Sulforaphane Ameliorate Cadmium-Induced Blood-Thymus Barrier Disruption by Targeting the PI3K/AKT/FOXO1 Axis.

Cadmium (Cd) is a transition metal ion that is extremely harmful to human and animal biological systems. Cd is a toxic substance that can accumulate in the food chain and cause various health issues. Sulforaphane (SFN) is a natural bioactive compound with potent antioxidant properties. In our study, 80 1 day-old chicks were fed with Cd (140 mg/kg BW/day) and/or SFN (50 mg/kg BW/day) for 90 days. The blood-thymus barrier (BTB) is a selective barrier separating T-lymphocytes from blood and cortical capillaries in the thymus cortex. Our research revealed that Cd could destroy the BTB by downregulating Wnt/ß-catenin signaling and induce immunodeficiency, leading to irreversible injury to the immune system. The study emphasizes the health benefits of SFN in the thymus. SFN could ameliorate Cd-triggered BTB dysfunction and pyroptosis in the thymus tissues. SFN modulated the PI3K/AKT/FOXO1 axis, improving the level of claudin-5 (CLDN5) in the thymus to alleviate BTB breakdown. Our findings indicated the toxic impact of Cd on thymus, and BTB could be the specific target of Cd toxicity. The finding also provides evidence for the role of SFN in maintaining thymic homeostasis for Cd-related health issues.

Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Cadmium Transforms Astrocytes into the A1 Subtype via Inducing Gap Junction Protein Connexin 43 into the Nucleus.

Cadmium is highly toxic and present in the environment and can be accumulated among various levels of the food chain. Both humans and animals are at risk from toxicity associated with cadmium. However, the neurological endpoint caused by cadmium has not been revealed. The aim of our research is to explore the potential target of cadmium attack when causing neurotoxicity. 80 male chickens (one day old, weighing 36.49 ± 2.88 g) were randomly divided into four groups and independently treated with 0, 35, 70, or 140 mg/kg CdCl2 in diet for 90 days. The result showed that the striatum was damaged due to a high dose of cadmium in the brain, which was characterized by degeneration of neurons and astrocyte dysfunction. Transcriptome analysis demonstrated that striatal astrocytes were transformed into the A1 state under cadmium exposure. Deeper investigation revealed that the internalization of gap junction protein connexin 43 was responsible for this transformation. Eventually, we can conclude that the internalized gap junction protein connexin 43 of astrocytes is the target of cadmium anchoring, and this process was accompanied by the transformation of astrocytes into the A1 subtype. This study provides a new direction for exploring the effects of cadmium on the nervous system and the treatment of subsequent nervous system diseases.

Abietane diterpenoids from Orthosiphon wulfenioides with NLRP3 inflammasome inhibitory activity.

Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC50 values ranging from 0.23 to 3.43 µM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1ß down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis.

Cadmium aggravates the blood-brain barrier disruption via inhibition of the Wnt7A/ß-catenin signaling axis.

Cadmium (Cd) is a non-biodegradable widespread environmental pollutant, which can cross the blood-brain barrier (BBB) and cause cerebral toxicity. However, the effect of Cd on the BBB is still unclear. In this study, a total of 80 (1-day-old) Hy-Line white variety chicks (20 chickens/group) were selected and randomly divided into four (4) groups: the control group (Con group) (fed with a basic diet, n = 20), the Cd 35 group (basic diet with 35 mg/kg CdCl2, n = 20), the Cd 70 group (basic diet with 70 mg/kg CdCl2, n = 20) and the Cd 140 group (basic diet with 140 mg/kg CdCl2, n = 20), and fed for 90 days. The pathological changes, factors associated with the BBB, oxidation level and the levels of Wingless-type MMTV integration site family, member 7 A (Wnt7A)/Wnt receptor Frizzled 4 (FZD4)/ß-catenin signaling axis-related proteins in brain tissue were detected. Cd exposure induced capillary damage and neuronal swelling, degeneration and loss of neurons. Gene Set Enrichment Analysis (GSEA) showed the weakened Wnt/ß-catenin signaling axis. The protein expression of the Wnt7A, FZD4, and ß-catenin was decreased by Cd expusure. Inflammation generation and BBB dysfunction were induced by Cd, as manifested by impaired tight junctions (TJs) and adherens junctions (AJs) formation. These findings underscore that Cd induced BBB dysfunction via disturbing Wnt7A/FZD4/ß-catenin signaling axis.

Nano-Selenium Antagonized Cadmium-Induced Liver Fibrosis in Chicken.

Cadmium is a global ecological toxic pollutant; in animals, hepatotoxic fibrosis is caused by bioaccumulation of Cd through food chains. We determined the path of nano-Se antagonism in Cd-induced hepatocyte pyroptosis by targeting the APJ-AMPK-PGC1α pathway, using an in vivo model of hepatotoxicity. All 1-day-old chicks were treated with Cd (140 mg/kg BW/day) and/or nano-Se (0.3 or 0.6 mg/kg BW/day) for 90 days. The result showed that Cd (1.55 ± 0.148) activated NLRP3 inflammasome 49.903% as compared to the Con group (1.034 ± 0.008) to release the inflammasome as a result of hepatocyte pyroptosis (2.824 ± 0.057). Compared with the Con group (1.010 ± 0.021), Kupffer cells were 219.109% more to activate astrocytes through the APJ-AMPK-PGC1α pathway, resulting in 185.149% more hepatic fibrosis. However, the fibrosis degree of the H-Se + Cd group (1.252 ± 0.056) was 56.5278% (p < 0.001) lower than that of the Cd group (2.880 ± 0.124). Therefore, this study established that pyroptotic hepatocytes and Kupffer cells could be targeted for nano-Se antagonizing Cd toxicity, which reveals a potential new approach targeting astrocytes for the treatment of liver fibrosis triggered by Cd pollution.

Callicarpanes A-L, Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima.

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 µM. Further study revealed that compound 10 repressed IL-1ß secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.

[Kinetics of MDSC in Patients Treated Steroids-Ruxolitinib as the First Line Therapy for aGVHD].

OBJECTIVE: To analyze the kinetic characteristics of lymphocyte subsets and myeloid-derived suppressor cell (MDSC) in patients who newly diagnosed intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy from a single-arm, open clinical trial (NCT04061876). METHODS: We prospectively observed the efficacy of 23 patients having intermediate- to high-risk aGVHD and treated with steroids-ruxolitinib as the first line therapy. The kinetic characteristics of lymphocyte subsets and MDSC were monitored, and then we compared them in steroids-ruxolitinib group (n=23), free-aGVHD group (n=20) and steroids group (n=23). RESULTS: Of the 23 patients, the CR rate was 78.26% (18/23) on day 28 after first-line treatment with steroids-ruxolitinib. On day 28 after treatment, patients had lower level of CD4+CD29+ T cells (P=0.08) than that of pre-treatment, whereas levels of other lymphocyte subsets in this study were higher than that of pre-treatment; CD4+CD29+ T cells in CR patients decreased, compared with refractory aGVHD patients. On day 28 of treatment, CD8+CD28- T cells (P=0.03) significantly increased in patients with aGVHD than that in patients without aGVHD, so did CD8+CD28- T / CD8+CD28+ T cell ratio (P=0.03). Compared with patients without aGVHD, patients with aGVHD had lower level of G-MDSC, especially on day 14 after allo-HSCT (P=0.04). Compared with pre-treatment, M-MDSC was higher in CR patients on day 3 and 7 post-treatment (P3=0.01, P7=0.03), e-MDSC was higher on day 28 post-treatment (P=0.01). Moreover, compared with CR patients, M-MDSC was lower in refractory aGVHD patients on day 3 post-treatment (P=0.01) and e-MDSC was lower on day 28 post-treatment (P=0.01). Compared with steroids group, MDSC in steroids-ruxolitinib group was higher, with the most significant difference in M-MDSC (P3=0.0351; P7=0.0142; P14=0.0369). CONCLUSION: We found that patients newly diagnosed intermediate- to high-risk aGVHD receiving first-line therapy with steroids-ruxolitinib achieved high response rate. Moreover, the novel first-line therapy has a small impact on the immune reconstitution of patients after allo-HSCT. Elevated MDSC might predict a better response in aGVHD patients receiving this novel first-line therapy. M-MDSC responded earlier to steroids-ruxolitinib than e-MDSC, G-MDSC.

High-intensity focused ultrasound treatment as an alternative regimen for myxofibrosarcoma.

Myxofibrosarcoma is a common soft-tissue sarcoma in elderly patients, characterized by an infiltrative growth pattern and a high risk for persistent local recurrence. A 35-years-old woman was diagnosed with myxofibrosarcoma on the right upper arm and the tumor is surgically resected. The tumor relapsed 7 months later. Then the patient received five cycles of low power cumulative high-intensity focused ultrasound (HIFU) treatments, which completely ablated the tumor without complications. Now the patient is disease free with a high quality of life more than 30 months. This case indicates HIFU ablation might be a novel, promising therapy for recurrent myxofibrosarcoma.

Association of cardiovascular diseases with milk intake among general Chinese adults.

BACKGROUND: The association of milk intake with cardiovascular disease (CVD) and cause-specific mortality remained controversial and evidence among the Chinese population was limited. We aimed to study the relationship between milk intake and CVDs among general Chinese adults. METHODS: A total of 104,957 participants received questionnaire survey. Results of physical examination such as anthropometric measurements and biochemical tests during 2007 to 2008, demographic data and their information on milk intake were collected through standardized questionnaires. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of CVD incidence, cause-specific mortality and all-cause mortality related to milk intake. Restricted cubic splines (RCSs) were applied to examine dose-response associations. RESULTS: Among the 91,757 participants with a median follow-up period of 5.8 years, we documented 3877 CVD cases and 4091 all-cause deaths. Compared with participants who never consumed milk, the multivariate-adjusted HRs (95% CIs) of CVD incidence for 1 to 150 g/day, 151 to 299 g/day, and ≥300 g/day were 0.94 (0.86-1.03) (P > 0.05), 0.77 (0.66-0.89) (P < 0.05), and 0.59 (0.40-0.89) (P < 0.05), respectively; each 100 g increase of daily milk intake was associated with 11% lower risk of CVD incidence (HR, 0.89; 95% CI: 0.85-0.94; P < 0.001), and 11% lower risk of CVD mortality (HR, 0.89; 95% CI: 0.82-0.97; P = 0.008) after adjustment for age, sex, residential area, geographic region, education level, family history of CVD, smoking, alcohol drinking, physical activity level, body mass index, and healthy diet status (ideal or not). RCS analyses also showed a linear dose-response relationship with CVD (P for overall significance of the curve <0.001; P for non-linearity = 0.979; P for linearity <0.001) and stroke (P for overall significance of the curve = 0.010; P for non-linearity = 0.998; P for linearity = 0.002) incidence, and CVD mortality (P for overall significance of the curve = 0.045; P for non-linearity = 0.768; P for linearity = 0.014) within the current range of daily milk intake. CONCLUSIONS: Daily milk intake was associated with lower risk of CVD incidence and mortality in a linear inverse relationship. The findings provide new evidence for dietary recommendations in CVD prevention among Chinese adults and people with similar dietary pattern in other countries.

Melatonin Attenuates ß-Glycerophosphate-Induced Calcification of Vascular Smooth Muscle Cells via a Wnt1/ß-Catenin Signaling Pathway.

BACKGROUND: Melatonin has been demonstrated to protect against calcification in cyclosporine nephrotoxicity. The wingless-type MMTV integration site family member 1 (Wnt1)/ß-catenin pathway is associated with cardiovascular calcification. This study aimed to explore whether melatonin could attenuate VSMC calcification through regulating the Wnt1/ß-catenin signaling pathway. METHODS: The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red Staining. Calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), α-smooth muscle actin (α-SMA), and cleaved caspase-3. RESULTS: Melatonin markedly ameliorated calcium deposition and ALP activity. Runx2 and cleaved caspase-3 were found to be reduced and α-SMA was found to be increased by melatonin, together with a decrease in apoptosis. Immunofluorescence assay revealed a lower Runx2 protein level in the melatonin group. Melatonin treatment significantly decreased the expression of Wnt1 and ß-catenin. Treatment with lithium chloride or transglutaminase 2 abrogated the protective effects of melatonin. CONCLUSION: Melatonin can attenuate ß-GP-induced VSMC calcification through the suppression of Wnt1/ß-catenin system.

Long-term follow up of percutaneous coronary intervention of coronary artery disease in women ≤45 years of age.

The aim of the present study was to report the short- and long-term clinical outcomes of percutaneous coronary intervention in young women with premature coronary artery disease. From February 2003 to December 2011, 168 consecutive women aged ≤45 years who underwent percutaneous coronary intervention with stent implantation were retrospectively analyzed. The primary end point was the incidence of major adverse cardiac events (MACEs) at short- and long-term follow-up. The mean age was 40.3 ± 2.0 years. Conventional coronary artery disease risk factors were common. Autoimmune or connective tissue diseases were present in 6.5% of the population, 4% had gynecologic diseases, 4 were postpartum, and 9 were taking contraceptives. The left anterior descending coronary artery was the most commonly affected vessel (83.3%) and the most common target vessel for stenting (76.8%). A total of 268 stents were implanted, 95.3% of which were drug-eluting stents. During the hospital stay, 1 patient died, and the incidence of MACEs was 1.2%. No additional events had occurred at 30-day follow-up. After a median follow-up duration of 36 months (interquartile range 12 to 60), cumulate MACE-free survival was 80.5%, the rate of target vessel revascularization was 16.5%, and the rate of stent thrombosis was 3.6%. Cox regression showed that hypertension, smoking, a left ventricular ejection fraction <50%, anterior myocardial infarction, and autoimmune disease were independent predictors of MACEs. In conclusion, percutaneous coronary intervention in young women tends to result in an increased rate of target vessel revascularization during long-term follow-up, which may be influenced by conventional and nonconventional risk factors.

Contemporary management and attainment of cholesterol targets for patients with dyslipidemia in China.

AIMS: It is well-established that lipid disorder is an important cardiovascular risk factor, and failure to reach optimal lipid levels significantly contributes to the residual cardiovascular risks. However, limited information is available on the management and the attainment of recommended cholesterol targets in real-world practice in China. METHODS AND RESULTS: A nationally representative sample of 12,040 patients with dyslipidemia from 19 provinces and 84 hospitals across China were consecutively enrolled in this survey. Risk stratification and individual cholesterol target was established for all participants. This survey identified a high-risk cohort, with over 50% of patients had hypertension, 37.5% had coronary artery disease, and more than 30% had peripheral artery disease. Thirty-nine percent of all participants received lipid lowering medications. And the majority of them (94.5%) had statins (42.5% with atorvastatin, 29.0% with simvastatin, and 15.2% with rosuvastatin). However, the overall attainment for low-density lipoprotein cholesterol (LDL-C) target is low (25.8%), especially, in female (22.2%), and in patients with increased body mass index (BMI) (38.3% for BMI<18.5, 28.1% for BMI 18.5-24.9, 26.0% for BMI 25.0-29.9, and 17.4% for BMI ≥ 30, P<0.0001). Subgroup analysis also showed the attainment is significantly lower in patients who were stratified into high (19.9%) and very high (21.1%) risk category. In logistic regression analysis, eight factors (BMI, gender, coronary artery disease, systolic and diastolic blood pressure, hypertension, family history of premature coronary artery disease and current smoking) were identified as independent predictors of LDL-C attainment. CONCLUSIONS: Despite the proven benefits of lipid-lowering therapies, current management of dyslipidemia continues to be unsatisfied. A considerable proportion of patients failed to achieve guideline-recommended targets in China, and this apparent treatment gap was more pronounced among patients with increased BMI, higher risk stratification and women.

The impact of recipient HLA-Cw and donor killer immunoglobulin-like receptor genotyping on the outcome of patients receiving HLA-matched sibling donor hematopoietic stem cell transplantation for myeloid malignancies.

BACKGROUND: The alloreactivity of natural killer cell and certain subsets of T lymphocyte are regulated by the interaction between killer immunoglobulin-like receptors (KIRs) of donor cells and human leukocyte antigen (HLA)-class I molecules on target cells. The interaction has been shown to influence the outcome of allogeneic haematopoietic stem cell transplantation (HSCT). Homozygous C1 or C2 and heterozygous C1/C2 were divided by HLA-Cw typing and they influenced the outcome of HSCT. OBJECTIVE: The purpose of the study was to analyse the impact of interaction between recipient HLA-Cw and donor KIR on outcome. METHODS: The genotypes of recipient HLA-Cw ligands and donor KIRs were correlated with the clinical outcomes of 52 patients who received HLA-matched, sibling donor HSCT for myeloid malignancies. RESULTS: The incidence of chronic graft versus host disease (GVHD) was significantly lower in C1 or C2 homozygotes than in C1/C2 heterozygotes (p = 0.000). Higher overall survival (OS) and disease-free survival (DFS) rates were observed in C1 or C2 homozygotes than in C1/C2 heterozygotes (OS, 81% ± 8% vs 54% ± 10%, p = 0.034; DFS, 81% ± 8% vs 54% ± 10%, p = 0.024). A lower incidence of chronic GVHD and higher OS and DFS were observed in the HLA-KIR mismatched group (chronic GVHD, p = 0.007; OS, 84% ± 7% vs 47% ± 13%, p = 0.003; DFS, 84% ± 7% vs 47% ± 13%, p = 0.002). CONCLUSION: The interaction between recipient HLA ligand and donor KIR had a significant impact on the outcome of patients receiving matched sibling HSCT. C1/C2 heterozygotes or HLA-KIR matched patients may benefit from additional intensified therapy with better outcome.

Viral deletions among healthy young Chinese adults with occult hepatitis B virus infection.

To investigate the mechanism and prognosis of occult hepatitis B virus (HBV) infection (OBI) at a molecular level among healthy young adults, the presence of HBV DNA in 1176 sera samples collected from healthy young people after neonatal vaccination was assessed by nested polymerase chain reaction (PCR) using specific primers designed for the X and S regions of the HBV genome. Full-length HBV DNA from 9 patients with OBI (OB1-OB9) was cloned and sequenced. Deletions in the pre-S, basal core promoter (BCP), core (C) and polymerase (P) regions were observed. The data indicate that there is still a substantial risk of OBI in China despite neonatal vaccination. All deletions that were observed in the pre-S, BCP, C and P regions play a direct or indirect role in OBI. The presence of a deletion mutation in the pre-S1 region was considered to play a pivotal role in hepatocarcinogenesis and was found to increase the risk of hepatocellular carcinoma in the cohorts studied.

[Analysis the advantage of autologous mobilized peripheral blood mononuclear cells transplantation on lower limbs ischemia disease].

OBJECTIVE: To analyze the efficacy and its correlation with species of transplant cells of autologous mobilized peripheral blood (PB) mononucleated cells (MNCs) transplantation on 59 patients with lower limbs ischemia. METHODS: Fifty-nine patients were evaluated with symptoms scores and after that their PBMNCs were mobilized and collected and then injected into the ischemic area at equal distance. They effectiveness and scores were evaluated at 7th day and 4th month after therapy. The correlation of CD34(+) cells and of MNCs with effectiveness was analysed respectively, and formula for correlations between them and effectiveness was calculated. RESULTS: After MNCs injection, the effectiveness was observed both at 7th day and 4th month. The correlation of MNCs with effectiveness was stronger than that of CD34(+) cells (the effectiveness was represented by nimodipine value), According to the formula of nimodipine value, the value of the latter = 0.484 + 1.055 × CD34(+) cells number and the former = 0.288 + 0.401 × MNCs number with a correlation coefficient of R = 0.461 (P = 0.047) and R = 0.473 (P = 0.000) respectively. CONCLUSION: Autologous mobilized PBMNCs number is a better indicator for effectiveness than CD34(+) cells number.

Impact of CYP2C19 polymorphism and smoking on response to clopidogrel in patients with stable coronary artery disease.

BACKGROUND: Dual anti-platelet treatment with aspirin and clopidogrel is established foundation for patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic events. The present study was conducted to examine whether the CYP2C19 681G > A polymorphism and cigarette smoking had independent or interactive effect on response to clopidogrel. METHODS: Among 722 Chinese Han patients undergoing elective coronary stent placement due to stable angina pectoris, a loading dose of 300 mg clopidogrel was given to all patients and a daily maintenance dose of 75 mg for a minimum of 12 months. CYP2C19 681G > A polymorphism was genotyped. The platelet reactivity was measured by light transmittance aggregometry (LTA) with 5 µmol/L adenosine diphosphate (ADP) induced. The poor response was defined as 10% or less absolute difference between aggregation at baseline and 24 hours after loading dose of clopidogrel. RESULTS: The results showed that the poor-response to clopidogrel was presented in 105 patients (14.5%). Overall, the genotype GA/AA carriers were likely to be poor-responsive cases (19.6% vs. 11.0%, P = 0.001) with odds ratio (OR) of 1.971 (95%CI: 1.296 - 2.998, P = 0.002), compared with the GG homozygotes. Meanwhile, compared with nonsmokers, the smokers showed lower rate of poor-response (10.9% vs. 17.3%, P = 0.015) with OR of 0.582 (95%CI: 0.374 - 0.904, P = 0.016). The smokers with GG genotype had the lowest risk with OR of 0.487 (95%CI: 0.246 - 0.961, P = 0.038) while nonsmokers with GA/AA genotype had the highest risk of poor-response with OR of 1.823 (95%CI: 1.083 - 3.068, P = 0.024), compared with nonsmokers with GG genotype. However, there was no significant interaction between genotype and smoking. CONCLUSION: Our study indicated that both CYP2C19 polymorphism and smoking independently affected response to clopidogrel.

[Effects of killer immunoglobulin-like receptor and human leukocyte antigen class I ligand on the prognosis of related donor hematopoietic stem cell transplantation].

OBJECTIVE: To study the genotype distribution and the effects of killer immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I ligand on related donor hematopoietic stem cell transplantation (HSCT). METHODS: The genotypes of donor/recipient HLA-Cw and donor KIR were determined by polymerase chain reaction-sequence specific primer (PCR-SSP) in 87 cases of related donor HSCT (40 cases were haploidentical HSCT, and the remaining 47 cases were HLA-identical sibling HSCT). RESULTS: All the donors possessed KIR2DL1, 2DL2/L3, 2DL4, 3DL2, and 3DL3, and 96.6% of donors possessed 3DL1. The rate of activating KIRs varied. 97.7% of the recipients expressed C1, while the rates of C2, Bw4, and HLA-A3/A11 were different. In haploidentical HSCT, KIR-HLA-mismatched group included 34 cases and the matched group included 6 cases. HLA-HLA-mismatched group included 31 cases and the matched group included 9 cases. In matched sibling donor HSCT, KIR-HLA-mismatched group included 42 cases and the matched group included 5 cases. KIR-HLA-mismatched group had higher 2-year disease-free survival (DFS) rate compared with KIR-HLA-matched group [ (71.5 +/- 6.5 ) % vs. (50.0 +/- 10.7)%, P < 0.05]. CONCLUSIONS: The rate of activating KIR is lower than inhibitory KIRs. Inhibitory KIR2DL1, 3DL1, and 3DL2 may play key roles in the natural killer cell alloreactivity. The DFS rate is higher in KIR-HLA-mismatched group than in KIR-HLA-matched group in related donor HSCT.

Comparison of drug-eluting stents and coronary artery bypass grafting for the treatment of multivessel coronary artery disease in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a strong predictor of mortality after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), but the relative efficacy of the 2 revascularization strategies in this context remains unknown. METHODS AND RESULTS: The 1,069 patients with CKD undergoing revascularization for multivessel coronary disease were evaluated. Of them, 532 patients were treated for 2-vessel disease (97 CABG, 435 PCI) and 537 for 3-vessel disease (248 CABG, 289 PCI). CKD was defined as estimated glomerular filtration rate <60 ml/min. No differences between the PCI and CABG groups in the 2-vessel population were observed in the composite of death, myocardial infarction (MI) or cerebrovascular events (10.6% vs 8.2%, P=0.493) and repeat revascularization (6.7% vs 3.1%, P=0.181) during the 2-year follow-up. In the 3-vessel population, patients undergoing PCI showed similar rate for the composite endpoint (6.7% vs 3.1%, P=0.181), but had a higher incidence of repeat revascularization (12.5% vs 4.4%, P=0.001) compared with the CABG group. After multivariate adjustment, revascularization strategy was not an independent predictor of the composite endpoint. CONCLUSIONS: Compared with PCI with a drug-eluting stent, CABG showed a similar incidence of death, MI or cerebrovascular events in patients with multivessel disease and CKD, but was associated with decreased repeat revascularization in the 3-vessel population.