Cyclooxygenase-2 (COX-2) plays an important role in the development of leukemia.COX-2 inhibitor plays a certain anti-leukemia role in the process.Many studies show that COX-2 inhibitor plays antileukemia role by inhibiting the proliferation of leukemia cell,promoting apoptosis,affecting cell cycle,inhibiting cell metastasis and reversing cell drug resistance and so on.Therefore,the researches about the anti-leukemia mechanisms of COX-2 inhibitor will provide a new target in clinical prevention and treatment of leukemia.

Objective To investigate the screening significance of transcranial Doppler (TCD) for patients with patent foramen ovale ( PFO) induced cerebral embolism and to improve the treatment aiming at the causes.Methods Thirty-six patients of less than 60 years old with unknown-cause cerebral embolism and transient ischemic attack were enrolled.Besides conventional examination,the 24 h Holter,transthoracic echocariiography,carotid artery Doppler ultrasonography (CAU),routine TCD,TCD foaming test,transesophageal echocardiography (TEE),CT angiography (CTA) of head and neck,ultrasonography of vein in bilateral lower limbs were examined in all patients.Results All the patients showed no atrial fibrillation.No structural heart disease and intracardiac occupying lesion were shown in transthoracic echocardiography.No carotid stenosis was shown in carotid artery Doppler ultrasonography.Routine TCD showed no intracranial artery stenosis.No thrombus was found in ultrasonography of deep veins in bilateral lower limbs.CTA of head and neck showed everything was normal.Fourteen patients were observed with right-to-left shunt in heart by TCD foaming test,including 10 cases with microbubble signals(MBS) in 10 s,and 4 cases with MBS after Valsalva maneuver.Among 14 patients,12 patients were proved PFO by TEE.Conclusions PFO is one of the causes of cardiogenic cerebral embolism.TCD is accurate and reliable for the screening of PFO.

Objective To explore the application value oftranscranial doppler (TCD) in carotid endarterectomy (CEA) through monitoring the hemodynamic changes of intracranial arteries during the perioperative period.Methods Eighty-two patients with internal carotid artery stenosis (ICAS),admitted to our hospital from January 2012-January 2013,were chosen in our study.Preoperative,intraoperative and postoperative TCD evaluations on these patients accepted CEA were performed; degrees of artery stenosis and fluency of lateral branch of the patients before CEA were evaluated; microembolic signals (MESs) and hemodynamics of the middle cerebral artery (MCA) in the surgery side were monitored during the perioperative period; the MCA velocity (VMCA) and the states of collateral circulation were observed after CEA.Results All 82 patients showed severe ICAS,low blood VMCA and low pulsatility index of MCA; anterior and posterior communicating branch did not exist in 6 patients; the other 76 patients showed different status of communicating artery.MESs were captured immediately after opening the clamp of common carotid artery (CCA) in 31 patients; when the ipsilateral CCA was clamped,2 patients showed a rapidly decreased VMCA to 0 cm/s,and a vascular shunt was used to ensure the brain blood supply.About 93.9％ patients presented an increase in the blood velocity and pulsatility index ofipsilateral MCA,together with a subsequent close of collateral circulation; over 1.5 times increase of VMCA was observed in about 24.7％ patients.Acute cerebral infarction in one patient occurred on the same day of CEA.Conclusions TCD could assess the hemodynamics of the contralateral MCA and the closure of collateral communication,thus,helping us predict the hyperperfusion and analyze the pathogenesis of cerebral infarction during perioperative CEA.

OBJECTIVE: To explore the clinicopathologic and molecular characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), and to improve the level of diagnosis and treatments of HNPCC. METHODS: Thirty HNPCC patients (HNPCC group) who were treated in Xiangya Hospital were retrospectively analyzed, and 25 patients with sporadic colorectal cancer in the same duration were randomly chosen as a control group. The onset of age, location of tumor, pathological type, treatment method, and prognosis were compared in the 2 groups. The expression loss rate of mismatch repair gene (MMR) MLH1 and MSH2 in the 2 groups was detected by immunohistochemistry. RESULTS: The onset age in the HNPCC group was earlier than that in the control group (P<0.05). The rate of proximal colonic tumor the occurrence of multiple tumors, and the proportion of well differentiated adenocarcinoma in the HNPCC group were all higher than those in the control group (P<0.05). The expression loss rate of MLH1 and MSH2 in the HNPCC group was higher than that in the control group (P<0.05). One third in the HNPCC group received subtotal proctocolectomy. The prognosis of HNPCC patients was comparable with that of patients with sporadic colorectal cancer (P>0.05). CONCLUSION HNPCC patients are characterized with early onset associating with multiple tumors. The accuracy of diagnosis can be improved by combining the detection of MMR gene. Optimal surgical treatment and close follow-up may bring good result to HNPCC patients.
Adaptor Proteins, Signal Transducing ; genetics ; metabolism ; Adenocarcinoma ; diagnosis ; genetics ; pathology ; surgery ; Aged ; Case-Control Studies ; Colorectal Neoplasms, Hereditary Nonpolyposis ; diagnosis ; genetics ; pathology ; surgery ; Endometrial Neoplasms ; pathology ; Female ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; metabolism ; Mutation ; Neoplasms, Second Primary ; pathology ; Nuclear Proteins ; genetics ; metabolism ; Retrospective Studies

Objective:To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion.Methods:The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed.Results:There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis.Conclusions:Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

Objective To investigate the mechanism of treatment of granulocyte colony-stimulating factor(rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2 (rhIL-2)on hematopoietic injuries induced by 4.5 Gy60 Coγ-ray irradiation in beagles,and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS).Methods Sixteen beagle dogs were given 4.5 Gy60 Co γ-ray total body irradiation(TBI),then randomly assigned into irradiation control group,supportive care group or cytokines+supportive care (abbreviated as cytokines)group.In addition to supportive care,rhG-CSF,rhlL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group.The percentage of CD34+cells,cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry.Results After 4.5 Gy 60 Co γ-ray irradiation,the CD34+cells in peripheral blood declined obviously(61.3%and 52.1% of baseline for irradiation control and supportive care group separately).The cell proportion of nucleated cells in Go/G1 phase was increased notably(99.27% and 99.49% respectively).The rate of apoptosis(26.93% and 21.29% separately)and necrosis(3.27% and 4.14%,respectively)of nucleated cells were elevated significantly when compared with values before irradiation(P<0.05) 1 d post irradiation.When beagles were treated with cytokines and supportive care,the CD34+cells in peripheral blood were markedly increased(135.6% of baseline).The effect of G0/G1 phase blockage of nucleated cells became more serious(99.71%).The rate of apoptosis(5.66%)and necrosis(1.60%)of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure.Conclusions Cytokines maybe mobilize CD34+cells in bone marrow to peripheral blood,indce cell cycle block at G0/G1 phase and reduce apoptosis,and eventually cure hematopoieticinjuries induced by irradiation.

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.

Objective To explore the clotting mechanism in beagles irradiated by 4.5 Gy γ-rays after treatment with supportive care,or supportive care and combined cytokines.Methods Sixteen beagles were divided into irradiation control group,Supportive care group and combined cytokines treatment group.Platelet aggregation test,thrombelagtography (TEG) and the time measurement were analyzed in vitro.Results In irradiation group and supportive care group,the platelet aggregation rates in beagles were decreased markedly and the k value of TEG was increased 7 d post-irradiation,while those indexes in combined cytokines treatment group changed little.At 14 d post-irradiation,each parameter of TEG in irradiated group changed obviously.The values of r,k,r+k and M were elevated significantly,clotting time and the maximum coagulation time of thrombus delayed,the Ma value was decreased markedly,and the maximum elasticity amplitude of thrombus was diminished.All parameters in combined cytokines treatment group were better than those in supportive care group.The thrombin time was prolonged obviously in irradiated group 14 d post-irradiation,while the thrombin time was the longest at 2-3 weeks post irradiation in supportive care group and combined cytokines treatment group(P>0.05).Conclusions Cytokines could improve the platelet aggregation and the blood clotting functions of beagles suffering from acute radiation sickness.

Objective To explore the mechanisms of cytokines on acute radiation disease in irradiated beagles.Methods The sera of beagles irradiated with 4.5 Gy γ-rays with cytokines treatment was collected at different time points post irradiation.The two-dimensional gel electrophoresis(2-DE)was used to isolate and compare the differentially expressed proteins in sera.HD-MS was used to analyze the differentially expressed proteins with significance,and the amino acid sequences should be determined. Results High resolution 2-DE gel map was obtained.There were six differentially expressed proteins in sera of irradiated beagles at different time points.Four protein spots were successfully identified by MS.A significant spot was identified as serum amyloid A(SAA)by HD-MS,with relative molecular mass of 13 077 and isoelectfie point of 6.26.Expression of SAA was not found 1 d pre-irradiation and 36 d postirradiation,but increased slightly 1 d(0.2166)and significantly 14 d post-irradiation(0.4577). Conclusions The expression of serum amyloid A was consistent with the process of acute radiation injury,which might indicate the turnover of the disease.

Objective To evaluate the effects of combined administration of recombinant human interleukin-11(rhIL-11),recombinant human G-CSF(rhG-CSF)and recombinant human interleukin-2 (rhIL-2)on acute radiation sickness(ARS)beagles.Methods Sixteen beagle were irradiated with 4.5 Gy60 Co γ-rays to establish ARS models,and were divided into irradiation control group,supportive care group and combined cytokines treatment group.After irradiation irradiation control group was given no treatment,the dogs in supportive care group received purely symptomatic treatment,while combined cytokines treatment group received rhIL-11 50μg/(kg·d)and rbG-CSF 10μg/(kg·d)subcutaneously(0-14 d)and rhIL-2 1×1 06 U/d(29-43 d)besides symptomatic treatment.Manifestation and characteristics of ARS beagles were observed,and the survival time were recorded.At last,post-mortem examination and histological examination were performed.Results All animals underwent nausea,diarrhea and fever.After irradiation,all animals in irradiation control group died in two weeks,and the mean survival time was 12.7 d,while only one died at 33 d in supportive care group.All dogs in combined cytokine group survived at 45 day after exposure,and their haematopoiesis and gastrointestinal tract were recovered.Conclusions Combination of rhIL-11 + rhG-CSF + rhIL-2 treatment could be significantly effective on ARS beagles irradiated by 4.5 Gy60 Co γ-rays,which could accelerate injured haemotopoiesis and intestinal tract recovery,increase the survival rate and improve the life quality of animals.