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Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.
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Autophagy is an intracellular degradation process that delivers cytoplasmic constituents to the lysosome. Abnormality of autophagy is related to many human diseases, which provides a new clue to the pathophysiology of human cancer. However, the role of autophagy in normal liver physiology and the pathogenesis of liver diseases need to be further clarified. This article reviews the role of autophagy in the occurrence and development of hepatocellular carcinoma and the molecular mechanisms.
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Objective:To explore the application value of two-dimensional speckle tracking imaging (2D-STI) in evaluating diaphragm function, and to compare the ability of 2D-STI and conventional diaphragm ultrasonography in diagnosing diaphragmatic dysfunction and evaluating disease severity in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods:A total of 58 AECOPD patients admitted to the First Affiliated Hospital of Xi′an Jiaotong University from January to October 2021 were retrospectively enrolled as AECOPD group, and 34 healthy subjects were recruited as control group during the same period. Repeatability test of diaphragmatic 2D-STI was performed. According to modified Medical Research Council (mMRC) dyspnea scores system and COPD Assessment Test (CAT), mMRC 0-1 and CAT<10 was classified as group A, mMRC≥2 and CAT≥10 was classified as group B. The baseline characteristics, conventional diaphragm ultrasonography parameters(thickening fraction and excursion) and 2D-STI parameters (longitudinal and radial strains) were compared between the AECOPD group and the control group, and the Spearman correlation between parameters of AECOPD group and forced expiratory volume in one second (FEV1) was analyzed. The differences of these parameters between group A and B were also compared. The ROC curve of conventional diaphragm ultrasonography parameters and 2D-STI parameters was plotted to differentiate group A from group B, and the diagnostic efficacy was evaluated.Results:Great intra- and inter-observer reproducibility was found for all diaphragmatic 2D-STI parameters, with ICCs above 0.80 for all measurements. The control group and the AECOPD group did not differ in age, sex and body mass index( P>0.05), whereas there were significant differences in smoking history, lung function, bilateral thickening fraction, excursion, longitudinal and radial strains( P<0.05). Compared with control group, patients in group A had a significant increase in diaphragm thickness ( P<0.05), while there was no significant difference in that between group B and control group ( P>0.05). The bilateral longitudinal strains, radial strains and thickening fraction of diaphragm were linearly correlated with FEV1 (right side rs=0.828, 0.794, 0.843, respectively; all P<0.001; left side rs=0.757, 0.704, 0.752, respectively; all P<0.001 ), while the correlation between excursion and FEV1 was not significant(right side rs=0.247, left side rs=0.253; all P>0.05). There were significant differences in bilateral longitudinal strains, radial strains and thickening fraction between group A and group B(all P<0.05), whereas there was no significant difference in excursion between the two groups ( P>0.05). ROC analysis showed bilateral longitudinal and radial strains had higher accuracy in distinguishing group A from group B than thickening fraction and excursion(right side AUCs 0.90, 0.84, 0.78 and 0.62, respectively; left side AUCs 0.85, 0.83, 0.77 and 0.62, respectively). Conclusions:2D-STI is a real-time noninvasive technique for diaphragm function assessment, which has high clinical value. Compared with conventional ultrasonography, 2D-STI shows more accuracy and effectiveness in diagnosing diaphragmatic dysfunction and evaluating disease severity of patients with AECOPD.
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Objective:To analyze the clinical characteristics of severe adenovirus pneumonia with bacterial infection in children, so as to provide clinical evidences for early diagnosis and reliable treatment.Methods:A total of 72 pediatric cases with severe adenovirus pneumonia admitted to Pediatric Intensive Care Unit at the First People′s Hospital of Chenzhou from January 2018 to August 2019 were included.The clinical features, laboratory and imaging data, efficacy of the treatments and prognosis were investigated retrospectively.Patients were divided into with bacterial infection group and without bacterial infection group.The clinical characteristics were analyzed.Results:Among the 72 children, there were 54 males and 18 females, aging from 3 months to 5 years, including 37cases with bacterial infection and 35 cases without bacterial infection.Compared with the group without bacterial infection, the group with bacterial infection had longer heat duration and hospital stay [12.0 (10.0, 18.5) days vs.10.0 (9.0, 12.0) days; 6.0(4.0, 7.0) days vs.11.0(6.5, 16.0) days, P<0.05], the incidences of diarrhea and hepatomegaly were higher[35.1% (13/37) vs.14.3%(5/35); 45.9%(17/37)vs.8.6%(3/35), P<0.05], the proportion of five lobes involved in lung imaging was higher [91.8% (34/37) vs. 57.1%(20/35), P<0.05]. The incidences of complications with respiratory failure, hemophagocytic lymphohistiocytosis, and bronchiolitis obliterans in the group with bacterial infection were significantly higher than those of without bacterial infection group ( P<0.05). Conclusion:For children under 2 years old age with severe adenovirus pneumonia, there are prolonged high fever and extensive pulmonary lesions.We should be highly alert to the combination of bacterial infection and timely anti-infection therapy.Children with severe adenovirus pneumonia with bacterial infection have severe clinical manifestations and many complications with respiratory failure, hemophagocytic lymphohistiocytosis, and bronchiolitis obliterans.
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【Objective】 To explore the value of deep learning reconstruction algorithm (DLIR) in improving image quality of portal vein. 【Methods】 We retrospectively enrolled 32 patients who underwent double-phasic enhanced abdominal CT scanning. Images at the portal venous phase were reconstructed using the 50% adaptive statistical iterative reconstruction (ASIR-V), DLIR at medium (DLIR-M) and high strength (DLIR-H). The CT value and image noise (standard deviation) of the main portal vein, the right portal vein branch, the left portal vein branch, and the paravertebral muscle were measured, and the contrast-noise-ratio (CNR) for vessels were calculated. Moreover, the edge-rising-slope (ERS) of the main portal vein edge was measured to evaluate image spatial resolution. The overall image noise, image contrast, and portal vein branch display were evaluated using a 5-point grading scale and image artifacts using a 4-point grading scare by two experienced radiologists. In addition, we calculated the display rate of small branches of the portal vein in the three reconstruction algorithms. 【Results】 Image noise of the DLIR images in the main portal vein, right branch and left branch was significantly lower than that of ASIR-V 50% images, of which the DLIR-H images had the lowest noise and highest CNR. The ERS of the DLIR images in the main portal vein was significantly higher than that of the ASIR-V 50% images. For qualitative analyses, the DLIR images were significantly better than the ASIR-V 50% ones (P<0.01). In addition, the display rates of small branches of the portal vein in DLIR images were (DLIR-M: 93.75%; DLIR-H: 100%), significantly higher than that of ASIR-V 50% (68.75%). 【Conclusion】 Compared with ASIR-V 50% images, DLIR images can significantly reduce the image noise and improve the spatial resolution of the portal vein and the display rate of small branches of the portal vein.
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OBJECTIVES@#There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM.@*METHODS@#The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0.@*RESULTS@#Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%).@*CONCLUSIONS@#In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.
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Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Immunologic Factors/therapeutic use , Multiple Myeloma/therapy , Neoplasm Staging , Pain , Prognosis , Proteasome Inhibitors/therapeutic useABSTRACT
er to detect the beam quality of the SC200 superconducting cyclotron,measure the beam at the extraction reference and the acceptance of the accelerator is realized.This article mainly introduces the design that use the scintillation screen at the extraction reference to measure the beam profile,position and use the Faraday cup to measure the current intensity with 2.5 level accuracy.The remoted controlling of probes and the acquisition and processing of signal based on LabVIEW and PLC.
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Proton TherapyABSTRACT
As a new model organism,Zebra.fish has been widely used in many aspects of life science research for its unique advantages in growth and development and the convenience of transgenic manipulation.Endemic disease is serious in China.Currently,on one hand,the pathogenesis of endemic fluorosis,endemic arsenism and iodine deficiency disorders is unclear,on the other hand,the cause of Keshan disease and KashinBeck disease is still unknown.This poses great difficulties in the prevention and control of endemic diseases.At present,there are some shortcomings and deficiencies in the animal models used to study the etiology and mechanism of endemic diseases.However,the advantages of Zebrafish as a new model organism just can make up for these deficiencies.Therefore,this paper reviews the application prospects of a new model organism,Zebrafish,in the field of endemic diseases.
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Objective To study the urinary arsenic safety guideline value of a population for evaluating the arsenic exposure level in a certain population and providing evidence for the implementation of prevention and control measures in endemic arsenicosis area.Methods According to the data from the national high-arsenic drinking water sources screening in endemic arsenicosis area of drinking water type and quality supervision and inspection for water-improving project to decrease arsenic from 2005 to 2014,census data on arsenic poisoning in endemic arsenicosis area,data on surveillance of endemic arsenicosis,10 722 people with detailed personal information,complete water arsenic exposure data and accurate urinary arsenic detection data were selected to be the research objects.The relationship between urinary arsenic and water arsenic was analyzed based on the surveillance data of 4 501 people from 2013 to 2014.The safety guidance value of urinary arsenic was determined based on the geometric mean value of urinary arsenic in people exposed to water arsenic in the range of (0.050 ± 0.005) mg/L,and verified using the data of 6 221 people from 2005 to 2012.Every time,a random sample of 2 000 people was taken as the verification sample,the sensitivity and specificity of the index for determining whether water arsenic exposure exceeded the standard were determined by area under the ROC curve (AUC),and a total of 10 sample tests was performed.Results When the water arsenic concentration was less than 0.01 mg/L,the correlation coefficient of water arsenic concentration with urinary arsenic concentration was 0.097 (P ＜ 0.01);when the water arsenic concentration was more than 0.01 mg/L and less than 0.05 mg/L,the correlation coefficient of arsenic concentration with water arsenic concentration was 0.456 (P ＜ 0.01);when the water arsenic concentration was more than 0.05 mg/L,the correlation coefficient of water arsenic concentration with urinary arsenic concentration was 0.630 (P ＜ 0.01).With increase of water arsenic concentration,the concentration of urinary arsenic increased significantly,and the difference was statistically significant (x2 =2 337.956,P ＜ 0.01).When water arsenic concentration was in the range of (0.050 ± 0.005) mg/L,the urinary arsenic geometric mean was 0.032 mg/L.AUC analysis of 10 random samples of 2 000 people showed that the geometric mean of urinary arsenic was 0.032 mg/L in the population,which can accurately distinguish whether the water arsenic level exceeded 0.05 mg/L,and the AUC value was higher than 0.94.And the sensitivity and specificity were achieved 0.898 and 0.844.Conclusions The geometric mean of urinary arsenic is 0.032 mg/L,which can be used as a safety guideline value for urinary arsenic in the population.When the geometric mean of urinary arsenic exceeds this value,the population may be exposed to high arsenic.
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Objective To observe the effect of fluoride on fibroblast growth factor 23 (FGF23) in bone tissue of mice,and to explore the role of FGF23 in fluoride-induced bone injury.Methods Sixty-four Balb/c mice,half male and female,were divided into 4 groups based on body weight via the random number table method and 16 mice were in each group.The mice in control group,low fluoride group,middle fluoride group and high fluoride group were treated with 0,25,50,and 100 mg/L F-distilled water,respectively.After three months,the mice were put to death and the prevalence of dental fluorosis was calculated.The fluoride contents in spine were detected via the fluoride-ion selective electrode method,serum content of calcium and phosphorus were detected by micro enzyme labeled method.The levels of FGF23,parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D3 [1,25 (OH)2D3] in serum were measured by enzyme-linked immunosorbent assay.The FGF23 protein expression levels in bone tissue were determined by immunohistochemistry and Western blotting.Results The rates of dental fluorosis in low,medium and high fluoride groups were 75％ (4/16),100％ (16/16) and 100％ (16/16),respectively.Compared with control group [0 (0/16)] the differences were statistically significant (P ＜ 0.05).The levels of fluoride in the fluoride group [low,medium,high fluoride groups:(1 730.86 ± 165.90),(2 400.58 ± 286.65),(3 980.88 ± 511.65) mg/kg] were higher than that of control group [(854.30 ± 89.05) mg/kg,P ＜ 0.05].There was no difference in serum calcium content among groups (F =0.05,P ＞ 0.05).The contents of phosphorus in the serum of the medium and the high fluoride groups [(2.46 ± 0.32),(2.48 ± 0.73) mmol/L] were lower than those in the control and the low fluoride groups [(2.89 ± 0.45),(3.25 ± 0.69) mmol/L,P ＜ 0.05].The serum PTH and 1,25 (OH)2D3 content increased first and then decreased.The expression of FGF23 in middle and high fluoride groups [(660.84 ± 64.18),(638.74 ± 121.23) ng/L] was up-regulated compared with that of control group [(613.53 ± 98.18) ng/L].The expression of FGF23 protein in cortical bone increased gradually with the dose of fluoride.Western blotting results showed that the content of FGF23 protein in the bone tissue of mice was significantly increased in the low fluoride group (1.58 ± 0.46) and the middle fluoride group (1.40 ± 0.41) compared with that of control group (1.00 ± 0.41),the differences were statistically significant (P ＜ 0.05).Conclusions The phosphorus,FGF23,PTH,and 1,25 (OH)2D3 levels in the serum and FGF23 protein levels in the bone tissue of fluorosis mice have changed.It may be suggested that FGF23 interacts with PTH and 1,25 (OH)2D3 to influence the level of calcium and phosphorus metabolism in the body and participate in the formation of skeletal fluorosis.
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Objective To investigate the relationship between single nucleotide polymorphism(SNP)of the peroxisome proliferator activated receptor γ (PPARγ) gene Rs1801282 and brick-tea type fluorosis. Methods From 2012 to 2013, this cross-sectional study was performed in 16 endemic fluorosis areas of brick-tea type in Inner Mongolia Autonomous Region,Qinghai and Xinjiang Uygur Autonomous Region of China,to select adults>18 years old as subjects, who were diagnosed as skeletal fluorosis by X-ray. All of the subjects filled in demography survey questionnaire; the survey contents included general characteristic s, and average daily brick tea intake. Drinking tea samples and urine samples of each subject were collected, and fluoride content of urine and brick-tea was determined via the ion selective electrode method (WS/T 89-2006). X-ray scintigraphy was used to diagnose skeletal fluorosis, according to the "Diagnostic Criteria of Endemic Skeletal Fluorosis" (WS/T 192-2007); the subjects were divided into skeletal fluorosis group (case group) and non-skeletal fluorosis group (control group). To collect venous blood 5 ml, whole blood DNA was extracted, and polymorphism at Rs1801282 of PPARγ was detected by MassARRAY time-of-flight mass spectrometry, to calculate odds ratio (OR) and 95% confidence interval (CI). Results There were 1 414 people included in this study,including 347 in case group and 1 067 in control group. By the Hardy-Weinberg balance test, the PPARγ gene Rs1801282 genotype was representative in case group, control group and each nationality (P > 0.05). The difference of PPARγ gene Rs1801282 genotype in case group and control group was not statistically significant (OR was 0.991, 95%CI: 0.704 - 1.395, the adjusted OR was 1.026, 95%CI: 0.707-1.489).The difference of PPARγ gene Rs1801282 genotype(CC,CG+GG)in case group and control group in different nationality was not statistically significant (Tibetan: OR was 1.400, 95%CI: 0.576 - 3.404, the adjusted OR was 1.258, 95%CI: 0.474 - 3.340; Kazak: OR was 0.898, 95%CI:0.516 -1.562,the adjusted OR was 0.936,95%CI:0.532 -1.648;Mongolia: OR was 1.148,95%CI:0.508-2.594, the adjusted OR was 1.644, 95%CI: 0.683 - 3.956; Han: OR was 1.058, 95%CI: 0.451 - 2.482, the adjusted OR was 0.959, 95%CI: 0.388 - 2.371; Russian: OR was 0.000, 95%CI: 0.000 - 0.000, the adjusted OR was 0.000, 95% CI: 0.000 - 0.000) with binary Logistic regression analysis. Conclusion We have found no association between SNP of PPARγ gene Rs1801282 and skeletal fluorosis of brick-tea type fluorosis in China.
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Objective To study the effect of fluoride exposure on bone growth in zebrafish.Methods The zebrafish larvaes at 3 days post fertilization (3 dpf) were exposed to the conventional fish water and 25,50,100 mg/L of NaF for 5 days until the skeletal bone was formed (8 dpf) and the temperature was kept at 28 ℃.The fluoride content of zebrafish embryos was detected by F-ion selective electrode.The fluoride exposure model was re-established as the control group (0.0 mg/L),the low doses group (0.5,1.0,4.0 mg/L) and the high doses group (50.0,100.0 mg/L).The survival rates of the zebrafish embryos were calculated and the morphology of zebrafish embryos was observed under 40 times microscope.The zebrafish skeleton was stained with alizarin red.The staining areas and the integrated optical density (IOD) of the bone staining were quantitatively analyzed by digital microscope to analyze the sclerotic and osteoporosis of the skull.Results The fluoride contents of the control group and 25,50,100 mg/L NaF groups were (0.32 ± 0.01),(0.63 ± 0.01),(0.86 ± 0.02) and (1.21 ± 0.01) μg/150 embryos.Compared with the control group,the fluoride contents of zebrafish embryos in fluoride exposed groups were increased (P ＜ 0.05),and the dose-response relationship was obvious.The survival rates of zebrafish embryos in control group and fluoride exposed groups were 96.67％,96.67％,96.67％,98.33％,98.33％ and 98.33％.There was no significant difference among different groups (x2 =7.309,P ＞ 0.05);under a 40 times microscope,there were no obvious deformities of the spin in different groups;the areas of the alizarin red staining of the skull were 84 380.51 ± 11 711.41 in the control group,92 592.16 ± 7 143.81,92 164.85 ± 10 136.18 and 95 112.26 ± 13 721.91 in the low doses exposure groups (0.5,1.0,4.0 mg/L NaF),67 778.92 ± 8 597.11 and 64 272.93 ± 9 302.57 in the high doses groups (50.0,100.0 mg/L NaF).The areas of the alizarin red staining of the skull in the low doses exposure groups were significantly higher than that of the control group (P ＜ 0.05),while the high doses exposure groups were lower (P ＜ 0.05);the IOD of the alizarin red staining of the skull was 25 094.13 ± 6 571.86 in the control group,29 754.95 ± 3 836.45,28 747.36 ± 4 677.86 and 30 776.49 ± 5 589.63 in the low doses exposure groups (0.5,1.0,4.0 mg/L NaF),19 263.10 ± 4 754.72 and 18 202.58 ± 4 897.15 in the high doses groups (50.0,100.0 mg/L NaF).The IOD of the alizarin red staining of the skull in the low doses exposure groups was significandy higher than that of the control group (P ＜ 0.05),while the high doses exposure groups was lower (P ＜ 0.05).Conclusion Low doses of fluoride exposure may cause bone sclerosis in zebrafish embryos,while the high dose of fluoride exposure may cause osteoporosis.
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Objective To explore characteristics and significance of the indexes of peripheral white blood cell (WBC) in patient with human brucellosis.Methods People checked by brucellosis physical checkup and routine physical checkup at Qiqihar Center for Disease Control and Prevention from December 2014 to December 2015,including 40 acute brucellosis patients (acute group),35 chronic brucellosis patients (chronic group) and 72 healthy people (control group),were selected.Automatic blood analyzer was used to determine the indexes of WBC,lymphocyte count (LY),lymphocyte percentage (LY％),monocytes count (MONO),monocytes percentage (MONO％),eosinophil count (EO),eosinophil percentage (EO％),basophilic granulocyte count (BASO),basophilic granulocyte percentage (BASO％),neutrophils count (NEUT) and neutrophils percentage (NEUT％).The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of WBC parameters in acute and chronic groups.Results Compared to control group,the levels of WBC,EO,EO％,BASO,BASO％,NEUT and NEUT％ were decreased in acute group [(5.222 0-± 2.551 2) × 109/L vs (6.352 5 ± 1.905 8) × 109/L,(0.030 0 ± 0.006 8) × 109/[,vs (0.083 9 ± 0.039 3) × 109/L,(0.54 ± 0.12)％ vs (2.31 ± 0.14)％,(0.009 0 ± 0.001 1) × 109/L vs (0.019 0 ± 0.002 4) × 109/L,(0.17 ± 0.09)％ vs (0.32 ± 0.20)％,(2.698 7 ± 1.948 4) × 109/L vs (4.012 9 ± 1.579 0) × 109/L,(48.13 ± 14.38)％ vs (62.13 ± 9.00)％,all P ＜ 0.05],and the levels of LY,LY％ and MONO％ were increased in acute group [(2.125 3 ± 0.949 9) × 109/L vs (1.794 4 ± 0.606 6) × 109/L,(43.37 ± 14.52)％ vs (29.10 ± 7.97)％,(7.84 ± 2.23)％ vs (6.55 ± 2.04)％,all P ＜ 0.05].Compared to control group,the level of NEUT％ [(54.63 ± 9.26)％] was decreased in chronic group (P ＜ 0.05),and the levels of LY,LY％ and EO [(2.212 0 ± 0.633 2) × 109/L,(36.41 ± 8.51)％,(0.153 9 ± 0.028 8) × 109/L] were increased in chronic group (all P ＜ 0.05).The levels of LY％ and MONO％ [(6.45 ± 1.58)％] in chronic group were lower than those in acute group (all P ＜ 0.05),and the levels of WBC [(6.175 7 ± 1.469 5) × 109/L],EO,EO％ [(2.32 ± 1.21)％],BASO [(0.021 8 ± 0.001 9) × 109/L],BASO％ [(0.37 ± 0.21)％] and NEUT％ were higher than those in acute group (all P ＜ 0.05).The areas under ROC curve (AUCs) of LY and MONO in acute group were 0.681 and 0.529,they were in 0.5-0.7,and the diagnostic value was low;the AUCs of EO,EO％,LY％,NEUT％,NEUT,BASO,BASO％,MONO％ and WBC in acute group were 0.816,0.816,0.806,0.790,0.766,0.760, 0.721,0.715 and 0.710,they were in ＞ 0.7-0.9,and the diagnostic value was medium.The AUCs of LY,NEUT,BASO,EO,BASO％,EO％,MONO％,MONO and WBC in chronic group were 0.693,0.617,0.586,0.584,0.581,0.541,0.500,0.513 and 0.510,they were in 0.5-0.7,and the diagnostic value was low;the AUCs of LY％ and NEUT％ in chronic group were 0.725 and 0.717,they were in ＞ 0.7-0.9,and the diagnostic value was medium.Conclusion The indexes of peripheral WBC in patient with acute and chronic human brucellosis are changed abnormally,which has a certain reference value in diagnosis of human brucellosis.
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Objective To investigate the effects of fluoride on trabecular bone of the tibia and lumbar in BALB/c mice.Methods Totally 64 four-week-old BALB/c mice were randomly divided into 4 groups by weight,16 per group:control group (treated with distilled water) and 3 sodium fluoride (NaF) exposure groups (treated with NaF at 25,50 and 100 mg/L F-),respectively.At 12 weeks,mice were killed and blood,two hind limbs and lumbar were collected.Bone fluoride content and incidence rates of dental fluorosis were determined.Serum content of alkaline phosphatase (AKP) and acid phosphatase (ACP) were detected by micro enzyme labeled method.The ultrastructure of osteoblasts and osteoclasts in lumbar were observed via transmission electron microscope.The pathological changes of the trabecular bone of the tibia and the lumbar were observed under optical microscope,the percentage of trabecular area (％Tb.Ar) was measured with Image-Pro Plus (IPP) software.Results Bone fluoride contents of low,middle and high fluoride groups [(1 828.62 ± 102.93),(3 308.27 ± 185.63),(4 933.36 ± 301.16) mg/kg] were higher than that of the control group [(775.23 ± 92.56) mg/kg,all P ＜ 0.05].The incidences of dental fluorosis in the 4 groups were 0(0/16),47％(7/15),93％(14/15) and 100％(16/16),respectively;the difference was statistically significant (x2 =27.23,P ＜ 0.05).In middle and high fluoride groups,serum AKP [(18.30 ± 1.99),(24.50 ± 3.14) king unit/100 ml] and ACP [(11.97 ± 1.73),(11.31 ± 1.46) king unit/100 ml] were significantly higher than those of control [(14.63 ± 1.21),(9.07 ± 1.47) king unit/100 ml,respectively,all P ＜ 0.05].Under the electron microscope,osteoblast had developed organelles in each fluoride group,rough endoplasmic reticulum,Golgi body,and mitochondria were abundant,and nucleolus was obvious in the osteoblast.Osteoclast was rich in mitochondria,ruffled border clear and distributed phagocytic vacuoles in low fluoride group and middle fluoride group.Compared with the control group (17.03 ± 3.73),HE staining of tibia ％Tb.Ar in high fluoride group (28.79 ± 8.26) was significantly increased (P ＜ 0.05).The lumbar spine ％Tb.Ar in low,middle and high fluoride groups (15.87 ± 2.59,18.28 ± 0.89,21.99 ± 1.81) were higher than that of the control group (12.06 ± 1.76,all P ＜ 0.05].Conclusions BALB/c mice could be used as a model of skeletal fluorosis.Osteoblast and osteoclast are activated in BALB/c mice with skeletal fluorosis.Bone formation is more obvious than bone resorption and bone mass is increased.What is more,bone mass has increased more significantly in the lumbar spine of mice.
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Objective To detect the modification levels of H2AKll9 ubiquitination (H2AK119ub) and H2BK120ub,and to analyze the relationship between the levels of H2AK119ub,H2BK120ub and arsenic exposure.Methods A cross-sectional study was conducted in typical areas of drinking water type of endemic arsenicosis in Shanxi and Jilin provinces.Totally 281 residents who had drank local water for more 10 years were enrolled in this study,these participants were divided into control group (water arsenic content ＜ 0.01 mg/L),low arsenic exposure group (water arsenic content ranged 0.01-0.05 mg/L),medium arsenic exposure group (water arsenic content ranged ＞ 0.05-0.10 mg/L) and high arsenic exposure group (water arsenic content ＞ 0.10 mg/L).Among them,including 60 subjects in control group (20 males and 40 females),61 subjects in low arsenic exposure group (27 males and 34 females),50 subjects in medium arsenic exposure group (17 males and 33 females),and 110 subjects in high arsenic exposure group (40 males and 70 females).Drinking water and urine samples were collected and the arsenic content was detected by the method of atomic fluorescence spectrometry.After extracting leukocytes histone from the peripheral venous blood that collected from the subjects,the levels of H2AK119ub and H2BK120ub were detected by dot blotting.The levels of water arsenic,urinary arsenic,water arsenic accumulative intake,H2AK119ub and H2BK120ub were expressed as medium and quartile [M (P25,P75)].Results Age,body mass index (BMI),gender,smoking and alcohol drinking between control group and water arsenic exposure groups had no statistical differences (x2 =3.780,3.572,1.938,4.937,6.025,all P ＞ 0.05).Compared the contents of water arsenic [0.005 (0.003,0.006),0.024 (0.017,0.037),0.076 (0.057,0.084),0.150 (0.124,0.185) mg/L],the contents of urinary arsenic [0.011 (0.006,0.017),0.018 (0.004,0.072),0.061 (0.032,0.124),0.134 (0.069,0.223) mg/L],the water arsenic accumulative intake [0.342 (0.248,0.477),1.641 (1.012,2.324),5.273 (3.690,7.036),7.716 (5.608,12.053) mg] among the control,low,medium and high arsenic exposure groups,the differences were statistically significant (Hc =256.041,88.615,218.610,all P ＜ 0.01).Compared the levels of H2AK119ub [1.231 (0.856,1.817),1.244 (0.792,1.884),1.376 (0.743,1.981),1.390 (0.906,2.045)],H2BK120ub [0.350 (0.186,0.589),0.363 (0.152,0.678),0.428 (0.134,0.788),0.276 (0.146,0.453)] in human peripheral blood leukocytes among control,low,medium and high arsenic exposuregroups,the differences were not statistically significant (Hc =2.130,4.330,all P ＞ 0.05).There were no correlations between H2AK119ub and water arsenic content,water arsenic accumulative intake (r =0.104,-0.008,all P ＞ 0.05);there was a positive correlation between H2AK119ub and urinary arsenic content (r =0.166,P ＜ 0.05).There were negative correlations between H2BK120ub and water arsenic content,water arsenic accumulative intake (r =-0.183,-0.159,all P ＜ 0.05);there was no correlation between H2BK120ub and urinary arsenic content (r =-0.101,P ＞ 0.05).There was a negative correlation between H2AK119ub and H2BK120ub (r =-0.127,P ＜ 0.05).Conclusion External exposure to arsenic may change the levels of H2BK120ub in human peripheral blood leukocytes.
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Objective To explore the effects of different doses of sodium fluoride (NaF) on cartilage lesion and expression of interleukin-6 (IL-6) in serum and cartilage tissue of Balb/c mice.Methods Sixty-four 5-week-old male Balb/c mice were divided into 4 groups based on body weight via the random number table method and 16 mice were in each group.The mice in control group were fed with distilled water,and experimental animals in low,middle and high fluoride groups were fed with distilled water containing NaF 25,50 and 100 mg/L,respectively.The mice were weighed once a week and fed for three months to establish the drinking water fluorosis model.The fluoride contents in spine were detected via the fluorin-ion selective electrode method.The pathological changes in articular cartilage and epiphyseal plate cartilage were observed through optical microscope.The levels of serum IL-6 and souble IL-6 receptor (sIL-6R) were detected via the enzyme-linked immunosorbent assay.The expression of IL-6 protein in articular cartilage and epiphyseal plate cartilage was examined by immunohistochemistry.Results From the sixth week of the experiment,compared with other 3 groups,the body weight of high fluoride group decreased significantly (all P ＜ 0.05);from the seventh week,compared with control and low fluoride groups,the body weight of middle fluoride group decreased significantly (all P ＜ 0.05);throughout the experiment,compared with control group,the body weight of low fluoride group had not changed significantly (all P ＞ 0.05).The fluoride contents of bone in control group,low fluoride group,middle fluoride group and high fluoride group were (842.46 ± 89.27),(1 705.05 ± 105.76),(2 614.17 ± 156.10) and (3 444.58 ± 233.69) mg/kg,respectively.The differences between groups were statistically significant (F =309.716,P ＜ 0.05),and fluoride contents of bone increased with increase of fluoride doses (all P ＜ 0.05).Under optical microscope,the cartilage tissue of control group was normal,while articular cartilage and epiphyseal plate cartilage showed different degrees of cartilage ossification in fluorosis mice and the changes increased with the increase of fluoride doses.The levels of serum IL-6 in control group,low fluoride group,middle fluoride group and high fluoride group were (5.98 ± 1.43),(7.54 ± 2.16),(5.25 ± 1.97) and (6.31 ±-1.36) ng/L,respectively.The differences between groups were statistically significant (F =3.840,P ＜ 0.05),low fluoride group was significantly higher than control group (P ＜ 0.05),and middle fluoride group was significantly lower than low fluoride group (P ＜ 0.05).The levels of serum slL-6R in control group,low fluoride group,middle fluoride group and high fluoride group were (0.83 ± 0.20),(0.93 ± 0.23),(0.82 ±0.27) and (0.92 ± 0.28) μg/L,respectively.The differences between groups were not statistically significant (F =0.738,P ＞ 0.05).Immunohistochemical results showed that articular cartilage full-layer cells in each group expressed IL-6 protein especially in the middle layer of chondrocytes,while IL-6 protein only expressed in hypertrophic chondrocytes of epiphyseal plate cartilage.Comparing with other groups,IL-6 positive cells were the most and had the deepest staining in low fluoride group.Conclusions Different doses of NaF could not only cause cartilage lesion,but also change the expression of IL-6 in serum and cartilage tissue of Balb/c mice.The results indicate that IL-6 may be involved in the cartilage lesion caused by fluoride.
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Objective To investigate the relationship between Cytochrome P-450 1A1 (CYP1A1) gene polymorphism and the ethnic differences to brick-tea fluorosis and the gene-environment interaction.Methods Inhabitants over the age of 16 years old in Inner Mongolia,Qinghai and Xinjiang were investigated.The questionnaire survey included basic information,dietary survey and total fluoride intake,and peripheral venous blood was collected.The CYP1A1 gene single nucleotide polymorphism (SNP) genotyping was determined using mass spectrometry;the diagnosis of skeletal fluorosis was based on the X-ray method;combined genetic factors with environmental factors,the interaction of gene-environment was analyzed.Results In the 1 414 copies of whole blood samples (308 Tibetans,290 Kazakhs,261 Mongolians,425 Han people,130 Russians),CYP1A1 genes rs1048943 sites were typed into AA,AG and GG genotypes,and gene distribution met Hardy-Weinberg equilibrium (P ＞ 0.05).The frequencies of genotypes AA,AG and GG in Tibetans were 55.8％ (172/308),37.3％ (115/308) and 6.8％ (21/308),respectively;the frequencies of the three genotypes in Kazakhs were 69.7％ (202/290),27.6％ (80/290) and 2.8％ (8/290),respectively;the frequencies of the three genotypes in Mongolians were 60.5％ (158/261),36.0％ (94/261) and 3.4％ (9/261),respectively;the frequencies of the three genotypes in Han people were 60.9％ (259/425),33.6％ (143/ 425) and 5.4％ (23/425),respectively;the frequencies of genotypes in Russians were 72.3％ (94/130),26.9％ (35/130) and 0.8％ (1/130),respectively;the differences of the three genotype frequencies between different ethnic groups were statistically significant (x2 =24.757,P ＜ 0.05).The skeletal fluorosis detection rates in different ethnic from high to low were Tibetans (39.94％,123/308),Kazakhs (33.79％,98/290),Mongolians (22.22％,58/261),Han people (13.41％,57/425) and Russians (8.46％,11/130),and the differences were statistically significant (x2 =100.156,P＜ 0.05).Skeletal fluorosis detection rates of different genotypes were AA (24.18％,214/885),AG/GG (25.14％,133/529),the difference was not statistically significant between the groups (x2 =0.165,P ＞ 0.05).After the ethnic stratification,the differences were also not statistically significant (P ＞ 0.05).Only in the group of Tibetans whose urine fluoride level was 1.6-3.2 mg/L and Mongolians under age 45 were found that the G gene was one of the risk factors in skeletal fluorosis [OR =2.035,95％ CI (1.003-4.128);OR =5.602,95％CI (1.461-21.479)];G gene might be a protective factor in the Mongolians aged 45 years and over [OR =0.422,95％CI(0.190-0.938)].Conclusion This study does not find a positive correlation between CYP1A1 gene polymorphism and the ethnic differences to bricktea fluorosis.
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Objective To investigate the diagnostic value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)in differentiating non-metastatic from metastatic mesorectal lymph nodes in rectal cancer.Methods IVIM-DWI and DCE-MRI were performed preoperatively in 38 patients with histologically proven rectal carcinoma.The short axis diameter,short-to-long axis diameter ratio,four IVIM-based parameters (ADC,D,D? and f) and six DEC-MRI semi-quantitative parameters (Slope,Maxslope,CER,Washout,TTP,iAUC90 and iAUC180 )were compared between the metastatic (n=28)and non-metastatic (n=27)lymph nodes.Results There were significant statistical significances between the metastatic and non-metastatic lymph nodes in mean short axis diameter (8.87 mm±2.829 mm vs 6.83 mm±1.075 mm),D value[(0.824±0.1 13)× 10 -3 mm2/s vs (1.033±0.244)× 10 -3 mm2/s],CER(1.588 ±0.664 vs 1.054 ±0.41 9),iAUC90 (22.89 ± 9.83 vs 13.59 ± 5.34)and iAUC1 80 (49.38±20.1 9 vs 30.31 ± 1 1.67)(P ≤0.001).The short-to-long axis diameter ratio,ADC,D? ,f,Slope,Maxslope,Washout and TTP values did not show significant differences between the two groups(P >0.05).The respectively optimal cut-off value (area under the curve,sensitivity and specificity)for distinguishing metastatic from non-metastatic lymph nodes were as follows:short axis diameter=7.1 mm(0.744,64.2%,85.1%),D=0.906×10 -3 mm2/s (0.821,81.5%,75.0%),CER=1.05(0.749,85.7%,62.9%), iAUC90 =13.42(0.780,85.7%,62.9%),iAUC180 =49.65 (0.770, 50.0%,100%)respecyively.Conclusion Both IVIM-DWI and DCE-MRI are useful for differentiating non-metastatic from metastatic mesorectal lymph nodes in rectal cancer.
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Objective To evaluate the value of energy spectrum CT with multimodal quantitative parameters in diagnosis of the metastatic lymph nodes of gastric adenocarcinoma compared with the conventional CT.Methods 37 patients with gastric adenocarcinoma diagnosed by gastroscopy underwent enhanced CT scan with gemstone spectral imaging mode.We positioned and marked the stomach lymph nodes on CT images and compared with postoperative pathologic results one to one.ROC was used to identify the critical quantitative index of energy spectrum CT in distinguishing the metastasis from benign lymph node,and to evaluate the diagnostic effect compared with CT features.Results The 40-80 keV single energy spectrum curve slope (λHU )and normalized iodine concentration (NIC)in metastasis group were lower than those in the benign one in the arterial phase with statistical differences (P <0.05 ),but without statistical differences in venous phase.The combination of arterialλHU and NIC showed significant advantages compared with CT features(P <0.01), with the sensitivity,specificity and accuracy of 84.3% vs 61.4 %,88.4% vs 81.3 % and 86.8% vs 73.6 %.Conclusion The energy spectrum CT can provide quantitative analysis for differential diagnosis of gastric cancer metastasis from benign lymph nodes,and significantly improve the diagnostic accuracy of lymph node metastasis of the cancer.
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Objective To observe the changes of serumγ?glutamyl transpeptidase(GGT)levels before and after the patho?gen treatment in patients with subclinical schistosomiasis,and explore its clinical value in the diagnosis and treatment of sub?clinical schistosomiasis. Methods Totally 109 patients with subclinical schistosomiasis,who were found in the endemic inves?tigation of schistosomiasis in Ezhou City,were selected as the investigation subjects,and then they were treated with praziquan?tel. The serum GGT levels of the subjects before and after the treatment were detected and compared. Results Before the treat?ment,the average value of the GGT levels of the 109 patients was(48.1 ± 45.9)IU/L,among which,the GGT levels of 69 cases (63.3%)were normal,and the levels of 40 cases(36.7%)were increased. After the treatment,the average GGT level of the pa?tients was(32.1 ± 23.4)IU/L,which decreased by 33.3%comparing with that before the treatment,and the difference had a statistical significance(U=2.17,P=0.01). The GGT levels of 65 patients decreased in different degrees. Among the 40 pa?tients whose GGT levels had increased before the treatment,the GGT levels of 31 ones returned to the normal. Conclusion The GGT level detection can accurately reflect the liver function in the patients with subclinical schistosomiasis ,and also it has certain clinical application value to judge the liver function damage and recovery of the patients before and after the pathogen treatment.