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Objective To analyze result of the external quality assessment for laboratories of toxicological pathology diagnosis in organizations in China. Methods A total of 86 organizations that participated in the 2020-2021 external quality assessment in laboratory of toxicological pathology diagnosis (hereinafter referred to as "reference units") were selected as research subjects using convenient sampling method, and the assessment results were analyzed. Results The median of total score was 92, and the 0-100 percentiles were 64-100 in these 86 reference units. Among these reference units, 76 were rated as excellent, 10 as qualified, with the excellent and the qualified rate of 88.4% and 11.6%, respectively. No reference unit was rated as unqualified. The rates of excellence of the reference units in public health institutions, pharmaceutical research institutions, drug safety evaluation centers and testing companies were 95.7%, 84.2%, 85.7% and 86.7%, and the qualified rates were 4.3%, 15.8%, 14.3% and 13.3%, respectively. The distribution of excellence and qualification among the four types of reference units showed no statistical difference (P>0.05). The distribution of sample scores according to the three grades of poor, good, and excellent were 4.9%, 20.7%, and 74.5% in public health institutions, 8.6%, 23.7%, and 67.8% in pharmaceutical research institutions, 12.5%, 25.0%, and 62.5% in drug safety evaluation centers, and 5.4%, 17.5%, and 77.1% in testing companies. The proportion of excellence unit in public health institutions was higher than that in pharmaceutical research institutions (P<0.05). Conclusion The overall toxicological pathology diagnostic capabilities in China are good, and various types of reference units demonstrate comparable technical capabilities. However, there is a need for standardization of diagnostic terminology.
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Background Occupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. Objective To explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. Methods From January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. Results A total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P50 (P25, P75) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g−1, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (ORint)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). Conclusion This study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.
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Objective To investigate the influence of intrahepatic cholestasis of pregnancy (ICP) on adverse pregnancy outcomes of hepatitis B virus (HBV)-infected pregnant women. Methods A retrospective analysis was performed for 232 pregnant women with chronic HBV infection who were admitted to Beijing YouAn Hospital, Capital Medical University, from March 2018 to March 2021. According to the presence or absence of ICP, the patients were divided into HBV infection group with 100 patients and HBV+ICP group with 132 patients; according to the severity of ICP, the patients in the HBV+ICP group were further divided into HBV+mild ICP group with 86 patients and HBV+severe ICP group with 46 patients. The above groups were compared in terms of the incidence rates of maternal complications during pregnancy, such as premature delivery, premature rupture of membranes, gestational diabetes mellitus, hypertensive disorder complicating pregnancy, and postpartum hemorrhage (PPH), as well as the adverse outcomes of fetus/neonate, such as intrauterine fetal death, neonatal asphyxia, amniotic fluid pollution degree Ⅲ(AFⅢ), neonatal respiratory distress syndrome, small-for-gestational-age (SGA), admission to the neonatal intensive care unit, pneumonia, and mother-to-child transmission (MTCT) of HBV. A one-way analysis of variance was used for comparison between multiple groups; the chi-square test, the chi-square test with continuity correction or the Fisher's exact test was used for comparison of categorical data between multiple groups. Results Compared with the HBV infection group in terms of maternal complications in late pregnancy, the HBV+ICP group had significantly higher incidence rates of premature delivery and PPH ( χ 2 =4.169 and 5.448, P =0.041 and 0.020), and in terms of the adverse outcomes of neonates, the HBV+ICP group had significantly higher incidence rates of neonatal asphyxia, AFⅢ, and SGA than the HBV infection group ( χ 2 =5.448, 16.567, and 11.053, P =0.020, P < 0.001, and P =0.002). In terms of the adverse outcomes of neonates, the HBV+severe ICP group had significantly higher incidence rates of AFⅢ and SGA than the HBV+mild ICP group ( χ 2 =4.200 and 4.511, P =0.040 and 0.034). Conclusion Compared with the pregnant women with HBV infection alone, the pregnant women with HBV infection and ICP have significantly higher incidence rates of adverse pregnancy outcomes in mothers and neonates, and the incidence rate of adverse outcomes in neonates increases with the increase in the severity of ICP. However, ICP has no influence on HBV MTCT.
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Objective:To investigate the prognosis and its influencing factors of elderly patients with diffuse large B-cell lymphoma (DLBCL), and to provide references for clinical treatment.Methods:The clinical data of 152 patients with DLBCL aged over 60 years old from January 2013 to June 2017 in Shanxi Provincial Cancer Hospital were retrospectively analyzed. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of factors affecting the prognosis of patients, and the Cox proportional hazard regression model was used for multivariate analysis.Results:The median overall survival (OS) time of 152 elderly patients with DLBCL was 36 months (32-40 months), and the 1, 2, and 3-year OS rates were 80.26%, 61.84%, and 57.24%, respectively. Univariate analysis showed that the differences in the 3-year OS rates of elderly DLBCL patients with different gender, clinical staging, lactate dehydrogenase (LDH), Ki-67, β 2-microglobulin (β 2-MG) levels, smoke history, use of rituximab and CHOP regimens were statistically significant (all P < 0.1). The results of multivariate Cox regression analysis showed that male, late clinical staging, elevated LDH, and elevated β 2-MG were risk factors for the OS of elderly DLBCL patients (all P < 0.05). The use of rituximab and CHOP regimens were the protective factors for the OS of elderly patients with DLBCL (all P < 0.05). Conclusions:The elderly male DLBCL patients with late clinical staging, elevated LDH and elevated β 2-MG have a poor prognosis, and the elderly DLBCL patients treated with CHOP regimen and rituximab have a better prognosis.
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Objective:To explore the factors influencing complete remission in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the effect of the interaction of Karnofsky performance status scale (KPS) scores and the level of lactate dehydrogenases (LDH) on whether patients with DLBCL are completely relieved.Methods:The clinical data of 373 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2014 to December 2020 were retrospectively analyzed. SPSS 25.0 logistic regression model and Cox proportional risk regression models were used to explore the factors affecting complete remission in patients with DLBCL and to explore whether there was a multiplicative interaction between the factors. For factors with multiplicative interactions, the Matrix package, epiR package, and survival package in R 4.2.0 software were used to analyze whether there was an additive interaction. The relative excess risk of interaction (RERI), attributable proportion due to interaction (AP), and the synergy index (S) were used to evaluate the presence of additive interactions.Results:Elevated β 2 macroglobulin (β 2-MG), KPS scores below 80, and elevated LDH were risk factors for incomplete remission in patients with DLBCL (all P < 0.05). The risk of incomplete remission in patients with elevated β 2-MG, KPS scores below 80 and LDH was 1.971 times ( OR = 1.971, 95% CI 1.161-3.346), 2.056 times ( OR = 2.056, 95% CI 1.057-4.000) and 3.351 times ( OR = 3.351, 95% CI 1.783-6.300) higher than those in patients with normal β 2-MG, KPS scores above 80 and non-elevated LDH, respectively. There was a negative multiplicative interaction between the two risk factors of KPS scores below 80 and elevated LDH ( OR = 0.317, 95% CI 0.126-0.785). The estimated value of RERI, AP and S was -2.07 (95% CI -4.79-0.64),0.50 (95% CI -1.68-0.32),0.50 (95% CI 0.22-1.13), respectively; and there was no additive interaction among them. Conclusions:Elevated β 2-MG, KPS scores below 80, and elevated LDH are risk factors influencing incomplete remission for patients with DLBCL. The combined effect in patients with the combination of elevated LDH and KPS scores below 80 is lower than the single effect of the multiple of the both. There is a negative multiplicative interaction and no additive interaction in DLBCL patients with KPS scores below 80 and elevated LDH level.
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Objective:To investigate the clinical characteristics of primary thyroid lymphoma (PTL) and the differences in clinical manifestations and survival between the two main pathological subtypes of PTL.Methods:The clinical data of 52 patients with PTL diagnosed in Shanxi Province Cancer Hospital from January 2011 to January 2022 were retrospectively analyzed. The clinical characteristics and survival between the two main pathological subtypes [diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue lymphoma (MALT)] were compared.Results:Among 52 PTL patients, there were 12 males and 40 females, with a median age of 65 years old (34-83 years old). All patients presented with anterior cervical mass at the time of visit. MALT was diagnosed in 12 cases (23.1%). DLBCL was diagnosed in 37 cases (71.2%), of which 5 cases were double/triple expression lymphoma. B-cell lymphoma (unclassified) was diagnosed in 2 cases (3.8%). Follicular lymphoma (FL) was diagnosed in 1 case (1.9%). There was statistical difference in the proportion of patients with cervical lymph node enlargement between MALT and DLBCL patients [66.7% (8/12) vs. 94.6% (35/37), χ2 = 4.23, P < 0.05]. The 3-year OS rates of MALT and DLBCL patients were 90.9% and 73.9%, and the difference in OS between the two groups of patients was statistically significant ( χ2 = 5.11, P = 0.024). Conclusions:Pathological subtypes of PTL are related to the prognosis of patients.
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Objective:To explore the relationship between rs671 (ALDH2), rs1229984 (ADH1B), RS141973904 (ADH1C), RS1799971 (OPRM1), rs1997794 (PDYN) polymorphism and individual's alcohol subjective response and drinking behavior.Methods:From January to December 2018, patients with alcohol dependence who were hospitalized in the First Affiliated Hospital of Xinjiang Medical University and Xinjiang mental health center and met the DSM-IV were selected (alcohol dependence group, n=100). Alcohol dependence patients and normal healthy subjects (control group, n=100) completed general demographic questionnaire, including drinking behavior such as the frequency of drinking each week and the maximum alcohol consumption at one drink, and informed consent, then were extracted of venous blood for DNA test.After that, alcoholics completed the alcohol challenge test.Biphasic alcohol effect scale(BAES) and drug effect questionnaire (DEQ) were completed before drinking and after drinking 30, 60, 120, 180 minutes respectively.Hardy-Weinberg equilibrium for genetic linkage analysis was calculated by utility program.Pearson Chi-square test was used to analyze the odds ratio(OR) value, and the chi-square test of repeated measured variables were used to analyze the variation trend of individual subjective response to alcohol after drinking. Results:rs671 allele A was associated with alcohol dependence risk (χ 2=23.97, P<0.01, OR=7.11, 95% CI=2.93~17.30), and for rs1229984 polymorphism the dominant genetic model " T/T-C/T" was taken as the best fitting model ( P<0.01, OR=0.16, 95% CI=0.08-0.32), which was a protective factor for alcohol dependence.Alcoholics with TT genotype in rs1229984 had lower maximum alcohol consumption ( F=4.86, P=0.01) and weekly alcohol consumption ( F=4.51, P=0.01) than those with CC and CT genotype.The maximum alcohol consumption ( F=20.28, P<0.01) and weekly alcohol consumption ( F=12.46, P<0.01) of individuals with GG and GA genotype in rs1799971 were higher than those with AA genotype.The AA genotype of rs1799971 showed lower stimulative effect ( F=7.99, P=0.01), higher sedative effect ( F=57.04, P<0.01), and lower " like" ( F=13.38, P<0.01) and " more" effect ( F=26.37, P<0.01) than that with GG and GA genotype. Conclusion:rs671 and rs1229984 are more closely related to individual drinking behavior and volume of alcohol consumption.rs1799971 is not only related to individual drinking behavior, but also has a more closed relationship with subjective response to alcohol.
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Objective:To investigate the role and mechanism of anterior gradient-2(AGR2)in intestinal mucosal barrier injury induced by tumor necrosis factor-α(TNF-α).Methods:Caco-2 cell monolayers were pre-transfected with an AGR2 plasmid and then exposed to TNF-α.Real-time PCR was employed to detect AGR2 mRNA expression, with western blot detection of AGR2 protein expression.Epithelial permeability was assessed by detecting transepithelial electrical resistance.Electron microscope was used to observe autophagic bodies.Results:Both AGR2 mRNA and protein expression levels were significantly reduced by TNF-α exposure compared with the levels in untreated control monolayers.AGR2 overexpression signifcantly ameliorated TNF-α induced epithelial barrier hyperpermeability, and mediated mitophagy in Caco-2 cell monolayers.Conclusion:This study suggested that AGR2 could inhibit TNF-α induced intestinal barrier dysfunction and this protective mechanism might be promoted by mediated mitophagy in Caco-2 cell monolayers.
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Atrial fibrillation is one of the most common arrhythmias.The incidence of atrial fibrillation increases with age.Increased cardiac late sodium currents are closely related to the occurrence of atrial fibrillation, and inhibition of the late sodium current has become a new target for antiarrhythmic therapy.Late sodium current inhibitors play an anti-atrial fibrillation role by inhibiting atrial late sodium currents and may become a new strategy for atrial fibrillation treatment due to their unique mechanisms and satisfactory safety.
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Objective@#To explore the factors influencing the mobilization and collection of autologous peripheral blood stem cells.@*Methods@#The clinical data of 62 patients who received autologous peripheral blood hematopoietic stem cell mobilization in Shanxi Provincial Cancer Hospital from April 2012 to March 2017 were collected. The effects of age, gender, disease type, chemotherapy cycle, disease status, different schemes and the number of CD34+ cells in peripheral blood of patients 1 d before collection on the number of CD34+ cells and the success rate of CD34+ cells collection were analyzed. Measurement data were compared by one-way ANOVA and t test; count data were compared by χ 2 test; multivariate analysis was performed by multiple linear regression analysis.@*Results@#There were statistically significant differences in the number of CD34+ cells between patients with chemotherapy >6 cycles and ≤6 cycles [(2.6±1.3)×106/kg vs. (5.8±2.2)×106/kg; t = 5.221, P < 0.01], and the difference in the success rate of CD34+ cell collection between the two groups was statistically significant [68.8% (11/16) vs. 97.8% (45/46); χ2 = 8.396, P = 0.004]. The difference in the CD34+ cells yield was not statistical significance between male and female patients [(5.4±2.2)×106/kg vs. (4.5±2.8)×106/kg; t = 1.302, P = 0.198)], but the collection success rate in males was higher than that in females [97.6% (40/41) vs. 76.2% (16/21)], and the difference was statistically significant (χ 2 = 5.017, P = 0.025). The success rate of CD34+ cell collection in patients with ≥10/μl CD34+ cell in the peripheral blood was significantly higher than that in patients with < 10/μl CD34+ cells 1 d before the collection[97.9% (47/48) vs. 64.3% (9/14)], and the difference was statistically significant (χ 2 = 10.668, P = 0.001). The differences in CD34+ cells yield and collection success rate between patients with different age, disease type, disease status and mobilization regimen were not statistically significant (all P > 0.05). Multi-factor analysis showed that > 6 cycles chemotherapy before mobilization was the adverse factor affecting stem cell collection (b = -3.435, P < 0.01).@*Conclusions@#The effective mobilization and collection of autologous peripheral blood stem cells are related to the number of chemotherapy cycles before mobilization. The stem cell mobilization and collection should be conducted as soon as possible when the chemotherapy is ≤ 6 cycles and the patient reaches partial remission or above. In addition, peripheral blood CD34+ cell count should be monitored during mobilization. When the peripheral blood CD34+ cell count is > 10/μl, the collection could be started on the next day to obtain a better collection effect, so as to improve the success rate of collection.
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Objective To explore the factors influencing the mobilization and collection of autologous peripheral blood stem cells. Methods The clinical data of 62 patients who received autologous peripheral blood hematopoietic stem cell mobilization in Shanxi Provincial Cancer Hospital from April 2012 to March 2017 were collected. The effects of age, gender, disease type, chemotherapy cycle, disease status, different schemes and the number of CD34+cells in peripheral blood of patients 1 d before collection on the number of CD34+cells and the success rate of CD34+cells collection were analyzed. Measurement data were compared by one-way ANOVA and t test; count data were compared by χ2 test; multivariate analysis was performed by multiple linear regression analysis. Results There were statistically significant differences in the number of CD34+cells between patients with chemotherapy＞6 cycles and≤6 cycles [(2.6±1.3)×106/kg vs. (5.8±2.2)×106/kg;t＝5.221, P<0.01], and the difference in the success rate of CD34+cell collection between the two groups was statistically significant [68.8% (11/16) vs. 97.8% (45/46); χ 2＝ 8.396, P ＝ 0.004]. The difference in the CD34+cells yield was not statistical significance between male and female patients [(5.4±2.2)×106/kg vs. (4.5± 2.8)×106/kg; t ＝ 1.302, P＝ 0.198)], but the collection success rate in males was higher than that in females [97.6% (40/41) vs. 76.2% (16/21)], and the difference was statistically significant (χ2＝5.017, P ＝0.025). The success rate of CD34 + cell collection in patients with ≥10/μl CD34 + cell in the peripheral blood was significantly higher than that in patients with < 10/μl CD34+cells 1 d before the collection[97.9% (47/48) vs. 64.3% (9/14)], and the difference was statistically significant (χ 2 ＝ 10.668, P＝ 0.001). The differences in CD34+cells yield and collection success rate between patients with different age, disease type, disease status and mobilization regimen were not statistically significant (all P＞ 0.05). Multi-factor analysis showed that ＞6 cycles chemotherapy before mobilization was the adverse factor affecting stem cell collection (b ＝ -3.435, P< 0.01). Conclusions The effective mobilization and collection of autologous peripheral blood stem cells are related to the number of chemotherapy cycles before mobilization. The stem cell mobilization and collection should be conducted as soon as possible when the chemotherapy is ≤ 6 cycles and the patient reaches partial remission or above. In addition, peripheral blood CD34+cell count should be monitored during mobilization. When the peripheral blood CD34+cell count is ＞10/μl, the collection could be started on the next day to obtain a better collection effect, so as to improve the success rate of collection.
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Objective To explore the impact of neoadjuvant therapy on the number of harvested lymph nodes in D2 radical resection of the proximal locally advanced gastric cancer (GC).Methods The retrospective cohort study was conducted.The clinicopathological data of 319 patients with proximal locally advanced GC who were admitted to the Beijing Cancer Hospital from January 2013 to September 2016 were collected.Of 319 patients,200 underwent D2 radical resection of GC and didn't undergo neoadjuvant therapy who were divided into the surgery group,88 underwent neoadjuvant chemotherapy into the chemotherapy group,and 31 underwent neoadjuvant chemoradiotherapy into the chemoradiotherapy group.Observation indicators and evaluation criteria:comparison of postoperative pathological results among 3 groups,according to tumor staging guideline of American Joint Committee on Cancer (AJCC) (8th version) Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA.Measurement data with skewed distribution were described as M (range),comparisons among groups were analyzed using the ANOVA,and pairwise comparisons were analyzed using nonparametric test.Comparisons of count data among groups were analyzed using the exact chisquare test,and pairwise comparisons were analyzed using the chi-square partition method.Results Comparison of postoperative pathological results among 3 groups:stage T0,Tla,Tlb,T2,T3,T4a and T4b of T staging were respectively detected in 0,2,10,24,99,58,7 patients in the surgery group and 5,1,2,11,41,26,2 patients in the chemotherapy group and 5,1,2,8,10,4,1 patients in the chemoradiotherapy group.Stage N0,N1,N2,N3a and N3b of N staging 56,41,34,47,22 patients in the surgery group and 29,17,27,10,5 patients in the chemotherapy group and 18,10,2,1,0 in the chemoradiotherapy group.Cases with and without lymphovascular invasion were respectively 124,76 in the surgery group and 43,45 in the chemotherapy group and 6,25 in the chemoradiotherapy group.Total number of harvested lymph nodes,number of lymph node metastases and rate of lymph node metastasis in the surgery,chemotherapy and chemoradiotherapy groups were respectively 31 (range,15-87),30 (range,15-62),21 (range,15-36) and 3 (range,0-39),2 (range,0-37),0 (range,0-7) and 9.2％ (range,0-91.3％),7.7％ (range,0-78.7％),0 (range,0-30.4％).There were statistically significant differences in the T staging,N staging,with and without lymphovascular invasion,total number of harvested lymph nodes,number of lymph node metastases and rate of lymph node metastasis among groups (x2 =35.799,32.489,21.076,Z =27.120,22.088,16.947,P ＜ 0.05).There were statistically significant differences in the above indicators between surgery group and chemoradiotherapy group (x2 =28.500,20.124,19.570,P＜0.05),and no statistically significant difference in the above indicators between surgery group and chemotherapy group (x2 =11.436,12.343,4.295,P＞ 0.05).There were statistically significant differences in the N staging,with and without lymphovascular invasion,total number of harvested lymph nodes,number of lymph node metastases and rate of lymph node metastasis between chemotherapy group and chemoradiotherapy group (x2 =14.027,8.313,P＜ 0.05),and no statistically significant difference in the T staging between chemotherapy group and chemoradiotherapy group (x2=11.742,P＞ 0.05).Conclusion Neoadjuvant chemoradiotherapy could reduce the total number of harvested lymph nodes and number of lymph node metastases after radical resection of proximal locally advanced GC.
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Objective@#To investigate the effects of cerebral cavernous malformation 3 (CCM3) gene knockout on the lead exposure-induced blood-brain barrier malfunction in mice brain, and the relationship between CCM3 knockout and the Alzheimer's disease (AD).@*Methods@#Wide type (WT) mice and CCM3+/- mice were divided into 4 groups, control group and lead exposed group in WT as well as CCM3+/- mice. Lead exposed groups were treated with 0.05% lead acetate in drinking water for 12 weeks, while control group drink deionized water freely. Blood lead and brain lead levels in each group were detected by graphite furnace atomic absorption spectrometry. The brain tissue of each group was made into paraffin sections, whose morphology were observed by HE staining. The expression of Aβ1-42 in brain tissue was detected by immunohistochemistry and the brain capillaries were labeled by VRGFR2. The protein expression of Claudin-5, ZO-1, and p-Tau was detected by Western blot. The brain tissue RNA was extracted and the relative expression of LRP-1 mRNA was detected by qRT-PCR.@*Results@#The levels of blood lead WT (216.07±84.16) and CCM3+/- (189.64±101.86) μg/L in lead exposed group were higher than those in control group WT (19.52±11.46) and CCM3+/- (11.79±8.20) μg/L, the difference was statistically significant (t=4.18, P=0.006; t=3.79, P=0.016). The levels of brain lead WT (1.78±0.69) and CCM3+/- (1.74±0.66) μg/L were higher than those in control group WT (1.06±0.87) and CCM3+/- (0.97±0.64) μg/L, the difference was statistically significant (t=3.67, P=0.018; t=3.88, P=0.015). The HE staining showed no obvious lesions in the brain of each group of mice. The results of immunohistochemistry showed that there was no Aβ1-42 deposition in the brain of mice in each group. The numbers of microvessels in the brain of CCM3+/- mice in the lead exposed group were decreased. Compared with the relative expression levels of Claudin-5 (WT: 1.30±0.03, CCM3+/-: 1.07±0.08) in control group mice brain, the relative expression of Claudin-5 (WT: 0.96±0.04, CCM3+/-: 0.59±0.01) was decreased with statistical significance (F=199.27, P<0.001). The relative expression level of LRP-1 gene mRNA in brain of lead exposed group (WT: 0.32±0.10, CCM3+/-: 0.06±0.01) was higher than that of unexposed group (WT:1.00±0.06, CCM3+/-:2.12±0.18), the difference was statistically significant (F=288.29, P<0.001). The relative expression level of LRP-1 gene mRNA in brain of CCM3+/- mice exposed to lead was lower than that of WT mice ((0.06±0.01)vs(0.32±0.10), t=26.90, P<0.001).@*Conclusion@#The mice did not show significant AD-like lesions under low-does lead exposure, but resulted in early damage of brain blood-brain barrier and early changes of AD-like lesions in mice, with CCM3+/- mice being sensitive to lead exposure stronger than that of WT mice, suggesting that deletion of CCM3 gene may be one of the potential risk factors for accelerating the development of AD in mice exposed to lead.
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Objective@#To establish the immortalized mouse brain microvascular pericytes model and to apply to the cerebrovascular toxicants screening study.@*Methods@#Brain pericytes were isolated from 3 weeks of mice by tissue digestion. Immortalized pericyte cell line was constructed by infecting with LT retrovirus. Monoclone was selected to purify the immortalized pericyte cell line. The pericyte characteristics and purity were explored by immunocytochemistry. Cell proliferation was measured by using the Pomega MTS cell Proliferation Colorimetric Assay Kit. Pericytes were treated with 0, 160, 320, 640, 1 280, 2 560 μmol/L lead acetate, 0, 5, 10, 20, 40, 80 μmol/L cadmium chloride and 0, 5, 10, 20, 40, 80 μmol/L sodium arsenite in 24 hours. Cell toxicity of each group was determined by MTS assay, median lethal dose (LD50) was calculated in linear regression.@*Results@#Mouse brain pericytes were successfully isolated by tissue separation and enzyme digestion method. After immortalized by LT retroviruses, monoclone was selected and expanded to establish pericyte cell line. The brain pericytes exhibited typical long spindle morphology and positive staining for α-SMA and Vimentin. The proliferation of brain pericytes cell lines was very slowly, and the doubling time was about 48 hours. The proliferation of immortalized brain pericytes cell lines was very quickly, and the doubling time was about 24 hours. After lead acetate, cadmium chloride and sodium arsenite treatment for 24 hours respectively, gradual declines in cell viability were observed. The LD50 of lead acetate was 2 025.0 μmol/L, the LD50 of cadmium chloride was 36.6 μmol/L, and the LD50 of sodium arsenite was 33.2 μmol/L.@*Conclusion@#The immortalized mouse brain microvascular pericyte model is established successfully by infecting with LT retrovirus, and can be applied to screen cerebrovascular toxicants. The toxicity of these toxicants to immortalized mouse brain microvascular pericyte is in sequence: sodium arsenite,cadmium chloride, lead acetate.
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The objective of this paper is to study the expression of caveolin-1 in the traumatic brain injury patients and its relationship with disease prognosis. Caveolin-1 was measured in 52 patients with ventricular hemorrhage within 8h, 24h, 48h, 72h and 1 week after onset by enzyme-linked immunosorbent assay [ELISA], to observe the changes of cerebrospinal fluid caveolin-1. The level of caveolin-1 in the brain of all patients was higher than that of the control group at 8 h, 24h, 48 h, 72h and 1 weeks after the onset [P<0.05] and the level of caveolin-1 in cerebrospinal fluid [CSF] of the severe group was higher than that of the light-medium group within 8h, 24h, 48 h and 72h after the onset [P<0.05]. The level of caveolin-1 in CSF was significantly increased in patients with ventricular hemorrhage within 8h, 24h, 48h, 72h and 1 weeks after onset, and the expression of caveolin-1 in brain was related to the severity of craniocerebral injury. Therefore, the expression of caveolin-1 can be used as an indicator of the prognosis of traumatic brain injury disease
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Objective@#To explore the advantage of radiofrequency catheter ablation under the three-dimensional mapping in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT) in reducing the X-ray exposure dose of interventional doctors.@*Methods@#79 patients with AVNRT, in the first hospital of Shanxi Medical University from January 2015 to June 2016, performed to do radiofrequency catheter ablation treatment were selected, and according to the random number method were divided into two-dimensional mapping group and three-dimensional mapping group. The two-dimensional mapping group was mapped the ablation target at the X-ray, while the ablation target was mapped by CARTO 3 system in the three-dimensional mapping group. Compare the X-ray fluoroscopy time, success rate, complications rate and doctor’s X-ray exposure dose between the two groups.@*Results@#Compared with the two-dimensional mapping group, acute success rate and complication rate of the three dimensional mapping group were not statistically significant (P>0.05) , while the X-ray fluoroscopy time and the X-ray dose of the three-dimensional mapping group decreased significantly, the difference was statistically significant (P<0.05) .@*Conclusion@#Three-dimensional mapping can significantly reduce the X-ray irradiation time and interventional doctor’s X-ray exposure dose in radiofrequency catheter ablation of AVNRT patients and the potential hazards of ionizing radiation on the human body.
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OBJECTIVE: To investigate the effects of knockout cerebral cavernous malformation(CCM) virulence gene CCM3 on the migration induced by lead acetate in immortalized human umbilical vein endothelial cells(HUVECs) and to explore the possible mechanism of endoplasmic reticulum stress(ERS). METHODS: CCM3 wildtype(CCM3-WT) and CCM3 knockout(CCM3-KO) HUVECs were used as experimental cells. a) CCM3-WT and CCM3-KO HUVECs were treated with lead acetate at 0,10,50 and 200 μmol/L for 24 hours. The migration of these cells was observed by woundhealing assay. b) CCM3-WT and CCM3-KO HUVECs were treated with lead acetate at 0,10,50 and 200 μmol/L for 24 hours,and at 50 μmol/L for 0,6,12,24 and 48 hours,and the mRNA expression of genes of unfolded protein response pathway were detected by quantitative real-time polymerase chain reaction; the protein expression of glucose-regulated protein 78(GRP78) was detected by Western blotting. c) CCM3-WT and CCM3-KO HUVECs were divided into lead exposure group and tauroursodeoxycholic acid(TUDCA) group. The former was treated with 50 μmol/L lead acetate for 24 hours,and the latter was pre-treated with ERS inhibitor TUDCA,followed by 50 μmol/L lead acetate. The migration of these cells was observed by wound-healing assay. RESULTS: a) The migration of CCM3-WT and CCM3-KO cells decreased and showed a dose-effect relationship with the increase of lead acetate concentration(P < 0. 05). b) The mRNA relative expression of the GRP78,protein kinase-like endoplasmic reticulum kinase(PERK),transcription activator 4(ATF4) and CCAAT enhancer binding homologous protein(CHOP) in CCM3-KO cells treated with 10,50 and 200 μmol/L lead acetate were higher than that in CCM3-WT cells at the same doses,except for the GRP78 in CCM3-KO cells treated with10 μmol/L lead acetate(P < 0. 05). The mRNA expression of PERK and CHOP in CCM3-KO cells increased in a timeeffect relationship with the increase of lead-exposure time(P < 0. 05). The mRNA relative expression of the four genes in CCM3-KO cells were higher than those in CCM3-WT cells at 48 hours(P < 0. 05). When cells were treated with 50μmol/L lead acetate,the protein expression of GRP78 in CCM3-KO cells was higher than that in CCM3-WT cells(P <0. 05),and the protein expression of GRP78 in CCM3-KO cells increased in a time-effect relationship with the increase of lead-exposure time(P < 0. 05). c) The cell migration of TUDCA group was lower than that of lead-exposure group(P <0. 05). CONCLUSION: Lead acetate may activate ERS by activating the PERK-ATF4-CHOP signaling pathway,thereby reducing the migration of HUVECs. CCM3 gene has a protective effect on cell migration.
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Atrial fibrillation (AF) is one of the most common arrhythmias in clinical practice.It often causes serious thromboembolic complications,which brings great harm to human health.The incidence and morbidity rates of AF are increasing year by year.The research on the pathogenesis of AF has been focused on the aspects of electrical remodeling and structural remodeling.Atrial electrical remodeling and structural remodeling are the main mechanism of AF for the maintenance and recurrence.The intervention of atrial remodeling is helpful to the treatment of AF.It is found that the rennin-angiotensin aldosterone system (RAAS) plays an important role in atrial remodeling.RAAS blockers can significantly reduce the onset of AF by inhibiting the activation of the renin axis,which can block the activation of RAAS and improve the atrial remodeling.This may provide a new choice for the treatment of AF.This article reviews the research progress of RAAS blocking agent in the prevention and treatment of AF.
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Objective]The paper summarizes academic thought of Professor ZHAO Zhiqiang syndrome differentiation and treatment of adenomatous polyp of colon. [Method]By learning from ZHAO Zhiqiang and studying the medical record of adenomatous polyp of colon,sum up professor ZHAO Zhiqiang′ s experiences from etiology and pathogenesis, differential treatment, administered medical herbs and prescription ,and with one case for detailed explanation. [Results] Professor ZHAO thinks that the pathogeny raletes to exopathy, diet, emotion, weakness of the spleen and stomach, physique, smoke poison,influence of other diseases,the key of pathogenesis is phlegm, blood stasis and toxin stagnation, accumulation of intestine, Qi is out of adjustment, the conduction loss of us, He believes that the syndrome diagnosis of the disease is different from others, the syndrome diagnosis should include disease syndrome elements, syndrome elements of disease location and morbid state, disease syndrome elements should need the help of the modern medical endoscope and pathology, and ill treatment to detoxify the anti-cancer variable as the core, supplemented with Ruanjian Sanjie,coordinating zang and fu, modification according to symptoms.[Conclusion] Professor ZHAO's treatment of adenomatous polyp of colon has rich experience and prominent features, it is worth clinical promotion.
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Objective To explore the impact of puerarin treatment on autophagy in rats with traumatic brain injury (TBⅠ) and the underlying mechanism.Methods Seventy five Sprague-Dawley (SD) rats were randomized into 5 groups:sham group (S group,n =15),traumatic brain injury group (TBⅠ group,n =15),TBⅠ + puerarin treatment group (TBⅠ + Pue group,n =15),TBⅠ + JNK inhibitor group (TBⅠ + SP group,n =15),and TBⅠ + JNK activator + Pue (TBⅠ + An + Pue group,n =15).Feeney method was applied to make rats with TBⅠ model.Mter that,head water content and neurological deficit score (NDS) were measured and recorded at day 1,3 and 7 in each group.Western blot was used to measure the JNK activity and autophagic marker proteins,including LC3B and Beclin1.Results Compared to S group,the head water content and NDS were decreased significantly among the others (P ＜ 0.05).The head water content and NDS in TBⅠ + Pue and TBⅠ + SP groups was decreased remarkably compared with TBⅠ group.Combined with puerarin and animycin treatments failed to reduce head water content and NDS compared to the TBⅠ + Pue group.Activated autophagy could be observed in TBⅠ group compared to S group.Compared to group S,LC3Ⅱ,Beclin1 and P-JNK1 were increased significantly.Pue and SP could reduce their expressions,respectively.Combined with puerarin and animycin treatments failed to reduce LC3Ⅱ,Beclin1 and P-JNK1 compared to TBⅠ + Pue group.Conclusions Puerarin could protect rats with TBⅠ via inhibiting autophagy,JNK signal pathway could involve the process of puerarin regulating autophagy.