1.Optimizing the schedules of fractionated irradiation in subclinical tumors of malignant glioma
Xin XU ; Weizhi YANG ; Li GAO ; Xue GAI ; Huizhen SHI ; Lijing SONG
Chinese Journal of Radiation Oncology 2012;(6):563-566
Objective To study dose-response relationship and screen the optimized fractionated irradiation schedules in subclinical tumors of malignant glioma.Methods Balb/c-nude mice bearing human malignant glioma xenograft were assigned randomly into control group,fractionated irradiation schedules group and nimotuzumab-conventional fraction group.The fractionated schedules were 200 cGy x 5f/w,300 cGy ×5f/w,160 cGy ×2f/d x5 d and 400 cGy ×3f/w with total dose of 40 Gy and 60 Gy,respectively.Measurement indexes were tumor-forming rate,average recurrence time and maximum diameter of the tumor bottom.The observation lasted 24 weeks.Results With the total dose of 40 Gy,none of the significant long-term tumor regression were detected in any fractionated irradiation schedules; 400 cGy x 3f/w with complete tumor response at the end of treatment showed a better short-term curative effect.With the total dose of 60 Gy,long-term control rate of each fractionated irradiation schedule group was improved with prolonged average recurrence time of varable degrees,except 200 cGy x 5f/w fractionated schedule (tumor formation rate was 100% at the end of treatment and average recurrence time was the poorest of 108 d).160 cGy × 2f/d × 5 d fractionated schedule showed the best curative effect with no tumor formation in 2 of 8 mice and longest recurrence time of 143 d.300 cGy x 5f/w fractionated schedule ranked second with no tumor formation in 1 of 8 mice and average recurrence time was 137 d.400 cGy x 3f/w fractionated schedule produced the poorest outcome with no case cured.There were no significant changes in the tumor-forming rate or average recurrence time when nimotuzumab was concurrently used for subclinical tumors of malignant glioma with total dose of 60 Gy.Conclusions Conventional fractionated irradiation is not the best option to control the sustained growth.160 cGy ×2f/d ×5 d and 300 cGy × 5f/w might be the optimized fractionated irradiation schedules for subclinical tumors of malignant glioma.
2.Radiobiological effect of different irradiation fractionated regimens in human brain glioma
Xue GAI ; Weizhi YANG ; Li GAO ; Heng JIANG ; Mianrong WANG ; Huizhen SHI
Chinese Journal of Radiation Oncology 2010;19(6):564-567
Objective To evaluate the radiobiological effect of different irradiation fractionated regimens in human glioma cells ( BT 325 cell line). Methods The xenografts in Balb/c-nude mice were irradiated with different single and fractionated regimens. The single fraction dose was 10, 20, 30, 40 and 60 Gy, respectively. The fractionated regimens were 2 Gy × 5 fractions ( irradiated every day), and 3 Gy ×3 fractions (irradiated every other day), 3 Gy × 5 fractions (irradiated every day) and 4 Gy × 3 fractions (irradiated every other day), with total doses of 125 Gy, 114 Gy, 126 Gy and 112 Gy, respectively. The growth curve was used to evaluate the tumor doubling time. clonogenic assays was performed to draw the cell survival curve and analyze the radiobiological parameters with doses of 1, 2, 4, 6, 8 and 10 Gy. T1/2 was measured by comet assay. Results Tumor regression were not observed by single fraction irradiation, 2 Gy × 5 fractons and 3 Gy × 3 fractions irradiation regimens. The tumor regress was more significant with the increas of fraction dose. The 4 Gy × 3 fractionrs inhibited tumor more though not curing tumor. The cell doubling time of the BT 325 cell was 30. 16 h and the tumor doubling time of the xenograft was 43 days.When fitted with L-Q model ,α was 0. 36 Gy -1 and β was 0. 057 Gy -2. When fitted with the single-hit multitarget model, D0 was 1. 394 Gy, Dq was 2. 127 Gy and SF2 was 0. 714, respectively. The T1/2 was 9. 999min. Conclusions Glioma is a radioresistant tumor. Increase of the fraction dose improves recent effect.Further study is needed to control the tumor stem cells.
3.Effect and safety of anaprazole in the treatment of duodenal ulcers: a randomized, rabeprazole-controlled, phase III non-inferiority study
Huiyun ZHU ; Xue PAN ; Li ZHANG ; Hongxin SUN ; Huizhen FAN ; Zhongwei PAN ; Caibin HUANG ; Zhenwang SHI ; Jin DING ; Qi WANG ; Yiqi DU ; Nonghua LYU ; Zhaoshen LI
Chinese Medical Journal 2022;135(24):2941-2949
Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.
4.T2WI MR-Based Radiomics Nomogram for Predicting Deep Stromal Invasion of Early-Stage Cervical Cancer
Huizhen SONG ; Yu WANG ; Maoyuan LI ; Xue LI ; Taoming DU
Chinese Journal of Medical Imaging 2024;32(9):928-933
Purpose To investigate the value of T2WI MR-based radiomics nomogram for predicting deep stromal invasion of cervical cancer preoperatively.Materials and Methods Retrospective analysis of 164 consecutive patients with early-stage cervical cancer with postoperative pathological findings and preoperative MR images admitted to two medical centers in the Affiliated Hospital of Southwest Medical University(first center)and the Huaihe Hospital of Henan University(second center)from May 2018 to August 2022.The data in the first center(n=1 14)and the second center(n=50)were divided into the training and validation cohorts,respectively.To segment T2WI images in the 3D Slicer software and to extract image features in the python software.The radiomic features were selected in the training cohort.Based on the selected features,support vector machine prediction model was constructed.Univariate Logistic regression was used to select clinicopathological risk factors,then,multi-variate Logistic regression combined with radiomics score was used to construct radiomics nomogram,diagnostic performance of the radiomics model,clinical prediction model and radiomics nomogram model were assessed by receiver operating characteristic analysis.The predictive efficacy of the different models were compared.Results The 12 radiomics features were selected out.The FIGO staging and radiomics score were included in the multifactor Logistic regression to build the radiomics nomogram for predicting deep stromal invasion.The results showed that the predictive performance for the radiomics nomogram model was better than the clinical prediction model(in validation cohort:area under the curve was 0.845 vs.0.717;Z=2.728,P=0.006).Conclusion Radiomics nomogram based on T2WI is of high value for predicting deep stromal invasion of cervical cancer preoperatively.
5.Clinical and genetic analysis of two children with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
Xue WU ; Dongxia FU ; Huizhen WANG ; Shengnan WU ; Dongxiao LI ; Yongxing CHEN
Chinese Journal of Medical Genetics 2024;41(2):199-204
Objective:To explore the clinical characteristics and genetic variants of two children with 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD).Methods:Two children with HMGCLD diagnosed at Henan Provincial Children′s Hospital respectively in December 2019 and June 2022 were selected as the study subjects. Clinical data and results of laboratory testing were analyzed retrospectively.Results:Both children had manifested with repeated convulsions, severe hypoglycemia, metabolic acidosis and liver dysfunction. Blood amino acids and acylcarnitine analysis showed increased 3-hydroxy-isovalyl carnitine (C5OH) and 3-hydroxy-isovalyl carnitine/capryloyl carnitine ratio (C5OH/C8), and urinary organic acid analysis showed increased 3-hydroxyl-3-methyl glutaric acid, 3-methyl glutaric acid, 3-methyl glutacoic acid, 3-hydroxyisoglycine and 3-methylprotarylglycine. Child 1 was found to harbor homozygous c. 722C>T variants of the HMGCL gene, which was rated as uncertain significance(PM2_Supporting+ PP3). Child 2 was found to harbor homozygous c. 121C>T variants of the HMGCL gene, which was rated as pathogenic(PVS1+ PM2_Supporting+ PP4). Conclusion:Acute episode of HMGCLD is usually characterized by metabolic disorders such as hypoglycemia and metabolic acidosis, and elevated organic acids in urine may can facilitate the differential diagnosis, though definite diagnosis will rely on genetic testing.
6.Phenotypic and molecular characterizations of 46, XY disorders of sex development due to variants of NR5A1 gene
Dongxia FU ; Yongxing CHEN ; Ai HUANG ; Xue WU ; Huizhen WANG ; Haiyan WEI
Chinese Journal of Medical Genetics 2024;41(8):909-915
Objective:The clinical and molecular genetic characteristics of 46, XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. Methods:The clinical data of children with NR5A1 gene variants diagnosed at the Children′s Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. Results:At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1~9), including micropenis (100.0%), hypospadia (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomol karyotypes were 46, XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. Conclusion:The clinical phenotype of 46, XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.
7.Clinical and genetic features of pediatric congenital hypogonadotropic hypogonadism: A case series of 95 children
Dongxia FU ; Yongxing CHEN ; Xue WU ; Huizhen WANG ; Jing GAO ; Haiyan WEI
Chinese Journal of Endocrinology and Metabolism 2024;40(11):948-955
Objective:To analyze clinical and genetic characteristics of congenital hypogonadotropic hypogonadism(CHH) in children.Methods:Clinical data of 0-18 year old CHH patients diagnosed in the Department of Endocrinology, Genetics and Metabolism of Children′s Hospital Affiliated to Zhengzhou University from January 1, 2016 to December 31, 2023 were retrospectively analyzed, including their hormone levels and genetic test results.Results:A total of 95 patients with CHH were included. Among them, 25 were diagnosed before the age of 3, 37 between the ages of 3-14, and 33 were over 14 years old at the time of first diagnosis. The primary manifestations were micropenis(95 cases, 100%) and cryptorchidism(46 cases, 48.5%). The incidence of cryptorchidism was the lowest in the group over 14 years of age. Hormonal analysis revealed that the peak levels of LH following statin B and GnRH stimulation, the peak levels of FSH after GnRH stimulation, and testosterone levels following hCG stimulation were the highest in the infant group. Genetic analysis identified 20 CHH-related genes in 61 out of 77 cases.Double-gene mutation accounted for 7.8%(6/77) and triple-gene mutation accounted for 3.9%(3/77). The most common mutations were FGFR1(18/77, 23.4%), CHD7(12/77, 15.6%), PROKR2(11/77, 14.3%) and ANOS1(6/77, 7.8%). The incidence of cryptorchidism in these four genotypes was 50%, 75%, 45.5% and 83.3%, respectively. The incidence of testicular dysfunction was 22.2%, 16.7%, 27.3%, and 16.7%, respectively, with no statistical significance.Conclusion:The primary manifestation of CHH is micropenis and cryptorchidism. In children with CHH, the incidence of testicular Leydig cell and Sertoli cell dysfunction increased with age in CHH children. FGFR1, CHD7, PROKR2 and ANOS1 were common variants of CHH.
8.Epidemiological characteristics of Chlamydia trachomatis infection in Hubei Province in 2008 - 2022
Danyang LI ; Huadao XIONG ; Xiong ZHOU ; Huizhen SUN ; Xue YANG ; Hui CHEN
Journal of Public Health and Preventive Medicine 2024;35(6):63-67
Objective To understand the epidemiological characteristics of Chlamydia trachomatis infection in Hubei province, and to provide scientific basis for prevention and control. Methods The data of Chlamydia trachomatis infection cases reported through the China Information System for Disease Control and Prevention from 2008 to 2022 were collected for epidemiological statistical analysis. Results The incidence of Chlamydia trachomatis infection in Hubei Province showed an increasing trend from 2008 to 2022, with an average annual reported incidence of 2.26/100 000. The top three reported incidence areas were Shiyan (6.04/100 000), Yichang (5.62/100 000) and Shennongjia (3.47/ 100 000). The reported incidence in southeast area was significantly higher than that in other areas (χ2=2869.603 , P < 0.001). The high incidence age group was 20-39 years old, accounting for more than 70%. The reported incidence in females was higher than that in males (χ2=1429.27 , P < 0.001). Housework and unemployment were the most common professions (43.54%). The case reporting institutions were mainly comprehensive hospitals (87.29%). Conclusion To effectively control the infection and transmission of Chlamydia trachomatis, it is necessary to strengthen the health popularization of STD knowledge, intervention and early active screening of high-risk groups.
9.Screening and identification of a polyurethane-degrading bacterium G-11 and its plastic degradation characteristics.
Zhitong JIANG ; Xue CHEN ; Jinhui LEI ; Huizhen XUE ; Bo ZHANG ; Xiaofan XU ; Huijing GENG ; Zhoukun LI ; Xin YAN ; Weiliang DONG ; Hui CAO ; Zhongli CUI
Chinese Journal of Biotechnology 2023;39(5):1963-1975
Polyurethane (PUR) plastics is widely used because of its unique physical and chemical properties. However, unreasonable disposal of the vast amount of used PUR plastics has caused serious environmental pollution. The efficient degradation and utilization of used PUR plastics by means of microorganisms has become one of the current research hotspots, and efficient PUR degrading microbes are the key to the biological treatment of PUR plastics. In this study, an Impranil DLN-degrading bacteria G-11 was isolated from used PUR plastic samples collected from landfill, and its PUR-degrading characteristics were studied. Strain G-11 was identified as Amycolatopsis sp. through 16S rRNA gene sequence alignment. PUR degradation experiment showed that the weight loss rate of the commercial PUR plastics upon treatment of strain G-11 was 4.67%. Scanning electron microscope (SEM) showed that the surface structure of G-11-treated PUR plastics was destroyed with an eroded morphology. Contact angle and thermogravimetry analysis (TGA) showed that the hydrophilicity of PUR plastics increased along with decreased thermal stability upon treatment by strain G-11, which were consistent with the weight loss and morphological observation. These results indicated that strain G-11 isolated from landfill has potential application in biodegradation of waste PUR plastics.
Plastics/metabolism*
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Polyurethanes/chemistry*
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RNA, Ribosomal, 16S
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Bacteria/genetics*
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Biodegradation, Environmental
10.Effects of raw and wine-processed Schisandra chinensis on neuro-endocrine-immune network in insomnia mice and its mechanism
Ruiying WANG ; Dan SU ; Huizhen LI ; Yali LIU ; Genhua ZHU ; Ming YANG ; Zhifu AI ; Tao LUO ; Bing XUE ; Yonggui SONG
China Pharmacy 2023;34(5):525-530
OBJECTIVE To investigate the effect of raw and wine-processed Schisandra chinensis on neuro-immune-endocrine network in insomnia mice and its mechanism. METHODS Fifty mice were randomly divided into blank group, model group, diazepam group, raw S. chinensis group and wine-processed S. chinensis group, with 10 mice in each group. Except for blank group, the mice in the other groups were intraperitoneally injected with thyroxine solution to establish mice model of insomnia; at the end of each day’s modeling, the corresponding doses of diazepam,raw and wine-processed S. chinensis were given by gavage. The blank group and model group were given constant volume of normal saline. The general state of the mice was observed and recorded, and the total activity distance and upright times of the mice were detected; the EEG and EMG signals of mice were recorded, and the time ratio of sleep wake time (wake), non-rapid eye movement (NREM) and rapid eye movement (REM) was analyzed; the contents of neurotransmitters [γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), cortisol (CORT)] in brain suprachiasmatic nucleus (SCN) were detected; and the expressions of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected; the mRNA expressions of clock gene Bmal1, circadian clock gene Clock and cycle gene Per2 were all detected. RESULTS Compared with the blank group, the mental state of the model group mice was relatively depressed, the amount of food and water increased, the body mass decreased, the hair was rough and shiny, and the circadian rhythm was irregular; the total activity distance and upright times decreased significantly; the time ratio of wake increased significantly, while the time ratios of REM and NREM decreased significantly; the content of 5- HT in brain SCN decreased significantly, while the content of NE, DA and CORT increased significantly; the fluorescence intensity of IL-1β and TNF-α was significantly increased; the relative expression level of Bmal1 and Clock mRNA was significantly increased, while the relative expression level of Per2 mRNA was significantly decreased (P<0.05 or P<0.01). Compared with the model group, the general state of mice in diazepam group, raw S. chinensis group and wine-processed S. chinensis group was improved obviously, and most of the above index levels were significantly reversed (P<0.05 or P<0.01). CONCLUSIONS Raw and wine-processed S. chinensis have a certain therapeutic effect on insomnia mice, the mechanism of which may be related to the regulation of neuro-endocrine-immune system related biological indicators in insomnia mice.