Corrigendum/Erratum to "Protein music of enhanced musicality by music style guided exploration of diverse amino acid properties" [Heliyon 7, Issue 9, SEPTEMBER 2021, Article e07933].

[This corrects the article DOI: 10.1016/j.heliyon.2021.e07933.].

Mechanisms and therapeutic potential of chinonin in nervous system diseases.

The flavonoid compound chinonin is one of the main active components of Rhizoma anemarrhena with multiple activities, including anti-inflammatory and antioxidant properties, protection of mitochondrial function and regulation of immunity. In this paper, we reviewed recent research progress on the protective effect of chinonin on brain injury in neurological diseases. "Chinonin" OR "Mangiferin" AND "Nervous system diseases" OR "Neuroprotection" was used as the terms for search in PumMed. After discarding duplicated and irrelevant articles, a total of 23 articles relevant to chinonin published between 2012 and 2023 were identified in our study.

Evans syndrome suggests disease progression in lung adenocarcinoma.

We admitted a 60-year-old male patient diagnosed with lung adenocarcinoma who had a shrinking lung cancer mass after radiotherapy and 6 cycles of chemotherapy, but developed facial inflammation 2 weeks after the end of the final chemotherapy treatment, and was admitted to the hospital with anemia and thrombocytopenia, and diagnosed with Evans syndrome, and brain metastasis of lung cancer was found in the course of the consultation, which suggested disease progression. Evans syndrome was seen as a paraneoplastic syndrome.

Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. METHODS: One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. RESULTS: We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CONCLUSION: CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Development of an artificial intelligence-based multimodal model for assisting in the diagnosis of necrotizing enterocolitis in newborns: a retrospective study.

Objective: The purpose of this study is to develop a multimodal model based on artificial intelligence to assist clinical doctors in the early diagnosis of necrotizing enterocolitis in newborns. Methods: This study is a retrospective study that collected the initial laboratory test results and abdominal x-ray image data of newborns (non-NEC, NEC) admitted to our hospital from January 2022 to January 2024.A multimodal model was developed to differentiate multimodal data, trained on the training dataset, and evaluated on the validation dataset. The interpretability was enhanced by incorporating the Gradient-weighted Class Activation Mapping (GradCAM) analysis to analyze the attention mechanism of the multimodal model, and finally compared and evaluated with clinical doctors on external datasets. Results: The dataset constructed in this study included 11,016 laboratory examination data from 408 children and 408 image data. When applied to the validation dataset, the area under the curve was 0.91, and the accuracy was 0.94. The GradCAM analysis shows that the model's attention is focused on the fixed dilatation of the intestinal folds, intestinal wall edema, interintestinal gas, and portal venous gas. External validation demonstrated that the multimodal model had comparable accuracy to pediatric doctors with ten years of clinical experience in identification. Conclusion: The multimodal model we developed can assist doctors in early and accurate diagnosis of NEC, providing a new approach for assisting diagnosis in underdeveloped medical areas.

The Chinese version of the Ohkuma questionnaire: reliability analysis and diagnostic value.

BACKGROUND: While the Ohkuma questionnaire is a simple, reliable, and easy-to-use tool to assess dysphagia, none of its versions can be used by the Chinese population. OBJECTIVE: The purpose of this study was to evaluate the internal consistency, reliability and clinical validity of a newly made Chinese version of the Ohkuma questionnaire, and to provide some objective basis for its application in screening dysphagia. MATERIALS AND METHODS: From September 21 to June 2022, 96 patients with dysphagia and 89 asymptomatic subjects were recruited from three hospitals in China to form an observation and a control group, respectively. All subjects completed the Ohkuma questionnaire, Eating Assessment Tool-10, and a Video Fluoroscopy Study of Swallowing. RESULTS: The Cronbach's α coefficient measured in the questionnaire was 0.867, indicating acceptable internal reliability. The analysis of variance generated four main factors to be assessed, showing a good aggregation effectiveness of the questionnaire. The AVE square root values of three factors were greater than the maximum absolute value of the correlation coefficients between factors, indicating good differentiation effectiveness. The sensitivity and specificity scores, together with the positive and negative likelihood as well as diagnostic odds ratios indicate a good reactivity of the questionnaire. Lastly, after adjusting for age and sex, the results of the stepwise linear regression analysis showed that there was a significant positive correlation between the Ohkuma questionnaire and the penetration aspiration scale. CONCLUSIONS: The Chinese version of the Ohkuma questionnaire has good reliability and validity, and can be used as a rapid and effective screening tool for dysphagia.

Long-Term Prognosis of Patients Undergoing Percutaneous Coronary Intervention: The Impact of Serum Creatinine Levels on All-Cause Mortality.

BACKGROUND The correlation between serum creatinine levels and the long-term prognosis of patients undergoing percutaneous coronary intervention (PCI) has not yet been systematically investigated. This study aimed to evaluate the association between long-term prognosis and serum creatinine levels in patients after PCI. MATERIAL AND METHODS This was an observational cohort study of 2533 patients who received PCI and completed serum creatinine and other tests in China. The study's primary prognostic indicators were the frequency of clinical adverse events, all-cause death, cardiac death, acute myocardial infarction, and stroke. All-cause death referred to death from all causes during the follow-up period, whereas cardiac death was death due to cardiac injury resulting in severe cardiac dysfunction or failure. Clinical events included death, ischemia, and stroke. Yao et al completed the entire study and uploaded the data to the DATADRYAD website. We used only this data for secondary analysis. RESULTS The study involved 2533 participants, with a mean age of 59.9±11.1 years and a median follow-up of 29.8 months. The analysis, controlling for confounding factors, revealed a positive correlation between serum creatinine and all-cause death (OR: 2.178, 95% CI: 1.317-3.603, P<0.05), which was confirmed by the results of sensitivity analysis (P for trend <0.05). However, no direct linear correlation was found between serum creatinine and acute myocardial infarction, cardiac death, or stroke. CONCLUSIONS There was a linear correlation between serum creatinine and all-cause death in the long-term prognosis of patients after PCI, independent of acute myocardial infarction, cardiac death, and stroke.

Exogenous methyl jasmonate enhanced kenaf (Hibiscus cannabinus) tolerance against lead (Pb) toxicity by improving antioxidant capacity and osmoregulators.

In this study, the effects of exogenous methyl jasmonate (MeJA) on metal uptake and its ability to attenuate metal toxicity in kenaf plants under Pb stress were investigated. The experiment was conducted with five different MeJA concentrations (0, 40, 80, 160, and 320 µM) as a foilar application to kenaf plants exposed to 200 µM Pb stress. The results revealed that pretreatmen of MeJA significantly increased plant dry weight, plant height, and root architecture at all concentrations tested, with the most significant increase at 320 µM. Foliar application of MeJA at 160 µM and 320 µM increased the Pb concentrations in leaves and stems as well as the translocation factor (TF) from root to leaf. However, the bioaccumulation factor in the shoot initially decreased and then increased with increasing MeJA concentration. By increasing enzymatic (SOD, POD, and CAT) and non-enzymatic (AsA and non-protein thiols) antioxidants, MeJA pretreatment decreased lipid peroxidation, O2- and H2O2 accumulation and recovered photosynthetic pigment content under Pb stress. Increased osmolytes (proline, sugar, and starch) and protein content after MeJA pretreatment under Pb stress restore cellular homeostasis and improved kenaf tolerance. Our results suggest that MeJA pretreatment modifies the antioxidant machinery of kenaf and inhibits stress-related processes that cause lipid peroxidation, hence enhancing plant tolerance to Pb stress.

STAT3 mediates ECM stiffness-dependent progression in ovarian cancer.

The treatment of ovarian cancer remains a medical challenge and its malignant progression is connected with obvious changes in both tissue and cell stiffness. However, the accurate mechanical-responsive molecules and mechanism remains unclear in ovarian cancer. Based on our previous results combined with the crucial regulatory role of STAT3 in the malignant progression of various cancer types, we want to investigate the relationship between STAT3 and matrix stiffness in ovarian cancer and further explore the potential mechanisms. Collagen-coated polyacrylamide gels (1, 6, and 60 kPa) were prepared to mimic soft or hard matrix stiffness. Western blotting, qRT-PCR, flow cytometry, IHC, EdU assays, and TEM were used to evaluate the effect of STAT3 in vitro under different matrix stiffnesses. Furthermore, a BALB/c nude mouse model was established to assess the relationship in vivo. Our results confirmed the differential expression of STAT3/p-STAT3 not only in normal and malignant ovarian tissues but also under different matrix stiffnesses. Furthermore, we verified that STAT3 was a mechanically responsive gene both in vitro and in vivo, and the mechanical response was carried out by altering the migration-related molecules (TNFAIP1) and adhesion-related molecules (LPXN, CNN3). The novel findings suggest that STAT3, a potential therapeutic target for clinical diagnosis and treatment, is a mechanically responsive gene that responds to matrix stiffness, particularly regulation in migration and adhesion in the progression of ovarian cancer.

Effect of Interdisciplinary Collaboration in Emergency Nursing Using the SWOT Model on Acute Myocardial Infarction.

Objective: To explore the effect of interdisciplinary collaboration in emergency nursing using the strengths-weaknesses-opportunities-threats (SWOT) model on patients with acute myocardial infarction (AMI). Methods: Eighty AMI patients undergoing rescue treatment at Affiliated Hospital of Inner Mongolia Medical University from October 2020 to June 2022 were selected and randomly divided into the SWOT group and the control group. The patients in the control group received routine emergency nursing intervention, while those in the SWOT group were given interdisciplinary collaboration using the SWOT model. The emergency-related time, cardiac function indicators, incidence of adverse events, quality of life, and nursing satisfaction were compared between the two groups. Results: The waiting time, triage assessment time, electrocardiogram examination time, emergency treatment time, PCI duration and ICU stay time in SWOT group were significantly shorter than those in control group. The left ventricular end-systolic diameter (LVESd), left ventricular end-diastolic diameter (LVEDd), and left ventricular ejection fraction (LVEF) in the SWOT group were all superior to those in the control group. The SWOT group had a significantly lower incidence rate of adverse events than the control group. The quality of life scores of SWOT group were higher than those of control group. The nursing satisfaction in the SWOT group was higher than that in the control group. Conclusion: Interdisciplinary collaboration using the SWOT model for AMI patients can effectively shorten the rescue time, ameliorate cardiac function indicators, reduce the risk of adverse events, improve patients' quality of life, and enhance nursing satisfaction.

CPU-GPU-coupled acceleration method for point flux calculation in Monte Carlo particle transport.

In Monte Carlo particle transport simulations, point flux tallying is a variance reduction technique that performs well with small detectors and finds broad application in source-detector problems and local point dose calculations. However, its use in large-scale point flux tallying computation adds substantial computational time. To address this issue, we propose a CPU-GPU-coupled acceleration method, which separates the complex logic and computationally intensive parts of particle transport calculation and assigns them to the CPU and GPU, respectively. This proposed method greatly enhances the efficiency of large-scale point flux tallies, providing significant convenience for subsequent dose calculations and other related steps. We validated our method by comparing the performance of a pure CPU program with our CPU-GPU accelerated program using the NUREG/CR-6115 PWR benchmark problem. The results indicate identical outcomes for photon point flux estimation, with the accelerated program being ~50 times faster.

Intercomparison of neutron personal dose equivalent measured by thermoluminescence dosimeters.

An intercomparison of neutron personal dose equivalent measured by the Harshaw thermoluminescence neutron dosimeters (TLDs) between the National Institute of Metrology of China (NIM) and the Institute for Nuclear Science and Technology of Vietnam (INST) was performed. Three sets of TLDs (each set consisting of five TLDs) were prepared for each laboratory. Each set was then irradiated to the corresponding same nominal standard value of neutron personal dose equivalent, Hp(10)n-stdi, of 1.0, 2.0, and 3.0 mSv, respectively at these two laboratories. The irradiated TLDs were then read-out at the INST using the Harshaw 4500-type TLD reader to obtain neutron personal dose equivalents at the NIM, Hp(10)n-NIMi and at the INST, Hp(10)n-INSTi, which are corresponding to different values of Hp(10)n-stdi. The TLDs' responses to different scattered components of neutrons in these two fields are also discussed. Comparisons between the corresponding pair values of Hp(10)n-NIMi and Hp(10)n-INSTi show good agreements within 10% with the standard uncertainty of 12.5% (k = 1). The measured values of Hp(10)n-NIMi and Hp(10)n-INSTi are satisfied the Trumpet curve criteria. This implies that the TLDs can be used for safety assessment of occupational neutron personal dose equivalents. This intercomparison result also confirms the capabilities of these two laboratories (i.e., NIM, INST) on deliveries of neutron personal dose equivalent standard values for calibrations.

Chromatin binding protein HMGN1 promotes HBV cccDNA transcription and replication by regulating the phosphorylation of histone 3.

BACKGROUND AND AIMS: Direct elimination of cccDNA remains a formidable obstacle due to the persistent and stable presence of cccDNA in hepatocyte nuclei. The silencing of cccDNA transcription enduringly is one of alternative strategies in the treatment of hepatitis B. Protein binding to cccDNA plays an important role in its transcriptional regulation; thus, the identification of key factors involved in this process is of great importance. APPROACHES AND RESULTS: In the present study, high mobility group nucleosome binding domain 1 (HMGN1) was screened out based on our biotin-avidin enrichment system. First, chromatin immunoprecipitation and fluorescent in situ hybridization assays confirmed the binding of HMGN1 with cccDNA in the nucleus. Second, functional experiments in HBV-infected cells showed that the promoting effect of HMGN1 on HBV transcription and replication depended on the functional region of the nucleosomal binding domain, while transfection of the HMGN1 mutant showed no influence on HBV compared with the vector. Third, further mechanistic exploration revealed that the silencing of HMGN1 increased the level of phosphorylase CLK2 and promoted H3 phosphorylation causing the reduced accessibility of cccDNA. Moreover, silenced HMGN1 was mimicked in HBV (r) cccDNA mouse model of HBV infection in vivo. The results showed that silencing HMGN1 inhibited HBV replication in vivo. CONCLUSIONS: In summary, our study identified that a host protein can bind to cccDNA and promote its transcription, providing a candidate strategy for anti-HBV targeting to interfere with the transcriptional activity of cccDNA microchromosomes.

Identification of Scolopendra Dispensing Granules by Allele-specific PCR / 中国实验方剂学杂志

ObjectiveTo establish an allele-specific polymerase chain reaction （PCR） method for identifying Scolopendra dispensing granules， so as to ensure the quality and therapeutic effects of Scolopendra and its preparations. MethodThe primer interval suitable for the PCR was selected based on the cytochrome c oxidase subunit 3（COX-3） gene sequence of Scolopendra， and the single nucleotide polymorphism （SNP） loci of Scolopendra and its adulterants were mined from the interval for the design of specific primers. The samples of Scolopendra and its adulterants were collected. The PCR system was established and optimized regarding the annealing temperature， cycles， Taq enzymes， DNA template amount， PCR instruments， and primer concentrations， and the specificity and applicability of this method were evaluated. ResultThe PCR system was composed of 12.5 μL 2×M5 PCR Mix， 0.4 μL forward primer （10 μmol·L-1）， 0.4 μL reverse primer （10 μmol·L-1）， 2.5 μL DNA template， and 9.2 μL sterile double distilled water. PCR parameters： Pre-denaturation at 94 ℃ for 3 min， 30 cycles （94 ℃ for 20 s， 62 ℃ for 20 s， 72 ℃ for 45 s）， and extension at 72 ℃ for 5 min. After PCR amplification with the system and parameters above， the electrophoresis revealed a bright band at about 135 bp for Scolopendra and no band for the adulterants. ConclusionThe established allele-specific PCR method can accurately identify the medicinal materials， decoction pieces， and standard decoction freeze-dried powder of Scolopendra， as well as the intermediates and final products of Scolopendra dispensing granules， which is of great significance for ensuring the quality and clinical efficacy of Scolopendra and its preparations.

Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Effect of domestic porous tantalum modified by osteogenic induction factor slow-release system on function of MG63 cells / 中国组织工程研究

BACKGROUND:Previous research by the research team found that domestically produced porous tantalum is beneficial for early adhesion and proliferation of MG63 cells,and can be used as a scaffold material for bone tissue engineering. OBJECTIVE:To investigate the effect of domestic porous tantalum modified by osteogenic induction factor slow-release system on the adhesion,proliferation,and differentiation of MG63 cells. METHODS:Osteogenic induction factor slow-release system was constructed by adding 15%volume fraction of osteogenic factor solution to poly(lactic-co-glycolic-acid)gel.The passage 3 MG63 cells were inoculated on a porous tantalum surface(control group),porous tantalum surface coated with poly(lactic-co-glycolic-acid)copolymer gel(gel group),and porous tantalum surface coated with osteoblastic induction factor slow-release system(slow-release system group),and co-cultured for 5 days.The surface cytoskeleton of the material was observed by phalloidine staining.Cell proliferation was detected by flow cytometry.Western blot assay and RT-qPCR were used to detect the protein and mRNA expressions of type Ⅰ collagen,osteopontin,and RUNX-2 on the surface cells of the material. RESULTS AND CONCLUSION:(1)Phalloidine staining showed that MG63 cells adhered to and grew on the surface and inside of the three groups of porous tantalum,and the matrix secreted by the cells covered the surface of the material.(2)Flow cytometry showed that the cell proliferation in the slow-release system group was faster than that in the control group and the gel group(P<0.05).(3)Western blot assay and RT-qPCR showed that the protein and mRNA expressions of type Ⅰ collagen,osteopontin,and RUNX-2 in the slow-release system group were higher than those in the control group and gel group(P<0.05).(4)The results showed that the domestic porous tantalum modified by the osteogenic induction factor slow-release system was beneficial to the adhesion,proliferation,and differentiation of MG63 osteoblasts.

Accuracy of sacroiliac screw placement in robot-assisted navigation / 中国组织工程研究

BACKGROUND:Orthopedic robots have been widely used in clinical practice,and relevant reports have shown that they have many advantages such as minimal trauma and short surgical time.However,there is currently no clear report on how accurate they are. OBJECTIVE:To evaluate the accuracy of robot-assisted sacroiliac screw insertion. METHODS:A total of 131 patients with sacroiliac joint fracture and dislocation and sacral fracture admitted to the Department of Trauma Surgery,Gansu Provincial Hospital from January 2020 to April 2023 were retrospectively collected,including 131 S1 screws and 46 S2 screws,totaling 177 screws.They were divided into two groups based on whether robot-assisted navigation was performed.There were 63 cases of sacroiliac screws inserted under robot-assisted navigation(observation group),with 36 males and 27 females,aged 19-72 years,with a mean age of(45.3±17.6)years.Among them,39 cases were fixed with only S1 screws,while 24 cases were fixed with S1S2 screws,resulting in a total of 87 sacroiliac screws.Under C-arm fluoroscopy,68 cases of sacroiliac screws were inserted with bare hands(control group),including 41 males and 27 females,aged 23-67 years,with a mean age of(42.6±21.3)years.Among them,46 cases were fixed with simple S1 screws,while 22 cases were fixed with S1S2 screws,resulting in a total of 90 sacroiliac screws.A postoperative CT scan was performed to evaluate the number of S1 screws,S2 screws,total screw level,and calculate accuracy based on the method introduced by SMITH et al. RESULTS AND CONCLUSION:(1)In the observation group,62 S1 screws were accurately placed(62/63),with an accuracy rate of 98%.24 S2 screws were accurately placed(24/24),with an accuracy rate of 100%.The total number of screws accurately placed was 86(86/87),with an accuracy rate of 99%.(2)In the control group,58 S1 screws were accurately inserted(58/68),with an accuracy rate of 85%.19 S2 screws were accurately inserted(19/22),with an accuracy rate of 86%.The total number of screws accurately inserted was 77(77/90),with an accuracy rate of 86%.(3)There was a statistically significant difference in the accuracy of the S1 screw,S2 screw,and total screw between the two groups(P<0.05).It is suggested that the placement of sacroiliac screws under robot navigation has higher accuracy compared to manual placement under C-arm fluoroscopy,but still has a lower error rate in placement.

Significance of PI3K/Akt/HIF-1α signaling pathway expression in nucleus pulposus cells at different oxygen concentrations in delaying intervertebral disc degeneration / 中国组织工程研究

BACKGROUND:Intervertebral disc degeneration is a condition caused by the combined effects of various factors,such as cellular apoptosis,oxidative stress,and inflammatory responses.Currently,it is believed that the core of this condition lies in the degeneration and apoptosis of nucleus pulposus cells(NPCs).However,the specific pathological mechanisms remain unclear. OBJECTIVE:By investigating the expression of the phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/hypoxia-inducible factor 1-alpha(HIF-1α)signaling pathway and the apoptosis of NPCs under different oxygen concentrations,to clarify the biological characteristics of NPCs under varying oxygen levels,and to explore the mechanisms of intervertebral disc degeneration. METHODS:Normal and degenerated NPCs were collected.The second-generation cells were used for imaging identification.The third-generation cells were cultured in the following conditions:37℃,air,100%humidity.Leibovitz's medium containing 100 μmol/L CoCl2 and 10%fetal bovine serum medium containing 100 μmol/L H2O2 were used to create distinct oxygen concentration environments for the third-generation cells,allowing for the investigation of cellular responses and behaviors under normal,low oxygen,and oxidative stress conditions.The third-generation cells were divided into six groups:normal NPCs+hypoxia,normal NPCs+normoxia,normal NPCs+oxidative stress,degenerated NPCs+hypoxia,degenerated NPCs+normoxia,and degenerated NPCs+oxidative stress groups.Cell viability and proliferation were assessed using the cell counting kit-8 method.Cell apoptosis was detected using flow cytometry.RT-PCR and western blot assay were utilized to examine the protein and mRNA expression levels of PI3K,AKT,and HIF-1α. RESULTS AND CONCLUSION:At different oxygen concentrations,the cell proliferation rate of both normal and degenerated NPCs decreased as the oxygen concentration increased.Conversely,the apoptosis rate increased as the oxygen concentration rose(P<0.05).With the normal NPCs+hypoxia group as the control group,the effect of degenerated NPCs on the apoptosis rate was highly significant(P<0.001).Oxygen concentration had a highly significant impact on both NPC proliferation rate and apoptosis rate(P<0.001).The interaction between cell degeneration and oxygen concentration significantly affected both NPC proliferation and apoptosis rates(P<0.05).At different oxygen concentrations,the protein and mRNA expression levels of PI3K,AKT,and HIF-1α in normal NPCs were highest under low oxygen concentration,followed by oxidative stress environment,and lowest under normoxia.In degenerated NPCs,the protein and mRNA expression levels of PI3K,AKT,and HIF-1α decreasd as the oxygen concentration increased.The protein and mRNA expression levels of PI3K and Akt in normal NPCs were significantly higher than those in degenerated NPCs(P<0.05).With the normal NPCs+hypoxia group as the control group,the effects of normal or degenerated NPCs,as well as oxygen concentration,on the protein and mRNA expression of PI3K,AKT,and HIF-1α were highly significant.The interaction between cell degeneration and oxygen concentration also had an extremely significant effect on the protein and mRNA expression of PI3K,AKT,and HIF-1α(P<0.001).To conclude,there is a close correlation between the proliferation and apoptosis of NPCs and both oxygen concentration and the cellular functional state.The PI3K/Akt/HIF-1α signaling pathway exhibits antagonistic regulatory effects under various cellular functional states and different oxygen concentration environments.The mechanism may be associated with the activation of the PI3K/Akt signaling pathway,which consequently transcribes HIF-1α,thus maintaining the balance of reactive oxygen species metabolism.This pathway plays a significant role in inhibiting oxidative stress,antagonizing NPCs apoptosis,and consequently delaying intervertebral disc degeneration.

Erythropoietin-overexpressed umbilical cord mesenchymal stem cells inhibit neuroapoptosis in ischemic-hypoxic SH-SY5Y and its mechanism / 中国组织工程研究

BACKGROUND:Previous studies have successfully constructed erythropoietin-overexpressed umbilical cord mesenchymal stem cells.It was found that the apoptosis of ischemic and hypoxic human neuroblastoma cell line(SH-SY5Y)was significantly reduced by erythropoietin-overexpressed umbilical cord mesenchymal stem cells. OBJECTIVE:To explore the possible neuroprotective mechanisms of erythropoietin-overexpressed umbilical cord mesenchymal stem cells against ischemic-hypoxic SH-SY5Y and their associated epigenetic mechanisms. METHODS:Oxygen-glucose deprivation was applied to ischemia-hypoxia-induced SH-SY5Y cell injury,and multifactorial assays were applied to detect the expression levels of inflammatory factors in the cells before and after hypoxia and co-culture,respectively,with mesenchymal stem cells,as well as lentiviral-transfected null-loaded plasmids of the negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression levels of supernatant inflammatory factors were detected by multifactor assay after co-culture.Proteomics was used to detect the differentially expressed proteins of negative control mesenchymal stem cells and erythropoietin-overexpressed umbilical cord mesenchymal stem cells.Cleavage under targets and tagmentation sequencing was applied to detect genomic H3K4me2 modification,and joint analysis was conducted with RNA-sequencing.Lentiviral vector infection was applied to construct the stable knockdown of REST in SH-SY5Y cells.qRT-PCR and western blot assay were performed to detect the expression level of REST.The apoptosis was detected by flow cytometry after co-culture of oxygen-glucose deprivation treatment with erythropoietin-overexpressed umbilical cord mesenchymal stem cells.The expression difference of H3K36me3 group proteins was detected by western blot assay,and transcriptome sequencing was performed to analyze the differentially expressed genes. RESULTS AND CONCLUSION:(1)Compared with the control group,monocyte chemotactic protein 1,interleukin-6,interleukin-18,and interleukin-1 beta,interferon α2,and interleukin-23 levels significantly increased in the cerebrospinal fluid supernatant of patients with ischemic-hypoxic encephalopathy(P<0.01).(2)After co-culturing SH-SY5Y cells with erythropoietin-overexpressed umbilical cord mesenchymal stem cells under ischemia and hypoxia,the expression levels of monocyte chemotactic protein 1 and interleukin-6 were significantly reduced.(3)Analysis of protein network interactions revealed significant downregulation of monocyte chemotactic protein 1,interleukin-6 related regulatory proteins CXCL1 and BGN.(4)Transcriptome sequencing analysis found that pro-inflammatory genes were down-regulated,and functional enrichment of histone modifications,and the expression of transcription factors REST and TET3 significantly up-regulated in the erythropoietin-overexpressed umbilical cord mesenchymal stem cell group compared with the negative control mesenchymal stem cell group.(5)Combined analysis of transcriptome sequencing and cleavage under targets and tagmentation revealed changes in epigenetic levels as well as significant activation of the promoter regions of transcription factors REST and TET3.(6)Stable knockdown REST in SH-SY5Y cells was successfully constructed;the transcript levels of REST mRNA and protein expression were both decreased.(7)After the REST knockdown SH-SY5Y cells were co-cultured with erythropoietin-overexpressed umbilical cord mesenchymal stem cells,apoptosis was significantly increased and H3K36me3 expression was significantly decreased.Transcriptome sequencing results showed that the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2 was reduced at mRNA transcription level(P<0.01).(8)It is concluded that erythropoietin-overexpressed umbilical cord mesenchymal stem cells activated the expression of REST and TET3 by altering the kurtosis of H3K4me2 and upregulated the modification level of H3K36me3,which in turn regulated the expression of inflammation-related genes Aldh1l2 and Cth,as well as apoptosis-suppressor genes Mapk8ip1 and Sod2,and facilitated neuronal survival.

Clinical application and progress of yttrium 90 microsphere selective internal radiation therapy in primary hepatic cancer / 中华消化外科杂志

Primary hepatic cancer is one of the major problems that need to be solved urgently in the field of public health, seriously endangering the life and health of Chinese people. Its treatment mode is multidisciplinary participation and synergy of multiple therapeutic methods. Even though there are many common clinical treatments for liver cancer in China, its therapeutic outcome is still unsatisfactory. yttrium-90 has been applied for more than 20 years, and a large amount of foreign clinical data have been accumulated. Combining the latest literature and clinical practice, the authors describe the clinical application and research progress of yttrium-90 micro-sphere selective internal radiation therapy in primary liver cancer.