BACKGROUND:Stem cel therapy has been used for prevention and treatment of degenerative disc disease. Considering the special microenvironment in the intervertebral disc, the survival rate and differentiation ability of transplanted cels are decreased, which may lead to the poor efficacy of stem cel therapy. How to improve the survival ability and therapeutic effect of the transplanted cels is the focus of stem cel therapy for degenerative disc disease.
OBJECTIVE: To investigate the effects of cobalt chloride combined with hypertonic solution pretreatment on bone marrow mesenchymal stem cels that wil be transplanted for treatment of degenerative disc disease.
METHODS:(1)In vitro cel experiment: bone marrow mesenchymal stem cels were divided into three groups and subjected to normal culture medium (normal control group), 1% hypertonic mother solution (hypertonic group), 100 μmol/L cobalt chloride (hypoxia group), or 1% hypertonic mother solution plus 100 μmol/L cobalt chloride (combined group) for 1 week. Then, 2% hypertonic solution and 200 μmol/L cobalt chloride cobalt chloride were used to simulate the anaerobic and hypertonic environment intervenes in pretreated and untreated bone marrow mesenchymal stem cels for 24 hours. After that, RT-PCR was used to detect the expression of caspase-3 for apoptosis evaluation. (2)In vivo animal experiment: Sprague-Dawley rats were divided into model, cel transplantation and hypertonic plus hypoxic groups. Rat models of intervertebral disc degeneration were made in these three groups. After modeling, rats in these three groups were given no treatment, bone marrow mesenchymal stem cel transplantation or transplantation of bone marrow mesenchymal stem cels which were subjected to hypertonic and hypoxia pretreatments into the intervertebral disc. Two weeks later, immunohistochemistry and RT-PCR methods were used to detect cel distribution and related gene expression, respectively, thereby to evaluate the therapeutic effect of stem cels.
RESULTS AND CONCLUSION: (1)In vitro cel experiment: caspase-3 mRNA expression was significantly reduced in pretreated bone marrow mesenchymal stem cels compared with the untreated cels (P < 0.05). (2)In vivo animal experiment: compared with the control group, the caspase-3 and interleukin-1β in the intervertebral disc and a number of degenerative indexes were decreased in the cel transplantation. Compared with the cel transplantation group, these indicators had better outcomes in the hypertonic plus hypoxic group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cels have therapeutic potential for degenerative disc disease, and have better adaptability and transplantation effects by hypertonic and hypoxia pretreatments.

To simplify the macrocyclic fragment and to modify the zinc binding group of the natural product apicidin, two series of S-hexyl (heptyl) ethanethioate derivatives were designed and synthesized. Twenty-six compounds were synthesized and confirmed with 1H NMR, IR, MS and HR-MS spectrum, which were not reported. Take vorinostat as control, their antiporliferative activities against cancer cell lines, MCF-7 and HL-60, were tested with MTT assay or trypan blue staining method. Generally in both series it was found that, the chiral carbon atom at 7 position is not necessary, compounds II-1, II-3, II-6 and II-13 showed good activity on HL-60 cells in vitro, with the IC50 values less than 10 micromol x L(-1). II-7 and II-8 showed stronger activity against MCF-7 than Vorinostat, with the IC50 of 3.19 and 6.29 micromol x L(-1), respectively.

Objective The purpose of this paper is to understand the advantages and disadvantages of the bone marrow smears and bone marrow biopsy in multiple myeloma diagnosis and efficacy judgment,explicit the value of bone marrow smears and bone marrow biopsy synchronous check in the diagnosis and treatment observation of multiple myeloma.Methods With two step-suction two biopsy specimens assay,obtained specimens of bone marrow smears and bone marrow biopsy,retrospective-ly analysed results of 283 multiple myeloma patients bone marrow smear and biopsy,and made a comparative study on the degree of bone marrow hyperplasia,myeloma cell morphology,the degree of tumor cell infiltration,proliferation pattern,bone marrow stromal pathological changes,and fibrosis cases.Results The degree of proliferation of bone marrow biopsy sections and infiltration of plasma cells was significantly higher than that of bone marrow smears,statistically there was a significant difference (P <0.01).Multiple myeloma diagnostic sensitivity by bone marrow biopsy sections was significantly higher than by the bone marrow smears,the difference was statistically significant (P < 0.05).Plasma cells in bone marrow biopsy tumor proliferation modes:clusterpiece nodular type 33 cases (11.66%),interstitial-type 86 cases (30.39%),among nodular interstitial type 112 cases (39.58%),diffuse cypriot real 52 cases (18.37%).Plasma cells in bone marrow smears tumor morphology:small mature plasma cell type 77 cases (27.21%),immature plasma cell type 148 cases (52.30%),protoplas-mic cell type 36 cases (12.72%),reticular plasma cell type 22 cases (7.77%).Conclusion Marrow biopsy can accurately reflect the degree of bone marrow hyperplasia,plasma cell tumor proliferation mode and infiltration degree,myelofibrosis sit-uation;bone marrow smears Wright-Giemsa staining,plasma cell tumor morphology was clear,typicalfeatured,and easily i-dentifiable.Bone marrow smear and biopsy synchronous check can improve the sensitivity and accuracy for multiple myeloma diagnosis,which has very important significance for multiple myeloma diagnosis and treatment observation.

Objective:To analyze the magnetic resonance imaging (MRI) features of diffuse midline gliomas with H3K27M mutation, and to quantitatively analyze the changes of apparent diffusion coefficient (ADC).Methods:The MRI images of 14 cases of diffuse midline gliomas with H3K27M mutation were retrospectively analyzed in the Affiliated Hospital of Qingdao University from April 2017 to November 2019. The location, edge, signal, peritumoral edema and enhancement characteristics of the lesions were observed, and the changes of ADC values were analyzed.Results:The tumors were located in thalamus in four cases, pons in six cases, medulla oblongata in two cases and spinal cord in two cases. In seven cases, the tumor was confined to the midline region, of which six cases had clear boundary, seven cases were located in the midline area, but infiltrated into the non midline area at the same time, and six cases had unclear boundary. Basilar artery entrapment was found in all six patients located in pons. Multiple large cystic changes were found in five cases, multiple small cysts in four cases and no cystic changes in five cases. Cystic changes were found in all seven cases of tumors involving the non midline region, of which six cases were located only in the non midline region, and only two of the seven tumors localized in the midline region had small cysts. Hemorrhage was found in four cases. Five cases showed mild heterogeneous enhancement, six cases showed moderate heterogeneous enhancement, two cases showed obvious enhancement, and one case showed no enhancement. There was no edema around the tumor in nine cases and mild edema in five cases. The average edema index was 1.13. The average ADC value of tumor parenchyma in 12 patients was (7.83±0.88)×10 -4 mm 2/s, which was 15.6% lower than that of the contralateral side [(9.28±0.69)×10 -4 mm 2/s, t=-6.336, P<0.05]. Conclusions:Diffuse midline gliomas with H3K27M mutation have a younger onset age and are more likely to occur in thalamus, brainstem and spinal cord. Most of the tumors have no peritumoral edema or mild peritumoral edema. The tumors confined to the midline region are regular in shape and clear in boundary. The masses involving the non midline area are prone to cystic necrosis. Diffuse midline gliomas with H3K27M mutation in pons are prone to basilar artery entrapment. ADC value can provide a quantitative basis for preoperative tumor grading.

Objective To investigate the genetic characteristic of whole-genome of influenza A/H3N2 viruses in severe acute respiratory infection cases in Beijing area.Methods From 2014 to 2016,the viral RNA was extracted from 32 strains isolated from SARI cases,then sequenced by Ion Torrent PGM Sequencer.The phylogeny and molecular features of whole-genome were analyzed by Mega and Consurf software.Results The HA gene of tested strains isolated in 2014-2015 influenza season belonged to lineage 3C.3a and 3C.2a,while those isolated in 2015-2016 influenza season belonged to cluster 3C.2a.Moreover,compared with the vaccine strains,7 variant amino acids of protein of HA1 were identified,and two of them were located in antigenic sites.All isolates were sensitive to neuraminidase inhibitors while showed resistance to blockers for M2 ion channel.Conclusion The phylogenetic features of isolates studied in this study are similar with that of current circulating strains.However,the difference between isolates and vaccines should not be overlooked.

Objective To explore the abnormal karyotype characteristics of myelodysplastic syndrome (MDS)patients and their correlation with clinical prognosis.Methods Analyzed the karyotypes of 281 MDS patients by use of G-banding tech-nique.Results Through analysis of the karyotypes of 281 MDS patients,found that the percentage of abnormal karyotypes was 48.75% (137/281),among 137 patients with abnormal karyotypes,43.07% (59 cases)presented with numerical aber-ration,31.39% (43 cases)with structural aberration,and 25.54% (35 cases)with both numerical and structural abnormali-ties.As for MDS subtypes,the occurrence rate of abnormal karyotype was 63.41% (26/41)in RAEB-2,58.73% (37/63)in RAEB-1,39.2% (49/125)in RCMD,15.38% (2/13)in RAS and 22.58% (7/31)in RA.The rates of abnormal karyotype in RAEB-1 and RAEB-2 were significantly higher than that in RA and RAS(P<0.01),and in RCMD (P <0.05).The fre-quent abnormal karyotypes were as follows:+8,-7/7q-,-20/20q-,complex karyotypes chromosomal translocation,i(17),-Y and +21.The follow-up study of 159 MDS patients indicated that the median survival time was 39 months for 68 patients with normal karyotypes and 21 months for 91 patients with abnormal karyotypes,the former was significantly prolonged than the latter (P < 0.05).As far as the leukemia transition rate was concerned,the patients with aberrant karyotypes (35.5%)were significantly higher than that with normal karyotypes (10.3%)(P < 0.01),among them,the cases with complex karyotypes and-7/7q-more easily transit into leukemia.Conclusion MDS was one kind of clonal hematological ma-lignancy with high heterogeneity.Chromosomal karyotype test plays an important role in the correct diagnosis,typing and prognosis evaluation of MDS.

Lead?time bias and length bias were common systematic errors in observational screening studies, which might be a common cause of overstating or distorting the true screening effects. One of key concerns in observational screening studies was how to estimate the screening effects based on the consideration of these two biases. This paper illustrated how to identify and correct the lead?time bias using the tumor volume doubling time and the non?homogeneous Poisson process, and how to correct the length bias using a weighted method. The application conditions of each method were also discussed to present several useful toolboxes to correct the lead?time bias and length bias appropriately and evaluate the effectiveness of the cancer screening program accurately.

Lead?time bias and length bias were common systematic errors in observational screening studies, which might be a common cause of overstating or distorting the true screening effects. One of key concerns in observational screening studies was how to estimate the screening effects based on the consideration of these two biases. This paper illustrated how to identify and correct the lead?time bias using the tumor volume doubling time and the non?homogeneous Poisson process, and how to correct the length bias using a weighted method. The application conditions of each method were also discussed to present several useful toolboxes to correct the lead?time bias and length bias appropriately and evaluate the effectiveness of the cancer screening program accurately.

Objective To explore the relationship between superantigen and M protein gene (emm)-types genes of Group A Streptococcus pyogenes (GAS) isolated from patients with scarlet fever in Beijing from May 2012 to July 2013 .Methods GAS was isolated from specimens of patients with scarlet fever . Superantigen genes (speA ,speB ,speC ,speF ,speG ,speH ,speI ,speJ ,speL ,speK ,speM ,ssa ,and smeZ) ,and emm gene were amplified by polymerase chain reaction .Rate and proportion were compared by chi-square test .Results Of the 423 GAS strains isolated from patients with scarlet fever from 2012 to 2013 ,most of the isolates possessed speB (97 .6% ) ,speC (99 .8% ) ,speF (98 .3% ) ,speG (99 .8% ) , smeZ (94 .1% ) and ssa (88 .4% ) ,and some of them possessed speH (54 .6% ) ,speI (53 .4% ) ,speA (45 .2% ) and speJ (43 .5% ) ,but very few isolates possessed speK (2 .4% ) ,speL (1 .4% ) and speM (1 .7% ) .Type emm12 (59 .5% ) and type emm1 (37 .4% ) were the main types of GAS .Most of the emm12-type isolates possessed speH (84 .8% ) and speI (84 .0% ) compared with only 4 .0% of speH and 3 .4% of speI in type emm1 .Most of type emm1 possessed speA (95 .3% ) and speJ gene (94 .6% ) compared with only 17 .3% of speA and 14 .8% of speJ in type emm12 .The superantigen genes profiles were significant different between emm 1-type and emm 12-type isolates (P< 0 .05) .Conclusion Type emm1 and type emm12 are epidemic strains in patients with scarlet fever from 2012 to 2013 in Beijing ,and emm gene-types are associated with superantigen genes profiles .

Objective:To analyze the magnetic resonance imaging (MRI) features of epithelioid glioblastoma (eGBM), and to quantitatively analyze the characteristics of apparent diffusion coefficient (ADC) , perfusion-weighted imaging (PWI) and magnetic resonance spectrum (MRS) of eGBM patients.Methods:The MRI results of eight cases of eGBM confirmed by pathology in the Affiliated Hospital of Qingdao University from October 2016 to November 2018 were analyzed retrospectively. The location, edge, signal, peritumoral edema, adjacent meningeal invasion and enhancement of the patients were observed, and the changes of ADC value, relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) and the ratio of choline (Cho)/N-acetyl-L-aspartic acid (NAA) were analyzed.Results:Among the eight patients, the main tumors were located in temporal lobe ( n=3), frontal lobe ( n=3) and parietal lobe ( n=2). The boundary of the lesion was clear in six cases and unclear in two cases. The lesions were superficial in five cases and in deep white matter in three cases. Bleeding could be seen in four cases. There were three cases with cystic change and four cases with necrosis, and there was no cystic necrosis only in one case. There was no edema around the lesion in one case, severe edema in five cases and moderate edema in two cases. The adjacent meninge was involved in four cases and the ependyma was involved in one case. Two patients had leptomeningeal metastasis within two months after operation. The average ADC value of tumor parenchyma in eight patients was 7.15×10 -4 mm 2/s, which was 17.6% lower than that of the contralateral side. MRS showed that the ratio of Cho/NAA in the lesions of two patients were 5.27, 0.81. PWI showed that the rCBV in the lesions of two patients was 3.51 ml/100 g and 3.32 ml/100 g, respectively, which was 36% and 29% higher than that of the contralateral side, respectively. And the rCBF of the lesions was 31.5 ml·100 g -1·min -1and 82.1 ml·100 g -1·min -1, respectively, which increased by 49% and 203% respectively compared with the contralateral side. Conclusions:eGBM has the characteristics of superficial location, easy to be cystic, but the wall of the cyst is not smooth and uneven, the boundary of the mass is clear, the adjacent meninges are easy to be involved and the meningeal tail sign appears, and it is easy to be spread by cerebrospinal fluid. ADC value, PWI and MRS can provide some help for preoperative tumor grading.