Objective:To evaluate the effect of low-dose recombinant interleukin-2(rIL-2)therapy on immunocyte subsets and its side effects in children with solid tumor.Methods:A total of 22 children(11 males and 11 females)with solid tumor in our department from December 2012 to November 2017 were selected,with a median age of 9(3-16)years old when starting IL-2 therapy.ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy,and 17 cases achieved complete remission(CR)and 5 cases achieved partial remission(PR).A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year:4 × 105 IU/(m2·d),s.c.for every other day,3 times per week.The immunocyte subsets were detected every 3 months until the end of treatment,meanwhile,disease condition and therapy-related side effects were followed up.Results:After low-dose rIL-2 therapy in 22 children,the absolute values of CD3+T cells,CD3-CD56+natural killer cells,CD3+CD4+helper T cells(Th)and CD3+CD8+cytotoxic T cells were up-regulated remarkably,as well as Th/suppressor T cells(all P＜0.05).While,there were no significant differences in absolute value and proportion of CD4+CD25+CD127-Treg cells during therapy.Among the 17 children who achieved CR before rIL-2 therapy,14 cases continued to maintain CR after therapy,while 3 cases relapsed,and with 2 died after treatment abandonment.The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment.In the early stage of low-dose rIL-2 therapy,1 child developed skin rashes at the injection sites,and 2 children ran a slight to mild transient fever.Their symptoms disappeared without any organ damage after symptomatic treatment.Conclusion:Low-dose rIL-2 therapy has good drug tolerance,and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Objective: To evaluate the predictive value of the proportion of hibernating myocardium (HM) in total perfusion defect (TPD) on reverse left ventricle remodeling (RR) after coronary artery bypass graft (CABG) in patients with heart failure with reduced ejection fraction (HFrEF) by ^99mTc-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with ¹⁸F-flurodeoxyglucose (FDG) gated myocardial imaging positron emission computed tomography (PET). Methods: Inpatients diagnosed with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2016 to January 2022 were prospectively recruited. MPI combined with ¹⁸F-FDG gated PET was performed before surgery for viability assessment and the patients received follow-up MPI and ¹⁸F-FDG gated PET at different stages (3-12 months) after surgery. Δ indicated changes (post-pre). Left ventricular end-systolic volume (ESV) reduced at least 10% was defined as RR, patients were divided into reverse remodeling (RR+) group and the non-reverse group (RR-). Binary logistic regression analysis was used to identify predictors of RR. Receiver operating characteristic (ROC) curve analysis was performed and the area under the curve (AUC) was calculated to assess the cut-off value for predicting RR. Additionally, we retrospectively enrolled inpatients with HFrEF at the Cardiac Surgery Center, Anzhen Hospital of Capital Medical University from January 2021 to January 2022 as the validation group, who underwent MPI and ¹⁸F-FDG gated PET before surgery. Echocardiography was performed before CABG and after CABG (3-12 months). In the validation group, the reliability of obtaining the cut-off value for the ROC curve was verified. Results: A total of 28 patients with HFrEF (26 males; age (56.9±8.7) years) were included in the prospective cohort. HM/TPD was significantly higher in the RR+ group than in the RR- group ((51.8%±17.9%) vs. (35.7%±13.9%), P=0.016). Binary logistic regression analysis revealed that HM/TPD was an independent predictor of RR (Odds ratio=1.073, 95% Confidence interval: 1.005-1.145, P=0.035). ROC curve analysis revealed that HM/TPD=38.3% yielded the highest sensitivity, specificity, and accuracy (all 75%) for predicting RR and the AUC was 0.786 (P=0.011). Meanwhile, a total of 100 patients with HFrEF (90 males; age (59.7±9.6) years) were included in the validation group. In the validation group, HM/TPD=38.3% predicted RR in HFrEF patients after CABG with the highest sensitivity, specificity and accuracy (82%, 60% and 73% respectively). Compared with the HFrEF patients in the HM/TPD<38.3% group (n=36), RR and cardiac function improved more significantly in the HM/TPD≥38.3% group (n=64) (all P<0.05). Conclusions: Preoperative HM/TPD ratio is an independent factor for predicting RR in patients with HFrEF after CABG, and HM/TPD≥38.3% can accurately predict RR and the improvement of cardiac function after CABG.
Male ; Humans ; Middle Aged ; Aged ; Stroke Volume ; Heart Failure ; Fluorodeoxyglucose F18 ; Retrospective Studies ; Reproducibility of Results ; Prospective Studies ; Coronary Artery Bypass ; Ventricular Dysfunction, Left ; Tomography, Emission-Computed, Single-Photon ; Perfusion ; Myocardium

Liver disease is one of the major problems affecting human health. Ultrasound plays an important role in diagnosis and treatment of diffuse and focal liver diseases. However, conventional ultrasound evaluation is subjective and provides limited information. Artificial intelligence (AI) technology may supplement the disadvantages of conventional ultrasound and has been widely used in the field of ultrasound in liver diseases. To date, remarkable progress has been achieved for the use of AI technology in the diagnosis, assessment of therapeutic efficacy and prognosis prediction of liver diseases. This paper reviews the research progress of ultrasound image-based AI technology in the diagnosis and treatment of diffuse and focal liver diseases.

Nowadays, malignant tumor has become an important killer endangering human health, and the research on tumor has become a hot spot in the medical field. The CKLF-like MARVEL transmembrane domain containing family of genes (CMTM family), previously called chemokine-like factor super family (CKLFSF). CMTM family is a novel gene family firstly discovered by Chinese scholars and has a wide range of biological functions, which is closely related to human immune, hematopoietic and reproductive systems as well as tumors. CMTM family is dysregulated in many common tumors, can participate in a variety of signaling pathways closely related to the occurrence and development of cancer, which is closely related to the biological behavior changes of tumor cells. CMTM family members play an important role in the signaling molecular mechanisms that regulate the biological function of tumor cells and are able to regulate the signaling pathways of the tumor cell cycle and apoptosis. Including epithelial-mesenchymal transition process, epidermal growth factor receptor related signaling pathways, and closely related to the tumor immune microenvironment by regulating programmed death receptor-ligand 1. In this paper, we review the signaling molecular mechanisms of CMTM family in the biological processes of tumor cell proliferation, migration, invasion and apoptosis, as well as the potential clinical applications of CMTM family in ovarian cancer, breast cancer, liver cancer, gastric cancer, colorectal cancer, pancreatic cancer and other common malignant tumors. At present, the detailed molecular mechanism ofCMTM family related to tumor has not been fully clarified. Further study of the expression, biological role and regulatory mechanism of CMTM family in tumor will provide new ideas and targets for tumordiagnosis, treatment and prognosis prediction.

Objective: To evaluate the effects of dietary behaviors on the risk of hypertension, diabetes and cardiovascular diseases. Methods: A total of 12 208 subjects aged 18-60 years old were investigated by questionnaires to collect demographic data, dietary behaviors and lifestyle information, when they did health examination in a tertiary hospital in Beijing from 2014 to 2019. During the observation period of five year, the incidence of hypertension, diabetes and cardiovascular diseases were collected through health examination files every year. The multivariate logistic regression model was employed to analyze the associations of dietary behaviors with hypertension, diabetes and cardiovascular diseases. Results: The study included 6 218 ( 50.93% ) males and 5 990 ( 49.07% ) females. The cumulative incidence rates of hypertension, diabetes and cardiovascular diseases were 7.75%, 2.72% and 3.49%, respectively. The multivariate logistic regression analysis indicated that the high-sodium diet ( OR=1.422, 95%CI: 1.191-1.697 ) , eating fast ( OR=1.457, 95%CI: 1.102-1.974 ), eating more refined grain ( OR=1.251, 95%CI: 1.050-1.490 ) and drinking milk less than once a week ( OR=1.316, 95%CI: 1.022-1.697 ) were risk factors for hypertension. The high-sodium diet ( OR=1.344, 95%CI: 1.048-1.725 ), eating fast ( OR=1.733, 95%CI: 1.046-2.871 ), eating more meat ( OR=1.651,95%CI: 1.263-2.158 ) were risk factors for diabetes. High-sodium diet ( OR=1.501, 95%CI: 1.192-1.889 ) was risk factors for cardiovascular disease. Conclusion The diet with high sodium, more meat and refined grain as well as eating fast can increase the risk of hypertension, diabetes and cardiovascular diseases.

OBJECTIVE: To investigate the clinicopathological features of intestinal diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical features, pathological morphology, immunophenotype, and EBER in situ hybridization of 136 DLBCL patients diagnosed in Jinan People's Hospital Affiliated to Shandong First Medical University from January 2007 to October 2014 were analyzed retrospectively. A total of 136 DLBCL samples were obtained, the DLBCL sites were categorized as: duodenum (n=23), ileocecal region (n=63), other small intestine (n=29), rectum (n=7), and other large intestine (n=14). Survival curves for the DLBCL patients were plotted using the Kaplan-Meier method and judged by the Log-rank test. RESULTS: Patients with DLBCL of the ileocecal region and other small intestine except duodenum were mainly male (P=0.042), and had a higher proportion of limited-stage tumors(P=0.015), and lower International Prognostic Index (IPI) (P=0.001). Patients with DLBCL of ileocecal region had higher incidence of lactate dehydrogenase elevation (P=0.007), and higher incidence of intestinal obstruction or perforation (P<0.001) than those with DLBCL of other regions. The 5-year overall survival and 5-year progression-free survival of patients with DLBCL in ileocecal and other small intestine sites were higher than those in other sites, but the differences were not statistically significant (P=0.135, 0.459). Fifty percent of intestinal DLBCL were germinal center B cell-like (GCB) subtypes. A low-grade B-cell lymphoma was found in 21% of 136 tumor samples. In ileocecal and other small intestinal specimens, the proportion of low-grade B-cell lymphoma was 29%, and the difference was statistically significant(P=0.025). About 16% of 136 DLBCL samples expressed follicular lymphoma while no mucosa-associated lymphoid tissue lymphoma . The Epstein-Barr virus-encoded RNA-1 (EBER1) positive rate of duodenal DLBCL was significantly higher than that of other sites (5/23, 22% vs 2/63, 3%, P=0.001). CONCLUSION The intestinal DLBCL is commonly observed in male, and ileocecal is the most primary site. Patients with DLBCL of the ileocecal region and small intestine except duodenum have low IPI, high proportion of limited-stage tumors, low level of lactate dehydrogenase, high incidence of intestinal obstruction or perforation, and low incidence of inert lymphoma. The EBER1 positive rate of DLBCL in duodenal is higher.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Prognosis ; Retrospective Studies

Lysophosphatidic acid (LPA), a bioactive lipid medium, plays an important role in the development and progression of ovarian cancer. Doxorubicin hydrochloride (DOX) is a first-line drug in the ovarian cancer clinical therapy, while the effect and molecular mechanism of LPA in the ovarian cancer with DOX treatment is still unclear. This study intended to explore the effect and molecular mechanism of LPA in ovarian cancer treated with DOX. SKOV3 and OVCAR-3 cells of human ovarian cancer and Chinese hamster ovary cells were treated with control, LPA (lOp-mol/L), DOX (2jjLmol/L) and LPA (10jJLmol/L) + DOX (2p,mol/L) respectively for 24 hours. The morphological changes of SKOV3 cells were observed under optical microscope and transmission electron microscope. Results showed that LPA reduced cell death and the degree of chromatin aggregation in SKOV3 cells treated with DOX; RT-qPCR showed that LPA treatment could down-regulate the mRNA levels of caspase-3 in DOX-treated SKOV3 cells (P<0. 05); Western blot showed that LPA treatment could reduce caspase-3 and cleaved caspase-3 levels treated with DOX in SKOV3, OVCAR-3 and CHO cells (P<0. 05); Flow cytometry using Annexin V/PI double staining showed that LPA could down-regulate apoptosis in SKOV3 cells treated with DOX (P<0. 05); DCFH-DA method was used to detect intracellular levels of reactive oxygen species (ROS) in SKOV3 cells. It was found that LPA reduced the intracellular ROS level treated with DOX (P<0. 05). Our preliminarily study showed the effect of LPA in the apoptosis of ovarian cancer treated with DOX, which may provide a reference for the drug therapy of ovarian cancer targeting LPA.

Objective To explore the effect of divided injection of fat grafting and to provide a new sight for the strategy of clinical particle fat transplantation.Methods Adipose tissue was aspirated from the healthy female abdomen by liposuction.In the control group,0.5 ml of adipose tissue was subcutaneously injected into the nude mice.The experimental group was injected with 0.25 ml first,followed by 0.25 ml injection of adipose tissue on the 7th,14th and 30th days.To assess graft retention rate and effectiveness we measured the wet weight and observed the pathological sections with HE or perilipin immunofluorescence.Results The wet weight of the tissue between the experimental group and the control group had no statistical difference,the experimental group had less necrosis and empty tissue than the control group.The proportion of perilipin positive staining tissue in 7 day group had statistical difference from that of the control group.Conclusions The strategy of preinjection of part of the adipose tissue and then supplement of the residual tissue after 7 days may increase the proportion of active adipose tissue in the graft.

BACKGROUNDChronic stress contributes to increased risks of atherosclerotic diseases including heart disease, stroke, and transient ischemic attack. However, its underline mechanisms are poorly understood. This study aimed to elucidate the mechanism via which chronic stress exerts its effect on atherosclerosis (AS).

METHODSFifty male New Zealand white rabbits were used. Aortic balloon-injury model was applied. Both social stress and physical stress methods were adopted to establish chronic stress models. The lumen stenotic degree, intimal and medial areas, maximum fibrous cap thickness, and plaque contents were measured with histological sections. Proteomic methods were applied to detect protein changes in abdominal aortas to identify the specialized mediators. Real-time reverse transcription-polymerase chain reaction was used for further verification and investigation.

RESULTSThe stress rabbits exhibited lower body weight, worse fur state, more inactivity behavior, and higher serum cortisol level. Chronic stress was significantly associated with the decreased medial area and increased plaque instability, which was manifested by thinner fibrous caps, larger lipid cores, more macrophages, and new vessels but fewer smooth muscle cells and elastic fibers. After chronic stress, the apoptosis-related genes UBE2K, BAX, FAS, Caspase 3, Caspase 9, and P53 were upregulated, and BCL-2/BAX was down-regulated; the angiogenesis-related genes ANG and VEGF-A were also highly expressed in atherosclerotic arteries.

CONCLUSIONSRabbit models of chronic stress were successfully established by applying both social stress and physical stress for 8 weeks. Chronic stress can reduce AS tunica media and accelerate plaque instability by promoting apoptosis and neovascularization.