Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Objective:To explore the correlation between peripheral blood B cell count and clinical features and prognosis of patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:The relationship of peripheral blood B cell count with clinical features,laboratory indexes and prognosis in 67 patients with newly diagnosed DLBCL was retrospectively analyzed.Results:Patients were divided into low B-cell count group(B cell＜0.1 × 109/L,n=34)and high B-cell count group(B cell≥0.1 × 109/L,n=33)according to the median B cell count values.Compared with the high B cell count group,the low B cell count group had a higher proportion of patients with Lugano stage Ⅲ-Ⅳ,elevated LDH,elevated β2-MG and IPI score 3-5 and increased CRP(P=0.033,0.000,0.023,0.001,0.033).The peripheral CD3+and CD4+cell counts of patients in the low B cell count group were significantly lower than those in the high B cell count group(P=0.010,0.017).After initial treatment,overall response rate(ORR)and complete remission(CR)rate in high B cell count group were significantly higher than those in low B cell count group(P=0.032,0.013).The median follow-up time of patients was 23(2-77)months,progression-free survival(PFS)and overall survival(OS)of patients in the high B cell count group were significantly better than those in the low B cell count group(P=0.001,0.002).Univariate analysis showed that pretreatment low B cell count in the peripheral blood was associated with shortened PFS and OS(HR=4.108,P=0.002;HR=8.218,P=0.006).Multivariate analysis showed that low B cell count was an independent prognostic factor for shortened PFS(HR=3.116,P=0.037).Conclusion:Decreased peripheral blood B cell count in newly diagnosed DLBCL patients is associated with high-risk clinical features and may affect the efficacy of immunochemotherapy,which is associated with poor clinical prognosis.

Objective:To explore the application effect of an intelligent teaching robot system of lifting manipulation in cervical spine manipulation teaching.Methods:60 doctors were randomly divided into an experimental group ( n = 30) and a control group ( n = 30). The control group was taught by a certified chief physician using a combination of "PowerPoint presentations, video demonstrations, and operation demonstrations" . Each part is 5 min. The experimental group was taught by the intelligent teaching robot system with a spinning technique. The teaching time is 15 min for both groups. At the end of the two teaching sessions, the two groups were trained five times under different BMIs and passed the system assessment. The qualified rates of pre-traction force, lifting and pulling force, maximum force, pre-traction time, lifting and pulling time, rotation amplitude, and pitch amplitude were compared between the two groups. Results:In normal, there was significant differences between the qualified rates of pre-traction force, lifting and pulling force, maximum force, pre-traction time, lifting and pulling time, rotation amplitude, and pitch amplitude in two groups (all P<0.05). For overweight people, there were significant differences in pre-traction force, pulling force, maximum force, and rotation amplitude (all P <0.05), while there were no significant differences in pre-traction time, pulling time, or pitching amplitude (all P >0.05). In obesity, there were significant differences in pre-traction force, lifting and pulling force, maximum force, and pitch amplitude (all P <0.05), but no significant differences in pre-traction time, lifting and pulling time, or rotation amplitude (all P >0.05). Conclusions:The proposed system can improve the pass rate of spinning manipulation, especially by effectively controlling the pre-traction force, pulling force, and maximum force.

Breast Neoplasms/metabolism* ; Female ; Humans ; Receptor, ErbB-2/metabolism*

OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.
Ascorbic Acid ; Cysteine ; Humans ; Infant, Newborn ; Metabolomics ; Methionine ; Neonatal Sepsis ; Pyruvates ; Sepsis

Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.

The important pathogenesis of knee osteoarthritis (KOA) lies in kidney deficiency and blood stasis. Therefore, Traditional Chinese Medicine (TCM) for tonifying the kidney and activating blood circulation is widely used in clinical practise with high response. The existing literature mainly focuses on single medicine for tonifying the kidney and activating blood circulation, as well as TCM compounds, such as classic prescriptions Yougui Pill, Duhuo Jisheng Decoction, which contain TCMs for tonifying the kidney and activating blood circulation, or self-made empirical prescriptions Bushen Huoxue Recipe and Bushen Tongluo Recipe, which are based on the idea of tonifying the kidney and activating blood circulation. The above TCMs mainly regulate oxidative stress response, inflammatory cytokine level, no level, lymphatic function and microcirculation Inhibit chondrocyte apoptosis, regulate cartilage metabolism, protect and repair cartilage, and inhibit matrix degrading enzymes to play a therapeutic role.

Breast/pathology* ; Breast Neoplasms/pathology* ; Carcinoma in Situ/pathology* ; Carcinoma, Lobular/pathology* ; Diagnosis, Differential ; Female ; Humans ; Hyperplasia/pathology*

Aim To study the protective effect of Qingjie HuaGong decoction ( QJHGD) for severe acute pancreatitis ( SAP ) model rats induced by cerulein based on TLR4/NF-kB/MYD88 pathway.Methods The effective component groups and potential targets of QJHGD were collected by network pharmacology method , and we constructed the component-target network.The GO and KEGG of important targets were enriched and analyzed by metascape database, and we selected the targeted pathways related with SAP inflammation mechanism.The rat model of severe acute pancreatitis was established by cerulein combined with lipopolysac- charide, followed by QJHGD gavage.Pancreatic tissues were observed by hematoxylin and eosin staining.We verified the therapeutic effect of QJHGD on SAP rats and the regulatory effect on TLR4/NF-kB/MyD88 target pathway, by Enzyme linked immunosorbent and immunohistochemistry methods.Results A total of 105 active components and 148 key targets for SAP were screened; KEGG was enriched 320 different channels including toll like receptor and NF-kB classical pathways.Animal experiments showed that QJHGD harl protective changes in pancreatic pathological tissues, which was observed by HE staining; QJHGD reduced amylase, lipase, 1L-6 and TNF-a in SAP rat serum, inhibiting the positive expression of key proteins on TLR4/N F- kB/MyD88 inflammatory transduction j j pathways.Conclusion The mechanisms of QJHGD protecting pancreatic injury of SAP rat may be related to reducing the expression of key proteins on TLR4/ NF-kB/MvD88 pathway.

Objective:To improve the understanding of adult primary hemophagocytic syndrome (HPS) with aggressive natural killer cell leukemia (ANKL).Methods:The clinicopathological data of one adult patient with suspected primary HPS complicated with ANKL in Huiqiao Medical Center, Nanfang Hospital of Southern Medical University in October 2017 were retrospectively analyzed, and literatures were reviewed.Results:A 21-year-old male patient presented with persistent fever, hemocytopenia, splenomegaly, low fibrinogen, a significant increase in ferritin, hemophagocytes in bone marrow, decreased natural killer (NK) cell activity, and increased soluble CD25. Flow cytometry detection showed that the expression of NK cells was abnormal, and there were familial lysosomal trafficking regulator (LYST) and UNC13D gene defects. He was suspected of primary HPS complicated with ANKL. The patient was given 4 courses of EPOCH+PEG-Asp (etoposide, dexamethasone, vindesine, cyclophosphamide, doxorubicin hydrochloride liposome, pegaspargase) regimen chemotherapy, 20 mg of citalopidine twice a week maintenance therapy and matched unrelated hematopoietic stem cell transplantation. After 35 months of follow-up, he got sustained remission.Conclusions:Even if there are secondary causes of adult HPS, it is necessary to screen out related genes to avoid misdiagnosis. HPS patients with ANKL progress rapidly, and the early mortality is high. EPOCH+ PEG-Asp regimen induction therapy and allogeneic hematopoietic stem cell transplantation should be used as early as possible after diagnosis.