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Background Arsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. Objective To investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. Methods A questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. Results We found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P<0.05). The urinary concentrations of molybdenum and barium in the kidney stone group were higher than those in the non-kidney stone group, and the differences were statistically significant (P<0.05). The logistic regression models demonstrated that urinary cobalt, arsenic, molybdenum, and barium were positively correlated with the risk of kidney stones (Ptrend<0.05). The WQS regression models showed that the mixed exposure to vanadium, cobalt, arsenic, molybdenum, and barium was positively associated with the risk of kidney stones (P<0.05). Among them, molybdenum, arsenic, and barium accounted for 0.391, 0.337, and 0.154, respectively. The BKMR results revealed a positive association between metal mixture exposure and the risk of kidney stones (P<0.05). When other metals were fixed at the 25th, 50th, or 75th percentile, arsenic, molybdenum, cobalt, and barium exhibited significant positive effects on the risk of kidney stones (P<0.05), while vanadium showed a significant negative effect (P<0.05). The interaction analysis demonstrated interactions between barium and cobalt, as well as between vanadium and cobalt (P<0.05). Conclusion In the occupational population of this smelter, occupational mixed metal exposure could increase the risk of kidney stones, and the main metals are molybdenum, arsenic, barium, and cobalt.
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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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Objective:To investigate the levels and diagnostic value of topoisomerase Ⅱα (TOP2A) and human epidermal growth factor receptor 2 (ERBB2) in early colorectal cancer (CRC) .Methods:Ninty-three early CRC patients (CRC group) admitted to Shijiazhuang Hospital of Traditional Chinese Medicine were selected for the study from January 2019 to April 2022, and 93 healthy subjects during the same period were selected as the healthy group, and 93 colorectal polyps patients diagnosed and treated in the same period were selected as the colorectal polyp group. TOP2A and ERBB2 mRNA levels in peripheral blood mononuclear cell (PBMC) and serum carcinoembryonic antigen (CEA) level were detected and compared in each group. The value of TOP2A, ERBB2 mRNA and serum CEA level in the diagnosis of early CRC were evaluated by using receiver operating characteristic (ROC) curve. The relationship between TOP2A and ERBB2 levels and clinicopathological features of early CRC patients was analyzed.Results:There were statistically significant differences in the PBMC TOP2A (1.04±0.35 vs. 1.72±0.57 vs. 2.83±0.71, F=246.73, P<0.001), ERBB2 mRNA (1.01±0.34 vs. 1.64±0.55 vs. 2.75±0.71, F=234.80, P<0.001) levels and serum CEA levels (1.29±0.52 vs. 1.93±0.64 vs. 3.17±0.81, F=190.78, P<0.001) in healthy group, colorectal polyp group and CRC group. Compared with the healthy group and colorectal polyp group, the levels of TOP2A and ERBB2 mRNA in PBMC and serum CEA level in CRC group were significantly increased (all P<0.05) ; Compared with the healthy group, the levels of TOP2A and ERBB2 mRNA in PBMC and serum CEA level in the colorectal polyp group were increased (all P<0.05). The ROC curve showed that the area under curve (AUC) of TOP2A and ERBB2 mRNA levels in PBMC and serum CEA level for the diagnosis of early CRC were 0.85, 0.85 and 0.84, respectively, and the AUC for the combined diagnosis of early CRC was 0.96, which was higher than that of TOP2A, ERBB2 and CEA alone ( Z=2.92, P=0.004; Z=3.16, P=0.002; Z=2.86, P=0.005). The combination of the three diagnosed early CRC with a sensitivity of 94.64% and a specificity of 85.96%. There were statistically significant differences in PBMC TOP2A and ERBB2 mRNA levels in early CRC patients with different differentiation degrees ( χ2=6.21, P=0.013; χ2=10.49, P=0.001) . Conclusion:The expression levels of TOP2A, ERBB2 mRNA in PBMC in CRC patients are higher. The combination of TOP2A, ERBB2 mRNA levels in PBMC and serum CEA level may be more helpful for clinical diagnosis of early CRC.
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Objective:To compare the efficacy of dapoxetine hydrochloride for the treatment of primary premature ejaculation when taken on time and on demand.Methods:This study was a randomized controlled study. Patients with primary premature ejaculation diagnosed at the Andrology Outpatient Department of the Second Affiliated Hospital of Xi'an Jiaotong University between September 2018 and June 2019 were included. Inclusion criteria included ①non-homosexual patients aged≥18 years, ②regular sexual partner and rapport relationship with their sexual partner for more than 1 year, ③no serotonin reuptake inhibitors application within 3 months before treatment, ④ejaculated within 2 minutes of penile entry into the vagina that lasts>6 months, ⑤on participation in other similar trials in the past 6 months, ⑥had sexual intercourse≥2 times/week. Exclusion criteria included ①erection hardness score<3 points, ②malformation or dysplasia of reproductive organs, ③genitourinary infection, ④patients with severe heart disease, hypertension, diabetes mellitus, ⑤hypogonadism, ⑥allergy to dapoxetine hydrochloride and excipients, ⑦ patients with moderate or severe liver damage. The enrolled patients were divided into an on-time medication group and an on-demand medication group according to the randomized number table method. Patients took dapoxetine hydrochloride 30 mg/time, once a day, immediately after dinner in the on-time medication group, and the patients took dapoxetine hydrochloride 30 mg/time 2-3 h before intercourse in the on-demand medication group. The latency of intravaginal ejaculation (IELT), the score of the diagnostic tool for premature ejaculation (PEDT), the score of premature ejaculation index (IPE), and the score of anxiety level (SAS) of the two groups were observed within 8 weeks of medication intaking and 8 weeks of medication withdraw.Results:A total of 136 patients were enrolled, and finally 88 completed the 8 weeks treatment, including 50 patients (73.53%) in the on-time medication group and 38 patients (55.88%) in the on-demand medication group. There was a statistically significant difference between the two groups in terms of patient adherence ( P = 0.048). There were no significant differences in pre-treatment IELT [(2.23 ± 1.81) min vs. (1.80 ± 1.51) min], PEDT scores [(16.52 ± 1.54) vs. (16.84 ± 1.59)], IPE scores [satisfaction (32.67 ± 7.36) vs. (32.37±5.90), control (23.31 ± 5.48) vs. (22.97 ± 4.82), pain severity (36.43 ± 3.51) vs. (35.82 ± 3.27)], and SAS scores [(51.80 ± 6.93) vs. (53.82 ± 4.47)] between the on-time medication group and on-demand medication group ( P>0.05). After 8 weeks of treatment for patients in the on-time versus on-demand medication groups, the IELT [(5.45 ± 2.64) min vs. (5.01 ± 2.31) min], PEDT scores [(13.68 ± 2.15) vs. (14.92 ± 9.39)], IPE scores [satisfaction (42.58 ± 5.13) vs. (43.39 ± 4.76), control (31.86 ± 4.49) vs. (32.75 ± 5.43), pain severity (62.94 ± 4.07) vs. s (61.22 ± 4.25)], and SAS score [(49.70 ± 4.16) vs. (51.66 ± 4.65)] were not statistically different ( P>0.05). However, the differences were statistically significant when compared with those at the initial consultation ( P<0.05). After 8 weeks of drug withdrawal, the scores of IELT, PEDT and IPE in the two groups were not significantly different from those before treatment( P>0.05). Conclusions:Taking dapoxetine hydrochloride on time and on demand can effectively alleviate the symptoms and anxiety of patients with primary premature ejaculation, and the compliance of the on-time medication group was better. Premature ejaculation symptoms recur after long-term discontinuation of the drug.
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Objective:To investigate the influencing factors of the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 431 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2013 to December 2020 were retrospectively analyzed. Univariate and multivariate time-dependent covariate Cox regression model were constructed. The relationship between the clinical characteristics and prognosis of patients was analyzed.Results:The age, tumor diameter, tumor width all met the proportion hazard hypothesis (correlation coefficients were 0.044, -0.015, and -0.680, respectively, all P > 0.05). The effects of disease grade, erythrocyte sedimentation rate (ESR) increased or not, and CD20 positive or not on survival time changed with time change. When the above indicators did not meet the proportional hazard hypothesis, they were time-dependent covariables (all P < 0.05). Time-dependent covariate Cox regression multivariate analysis showed that lactate dehydrogenase (LDH) increased or not ( χ2 = 13.78, P < 0.001), β 2 microglobulin (β 2-MG) increased or not ( χ2 = 5.36, P = 0.021), tumor diameter ( χ2 = 4.12, P = 0.042) and CD20 positive or not ( χ2 = 7.09, P = 0.008) and ESR increased or not ( χ2 = 5.46, P = 0.019) were independent influencing factors of the death of DLBCL patients. Conclusions:Patients with elevated LDH, increased β 2-MG, tumor diameter, increased ESR and CD20 positive have poor prognosis. Clinicians should take further treatment measures for these patients to reduce the mortality.
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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 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 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 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 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 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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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 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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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 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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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 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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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 computed tomography (CT) features of gastric cancer invasion to the pancreas and significance in the assessment of resectability of primary lesions.Methods The retrospective cohort study was conducted.The clinical data of 31 gastric cancer patients who were admitted to the Peking University Cancer Hospital between February 2011 and August 2016 were collected.Of 31 patients receiving CT examinations,11 who were diagnosed with suspected pancreas invasion by preoperative CT examinations but operation confirmed no invasion were allocated into the pancreas negative (PN) group,11 who were confirmed as pancreas invasion and under vent radical gastrectomy of gastric cancer combined with pancreas resection were allocated into the pancreas invasion (PI) group,and 9 who were confirmed as pancreas invasion and had unresectable primary lesions were allocated into the pancreas invasion non-resected (PI-NR) group.Observation indicators:(1) morphologic type of contact surface between gastric cancer and pancreas;(2) comparison of CT findings among the 3 groups:primary lesion location,tunor thickness,Borrmann type,serosa pattern of gastric cancer,judging obvious region invaded by gastric cancer,contact or invasion site with pancreas,contact length between gastric cancer and pancreas,pattern,clarity and CT values of contact surface or peripancreas invaded and normal peripancreas;(3) treatment or follow-up situations.All the patients underwent radical resection and palliative resection for gastric cancer or non-operation according to results of exploration.Telephone interview was performed to detect the survival of patients up to February 2017.Measurement data with skewed distribution were described as M (Qn),and comparisons among groups were done by the Kruskal-Wallis test.Comparison of count data were done by the Fisher exact probability.Results (1) Morphologic type of contact surface between gastric cancer and pancreas:there were 4 types according to results of CT examination.Type Ⅰ.pancreas contacted with gastric cancer and there was no change in the morphology and radian of contact surface.Type Ⅱ:pancreas contacted with gastric cancer and radian of contact surface became flattened or shallow depression.Type Ⅲ:contact surface showed a inserted sign or obvious depression.Type Ⅳ:pancreas didn't contact with gastric cancer and there was increased density in fat space between pancreas and gastric cancer,with a smudge sign or strip-and sheet-like opacity.Of 31 patients,type Ⅰ,Ⅱ,Ⅲ and Ⅳ were detected in 5,10,4 and 12 patients,respectively.(2) Comparison of CT findings among the 3 groups:nodular protrusion,spiculation and strip shape,clounding patch opacity of serosa panern of gastric cancer were detected in 1,6,4 patients in the PN group and 5,4,2 patients in the PⅠ group and 0,2,7 patients in the PI-NR group,respectively,with a statistically significant difference (X2=10.054,P＜0.05).Two,8 and 8 patients in the PN,PI and PI-NR groups had obvious tumor invasion located at a adjacent region between stomach and pancreas,with a statistically significant difference (X2 =11.259,P＜0.05).Contact or invasion site with pancreas located at head,body and tail of pancreas was detected in 6,5,0 patients in the PN group and 1,7,3 patients in the PI group and 5,4,0 patients in the PI-NR group,respectively,with a statistically significant difference (X2=8.390,P＜0.05).Type Ⅰ,Ⅱ,Ⅲ and Ⅳ of contact surface between gastric cancer and pancreas were detected in 5,6,0,0 patients in the PN group and 0,4,4,3 patients in the PI group and 0,0,0,9 patients in the PI-NR group,respectively,with a statistically significant difference (X2=29.291,P＜0.05).Number of patients with clear and ambiguous contact surface was 10,1 patients in the PN group and 0,11 patients in the PI group and 0,9 patients in the PI-NR group,respectively,with a statistically significant difference (X2 =26.227,P＜ 0.05).CT values of contact surface or peripancreas invaded were-46 HU (-57 HU,-20 HU) in the PN group and-34 HU (-41 HU,-25 HU) in the PI group and-10 HU (-15 HU,-10 HU) in the PI-NR group,respectively,with a statistically significant difference (Z=15.306,P＜0.05).CT values of normal peripancreas were-87 HU (-96 HU,-76 HU) in the PN group and-88HU (-70 HU,-1 HU) in the PI group and-83 HU (-98 HU,-74 HU) in the PI-NR group,respectively,with statistically significant differences in CT values between contact surface or peripancreas invaded and normal peripancreas among the 3 groups (Z=12.581,13.780,7.793,P＜0.05).(3) Treatment or followup situations:of 31 patients,22 underwent radical gastrectomy and 9 underwent simplex exploration or short surgery.All the 31 patients were followed up for 6.0-71.0 months,with a median time of 13.5 months.Postoperative 1-and 2-year survival rates were 82.6％ and 77.1％.Conclusions There are significant differences in pancreatic invasion and resectability between CT features of contact surface of gastric cancer and pancreas and tumor classification.CT features include that pancreas contacts with gastric cancer in the PN group,radian of contact surface becomes flattened and with a inserted sign in the PI group,and there are increased density in fat space between pancreas and gastric cancer and a smudge sign or strip-and sheet-like opacity in the PI-NR group.