluorescent quantitative RT-PCR. Plasma levels of IFN-α were determined and compared between two groups using ELISA. RT-PCR was performed to measure the levels of ISG56 mRNA, an IFN-inducible gene (IFNG), in the peripheral blood mononuclear cells (PBMC) of both groups. miRNA-126 expression was interfered in PBMC of SLE patients by introducing the mimic and inhibitor of miRNA-126. Levels of ISG56 mRNA in transfected PBMCs were determined using RT-PCR. RESULTS: Levels of miRNA-126 were significantly lower in the plasma of SLE patients than normal controls (p < 0.05). Plasma levels of IFN-α were significantly higher in SLE patients than normal population (p < 0.05). ISG56 mRNA in PBMC was significantly higher in SLE patients than controls (p < 0.05). As for SLE patients, levels of IFN-α and ISG56 mRNA were significantly decreased in PBMCs with high expression of miRNA-126 but were significantly increased in PBMCs with low expression of miRNA-126 (p < 0.05). CONCLUSIONS: miRNA-126 expression is reduced in SLE patients. miRNA-126 may be involved in the initiation and development of SLE by inhibiting the production of IFN.

Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein.

Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element.

Mapping motion of antiferromagnetic interfacial uncompensated magnetic moment in exchange-biased bilayers.

In this work, disordered-IrMn3/insulating-Y3Fe5O12 exchange-biased bilayers are studied. The behavior of the net magnetic moment ΔmAFM in the antiferromagnet is directly probed by anomalous and planar Hall effects, and anisotropic magnetoresistance. The ΔmAFM is proved to come from the interfacial uncompensated magnetic moment. We demonstrate that the exchange bias and rotational hysteresis loss are induced by partial rotation and irreversible switching of the ΔmAFM. In the athermal training effect, the state of the ΔmAFM cannot be recovered after one cycle of hysteresis loop. This work highlights the fundamental role of the ΔmAFM in the exchange bias and facilitates the manipulation of antiferromagnetic spintronic devices.

Atomistic spin model simulations of magnetic nanomaterials.

Atomistic modelling of magnetic materials provides unprecedented detail about the underlying physical processes that govern their macroscopic properties, and allows the simulation of complex effects such as surface anisotropy, ultrafast laser-induced spin dynamics, exchange bias, and microstructural effects. Here we present the key methods used in atomistic spin models which are then applied to a range of magnetic problems. We detail the parallelization strategies used which enable the routine simulation of extended systems with full atomistic resolution.