1.Research progress on animal models of combined radiation-wound injury
Ruolin HAO ; Guifang DOU ; Zhiyun MENG ; Tong YE ; Nanxi LI ; Xiaoxia ZHU ; Ruolan GU ; Zhuona WU ; Hui GAN
Chinese Journal of Radiological Health 2024;33(2):209-214
A combined radiation-wound injury refers to a radiation injury combined with a traumatic wound, with the characteristics of repeated ulceration and a long and difficult healing process, which is a focus in the field of research on difficult-to-heal wounds. To research combined radiation-wound injuries, the establishment of animal models is a key part, and appropriate animal models are a guarantee of reliable experimental results. This review summarizes the current research progress on various animal models of combined radiation-wound injuries in terms of radiation types, animal species, and injury types and location, aiming to provide a scientific basis for establishing standardized animal models, studying injury mechanisms, and evaluating prevention and treatment efficacy for combined radiation-wound injuries.
2.UHRF1/DNMT1-MZF1 axis-modulated intragenic site-specific CpGI methylation confers divergent expression and opposing functions of PRSS3 isoforms in lung cancer.
Shuye LIN ; Hanli XU ; Lin QIN ; Mengdi PANG ; Ziyu WANG ; Meng GU ; Lishu ZHANG ; Cong ZHAO ; Xuefeng HAO ; Zhiyun ZHANG ; Weimin DING ; Jianke REN ; Jiaqiang HUANG
Acta Pharmaceutica Sinica B 2023;13(5):2086-2106
As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.
3.Effects of radon exposure on lung function and metal balance in mice
Huimeng LIU ; Meiyu WANG ; Guangrui CHEN ; Huiyu ZHOU ; Yong YUAN ; Zhiyun MENG ; Ruolan GU ; Hui GAN ; Zhuona WU ; Guifang DOU
Chinese Journal of Radiological Medicine and Protection 2022;42(11):845-850
Objective:To explore the disturbance of metal element balance in mice after exposure to radon.Methods:Mice were randomly divided into control group, radon exposure of 30 WLM group, 60 WLM group and 120 WLM groups, with 10 mice in each group. After radon exposure with the cumulative dose, the lung function of mice was detected by a non-invasive pulmonary function testing instrument. Mice blood was taken from eyeballs. The lungs, heart, liver, kidney and spleen were also collected. HE staining was used to observe the pathological changes of lung tissue. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the content of metal elements, including essential trace elements in the body: chromium (Cr), molybdenum (Mo), cobalt (Co), selenium (Se), copper (Cu), zinc (Zn), manganese (Mn), nickel (Ni), and potentially toxic elements: arsenic (As), tin (Sn), lead (Pb), aluminum (Al), mercury (Hg), cadmium (Cd), and silver (Ag).Results:Compared with the control group, lung ventilation function of the radon-exposed mice was decreased, alveolar structure was destroyed, and the contents of pulmonary metal elements Cr, Al, Pb, Sn( F=0.34, 0.66, 3.14, 1.16, P<0.05) and essential trace elements Mn, Cr, Zn, and Mo in the blood were decreased( F=0.65, 1.44, 0.97, 2.08, P<0.05), while the elements of Cu, Mo, Se and As in the lungs were increased( F=1.31, 1.26, 0.81, 2.04, P<0.05), and the element contents in other tissues also fluctuated. Conclusions:Inhalation of a certain cumulative dose of radon can reduce the lung ventilation function of mice and induce lung inflammation, as well reduce the content of essential trace elements in the lung and blood so that the content of metal elements in the body fluctuates.
4.Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells
Liyun NIU ; Huiyu ZHOU ; Yueru LIAN ; Ya GAO ; Yulu LIU ; Ruolan GU ; Zhuona WU ; Xiaoxia ZHU ; Hui GAN ; Zhiyun MENG ; Guifang DOU
Journal of Pharmaceutical Analysis 2022;12(5):766-773
PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.
5.Exploring the Rule of the Diagnosis and Treatment of Stroke Based on the Tibetan Medical Theory of White Meridian
Lijuan ZHENG ; Xiaoqiao REN ; Mingqiang WANG ; Meng MAO ; Junqiao GAO ; Ziyan ZHOU ; Zhiyun DENG ; Longmei LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(2):370-374
Meridians in human body were classified as white meridian and black meridian according to Tibetan medicine.Season and environment,improper diet,toxic heat and trauma were recognized as main reasons damaging the white meridian in Tibetan Medicine,leading to the emerge of white meridian disease induced by Long (one of the three factors) and blood disorder.White meridian disease in Tibetan medicine involved a series diseases,such as many clinical diseases,due to the damage of white meridian system caused by pathogenic factors.Stroke also belonged to white meridian disease.Drugs and treatments were selected based on the nature of disease such as cold and heat,onset,thelocation of disease and the three factors (Chi Ba,Long and Pei Gen).It was the fundamental principle of the treatment rules of white meridian disease in Tibetan medicine,namely,prescribing medication with the rule of diagnosis and treatment,comprehensive analysis of the causes of diseases and mastering the change law of diseases and syndromes in clinic.
6.Effect of hair transplantation for restoration of eyebrow defect
Wenjie JIANG ; Meng WANG ; Xiaoying MA ; Bo WANG ; Qianqiu CHENG ; Zhiyun TANG
Chinese Journal of Plastic Surgery 2017;33(z1):84-87
Objective To explore the effect of single follicular unit transplantation on eyebrow defects caused by burn , trauma, resection, inappropriate eyebrow trimming , congenital sparse or ill eyebrows .Methods A total of 252 patients with 387 eyebrow defects were recruited .The eyebrow contour was designed based on the contra-side eyebrow .The template was needed for bilateral eyebrow defects .The scalp strips from the back occipital or retroauricular region were taken and the grafts were harvested by scalp strip cutting or FUE .Grafts were cut into single follicular unit hair with a stainless steel blade .The recipient area was punched with 21 G or 22 G syringe needle .Then the hair shaft was clamped with microscope slide forceps and the follicles were transplanted to the defect area .Results 17 patients underwent secondary hair transplantation due to sparse hair 6 months after the first operation .12 patients had an obvious difference between the reconstructed eyebrow and the healthy one which can be improved by make-up.3 burn cases developed local infection and then healed after dressing .Transplanted hairs survived well in all the other patients with satisfactory hair direction and appearance .Conclusions It is feasible to use the hair at back occipital region and retroauricular region as donor sites .Hair transplantation could be an optimal choice for the eyebrow defect due to scar , skin graft or skin flap .The syringe needle is convenient as a punch device .Clamping the hair shaft with microscope slide forceps may help to achieve a simulation effect on the eyebrow appearance .
7.Effect of hair transplantation for restoration of eyebrow defect
Wenjie JIANG ; Meng WANG ; Xiaoying MA ; Bo WANG ; Qianqiu CHENG ; Zhiyun TANG
Chinese Journal of Plastic Surgery 2017;33(z1):84-87
Objective To explore the effect of single follicular unit transplantation on eyebrow defects caused by burn , trauma, resection, inappropriate eyebrow trimming , congenital sparse or ill eyebrows .Methods A total of 252 patients with 387 eyebrow defects were recruited .The eyebrow contour was designed based on the contra-side eyebrow .The template was needed for bilateral eyebrow defects .The scalp strips from the back occipital or retroauricular region were taken and the grafts were harvested by scalp strip cutting or FUE .Grafts were cut into single follicular unit hair with a stainless steel blade .The recipient area was punched with 21 G or 22 G syringe needle .Then the hair shaft was clamped with microscope slide forceps and the follicles were transplanted to the defect area .Results 17 patients underwent secondary hair transplantation due to sparse hair 6 months after the first operation .12 patients had an obvious difference between the reconstructed eyebrow and the healthy one which can be improved by make-up.3 burn cases developed local infection and then healed after dressing .Transplanted hairs survived well in all the other patients with satisfactory hair direction and appearance .Conclusions It is feasible to use the hair at back occipital region and retroauricular region as donor sites .Hair transplantation could be an optimal choice for the eyebrow defect due to scar , skin graft or skin flap .The syringe needle is convenient as a punch device .Clamping the hair shaft with microscope slide forceps may help to achieve a simulation effect on the eyebrow appearance .
8.Value of visualization of the intraparotid facial nerve and parotid duct using a micro surface coil and three-dimensional fast imaging with steady state precession with fat-suppression sequence
Guixun HONG ; Jianping CHU ; Zhou ZHOU ; Liangjun RAO ; Shurong LI ; Bitao PAN ; Zhuhao LI ; Zhiyun YANG ; Quanfei MENG
Chinese Journal of Radiology 2015;(9):641-645
Objective To explore the value of small surface coil combine with three-dimensional fast imaging with steady state precession and fat-suppression (3D-FISP-FS) sequence in displaying intra-parotid facial nerves segment and parotid ducts.Methods The parotid regions of 18 healthy volunteers who were excluded any parotid diseases were scanned by head&neck coil (36 sides) and 4 cm small surface coil (32 sides) combined with 3D-FISP-FS sequence prospectively. The obtained original
images were treated through MIP, MPR and CPR, The MRI signal characteristics of parotid region structure, the subjective score of image quality, the signal intensity ratio (SIR) of facial nerve/parotid tissue (SIR N) and parotid duct/parotid tissue (SIRD) was calculated, and the displaying rates of the facial nerves and parotid ducts were observed. Wilcoxon matched-samples signed rank sum test was used to compare the scores of head&neck coil and small coil 3D-FISP-FS sequence images, paired t test was used to compare SIRN, SIRD of the two groups, Chi-square test was used to compare of the displaying rate of the facial nerves and parotid ducts in two groups. Results Eighteen volunteers were successfully performed MRI scan of parotid gland. On 3D-FISP-FS sequence images, the parotid gland was showed slightly low signal intensity, muscle tissue was showed medium signal intensity, the vessels were showed slightly high or high signal, parotid segment of facial nerve was showed tortuous line-like high signal intensity, and parotid duct was showed curve high signal intensity, lymph nodes were showed kidney shaped, oval or spindle shaped high signal intensity structures. The subjective scores for head and neck coil and coil images were (2.0 ± 0.9) and (1.5 ± 0.7) respectively, and the difference was statistically significant (Z=-2.714, P=0.007), image quality of small coil group was better than that of head and neck coil group. The SIRN of the two groups was 1.7±0.8 and 2.1± 1.2 respectively, and the SIRD was 1.8±0.7 and 2.5±1.7 respectively, which showed a statistically significant difference between the two groups (t value was 2.978, 2.427 respectively, P value was 0.006, 0.031 respectively).All facial nerve trunks could be displayed by head and neck coil and small coil. On head and neck coil images, 25 sides of temporofacial truck, 15 sides of cervicofacial truck, 17 sides of temporofacial branches, 11 sides of cervicofacial branches, 16 sides of the parotid duct could be displayed. On small coil images, 30 sides of temporofacial truck, 28 sides of cervicofacial truck, 26 sides of temporofacial branches, 23 sides of cervicofacial branches, 27 sides of the parotid duct could be displayed, which showed a statistically significant difference (P<0.05). Conclusion Small surface coil performed better in parotid MR imaging with 3D-FISP-FS sequence than that of head and neck coil, which can simultaneous clearly display the trunk and branches of the intra-parotid facial nerves and parotid ducts.
9.MRI features of different sizes of small coil using a water phantom
Guixun HONG ; Jianping CHU ; Liangjun RAO ; Shurong LI ; Bitao PAN ; Zhiyun YANG ; Quanfei MENG
Chinese Journal of Radiology 2014;48(11):938-942
Objective To explore the imaging characteristics of different sizes of MR small surface coil.Methods A water phantom with NiSO4· 6H2O for Siemens was scanned with 4 cm,7 cm and 11 cm small surface coils in Siemens 3.0 T MR system.T1WI,T2WI,three dimensional reversed fast imaging with steady state precession with diffusion-weighted(3D-PSIF-DWI) and three dimensional fast imaging with steady state precession and fat suppression(3D-FISP-FS) images were obtained.The imaging area,signal intensity (SI),standard deviation (SD) and signal-to-noise ratio (SNR) variations of different depths (from the near to the distant) were measured and compared.Curves according to the SI and SNR data were draw.SI and SNR characteristics of images obtained by L11 separately and used together with spine matrix coil were compared by using signed rank sum test.Results The signal intensity of images scanned by 4 cm,7 cm small surface coil decreased gradually in the depth of 0.2 to 2.2 cm,maintain good signal uniformity in the depth of 2.2 to 4.2 cm,and the signal intensity obtained by 11 cm coil maintain good signal uniformity in the depth of 5.2 cm.The optimum imaging widths of 4 cm,7 cm and 11 cm coil were about 7.0,8.5 and 11.0 cm.As the diameter of the coil increased,the imaging width and depth increased,but the received noise also increased.The SNR gradually reduced from the center to the edge of the coils.The imaging area increased but the local SNR decreased when using L11 coil combine with spine matrix coil,which showed a statistically significant difference (Z=-2.354,P=0.019).Conclusions A suitable size of small surface coil should be chosen according to the location and size of the organ or lesion before clinical MR examination.Other coils should be turned off to improve the SNR.
10.Determination of yogliptin and its metabolite in Wistar rat plasma by liquid chromatography-tandem mass spectrometry.
Junting DAI ; Zhiyun MENG ; Xiaoxia ZHU ; Hui GAN ; Ruolan GU ; Bo YANG ; Liying YU ; Guifang DOU
Acta Pharmaceutica Sinica 2014;49(7):1044-8
A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.

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