1.Preoperative diagnosis of pancreatic neuroendocrine neoplasms with computed tomography and magnetic resonance imaging
Xiaozhu LIN ; Huanhuan XIE ; Qingrou WANG ; Weimin CHAI ; Nan CHEN ; Fei MIAO ; Kemin CHEN ; Fuhua YAN
Chinese Journal of Digestion 2017;37(5):308-312
Objective To assess the value of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of pancreatic neuroendocrine neoplasms (PNEN) and to analyze the factors influencing thepreoperative imaging diagnosis of PNEN.Methods From January 2016 to November 2016, patients with PNEN diagnosed by surgery and biopsy were collected. CT and MRI data of them were analyzed. The CT values or signal intensity of the lesions and the pancreatic parenchyma were measured and the contrast-to-noise ratio (CNR) of the lesion was calculated. Detecting sensitivity and diagnosis accuracy of CT and MRI were compared. Detecting sensitivity of different MRI sequences was also analyzed. Diagnosis accuracy of non-functional PNEN and functional PNEN was compared and analyzed. Lesion CNR was compared between arterial phase and portal venous phase of the contrast enhanced CT. The sensitivity, accuracy and constituent ratio were compared by nonparametric analysis. Independent sample t test and one-way analysis of variancewere performed for the quantitative parameters comparison. Results A total of 54 patients with 56 lesions of PNEN were included for two of whom had two lesions each. CT and MRI were both performed in 44 patients (46 lesions).Detecting sensitivity and diagnosis accuracy of CT were 97.8% (45/46) and87.0% (40/46), respectively. Detecting sensitivity of MRI were 97.8% (45/46) and89.1% (41/46), respectively. There was no significant difference in detecting sensitivity and diagnosis accuracy between CT and MRI (both P>0.05). The CNR of lesion in arterial phase was higher than that of portal venous phase(4.7±3.8 vs 3.4±2.5), and the difference was statistically significant (t=2.949, P<0.05). Detecting rates of T1 weighted imaging with fat suppression (T1WI-FS) image, T2 weighted imaging with fat suppression (T2WI-FS) image, diffusion weighted imagingand dynamic contrast enhanced T1WI-FS image were 90.0% (45/50), 88.0%(44/50), 86.0%(43/50), and 91.7% (44/48), respectively. There was no significant difference in detecting rate among these images sequences (Q=2.526, P=0.510). Tumor diameter in non-functional PNEN was significantly larger than that in functional PNEN ((2.9±1.6) cm vs (1.7±0.7) cm)(t=3.479,P<0.05). The overall diagnosis rate of non-functional PNEN with CT and MRI before operation was 70.8% (17/24), which was significantly lower than that of functional PNEN (100.0%, 31/31) (χ2=10.360,P=0.002).Conclusions CT and MRI are both sensitive in detectingPNEN, and they were two complementary modalities. CT image in arterial phase delineated the lesion better than that in portal venous phase. MRI images with different sequences can becomplementary and there is no significant difference in detecting sensitivity for PNEN among different sequences. CT and MRI play an equal rolein the diagnosis of PNEN before operation. Because of atypical CT and MRI findings, the diagnosis of non-functional PNEN is more difficult thanfunctional PNEN.
3. Distribution of donor-specific aKIR after unrelated allogeneic hematopoietic stem cell transplantation
Huanhuan ZHANG ; Jun HE ; Xiaojing BAO ; Xing HU ; Miao WANG ; Jing ZHANG ; Xiaojin WU
Chinese Journal of Hematology 2017;38(5):421-426
Objective:
To analyze the distribution and proportion of donor-specific activated killer cell immunoglobulin like receptor (aKIR) genes and their clinical application values in unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) .
Methods:
Retrospective analyses of KIR genotyping using polymerase chain reaction with sequence specific primers (PCR-SSP) were performed in 216 pairs of donors and recipients.
Results:
The frequency of donor-specific KIR genes was 53.7% (116/216) in 216 patients receiving unrelated allo-HSCT, with the frequency of 78.3% (112/143) in the KIR genes mismatched group and 5.5% (4/73) in matched group. Of the 116 patients with detectable donor-specific KIR genes, 99.1% (115/116) patients had various donor-specific aKIR genes. Among 55 pairs of donors’ KIR-Bx genotype and patients’ KIR-AA genotype group, the most commonly observed genotypes were Bx1, Bx2, Bx3, Bx4, in which the donor-specific KIR genes were respectively KIR 3DS1, 2DL5A, 2DS5, 2DS1; KIR 3DS1, 2DL5A, 2DS3, 2DS1; KIR 2DS2, 2DL2; KIR 2DS2, 2DL2, 3DS1, 2DL5A, 2DS5, 2DS1. Of 44 pairs of donors’ KIR-AA genotype and patients’ KIR-Bx (AB) genotype group, 36.4% (16/44) recipients had donor-specific KIR2DS4 (FUL) gene. In 143 pairs of KIR mismatched group, the frequencies of donor-specific KIR genes were KIR2DS1 (35.7%) , KIR3DS1 (32.9%) , KIR2DS5 (29.4%) , KIR2DS4 (FUL) (25.9%) , KIR2DL2 (25.2%) , KIR2DS2 (24.5%) , KIR2DS3 (21.7%) and KIR3DL1 (8.4%) , respectively.
Conclusion
The donor-specific aKIR genes mainly existed in KIR mismatched group after unrelated allo-HSCT, and the different pairs of donors’ and patients’ KIR genotypes led to the diverse donor-specific aKIR. But there were higher specific aKIR genes in higher frequency of KIR AA, Bx1, Bx2, Bx3, Bx4 genotypes. All these can provide the experimental basis for studying the role of the donor-specific aKIR genes on the prognosis of HSCT.
4. Immune reconstruct regularity profile of KIR2DL1 and KIR3DL1 in unrelated-donor allogeneic hematopoietic stem cell transplantation
Xing HU ; Jun HE ; Huanhuan ZHANG ; Xiaojing BAO ; Miao WANG ; Jing ZHANG ; Jiannong CEN ; Xiaojin WU ; Xiaojing YANG
Chinese Journal of Hematology 2017;38(8):667-672
Objective:
To investigate the immune reconstruct regularity profile of KIR2DL1 and KIR3DL1 in unrelated-donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) with KIR-AA genotype.
Method:
75 donor-recipient pairs were performed by KIR genotying using PCR-SSP, and all donors were identified with KIR-AA genotype. Dynamic detections (including unrelated-donor on the day of transplantation and the recipient each month post allo-HSCT) of the expression of KIR2DL1/3DL1 on NK cell and mRNA level were performed in 291 cases using flow cytometry (FCM) and real-time fluorescent quantitation PCR (RT-qPCR) .
Result:
①The median expression of KIR2DL1 in unrelated-donor on transplant’s day was 21.60%, the median expression of KIR2DL1 in recipient 1M, 2M, 3M and 3-6M after transplantation were 7.40%, 12.00%, 16.92%, 17.64% respectively. The median expression of KIR2DL1 in unrelated-donor on transplant’s day was 265.14 copies/10 000abl copies, the median expression of KIR2DL1 in recipient 1M, 2M, 3M, 3-6M, 6-9M, 9-12M after transplantation were 332.17, 438.31, 723.25, 414.17, 180.76 and 234.67 copies/10 000abl copies respectively. The median expression of KIR2DL1 on NK cells and mRNA level gradually increased at all time points after transplantation, and reached the highest expression at 3 months after transplantation. But mRNA expression levels increased earlier than NK cell membrane proteins. ②The median expression of KIR3DL1 in unrelated-donors on transplant’s day was 18.56%, the median expression of KIR3DL1 in recipient 1M, 2M, 3M, 3-6M after transplantation were 23.83%, 22.57%, 23.02%, 21.60% respectively. The median expression of KIR3DL1 in unrelated-donor on transplant’s day was 572.29 copies/10 000abl copies, the median expression of KIR3DL1 in recipient 1M, 2M, 3M, 3-6M, 6-9M, 9-12M after transplantation were 1 233.74, 1 140.42, 876.73, 1 057.07, 739.02 and 514.43 copies/10 000abl copies respectively. The median expression of KIR3DL1 on NK cells and mRNA level were higher than donors at 1 month after transplantation, and stable expression at all time points after transplantation, so mRNA and NK cell membrane proteins expression increased at the same time.
Conclusion
The immune reconstruct regularity of KIR2DL1 and KIR3DL1 gene were different, which provided an experimental basis for selecting the best time to detect the expressions of KIR2DL1 and 3DL1 after transplantation.
5.Dosimetric analysis of 3D-printed minimally invasive-guided template in the brachytherapy treatment of locally advanced cervical cancer
Yongxia ZHANG ; Xiangkun YUAN ; Junjun MIAO ; Guangying HOU ; Yuanyuan CHEN ; Qiong LIU ; Huanhuan LYU
Chinese Journal of Radiological Medicine and Protection 2020;40(7):519-523
Objective:To investigate the dosimetry advantage of 3D-printed minimally invasive guided template used in local advanced cervical cancer intracavitary combined with interstitial radiotherapy.Methods:A total of 68 cases with locally advanced cervical cancer who were admitted to Hebei Cangzhou Hospital of intergrated traditional Chinese medicine and western medicine from May 2016 to August 2019 were selected. All the patients had eccentric tumor or large tumor (tumor diameter >5 cm) after radiotherapy. Intensity modulated radiotherapy was used for external radiotherapy, and intracavitary combined with interstitial radiotherapy was used for brachytherapy. The prescription dose of high-risk clinical target volume (HR-CTV) is 6 Gy/fraction, once a week, five fractions in total. Sixty-eight patients were randomly divided into two groups, 35 cases in the template group who received minimally invasive 3D printing guided template assisted intrauterine tube implantation and insertion needle implantation, and 33 patients in the free implantation group who received free hand intrauterine tube implantation and insertion needle implantation. The position and depth of the insertion needle were adjusted by CT-guidance, and the final CT image was transmitted to the Oncentra Brachy treatment planning system, then the target volume and organs at risk were delineated for planning and treatment.Results:A total of 340 brchytherapy plans were made, including 175 in the template group and 165 in the free implantation group. The D90 values of the HR-CTV and intermediate-risk clinical target volume (IR-CTV) in the template group were increased ( t=3.63, 2.45, P<0.05), and D2 cm3 values (dose of 2 cm 3 of organ at risk) of bladder, rectum and sigmoid colon were significantly decreased ( t=-2.81, -2.54, -2.33, P<0.05). At the same time, the average CT scanning times of each treatment in the template group was (1.78±0.53) times, the average duration of each treatment was (11.35±3.98) min, and the average number of needles used in each implant treatment was (5.21±1.37). The result of free implantation group was higher than that of the template group. The differences were statistically significant ( t=-2.26, -4.53, -3.21, P<0.05). Conclusions:For localized advanced cervical cancer patients with eccentric or large tumors, the 3D printed minimally invasive guided template for intracavitary and interstitial implantation has obvious dosimetry advantages, and the operation is simpler and the duration is shorter.
6. Sequoiaflavone inhibits stem cell properties such as proliferation and invasion of gastric cancer cells by down-regulating PI3K/AKT signaling pathway
Yan WANG ; Jinhui ZHANG ; Yongchen ZHAO ; Hongxiang LIU ; Yawei LIU ; Huanhuan MIAO ; Xincai YANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2023;28(5):508-513
AIM: To explore the molecular mechanism of sequoiaflavone affecting gastric cancer cells. MEHTODS: Gastric cancer cell line AGS cells were treated with gradient concentrations of sequoiaflavone, and then induced by PI3K/AKT signaling pathway activator. The optimal inhibitory concentration and time of semi-inhibitory concentration of red cedar flavonoid on AGS cells were detected by CCK-8, and the changes of cell proliferation, migration and invasion ability were detected by colony formation assay, transwell assay and wound healing assay. PI3K/AKT signal pathway related proteins p-PI3K, PI3K, p-AKT and AKT were detected by western blot. RESULTS: Sequoiaflavone inhibited AGS cells in a concentration-dependent manner. The half inhibitory concentration was 0.5 mmol/L, the optimal treatment time was 48 h. The protein expression of p-PI3K and p-AKT was down regulated. The proliferation, migration and invasion of AGS cells were decreased after treated with sequoiaflavone. After treated with PI3K / AKT signal pathway activator, the protein expression level of pPI3K and p-AKT was partially reversed, and the ability of cell viability, proliferation, migration and invasion was also partially improved. CONCLUSION: Inactivation of PI3K/AKT signaling pathway caused by sequoiaflavone inhibited gastric cancer cells proliferation, migration and invasion ability.
7.Pharmacodynamic study of sinapine thiocyanate dissoluble microneedle for acupoint administration against bronchial asthma
Jianan SHI ; Xinli SONG ; Xingde LIU ; Huanhuan CHEN ; Xiaoshuang YANG ; Shenglei YANG ; Li SHEN ; Kailong WAN
China Pharmacy 2022;33(22):2728-2732
OBJECTIVE To study the efficacy of sinapine thiocyanate dissoluble microneedle (ST-DMN) for acupoint administration against bronchial asthma (BA). METHODS The network pharmacology and molecular docking techniques were used to screen the core targets of sinapine thiocyanate (ST) against BA, and the pharmacodynamics of the top 3 core targets was studied. Firstly, ST-DMN was prepared (drug loading of ST was 1 mg/tablet); secondly, 30 rats were divided into blank control group, model control group, blank microneedle group, Sinapine powder plaster group (positive control group) and ST-DMN group. Except for the blank control group, rats of other groups were sensitized with 10% ovalbumin (containing aluminum hydroxide adjuvant) and nebulized with 1% ovalbumin to induce the BA model. After modeling, blank control group did not receive any intervention; normal saline was applied to the Feishu acupoint and Dazhui acupoint of the rats in the model control group, while the blank microneedle group, Sinapine powder plaster group and ST-DMN group were given blank microneedle, Sinapis alba powder (plaster, 1.5 g) and ST-DMN (3 tablets at 2 acupoints) at same acupoint, once a day, for 28 consecutive days. After administration, the general symptoms were observed and the body mass of the rats was measured.pathological changes of lung tissues in rats was observed; the levels of prostaglandin endoperoxide synthase 2 (PTGS2), GNYL matrix metalloproteinase-9 (MMP-9) and interleukin-2 (IL-2)in serum, bronchoalveolar lavage fluid (BALF) and lung tissues were determined. RESULTS Results of network pharmacology and molecular docking showed that the key targets of ST against BA were identified as PTGS2, MMP-9, IL-2, epidermal growth factor receptor, heat shock protein90AA1, etc. Pharmacodynamic experiments showed that compared with model control group, relieved cough, restored hair color, sensitive behavior, stable respiration and increased body weight were all found in ST-DMN group; the histopathological changes as the structure of lung tissue, infiltration of alveolar epithelial cells and pulmonary interstitial inflammatory cells were improved to different extent; the levels of PTGS2, MMP-9 and IL-2 in serum, BALF and lung tissue were significantly reduced (P<0.05 or P<0.01). CONCLUSIONS The anti-BA effect of ST-DMN acupoint administration is good, the mechanism of which may be associated with decreasing the levels of PTGS2, MMP-9 and IL-2 in serum, BALF and lung tissue.
8.Analysis of KIR3DL1 expression levels on 92 cases of normal donors for hematopoietic stem cells transplant.
Jing ZHANG ; Miao WANG ; Xiaojing BAO ; Xiaojin WU ; Huifen ZHOU ; Huanhuan ZHANG ; Depei WU ; Jun HE
Chinese Journal of Hematology 2015;36(12):994-998
OBJECTIVETo study KIR3DL1 expression level on NK cell surface of normal donors for hematopoietic stem cell transplantation(HSCT).
METHODSNinety- two donors were performed by using of KIR genotyping, HLA high resolution genotyping and KIR3DL1 expression level using sequencebased testing(SBT), PCR- sequence specific primer(SSP)and flow cytometry methods.
RESULTSIn 92 donors, the frequencies of KIR-A/A, Bx1, Bx2 for common genotypes were 46.74%(43/92), 18.48% (17/92)and 9.78%(9/92)respectively(P<0.001); KIR-A, B1, B2, B3 for common KIR haplo-type were 70.33%(128/182), 10.99%(20/182), 7.14%(13/182) and 4.39%(8/182) respectively(P<0.001); the frequencies of HLA-BW4/BW4, HLA-BW4/BW6, BW6/BW6 ligands were 13.79%, 67.81% and 18.39% respectively(P<0.001). KIR3DL1 middle expression level among haplo- type KIR- A/A and KIR- Bx, KIR-B/B were 18.77%(3.11%-49.24%), 13.14%(1.70%-63.32%)and 0.37%(0.20%-2.60%)respectively (P<0.05). KIR3DL1 expression level[18.77%(3.11%-49.24%)]in haplo-type KIR-A/A was higher than haplo-type KIR-Bx at the same time did not express 2DL2 group[11.20%(3.50%-36.08%)](P=0.019). KIR3DL1 expression level in recognition group(HLA-BW4 positive group)[17.61%(1.40%-49.24%)] was higher than KIR3DL1 unrecognized group(HLA-BW4 negative group)[10.60%(3.50%-18.56%)] (P=0.006).
CONCLUSIONThe expression levels of KIR3DL1 in different KIR genotypes, haplotypes and HLA ligands were statistically significance.
Genotype ; HLA-B Antigens ; genetics ; Haplotypes ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Killer Cells, Natural ; metabolism ; Ligands ; Receptors, KIR3DL1 ; genetics ; Tissue Donors