Objective To investigate ASPS induced G_2/M arrest in lung cancer cell line H446 and its effect on ERK MAP kinase signal transduction pathways. Methods Cell cycle phases were inspected by flow cytometery (FCM) ; Western blot analysis was used to inspect the proteins of ERK, p-ERK. Results Compared with control group, G_2/M phase cells increased with concentration significantly, G_0/G_1 phase cells were not different, G_2/M phase cells and G_0/G_1 phase cells were not different when pre-incubated with PD98059 prior to exposure to ASPS of different concentrations, protein of p-ERK was significantly increased, expression of ERK was no different. Conclusion ASPS may induce G_2/M arrest of H446 cells possibly by activation ERK MAP kinase pathways.

OBJECTIVE To investigate the distribution and resistance of fungi isolated from hemopathy patients,and to provide the laboratorial data in order to prevent and treat infection caused by fungi more effectively.METHODS Strains were isolated from the upper respiratory tract,lower respiratory tract,genitourinary tract,alimentary tract;and perianal region,perineum,and the soft tissue and skin wounds.Antimicrobial susceptibility of clinical isolates was tested by broth microdilution susceptibility test.RESULTS Candida albicans,Aspergillus,tropicalis,C.krusei,and C.glabrata were the main fungi of total 3104 detected isolates.The resistance rates of C.albicans and C.tropicalis to fluconazole,itraconazole and 5-flucytosine were no more than 1.4%.The MIC50-MIC90 range of C.tropicalis for itraconazole was narrow(0.25-0.5 mg/L),but that was wide for fluconazole(0.25-4.0 mg/L).CONCLUSIONS C.albicans,Aspergillus,C.tropicalis,C.krusei,and C.glabrata are possibly the most common pathogens causing endogenous and exogenous fungi infection.The main infection sites of Aspergillus are the upper respiratory tract and lower respiratory tract,which may be associated possibly with ward's air quality.The MIC50to MIC90 range of C.tropicalis is wider for fluconazole than for itraconazole,which is possibly correlated with overexpression of CtMDR1 in C.tropicalis caused by the widely application of fluconazole in therapy.

Objective To study the expression and clinical significance of Survivin and PTEN in cervical carcinoma. Methods The expression of Survivin and PTEN in 60 cases of cervical carcinoma, 15 cases of CIN Ⅰ , 15 cases of CIN Ⅱ, 15 cases of CIN Ⅲ and 15 cases of normal cervical tissues were detected by immunohistochemical staining. Results The expression positive rates of Survivin were 86.67 %, 80.00 %,33.33 %, 20.00 % and 0, respectively, and those of PTEN were 21.67 %, 40.00 %, 80.00 %, 86.67 % and 100.00 % in cervical carcinoma, CIN Ⅲ, CIN Ⅱ, CIN Ⅰ and normal cervical tissues, respectively. The expression positive rates of Survivin were increased along with normal cervical epithelium, CIN Ⅰ, CIN Ⅱ,CIN Ⅲ and invasive carcinoma of cervix;while those of PTEN were inverse order.Compared with the expression positive rates of Survivin and PTEN protein in the CIN Ⅱ group, those in the CIN Ⅲ group had significant differences (P <0.01 and P <0.05, respectively). Expressions of Survivin and PTEN were correlated to the size of focus(P <0.05), the depth of tumor and pelvic lymphnode metastasis (P <0.05), but not to clinical staging, pathological types, pathological grading and age(P >0.05). There was a negative correlation between the expression of PTEN and Survivin in cervical carcinoma. Conclusion The expressions of Survivin and PTEN are correlated with invasion and metastasis of cervical carcinoma, and be related to clinical pathotology.Survivin and PTEN may play a important role in the formation, proliferation, differentuation and metastasis of cervical carcinoma. They may be used as markers of early diagnose, efficacy and prognosis evaluation.

Objective The present study is to investigate IL-24 gene(Ad5F35-hIL-24) effect on the topoisommeraseⅡα(topoⅡα) and Caspase-3 expression in glioma cell line U251. Methods After transfected the U251 glioma cells with the Ad5F35-hIL-24, the methyl thiazolyl tetrazolium (MTT) was used to analyse the inhibition rate of Ad5F35-hIL-24 on the cells. Hoechst 33258 fluorescent staining and flow cytometric assay were used to detect apoptosis. The immunohistochemistry assay was used to detect topoⅡα expression, and Western blotting was applied to detect the protein expression of topoⅡα and caspase-3. Transwell experiment was used to test the invasiveness of the cells. Results It was found that the Ad5F35-hIL-24 could inhibit U251 cell proliferation and induce apoptosis in a dose dependent manner compared with the control groups. It showed that Ad5F35-hIL-24 could inhibit topoⅡα expression reveled by immunohistochemistry and Westeren blotting, while it increased caspase-3 protein expression. The Transwell experiment showed that the Ad5F35-hIL-24 could reduce the invasiveness of the U251 glioma cells.Conclusion The exogenous IL-24 gene can inhibit the cell proliferation and induce apoptosis of U251 glioma cells. The topoⅡα and Caspase-3 are the important molecular targets of the IL-24 gene. These results may give support for the IL-24 gene usage in clinical treatment for glioma patients.

Objective To compare the efficacy of conventional radiotherapy and Tomo radiotherapy com -bined with zoledronic acid in spinal metastase .Methods Seventy -nine patients with spinal metastases in our department of Air Force General Hospital were recruited from January 2011 to December 2012 .All patients were divided into two groups:group A:39 cases were treated with conventional radiotherapy combined with zoledronic ( PTV:30~40 Gy/10~20 f);40 patients with target in target Tomo radiotherapy combined with zoledronic acid were separated into group B(PTV/GTV/40~50 Gy/50~60 Gy/15~20 f).Results The overall following -up rate was 96.2%.The total response rate was 88.61%,the analgesic effect of radiotherapy in group A and group B were 84.62%、92.5%,respectively.The average pain scores were decreased by 2.55 and 3.54 in two gourps u-sing a numerical rating scale;the average pain relieve time were 7.25d and 8.32d,respectively;the median last-ing time of pain relieves were 6.68 and 8.41months;and the pain recurrence rate were 25.81% and 5.41% in corresponding group A and group B .The main acute side effects were hematologic toxicity , in which occurring rates were 12.82%and 12.5%in RTOG gradeⅠ,23.08% and 20%in RTOG grade Ⅱ,2.56% and 2.5% in RTOG gradeⅢ,2.46%and 0%in RTOG grade Ⅳin group A and group B,respectively.There were no signifi-cant differences in pain relief rate ,start-effect time,lasting time and acute side effects between the two different radiotherapy methods .However ,the decreased degree of pain relief and recurrence rate were obviously decreased in group B when compared with group A ,and the differences were statistically significance (P<0.05).Conclu-sion Target in target Tomo radiotherapy combined with zoledronic acid in the treatment of spinal metastasies is safe and effective,mild toxicity,and the degree of pain relief was significantly improved .Moreover,pain recurrence rate is lower than conventional radiotherapy .Hence ,it is worth of recommendation in clinical practice .

Oblectlv To detect the Iocation of inducible nitlic oxide synthetase (iNOS) protein and mRNA in lung during endotoxemia in rabbits. Methods blotting was perfomed before, 1 hour and 5 houm after the intravenous administration of lipolysaccharide (LPS) in rabbits. Immuno histonbernical analysls (IA), in situ hybridization and in situ ireverse transcfipfiorl-polymerase chain reaction (in sltoJ RT-PCR) were also pedormed in lung sections. Results iNOS mRNA expression was found using Nodhem blotting in lung 5 hours after LPS injection, while It was not found in contrei. Tbe positive stain was found only in macrophages in lung 5 hours after LPS inljecfion by standard hybddization and IA; while by in situ RT- PCR, tbe amplifation products were found in macrophaoes, aJlway epitheiial oells, vascular endotbeliei cells, smooth muscle cells and leukocytes, in addition to macrophages distributed abundantly thriygout the lung. The signal was absent in control or samples. Cencluslons Using an in situ RT-PCR technique, iNOS expressson was riot only observed in macriogaqss also in many other kinds of cells in ybg during endotoxemla in rabbits. This suggests that n situ RT-PCR ls much more sensirtive than in situ hybridization, and can be usad to examine gones with Iow expreseion.

Objective To explore the relationship between folic acid levels of cord blood and birth weight, hyaline membrane disease in newborns. Methods Eighty-seven newborns were divided into premature infant group(42 cases) and term infant group(45 cases),intrauterine growth retardation group( 28cases) and control group (59 cases), hyaline membrane disease of premature infant group ( 13 cases) and premature infant control group(15 cases) according to the gestational age, birth weight, clinical manifestation and chest X-ray, respectively. Folic acid levels of cord blood were measured. Results The folic acid level of cord blood in premature infant group was lower than that in term infant group [(10.87 ±4.31) nmol/L vs.( 13.56 ± 5.07) nmol/L,P ＜0.05 ]. The folic acid level of cord blood in intrauterine growth retardation group was lower than that in control group [(11.01±4.29)nmol/L vs.( 14.87 ± 5.14)nmol/L,P＜0.05]. The folic acid level of cord blood in hyaline membrane disease of premature infant group was lower than that in premature infant control group [(9.15 ±4.02) nmol/L vs.(12.91±4.51) nmol/L,P＜0.05]. The positively correlation was found between the folic acid level of cord blood and birth weight in newborns (r =0.1825).Conclusion The folic acid level of cord blood is correlated with the occurrence of premature infants,intrauterine growth retardation and hyaline membrane disease in newborns.

Objective To examine the brain metabolic changes in WD patients receiving copper chelation by us?ing 1H-MRS. Method Thirty-nine patients with WD was randomly divided into four groups: non-brain type group (18 cases), brain type prior-treatment group and short-term treatment group (21 cases), long-term treatment group (20 cases) from short-term treatment group, and 20 healthy volunteers served as a control group. 1H-MRS and MRI were performed on patients on 1.5/MR/MRS system to detect these above-mentioned items before and after treatment. Result The mean of NAA/Cr was significantly lower in the left putamen and head of the caudate nucleus than in the left basal ganglion in the 39 patients with WD. The mean of NAA/Cr and Cho/Cr in the left putamen and basal ganglion was significantly lower in non-brain type group than in control group(P<0.01). The mean of NAA/Cr Cho/Cr and NAA/Cho in the left putamen,head of the caudate nucleus and basal ganglion were significantly lower in brain type group than in control group(P<0.01 or P<0.05). The mean of NAA/Cr in the left putamen was much lower in brain type group than in non-brain type group (P<0.01). The mean of NAA/Cr, Cho/Cr and NAA/Cho of short-term treatment group in the left putamen, head of the caudate nucleus and basal ganglion was not significantly different between brain type group and short-term treatment group(P>0.05). The mean of NAA/Cr and NAA/Cho in the left putamen and basal ganglion was much higher in long-term treatment group than in brain type group(P<0.01 or P<0.05). The mean of Cho/Cr in the left head of caudate nucleus were much higher after treatment compared with prior-treatment group(P<0.05). The mean of NAA/Cr in the left putamen, head of the left caudate nucleus and basal ganglion in all groups was negatively correlated with course of the disease. Conclusion There are significant differences in brain metabolism among different type of WD. The long-term but not short-term copper chelation significantly improves brain metabolism. NAA/Cr may be used as a non-invasive indicator to examine the efficacy of treatment.

Objective To explore the correlation between the pathogenesis of coronary heart disease and the polymorphism of methylenetetrahydrofolate reductase ( MTHFR ) .Methods 130 cases of coronary heart disease diagnosed and treated in Heze Municiple Hospital from July 2015 to July 2017 were selected as observation group .At the same time,130 healthy people were selected as control group .The serum folate and homocysteine ( HCY) levels were compared between the two groups .At the same time, polymerase chain reaction -restriction fragment length polymorphism was used to analyze the MTHFR gene polymorphisms .The distribution of MTHFR gene polymorphism was compared between the two groups .Results The level of serum folic acid in the observation group was (5.76 ± 2.14)g/L,which was significantly lower than (7.34 ±2.43)g/L in the control group (t=5.64,P<0.05).The level of serum HCY in the observation group was (15.46 ±5.74)μmol/L,which was significantly higher than (10.28 ± 4.38)μmol/L in the control group (t=6.43,P<0.05).The frequencies of TT type,TC type and CC type of MTHFR gene in the observation group were 36.92％,46.92％and 16.15％,respectively.The frequencies of TT type,TC type and CC type of MTHFR gene in the control group were 21.54％,55.38％ and 23.08％,respectively.The frequency of TT type in the observation group was significantly higher than that of the control group (χ2 =8.25,P<0.05). There were no statistically significant differences in folic acid levels among different gene types in the observationgroup(t=1.31,0.55,0.73,all P>0.05),but the serum HCY level of TT type was significantly higher than that of CT type and CC type in the observation group (t=5.33,4.62,all P<0.05).Conclusion Serum folic acid level, HCY level and homozygous mutations of MTHFR gene type have certain relationship with the occurrence of coronary heart disease ,the body serum folic acid level and the distribution of MTHFR genotypes can affect the concentration of HCY,thus affecting the occurrence of coronary heart disease .

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.