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Background Perfluoroalkyl substances (PFASs) are classified as persistent organic pollutants and have been widely detected in human. Studies investigating the associations between PFASs exposure and estimated glomerular filtration rate (eGFR) yielded inconsistent results, and little is known about the effects of PFASs on eGFR in population without kidney disease. Objective To explore the associations of exposure to PFASs with eGFR and renal dysfunction in population without kidney disease. Methods A total of 609 participants with an eGFR > 60 mL·min−1·1.73 m−2 and without renal impairment matched for sex and age (1∶1) were recruited from endocrinology department and medical examination center of two hospitals in Tianjin, China, from April 2021 to March 2022. Each subject was interviewed using a structured questionnaire to collect information about sex, age, height, weight, disease history, smoking, alcohol intake, etc. Clinical parameters were obtained from medical record, such as fasting blood glucose (FBG), creatinine (Cre), total cholesterol (TC), and triglyceride (TG). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by professionals using standard methods. The serum concentrations of PFASs were determined by liquid chromatography/mass spectrometry. Multivariable linear and logistic regression models were performed to evaluate the associations of PFASs exposure with eGFR and renal dysfunction, respectively. Subgroup analyses stratified by age and sex were also performed to assess the modified effects of covariates on the associations of PFASs exposure with eGFR. Results There were 283 males, accounting for 46.5% of the total population. The mean age of the participants was (56.86±12.47) years, and the average body mass index (BMI) was (25.59±3.84) kg·m−2. Perfluoro-n-octanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoro-n-nonanoic acid (PFNA), perfluoro-n-decanoic acid (PFDA), perfluoro-n-undecanoic acid (PFUnDA), sodium 1H, 1H, 2H, 2H-perfluoro-1-octanesulfonate (6:2 FTS), and perfluoropentane sulfonic acid (PFPeS) were positive in more than 75% of serum samples, and the corresponding median concentrations were 9.50, 1.67, 17.22, 1.86, 1.41, 0.78, 0.42, and 0.43 μg·L−1, respectively. After full adjustments of sex, age, BMI, hypertension, diabetes, TC, TG, smoking, and drinking, the linear regression models showed that log2-transformed PFHxS concentration was negatively associated with eGFR (b=−1.160, 95%CI: −2.280, −0.410). Compared with the lowest exposure tertile, the estimated change of eGFR in the highest tertile for PFHxS was significantly decreased (b=−2.471, 95%CI: −4.574, −0.368). Furthermore, compared with males, the negative association of PFHxS with eGFR was strengthened among females (female: b=−1.281, 95%CI: −2.388, −0.174; male: b=−0.781, 95%CI: −2.823, 1.261, Pinteraction=0.043). Conclusion A significant negative association between serum PFHxS and eGFR is observed in the sampled population without kidney disease, and females are more susceptible to PFASs exposure than the males.
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Objective:To explore the role of hippocampal γ oscillation abnormality in sepsis-associated encephalopathy (SAE).Methods:Seventy male Sprague-Dawley rats (2-3 months) were randomly (random number) divided into three groups according to the random digital table method: sham, CLP, and CLP + dopamine 4 (D4) receptor agonists RO-10-5824 group. The SAE animal model was established by cecal ligation and puncture (CLP). On day 10-14 after surgery, the open field, novel object recognition, and fear conditioning tests were performed. After that, the hippocampus was collected to measure expressions of parvalbumin (PV) and D4 receptor. In another set of experiment, CA1 local field potential (LFP) were recorded, and the relationship between LFP and time with novel object was analyzed. Independent sample t-test was used for pairwise comparisons, and multiple comparisons were performed by one-way ANOVA, followed by the Tukey multiple comparisons test. Correlation was analyzed using Pearson correlation. Statistical significance was assumed when P<0.05. Results:Compared with the sham group, hippocampal PV (77.54±4.61)%, D4 expression (56.36±3.88)% and γ oscillation power (41.1±8.62)%, object exposure time (36±3) s, new object recognition rate (49±4)%, and scene stiffness time (56±7) s were decreased significantly ( P<0.05). However, RO-10-5824 treatment could increase hippocaml γ oscillation power (92.3±6.7)%, and reverse the decreased new object exposure time (44±3) s and new object recognition rate (63±4)%. Correlation analysis showed that hippocampal γ oscillation power was positively associated with new object exposure time ( r=0.609 2, P=0.015 9). There was no difference in total distance traveled or time spent in the center among groups ( P>0.05). Conclusion:Hippocampal γ oscillation abnormality might play a key role in cognitive impairment associated with SAE.
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Objective To investigate the effects of Nod-like receptor protein 3 inhibitor MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy (SAE).Methods Ninety adult male C57BL/6 mice were randomly (random number) divided into three groups:the sham + saline group (n=20,sham group),CLP + saline group (n=35,CLP group),and CLP + MCC950 group (n=35,MCC950 group).SAE mouse model was established by cecal ligation and puncture (CLP) surgery.Saline (10 mL/kg) or MCC950 (10 mg/kg) was intraperitoneally injected 30 min before surgery and on day 1,2,4 and 6 after surgery according the grouping.Seven days after surgery,six mice were taken from each group.Western blot was used to detect the hippocampal content of NLRP3,apoptosis-associated specklike protein (ASC),interleukin-1β (IL-1β) and IL-18.The number of NLRP3-positive cells in CA 1 region were detected by immunohistochemical analysis.The remaining mice in each group were used for open field and fear conditioning tests 14 days after surgery.One-way analysis of variance was used for inter-group comparison,and SNK-q test was used for pairwise comparison.A P value ＜0.05 was considered statistically significant.Results Compared the MCC950 group with the CLP group,the freezing time of context test was significantly increased [(137±21) s vs (84±15) s,P=0.013],the hippocampal content of NLRP3,IL-1β and IL-18 were significantly reduced (P＜0.01),and the number of NLRP3-immunoreactive cells per mm2 in CA region were significantly decreased (23±5 vs 74±13,P＜0.01).There was no significant changes in protein level of ASC and results of open field tests (P＞0.05).Conclusions MCC950 administration can improve cognitive function in a mouse model of SAE,which is probably due to the inhibition of NLRP3 inflammasome and downstream inflammatory cytokines IL-1β and IL-18.
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Objective@#To explore the correlation of non-coding RNA and the tumor-associated antigen midkine (MK) in SKOV3cells and the clinical significance for diagnosis of ovarian cancer. @*Methods@#The Agilent′s gene chips (miRNAs chip and lncRNAs chip) were used to analyze the differential expression of miRNAs and lncRNAs in both MK-overexpressing SKOV3-MK cells and the control SKOV3-Con cells to screen the potential biomarkers in ovarian cancer. The clinical significance of midkine in the serum and tissues samples was analyzed for the patients with ovarian cancer by quantitative PCR combined with clinical data. @*Results@#Compared with control SKOV3-con cells, MK overexpression significantly promoted the expressions of 11 miRNAs and 7 lncRNAs in SKOV3 cells (P＜0.01, ratio＞3 fold), reduced the expressions of 8 miRNAs and 13 lncRNAs (P＜0.01, ratio＜0.3). Results of qPCR showed that the expression level of miR489 was significantly lower in ovarian cancer tissues than that of the contralateral normal ovarian tissues, while HOTAIR was significantly elevated (P＜0.05). The expression level of HOTAIR in the serum of ovarian cancer patients was significantly higher than that in healthy controls group with same age (0.036±0.024 vs 0.019±0.020, P=0.002). ROC curve analysis of HOTAIR showed that the specificity was 66.7%, the sensitivity was 75.6% and the AUC value was 0.749 as a marker for serum detection of ovarian cancer when the cutoff value was 0.017 6. @*Conclusion@#Long-chain non-coding RNA HOTAIR may be served as a potential biomarker in serum of ovarian cancer patients.
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Objective@#To investigate the expression levels of long non-coding RNA LincROR in plasma and tissues of ovarian cancer patients and its value in the screening of ovarian cancer. @*Methods@#The plasma samples from 30 healthy women, 56 cases of ovarian cysts, 23 cases of endometriosis, 38 cases of endometrial carcinoma, 35 cases of cervical cancer, 42 cases of ovarian cancer, 21 cases of ovarian cancer after operation and 26 cases of ovarian cancer after chemotherapy were collected, and the expression levels of LincROR in these samples were detected by quantitative PCR. The diagnostic value of LincROR in common clinical gynecological diseases was evaluated combined with clinical data. @*Results@#The expression levels of LincROR in plasma of ovarian cancer patients (2.90± 4.42 ) were significantly higher than that in healthy women (0.23±0.28) and the patients with benign ovarian cysts (0.62±0.55, P ＜ 0.01 ). The results of ROC curve analysis showed that the diagnostic value of plasma LincROR in the screening of breast cancer was better than that of CA125, CA199, CA153, AFP and CEA. The sensitivity and specificity of combined screening of LincROR and CA125 for ovarian cancer were 89.7% and 86.7%, respectively (AUCROC=0.918, 95% CI :0.817-0.973). In addition, the expression levels of plasma LincROR in the postoperative patients were significantly lower than that in the ovarian cancer patients without any treatment (0.50±1.72 vs 2.90±4.42, P ＜0.01). The ROC curve analysis showed that plasma LincROR was more sensitive than CA125 in evaluating the efficacy of chemotherapy for ovarian cancer (AUCROC: 0.866 vs 0.738). @*Conclusion@#LincROR is expected to be an ideal biomarker for the screening of ovarian cancer, and has potential clinical value in evaluating the efficacy of chemotherapy for ovarian cancer. Combination of LincROR with CA125 may improve the sensitivity and specificity of the screening of ovarian cancer
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Objective To investigate the efficacy of preemptive analgesiawith ultrasound-guided modified dorsal penile nerve block combined ketorolac tromethamine for circumcision in pediatric patients.Methods Forty-five pediatric patients with ASA grade Ⅰ undergoing elective circumcision were randomly divided into 3 groups (n=15 each).The same intravenous compound anesthesia was used in the three groups.The pediatric patients underwent ultrasound-guided modified dorsal penile nerve block with a mixture of 0.1 ml/kg of 0.2% ropivacaine and 0.8% lidocaine before operation in group A and group B.The pediatric patients were given ketorolac tromethamine 1 mg/kg intramuscular injection before operation in group A and group C.The total consumption of propfol and sufentanil, occurrence of intraoperative body movement and respiratory depression, emergence time, time from waking up to going out of PACU and adverse reactions such as postoperative agitation, nausea, vomiting and pruritus were aslo recorded.The requirement for postoperative paracetamol suppositories was recorded.Results Compared with group C, the total consumption of propfol and sufentanil were significantly decreased, incidence of body movement andrespiratory depression were significantly decreased, the emergence time and time from waking up to going out of PACU was significantly shortened, requirement for paracetamol suppositories were significantly decreased in group A and group B(P<0.05).Compared with group B, incidence of requirement for paracetamol suppositories was significantly decreased in group A (P<0.05).No pediatric patients developed postoperative nausea, vomiting, pruritus and incidence of emergence agitation had no statistical difference in the three groups.Conclusion Preemptive analgesia with ultrasound-guided modified dorsal penile nerve block combined ketorolac tromethamine is safe and effective when used for circumcision in pediatric patients, and it has good efficacy of postoperative analgesia.
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Objective To investigate the relationship between subclinical hypothyroidism (SCH) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).Methods A total of 792 patients of T2DM were enrolled in the study.There were 448 males and 344 females,with an average age of (54.13 ± 13.06)years.The average duration of diabetes was (8.03 4±6.70) years.The patients were grouped according to the degree of DR and thyroid function.Among them,483 patients (61.0％) were no DR,240 patients (30.3％) were mild DR,69 patients (8.7％) were severe DR.725 patients (91.5％) were normal thyroid function,67 patients (8.5％) were SCH.The prevalence of SCH among no DR group,mild DR group and severe DR group was compared.And the prevalence of DR between normal thyroid function group and SCH group was compared.Logistic regression analysis was used to estimate the association between SCH and DR.Results No significant differences among the three groups (no DR group,mild DR group,severe DR group) were found in the prevalence of SCH (x2=1.823,P=0.402).There were no significant differences in the incidences of DR between normal thyroid function group and SCH group (x2=1.618,P=0.239).Logistic regression analysis demonstrated that SCH was not significant associated with DR [mild DR:odds ratio (OR)=1.361,95％ confidence interval (CI)=0.773-2.399,P=0.286;severe DR:OR=1.326,95％CI=0.520-3.384,P=0.555;DR:OR=1.353,95％ CI=0.798-2.294,P=0.261).Conclusion SCH is not significant associated with DR in patients with T2DM.
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The aim of the present research was to investigate and analyze the hunting intentions of medical students for rural grassroots in Gansu and to provide a reference for decision-making on rural health human resource . A questionnaire is the research tool which was used to investigate the views of the senior students from six medical schools , and we studied their employment willingness to rural healthcare institutions .Chi-square test and non-condi-tional logistic regression analyses were used for data analysis .A sample of 600 medical graduates was involved in this investigation.The results of this study show that more than a half (55.6%) of the students would like to work in ru-ral, but only 13.8%of which were “very willing” to work at the rural healthcare institutions .According to the out-comes of this investigation , the number of junior college students who would like to work at the grassroots was 2.3 times the number of the undergraduate students .Medical students whose monthly salary expectations were not high ,with the household registration in rural areas , and having a better understanding of the policy of rural grass-roots em-ployment were more likely to work at the rural healthcare institutions .Based on the findings of this investigation , it can be concluded that the grassroots medical career intention of medical students is not only influenced by its own fac -tors, such as education and household registration , but also the policy of the government , school employment guid-ance and social atmosphere play an important role .The above-mentioned factors should be considered by decision-making and management departments of public healthcare .The departments should introduce a reasonable recruit-ment policy and strengthen the construction of grass-roots medical technology , equipment , and infrastructure , im-prove the grass-roots of employment environment and career development opportunities and strengthen the medical students'employment guidance work to make medical students more willing to work at rural healthcare institutions .
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Objective To establish a triplex TaqMan real-time PCR system containing internal amplification control(IAC)to detect cholera toxin gene ctxA and enterotoxigenic Escherichia coli(ETEC)heat-labile enterotoxin gene elt. Methods Primers and probes were designed based on the sequences of ctxA,elt and IAC. Both sensitivity and specificity were analyzed and interactions between different reactions were evaluated. Results This system showed that the sensitivity of ctxA was 94 copies/reaction while the elt 79 copies/reaction and the amplification efficiency were 94.7%and 98.1%,respectively. Under the ratio of copy numbers on gene ctxA to elt as between 1∶1-1∶10, when both targets were detected,with impact was less on each other. However,when the amount of elt or ctxA was 100 times of IAC,the amplification of IAC was significantly inhibited. Conclusion This system showed both satisfactory sensitivity and specificity, thus could be used to detect pathogenic bacteria in diarrhea stools. The detection of IAC could prompt the presence of PCR inhibitors in samples being tested.
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Objective To establish a triplex TaqMan real-time PCR system containing internal amplification control(IAC)to detect cholera toxin gene ctxA and enterotoxigenic Escherichia coli(ETEC)heat-labile enterotoxin gene elt. Methods Primers and probes were designed based on the sequences of ctxA,elt and IAC. Both sensitivity and specificity were analyzed and interactions between different reactions were evaluated. Results This system showed that the sensitivity of ctxA was 94 copies/reaction while the elt 79 copies/reaction and the amplification efficiency were 94.7%and 98.1%,respectively. Under the ratio of copy numbers on gene ctxA to elt as between 1∶1-1∶10, when both targets were detected,with impact was less on each other. However,when the amount of elt or ctxA was 100 times of IAC,the amplification of IAC was significantly inhibited. Conclusion This system showed both satisfactory sensitivity and specificity, thus could be used to detect pathogenic bacteria in diarrhea stools. The detection of IAC could prompt the presence of PCR inhibitors in samples being tested.
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<p><b>OBJECTIVE</b>To establish a triplex TaqMan real-time PCR system containing internal amplification control (IAC) to detect cholera toxin gene ctxA and enterotoxigenic Escherichia coli (ETEC)heat-labile enterotoxin gene elt.</p><p><b>METHODS</b>Primers and probes were designed based on the sequences of ctxA, elt and IAC. Both sensitivity and specificity were analyzed and interactions between different reactions were evaluated.</p><p><b>RESULTS</b>This system showed that the sensitivity of ctxA was 94 copies/reaction while the elt 79 copies/reaction and the amplification efficiency were 94.7% and 98.1%, respectively. Under the ratio of copy numbers on gene ctxA to elt as between 1 : 1-1 : 10, when both targets were detected, with impact was less on each other. However, when the amount of elt or ctxA was 100 times of IAC, the amplification of IAC was significantly inhibited.</p><p><b>CONCLUSION</b>This system showed both satisfactory sensitivity and specificity, thus could be used to detect pathogenic bacteria in diarrhea stools. The detection of IAC could prompt the presence of PCR inhibitors in samples being tested.</p>
Subject(s)
Cholera Toxin , Genetics , Enterotoxigenic Escherichia coli , Genetics , Enterotoxins , Genetics , Real-Time Polymerase Chain Reaction , Methods , Sensitivity and SpecificityABSTRACT
Objective To observe the effect of adding on glimepiride in treating type 2 diabetic patients who had suffered the disease for more than 10 years and were poorly controlled with insulin combined with nonsulfonylureas drugs. Methods Seventy-five type 2 diabetic patients poorly controlled with insulin combined with non-sulfonylureas drugs were randomly divided into glimepiride-added group (INS+GM, n = 39 )and continuation of insulin group ( INS, n = 35 ). HbA1c, plasma glucose, daily insulin dose, number of hypoglycemic events, body weight, plasma lipid concentration,and high-sensitive C-reactive protein (hs-CRP)were recorded at weeks 0, 12,and 24. The levels of plasma free fatty acid ( FFA), adiponectin, and tumor necrosis factor-α ( TNF-α ) were measured before and 24 weeks after the therapy. Results At 12 and 24 weeks, fasting blood glucose, 2 h postprandial blood glucose,and HbA1c were improved in INS+GM group more markedly than in INS group, and daily insulin dose and body weight were decreased in INS+GM compared with INS ( P＜0. 05 ). The number of hypoglycemic events and plasma lipid concentration did not differ between two groups ( P＜0.05 ). The levels of plasma FFA,TNF-α,hs-CRP, and HOMA-IR were lower in INS+GM than INS ( P＜0.05 ), the adiponectin was higher in INS + GM than INS ( P ＜ 0.05 ). Conclusion Adding glimepiride to insulin therapy resulted in a sustained better glycemic control with less insulin daily dose, decresed body weight, and no increase in hypoglycemic events as compared with the continuing insulin therapy group. Increased adiponectin, as well as decreased plasma FFA and TNF-α may underlie the improvement of insulin resistance with glimepiride treatment.
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Objective To investigate the effect of pentoxifyccine (FIX) on the pathway of high glucosd-induced expression of CTGF in mesangial cells. Methods Cultured rat mesangial celld were used to study the influence of different concentration of high glucose on the expression of TGF-β, CTGF, p-Smad2/3, Smad7 and FN in different exposure time. Furthermore the effect of high glucose plus TGF-β neutral antibody and different concentration of FIX on the obove expression was evaluated as well. Results High glucose could increase TGF-β, CTGF mRNA and protein expression in mesangial cells (P<0.05) in time-and dose-dependent manner, and at the same time p-Smad2/3 expression increased and Smad7 expression decreased (P<0.05).The blockage of TGF-β could decrease high glucose-induced CTGF mRNA and protein expression by 86.4% and 91.8%. PTX could suppress high glucose-induced CTGF expression in mesangial cells. When the PTX dosage increased, the suppressive effect became more remarkable, but PTX had no influence on the TGF-β expression. Conclusions High glucose up-regulates CTGF mRNA and protein expression mainly through TGF-β-Smads pathway. PTX can suppress CTGF expression effectively, but has no direct inhibition of TGF-β expression.