Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Associations of arsenic and estrogen levels with the risk ofpapillary thyroid carcinoma / 预防医学

Objective@#To examine the associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma, so as to provide insights into prevention of papillary thyroid carcinoma.@*Methods@#Totally 57 patients with papillary thyroid carcinoma admitted to two tertiary hospitals in Urumqi, Xinjiang Uygur Autonomous Region in 2018 were selected as the case group, while 57 subjects with normal thyroid functions during the same period were selected as the control group. Subjects' gender, age, ethnicity, occupation and medical history of thyroid disease were collected using questionnaire surveys. Serum dimethyl arsenic acid (DMA) and monomethyl arsenic acid (MMA) were determined using high-performance liquid chromatography (HPLC) coupled to hydride generation-atomic fluorescence spectrometry (HG-AFS), serum thyroid hormone (TSH) by radioimmunoassay, estradiol (E2) by enzyme-linked immunosorbent assay and estrogen receptor ERα and ERβ by western blotting. The associations of arsenic and estrogen levels with the risk of papillary thyroid carcinoma were evaluated using a multivariable logistic regression model.@*Results@#There were 16 males (28.07%) and 41 females (71.93%) in the case group, with a mean age of (42.63±11.01) years, and there were 21 males (36.84%) and 36 females (63.16%) in the control group, with a mean age of (40.89±11.30) years. There were no significant differences between the case and control groups in terms of age (χ2=0.373, P=0.542), gender (χ2=1.000, P=0.317) or ethnic composition (χ2=0.291, P=0.590). The serum levels of TSH [2.85 (1.61) vs. 2.45 (1.79) μmol/L], E2 [74.93 (120.44) vs. 61.60 (37.35) pmol/L], ERα [1.49 (1.13) vs. 0.70 (0.31)], ERβ [1.59 (0.55) vs. 0.72 (0.36)], DMA [116.02 (100.48) vs. 32.33 (56.06) μg/L] and MMA [56.92 (47.90) vs. 27.90 (24.99) μg/L] were all significantly higher in the case group than in the control group (Z=-2.414, -2.292, -4.923, -5.167, -5.448 and -4.019, all P<0.05). Multivariable logistic regression analysis showed DMA (OR=1.013, 95%CI: 1.003-1.024) and E2 levels (OR=1.020, 95%CI: 1.004-1.036) were associated with the risk of papillary thyroid carcinoma.@*Conclusion@#Increased arsenic load and elevated estradiol levels may be associated with the risk of papillary thyroid carcinoma.

20()-Protopanaxatriol promotes the binding of P53 and DNA to regulate the antitumor network multiomic analysis

Although the tumor suppressor P53 is known to regulate a broad network of signaling pathways, it is still unclear how certain drugs influence these P53 signaling networks. Here, we used a comprehensive single-cell multiomics view of the effects of ginsenosides on cancer cells. Transcriptome and proteome profiling revealed that the antitumor activity of ginsenosides is closely associated with P53 protein. A miRNA-proteome interaction network revealed that P53 controlled the transcription of at least 38 proteins, and proteome-metabolome profiling analysis revealed that P53 regulated proteins involved in nucleotide metabolism, amino acid metabolism and "Warburg effect". The results of integrative multiomics analysis revealed P53 protein as a potential key target that influences the anti-tumor activity of ginsenosides. Furthermore, by applying affinity mass spectrometry (MS) screening and surface plasmon resonance fragment library screening, we confirmed that 20()-protopanaxatriol directly targeted adjacent regions of the P53 DNA-binding pocket and promoted the stability of P53-DNA interactions, which further induced a series of omics changes.

A retrospective study of endoscopic ultrasonography for predicting progression of esophageal varices in patients with hepatitis B virus-related hepatocirrhosis / 中华消化内镜杂志

Objective To assess the clinical value of endoscopic ultrasonography ( EUS ) for predicting esophageal varices ( EV ) progression in patients with hepatitis B virus ( HBV )-related hepatocirrhosis. Methods A retrospective cohort study was performed on 299 HBV-related hepatocirrhosis patients with light EV in Tianjin Second People′s Hospital admitted from September 2014 to September 2015. The diameter and number of peri-esophageal collateral veins ( ECV ) and para-ECV were measured and described by EUS. The first EUS examination time was the starting point, and the follow-up of 24 months or EV progression was the end. Risk factors of EV progression were evaluated by multivariate Cox regression model, and the predictive value of EUS for EV progression was analyzed by receiver operating characteristic ( ROC) curve. Results The cumulative incidence of EV progression was 2. 3％ ( 7/299 ) , 14. 8％( 44/297) , 33. 7％ ( 96/285) and 40. 0％ ( 120/273) at 6 months, 12 months, 18 months and 24 months of follow-up, respectively. The results of multivariate Cox regression analysis showed that the diameter of peri-ECV ( P=0. 0112, HR=1. 3232, 95％CI: 1. 0656-1. 6429 ) , the number of peri-ECV ( P=0. 0001, HR=1. 3666, 95％CI:1. 1634-1. 6052) and para-ECV diameter ( P=0. 0002, HR=1. 3641, 95％CI:1. 1558-1. 6100) were risk factors for EV progression. The use of nucleoside analogues treating HBV (P=0. 0020, HR=0. 4969, 95％CI: 0. 3186-0. 7751) and non-selective β-blockers descending portal venous pressure ( P=0. 0765, HR=0. 5732, 95％CI:0. 3097-1. 0611) were the protective factors for EV progression. The results of ROC curve analysis showed that the diameter of peri-ECV[ P<0. 001, area under the curve (AUC)= 0. 850, 95％CI: 0. 804-0. 895], the number of peri-ECV (P<0. 001, AUC=0. 831, 95％CI: 0. 784-0. 878), the diameter of para-ECV (P<0. 001, AUC=0. 924, 95％CI: 0. 895-0. 954) , and the number of para-ECV ( P<0. 001, AUC=0. 761, 95％CI: 0. 704-0. 817 ) had higher predictive value for EV progression;and the optimum cut-off values of each index were 1. 85 mm, 3. 5, 3. 35 mm, and 4. 5, respectively. The accuracies of prediction for EV progression were 76. 60％, 75. 19％, 84. 48％ and 70. 29％, respectively. Conclusion EUS can be used to predict EV progression in HBV-related hepatocirrhosis patients. Peri-ECV diameter>1. 85 mm, number>3. 5, and para-ECV diameter>3. 35 mm, number>4. 5 suggest a high risk of EV progression. For patients with HBV-related hepatocirrhosis complicated with mild EV, nucleoside analogues to anti-HBV and non-selective β-blockers to reduce portal hypertension can prevent EV progression.

Analysis of risk factors related to the prognosis in patients with late-onset severe pneumonia after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To investigate the prognostic factors of late-onset severe pneumonia ( LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods From January 2009 to December 2015, 68 patients with LOSP after allo-HSCT at Peking University Institute of Hematology were enrolled.In this retrospective study , univariate and multivariate analysis were used to evaluate the prognostic factors for LOSP after allo-HSCT.Results The median time from allo-HSCT to the development of LOSP was 213 ( 90-2330 ) days.The overall survival rate was 42.6% ( 29/68 ) .The median survival time from LOSP to death was 21 days.Early mortality was defined as death within 21 days after LOSP, as late death more than or equal to 21 days.The median oxygenation index was 199.15 (92.21-290.48) mmHg.LOSPs in thirty-two patients (36.8%) were caused by virus, bacteria, fungi or mixed pathogens.The median C-reactive protein (CRP) was 75.65 (0.94-451.00) mg/L.The median procalcitonin ( PCT) was 0.66 ( 0.00 -249.00 ) μg/L.The higher PCT value indicated an early higher mortality rate by the ROC curve (PCT:cut-off≥0.94μg/L).Furthermore, multivariate analysis suggested that PCT more than or equal to 0.94 μg/L was a risk factor for early death of LOSP ( OR=5.77, 95%CI 1.66-20.11, P=0.006).LOSP occurred later or equal to 213 days after allo-HSCT was also a risk factor of early death in LOSP ( OR=4.74, 95%CI 1.33 -16.89, P=0.017 ) .No previous history of chronic graft versus host disease (GVHD) (OR=4.50, 95%CI 1.58 -12.83, P=0.005) and LOSP later or equal to 213 days ( OR=4.40, 95%CI 1.61 -11.99,P=0.004) were the risk factors of late death in LOSP.Conclusions PCT more than or equal to 0.94 μg/L and LOSP later or equal to 213 days are the risk factors of early death in LOSP .No previous chronic GVHD and LOSP later or equal to 213 days are the risk factors of late death in LOSP .

Clinical value of PCR for viral detection of bronchoalveolar lavage fluid in the diagnosis and treatment of pneumonia after allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective@#To analyze the clinical value of real-time PCR for virus detection in the diagnosis and treatment of patients after allo-HSCT who had no infection evidence of pneumonia using routine pathogen detection panel.@*Methods@#The clinical data of 71 episodes with acute lung injury from May 2015 to March 2017 after allo-HSCT in hematology department of Peking University People’s Hospital (PKUPH) were retrospectively analyzed. PCR for virus detection and other routine pathogen detection tests were performed on bronchoalveolar lavage fluid (BALF) samples.@*Results@#Among 71 episodes with acute lung injury, a total of 15 patients were diagnosed as lower respiratory tract disease merely associated with virus (detection rate of 21.13%) , 19 episodes were absent of lower respiratory tract infection. The median time from allo-HSCT to the occurrence of lung injury were 176 (49-1 376) d and 196 (57-457) d respectively (z=-0.191, P=0.864) . There were no statistical differences for baseline characteristics and clinical features between two groups. The 100-day attributable mortalities were 13.3% (2/15) and 26.3% (5/19) (χ2=0.864, P=0.426) . Patients with low-dose steroids treatment had favorable outcome than those with high-dose steroids treatment (the dose of methylprednisolone ≥250 mg/d as standard) [4.2% (1/24) vs 60.0% (6/10) ]. In patients with detectable virus in BALF, 2 patients died with early high-dose steroids treatment, while 11 patients survived with no steroids treatment or late application.@*Conclusions@#Virus infection should be considered in post-HSCT pneumonia patient with negative result using routine pathogen detection panel. Expanding virus detection panel by PCR in BALF could increase diagnostic precision and might be instructive to treatment.

Effects of concentrated growth factor extract on the proliferation and differentiation of MC3T3-E1 cells attached to titanium surfaces / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of concentrated growth factor extract (CGFe) on the proliferation and differentiation of MC3T3-E1 osteoblasts attached to sandblasted and acid etched titanium surfaces.</p><p><b>METHODS</b>Trials were divided into experimental and control groups. The experimental group used a-MEM that contained CGFe (10% FBS), whereas the control group only used a-MEM (10% FBS). MTT assay was employed to detect the number of osteoblasts on the first, third, and fifth days. Alkaline phosphatase (ALP) activity and scanning electron microscope (SEM) were used to detect the osteoblast differentiations on the third and fifth days and to observe the osteoblast extensions on titanium surfaces for 12 h, respectively. Meanwhile, the levels of the osteogenetic biomarkers Runt-related transcription factor-2 (Runx2) and Osterix (Osx) on the third and seventh days were quantified via real-time polymerase chain reaction (PCR).</p><p><b>RESULTS</b>MTT assay indicated that on the first, third, and fifth days, the absorbance in the experimental group significantly increased than that in the control group (P < 0.05). ALP activity: on the third and fifth days, the absorbance of the experimental group was significantly higher than that of the control group (P < 0.05). SEM: at 12 h, the extension of the experimental group cells was larger than that of the control group. Real-time PCR: given the standardization in the group, the gene expression level of the control group on the third day was 1, and the Runx2 and Osx gene expressions in the experimental group were larger than those of the con- trol group.</p><p><b>CONCLUSION</b>CGFe can efficiently stimulate the proliferation, differentiation and extension of MC3T3-E1 cells.</p>

Low carbohydrate diet before 18F-FDG tumor imaging contributes to reduce myocardial 18F-FDG uptake / 中华核医学与分子影像杂志

Objective To evaluate whether low carbohydrate diet before 18F-FDG tumor imaging could reduce myocardial 18F-FDG uptake.Methods From April 2011 to January 2012,70 patients were enrolled in this study.They were randomly divided into control group (34 cases) and test group (36 cases).Patients in control group were on regular diet,while those in test group had low carbohydrate diet in the evening before imaging.Blood samples were taken before injection of 18F-FDG for the measurement of serum glucose,free fatty acid,insulin and ketone body.Whole body 18F-FDG tomography was performed with dualhead coincidence SPECT.The myocardial uptake of FDG was assessed visually and scored as 0 for no uptake,1 for uptake lower than liver,2 for uptake similar to liver,3 for uptake higher than liver,and 4 for remarkable uptake.The ratio of myocardium to liver (H/L) was calculated.Two-sample t test,Wilcoxon rank sum test and linear correlation analysis were performed.Results The myocardial uptake in test group was significantly lower than that in control group with H/L ratios of 0.94±0.57 and 1.50±1.04,respectively(t=-2.75,P＜0.05).The concentrations of serum free fatty acid and ketone body in test group were significantly higher than those in control group: (0.671±0.229) mmol/L vs (0.547±0.207) mmol/L and (0.88±0.60) mmol/L vs (0.57±0.32) mmol/L,t=2.38 and 2.67,both P＜0.05.The concentrations of glucose and insulin were (5.28±1.06) mmol/L and (35.16±33.70) pmol/L in test group,which showed no significant difference with those in control group ((5.19±0.78) mmol/L and (41.64±35.13) pmol/L,t=0.39 and-0.79,both P＞0.05).A negative correlation was found between the myocardial uptake of 18F-FDG and serum free fatty acid/ketone body concentration (r=-0.40,-0.33,both P＜0.01),respectively.There was no correlation between the myocardial uptake of 18 F-FDG and glucose/insulin (r =-0.02,0.13,both P＞0.05),respectively.Conclusion Low carbohydrate diet before 18F-FDG tumor imaging can reduce myocardial uptake,thus facilitating detection of lesions near the heart.

Design, synthesis and characterization of cyanopyrrolidine-bearing compounds as DPP-4 inhibitors / 南方医科大学学报

<p><b>OBJECTIVE</b>To synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro.</p><p><b>METHODS</b>Eleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl bromide with substituted phenyl piperazine pyridazinones.</p><p><b>RESULTS</b>The structures of the compounds were characterized by (1)H-NMR and MS spectra. Biological evaluation indicated that most of the compounds exhibited moderate inhibitory activities against DPP4.</p><p><b>CONCLUSION</b>The preliminary bioassay indicates that all the synthesized compounds have moderate DPP-4 inhibition activity, especially the compounds 1j and 1k with inhibition rates reaching 26.14% and 34.15% at the concentration of 1×10(5) nmol/L, respectively.</p>

The association of single nucleotide polymorphism in human ABCA2 gene with gallstone disease / 中华肝胆外科杂志

ObjectiveTo investigate the single nucleotide polymorphisms (SNPS) in the coding regions of the human ABCA2 gene and to determine the association of some of these SNPs with gallstone disease in a Chinese population. MethodsThe exons and part of the introns of the ABCA2 gene were sequenced using a fluorescent labeling automatic method in 24 patients with gallstone disease to identify and characterize the SNPs in a Chinese population. For SNPs in the exons, case-control studies were performed on patients and controls. ResultsTwelve SNPs were found within a 16911 bp region of the ABCA2 gene. Among them, two were in the exons, ten in the introns and five were novel SNPs. There was no significant difference in the SNPs genotype between the patients and the controis. ConclusionsThere is an important ethnic difference in the SNPs distribution of the human ABCA2 gene. The distribution of SNPs in the coding regions of the human ABCA2 gene is not significantly different between the patients and the controls.

The anti-HIV-1 entrance activity and mechanism of action of myriceric acid B from Rhoiptelea chiliantha Diels et Hand-Mazz / 中国药理学通报

Aim To investigate the HIV-1 entry inhibitory activities of myriceric acid B and C isolated from Rhoiptelea chiliantha Diels et Hand-Mazz and their mechanism of action.Method The plasmids encoding envelope proteins of HIV-1 (pHXB2) and VSV (pVSV-G) were cotransfected 293T cells with pNL4-3.Luc.R-E- to produce HIV-1 Env pseudovirus and VSV-G pseudovirus,respectively,which were used for testing the antiviral activities of these compounds.ELISA and molecular docking were used to study the mechanism of action of the active compounds.Results Myriceric acid B could significantly inhibit the infection of HIV-1 Env pseudovirus with an IC_(50) of(8.3±0.2)mg·L~(-1).The carbonoxyl group at C-28 position and the hydroxyl group at the C-3 position of myriceric acid B are important for its anti-HIV-1 activity.Like other HIV-1 entry inhibitors targeting gp41 (eg,ADS-J1 and NB-64), myriceric acid B could also block the gp41 six-helix bundle formation.Molecular docking analysis suggests that myriceric acid B may bind to the hydrophobic cavity of the gp41 N-trimeric coiled coil.Conclusion Myriceric acid B is a potent HIV-1 entry inhibitor targeting gp41 and can serve as a lead compound for developing novel anti-HIV-1 drug.

Expression of liver receptor homolog 1 gene in patients with cholesterol gallstone disease / 中华消化杂志

Objective To investigate the mRNA expression of liver receptor homolog 1 (LRH-1) gene in patients with cholesterol gallstone disease so that to elucidate the biomolecular pathogenesis of gallstone for- mation.Methods Twenty-seven patients with cholesterol gallstone (CGS) and 14 controls were included in this study.Biliary composition was assayed and mRNA expression of hepatic LRH 1 gene was determined by real time polymorphism chain reaction.Results In CGS patients,expression of LRH-1 was significantly higher than that in controls (14.18?9.37 vs 7.86?6.19,P＜0.05),and cholesterol of bile was oversaturated (1.17?0.27).Conclusion The formation of CGS may be related to increased expression of hepatic LRH-1 gene.