Objective To investigate the effect of erythroid differentiation associated gene(EDAG)on hematopoietic stem/progenitor cells(HSPCs)under chronic inflammation.Methods In this study,EDAG-/-and wild type(WT)mice were divided into the experiment group and control group.An infectious chronic inflammation model was established via multiple intraperitoneal injections of Listeria monocytogenes(LM),while a sterile chronic inflammation model was generated via multiple intraperitoneal injections of polyinosinic-polycytidylic acid[Poly(I∶C)].The effect of EDAG on HSPCs was explored under chronic inflammation conditions.Results In the LM repeated infection model,EDAG deletion led to a decrease in HSPCs and long-term hematopoietic stem cells(LT-HSCs)in mice as well as a significant bias towards myeloid differentiation in peripheral blood.Similarly,EDAG knockout also resulted in reduced numbers of HSPCs and decreased colony-forming ability in aseptic chronic inflammation models.Conclusion EDAG deficiency accelerates HSPC depletion in young mice under chronic inflammation,indicating strong protection of EDAG against HSPC damage induced by chronic inflammation.

Objective:To investigate the difference in the radiation sensitivity of hematopoietic stem and progenitor cells (HSPCs) derived from fetal liver and bone marrow.Methods:HSPCs from fetal liver of 14.5 d embryo or bone marrow of 8 week-old mice were isolated to receive a single dose of 5 or 10 Gy irradiation in vitro using a 60Co irradiator. Twelve hours later, the cell apoptosis, mitochondrial reactive oxygen species (ROS) level, colony formation ability and DNA damage in HSPCs were detected. Freshly isolated HSPCs were injected into lethally irradiated CD45.1 + C57BL/6J mice (4.5 Gy+ 5 Gy with an interval of 30 min) Chimerism rate, lineage constitution, and cell cycle were analyzed 12 weeks after transplantation. Results:Compared with bone marrow HSPCs after irradiation, the percentage of apoptosis in fetal liver HSPCs was significantly higher ( t=16.21, 12.27, P<0.05), the level of ROS was dramatically elevated ( t=68.72, 18.89, P<0.05). At 10 Gy, fetal liver HSPCs could not form colonies at all ( t=12.41, 15.67, 9.46, P<0.05). γ-H2AX immunofluorescence staining showed that the DNA damage of fetal liver HSPCs was more severe after irradiation, and the number of Foci formed was significantly higher than that of bone marrow HSPCs ( t=2.27, 2.03, P< 0.05), which indicated that fetal liver HSPCs were more sensitive to radiation. The chimerism rate of transplanted fetal liver HSPCs was lower than that of bone marrow cells ( t=5.84, P<0.05) with a higher proportion of myeloid lineage, suggesting that fetal liver HSPCs had lower in vivo reconstitution capacity than bone marrow HSPCs and were more prone to myeloid differentiation. The cell cycle of bone marrow HSPCs from transplanted chimeric mice was examined, and the proportion of S-phase was significantly higher in the fetal liver group than that in the bone marrow group ( t=2.89, P<0.05). Mitochondrial stress results showed that fetal liver HSPCs had higher basal respiratory capacity ( t=39.19, P<0.05), proton leakage ( t=6.64, P<0.05), ATP production ( t=9.33, P<0.05), and coupling efficiency ( t=7.10, P<0.05) than bone marrow c-Kit + cells, while respiratory reserve capacity ( t=5.53, P< 0.05) was lower than that of bone marrow c-Kit + cells. Conclusions:HSPCs derived from fetal liver display higher radiosensitivty compared with bone marrow HSPCs, laying the foundation for an in-depth illustration of the effects of radiation on hematopoietic stem cells at different developmental stages.

Objective:To study the effect of different doses of 60Co γ-ray ionizing radiation on mitochondrial function in mouse hematopoietic stem and progenitor cells (HSPCs). Methods:C57BL/6 mice were divided into control group, 1 Gy irradiation group and 4.5 Gy irradiation group. The mitochondrial functions were detected at 12 h and 24 h after irradiation, including ROS level, membrane potential, mitochondrial structure, and mitochondrial stress. Bone marrow c-Kit + cells received a single 15 Gy irradiation in vitro, after 24 h, mitochondrial function was detected. Results:It was found that mice leukocytes ( t=12.41, 18.31, 16.48, 14.16, 19.08, 20.25, P<0.05), red blood cells ( t=4.81, 6.62, P<0.05) and platelets ( t=4.33, 6.68, P<0.05) were significantly reduced. The numbers of bone marrow colony formation unit ( t=16.27, 55.66, 17.06, 43.75, P<0.05), and HSPCs ( t=5.16, 11.55, P<0.05) were decreased dose-dependently post-irradiation. Under 1 Gy irradiation, the mitochondrial function and mitochondrial basal metabolic index of HSPCs ( t= 7.36, 3.68, 4.58, 3.15, 3.15, P<0.05) were enhanced at 24 h post-irradiation. Under 4.5 Gy irradiation, mitochondrial number, mitochondrial membrane potential ( t=12.29, 10.46, P<0.05), maximal respiration and spare respiratory capacity were decreased ( t=7.81, 5.78, 6.70, 5.83, P<0.05), ROS level was increased ( t=4.63, 4.12, P<0.05). The basal respiration and oxidative phosphorylated ATP production were reduced at 12 h after irradiation ( t=8.48, 3.80, P<0.05); and the proton leakage was increased ( t=6.57, P<0.05) and coupling efficiency was reduced ( t=11.43, P<0.05) at 24 h after irradiation. In cultured c-Kit + cells, the level of ROS ( t=11.30, P<0.05) and the maximum respiration and spare respiratory capacity were increased ( t=4.25, 3.44, P<0.05) while the mitochondrial membrane potential was decreased ( t=34.92, P<0.05) significantly. Conclusions:A method for systematically assessing mitochondrial function in HSPCs was established, and the effect of ionizing radiation on mitochondrial function of HSPCs was clarified, laying a foundation for further revealing the mechanism of ionizing radiation-induced mitochondrial damage in HSPCs.

Objective:To observe the efficacy of methimazole (MMI) combined with 1α-hydroxyvitamin D3 (alfacalcidol, ALF) in patients with Graves disease of high-titer thyrotropin receptor antibodies (TRAb) and to explore new clinical strategies to reduce serum TRAb in Graves disease.Methods:120 patients with Graves disease initially diagnosed in Quanzhou First Hospital Affiliated to Fujian Medical University and the People′s Hospital Affiliated to Quanzhou Medical College from June 2017 to June 2019 were prospectively selected as the research objects. All patients received conventional dose of MMI for anti hyperthyroidism treatment. The patients were randomly divided into three groups: group A [ n=40, treated with MMI combined with high-dose ALF (0.5 μg/d)], group B [ n=37, treated with MMI combined with low-dose ALF (0.25 μg/d)] and group C ( n=43, treated with MMI only). The treatment lasted for 24 weeks. The serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH) and TRAb in patients before and after above treatments were detected. The blood routine, liver function, alkaline phosphatase (ALP), 25(OH)D, serum calcium (CA) and serum phosphorus were detected regularly. Results:After drug treatment: ⑴ the thyroid function of the three groups returned to normal. The average daily dosage of MMI in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05), with significant difference. After 24 weeks of treatment, the daily dosage of MMI in group A and B was significantly lower than that in group C ( P<0.05). ⑵ There was no significant difference in thyroid function among the three groups. The concentration of serum TRAb in group A was significantly lower than that in group B and C ( P<0.05), and that in group B was also lower than that in group C ( P<0.05). ⑶ During the 24 week follow-up, there was no significant difference in serum 25(OH)D, ALP, Ca and P among the three groups ( P>0.05); no leukopenia in peripheral blood and no abnormal liver function were found in the three groups. Conclusions:MMI combined with ALF can effectively treat Graves′ disease, reduce the dosage of MMI drugs, decline the level of TRAb in the serum of Graves′ patients, and improve the prognosis of Graves′ disease.

Objective:To explore the correlations between 11C-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) microPET/CT imaging and the degree of damage to dopamine neurons in the substantia nigra of midbrain and the severity of Parkinson′s disease (PD). Methods:Sixty male Sprague-Dawley (SD) rats were divided into PD model group ( n=48) and control group ( n=12) by random number table method. The PD model was established by injecting 6-hydroxydopamine (6-OHDA) into the right striatum. The rotational behavior test and 11C-CFT microPET/CT imaging were performed at 1, 2, 3 and 4 weeks after the establishment of PD model. The radioactivity uptake values of bilateral striatum were analyzed and the radioactivity uptake ratio of injured side to healthy side was calculated. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in the pars compacta of substantia nigra was counted by immunofluorescence staining, and the ratio of total number of TH positive neurons in injured side to healthy side was calculated. Data were analyzed by one-way analysis of variance, the least significant difference t test and Pearson correlation analysis. Results:At 1, 2, 3 and 4 weeks after the establishment of PD model, the rotation speed of PD model to the healthy side was (4.55±1.37), (8.64±1.64), (9.96±1.83) and (11.67±2.77) r/min, respectively, while there was no rotation behavior in the control group. Meanwhile, the ratios of 11C-CFT uptake and the number of TH positive neurons in the PD model group were 0.658±0.038, 0.580±0.094, 0.513±0.042, 0.394±0.065 and 0.698±0.066, 0.604±0.062, 0.546±0.064, 0.315±0.082, respectively, which were significantly lower than those in the control group (0.997±0.048 and 0.996±0.054; F values: 167.50, 169.20, both P<0.05). Correlation analysis showed that 11C-CFT uptake ratio was correlated with rotation behavior (rotation speed) and TH positive neuron ratio ( r values: -0.877, 0.897, both P<0.001). Conclusion:In the PD animal model, the ratios of 11C-CFT uptake has a good correlation with the degree of damage to dopamine neurons in the substantia nigra of the midbrain (TH positive neuron ratio) and the severity of PD.

Objective To investigate the research hotspots and trends in the field of immunotherapy for liver cancer in 2011-2020 based on bibliometric methods. Methods The Web of Science-SCI Expanded database was searched with the following search strategy: #1 TS = (Liver Neoplasms OR Neoplasms, Hepatic OR Neoplasms, Liver OR Liver Neoplasm OR Neoplasm, Liver OR Hepatic Neoplasms OR Hepatic Neoplasm OR Neoplasm, Hepatic OR Cancer of Liver OR Hepatocellular Cancer OR Cancers, Hepatocellular OR Hepatocellular Cancers OR Hepatic Cancer OR Cancer, Hepatic OR Cancers, Hepatic OR Hepatic Cancers OR Liver Cancer OR Cancer, Liver OR Cancers, Liver OR Liver Cancers OR Cancer of the Liver OR Cancer, Hepatocellular) AND #2 TS = (Immunotherapy OR Immunotherapies OR Immunity therapy); time span: 2011-2020; type of literature: Article; language: English. CiteSpace software was used to perform a visualized analysis of the articles in the field of immunotherapy for liver cancer published in 2011-2020 from the aspects of the distributions of year, country, institution, author, journal, and fund, times cited, and keywords, and the frequency, centrality, and clustering of keywords were discussed. Results A total of 1972 articles on immunotherapy for liver cancer were included, and the analysis showed that China was the country with the largest number of articles, Sun Yat-sen University was the institution with the largest number of articles, and Journal for Immunotherapy of Cancer was the journal with the largest number of articles. The research hotspots in this field included tumor-associated macrophages, oncolytic virus (such as adenovirus), tumor vaccine therapy, adoptive cellular immunotherapy, immune checkpoint inhibitors, and combined immunotherapy. The trend of this field was tumor vaccine therapy → immunotherapy for oncolytic virus → adoptive cellular immunotherapy → immune checkpoint inhibitor therapy. Conclusion Immunotherapy for liver cancer has undergone continuous development in the recent ten years, and with the research and development of tumor vaccine therapy, oncolytic virus, and immune checkpoint inhibitors and the improvement of immune checkpoint inhibitors, combined treatment based on immunotherapy is expected to further improve the clinical outcome of liver cancer.

Objective To explore the research hotspots and trends in the field of CSCs through the bibliometric analysis of the literature on CSCs. Methods Based on the core database of Web of Science, CiteSpace was used to analyze the annual distribution of published articles, authors, institutions, countries, journals, citations and keywords, and to explore the frequency, centrality and clustering of key words. Results (1) A total of 8131 articles were included after screening. China was the country with the largest number of articles, and Sun Yat-Sen University was the organization with the largest number of articles; (2) The hot spots in the field of CSCs are the research of CSCs in breast cancer and pancreatic cancer, the research of CSCs sorting and identification of molecular markers ALDH and genes PTEN, Sox2, C-myc, EZH2, the mechanism of EMT inducing the production of CSCs and promoting tumor metastasis, cellular and molecular mechanisms of CSCs resistance to chemical, radiation and targeted drug attacks, Wnt/β-catenin signaling pathway and tumor microenvironment regulate the differentiation of CSCs and targeted inhibition of CSCs in the treatment of malignant tumors; (3) The research trend of CSCs is CSCs stem research-biological mechanism of CSCs-CSCs application in the treatment of cancer. Conclusion The focus and direction of CSCs research are EMT inducing CSCs to promote tumor metastasis, CSCs resisting chemical attack, mesenchymal stem cells regulating CSCs, the metabolism of CSCs, and inhibitors targeting CSCs at present and in the future.

Objective To investigate the clinical outcome and treatment characteristics of viral encephalitis with bilateral thalamic damage so as to improve its prognosis.Methods Twelve cases of viral encephalitis with bilateral thalamic damage were collected during September 2012 to June 2013 by head MRI.These cases were retrospectively studied with the data of medical history,physical examination,laboratory and brain function monitoring and treatment.The relationship between treatment and prognosis was studied during 2 years of follow-up.Results All patients began with the rapid onset,accompanied by fever,coma,and convulsions.Delirium and involuntary movement occurred during the recovery period.Six cases(50.0％) received ventilator assisted ventilation.In the acute phase,electroencephalogram (EEG) showed diffuse slow wave and 4 cases(33.3％) had status epilepticus on EEG.Ten cases discharged from hospital had long-term oral anti epileptic drugs,which lasted 6 months in 3 cases,1 year in 4 cases,and 2 years in 3 cases for maintaining EEG stability.Head MRI indicated white matter demyelination besides the gray matter damage within the thalamus.All 12 patients underwent methylprednisolone impact treatment and 6 cases had effective reversal within 1 week of onset with better tolerance,and the other 6 cases received treatment in subacute stage and 5 of them accelerated recovery and 1 case had sense improvement,but died after giving up therapy.After 3 months courses,8 cases(66.7％) got gross motor and swallowing function recovered to normal,and 3 cases had left unilateral limb movement disorder.After 2 years of follow-up,11 cases had normal motor,intelligence returned to normal in 9 cases,and 2 cases had mild mental retardation.Conclusions Viral encephalitis complicated with bilateral thalamic damage is characterized by acute onset,serious manifestations,idiopathic progress;in the subacute stage it is most likely to develop white matter demyelination.The key to control the disease is to block the inflammatory immune response quickly,and give patients large dose methylprednisolone treatment can effectively curb the progress of the disease.In the sub acute phase,it can promote the recovery,safe and effective.The long-term prognosis will be good with the reasonable treatment at early stage of the disease.

Objective To investigate toe-brachial index ( TBI) in the diagnosis of peripheral artery disease ( PAD) and its risk factors in the patients with type 2 diabetes.Methods TBI was examined in the 238 patients with type 2 diabetes.The patients were divided into the group with low TBI ( TBI≤0.7 ) and the group with normal ABI ( TBI>0.7 ) .The two groups were compared for clinical parameters.Results Thirty two patients (13.4%)with abnormal ABI (TBI≤0.7) showed older age [(63.8 ±9.9) yrs vs (54.9 ±10.8) yrs, P =0.000] , lower diastolic blood pressure [(70.5 ±6.9) mmHg vs (74.9 ±9.1) mmHg, P =0.003], more frequency of hypertension (56.3%vs 38.3%, P =0.043), coronary artery heart disease (28.7%vs 10.7%, P =0.020) and cere-bral vascular disease (15.6%vs 4.4%, P =0.025).Step-wise analysis screened that age and diastolic blood pressure were the inde-pendent risk factors for TBI .Conclusions Aging and hypertension were the risk factors in the patients with abnormal TBI in type 2 di-abetes.TBI was an easy and economical method for diagnosing PAD in patients with type 2 diabetes.

ObjectiveTo evaluate the local failure and the impact on survival by prospectively comparing involved field radiotherapy (IFRT) and elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer ( LA-NSCLC ).Methods LANSCLC patients were treated with 2 cycles of carboplatin ( AUC =5 - 6,d1 ) combined with paclitaxel ( 175mg/m2 ),followed assessment without distant metastasis,then randomized into IFRT (45 patients) or ENI (54 patients) arm.IFRT included primary tumor,ipsilateral hilar and positive mediastinal lymph nodes;ENI included the primary lesion,ipsilateral hilar,hilateral mediastinal lymph node drainage and bilateral supraclavicular area.The prescription dose was given as high as possible with V20 ≤35％ and spinal cord dose ≤50 Gy,combined weekly paclitaxel 40 mg/m2 concurrent chemotherapy.The Kaplan-Meier method was used to estimate survival data and the log-rank method was used to test distribution of survival time between arms.ResultsThe follow-up rate was 99％.49,29 and 17 patients were followed-up for 1-,2-and 3-year,respectively.More patients from group IFRT received ＞60 Gy than ENI (49％ vs.26％,x2 =5.59,P =0.018 ).The local failure rates were 29％ and 36％,respectively ( x2 =0.46,P =0.497 ).The 1-,2-and 3-year local tumor progression-free survival rates were 76％,69％,65％ and 80％,53％,49％ ( x2 =0.74,P =0.389),respectively; the 1-,3-and 5-year overall survival rates were 80％,41％,33％ and 69％,32％,13％ (x2 =3.97,P =0.046),respectively.There were no significant differences in acute and late toxicities between the arms ( x2 =3.910 - 0.155,P =0.142 - 0.925 ).ConclusionsIFRT improved radiation dose and survival rate and did not increase the failure of elective lymph node region compared with ENI.The toxicities were no differences between IFRT and ENL Further investigation with big size sample is warranted.