Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke.

BACKGROUND: Hepatocyte nuclear factor-1α gene (HNF1A) single nucleotide polymorphisms (SNPs) have been associated with serum lipid traits in several previous genome-wide association studies. However, little is known about such associations in the Chinese populations. The present study aimed to determine the association of the HNF1A rs1169288, rs2259820, rs2464196 and rs2650000 SNPs and serum lipid traits, the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: The genotypes of the four SNPs in 562 CAD and 521 IS patients, as well as 594 healthy controls, were detected using the Snapshot technology. RESULTS: The genotype and allele distribution of the four SNPs was not different between controls and CAD or IS patients (p > 0.05 for all). rs1169288, rs2259820 and rs2464196 SNPs were significantly associated with serum lipid levels in both controls and CAD patients (p < 0.004-0.009). rs2259820 and rs2464196 SNPs were significantly associated with a lower risk of CAD [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44-0.91, p = 0.015 and OR =0.62, 95% CI = 0.43-0.89, p = 0.010, respectively]. Significant linkage disequilibrium was noted among the four SNPs (r2  > 0.5, D' > 0.8). The haplotype of rs1169288A-rs2259820C-rs2464196G-rs2650000A was associated with an increased risk of CAD (OR =1.95, 95% CI: 1.13-3.37, p = 0.015). Interactions of SNP-SNP (rs1169288-rs2464196-rs2650000) and haplotype-environment on the risk of CAD (A-C-G-A-smoking) or IS (A-C-G-A-sex and A-T-A-C-alcohol consumption) were also observed among these SNPs. CONCLUSIONS: These findings suggest that the HNF1A polymorphisms may be the genetic risk factors for CAD and IS.

Transient cardiac injury during H7N9 infection.

BACKGROUND: Recent reports have characterized virological and clinical features of the novel reassortant avian-origin influenza A (H7N9) virus. However, cardiovascular involvement during H7N9 infection is still unclear. In this study, we evaluate cardiac injury among H7N9-infected patients. MATERIALS AND METHODS: A total of 40 patients who were laboratory-confirmed with H7N9 infection were retrospectively included and grouped by Acute Physiology and Chronic Health Evaluation II (APACHE II) score into four subgroups I(0-10), II(11-20), III(21-30) and IV(31-71). Cardiovascular complications and markers of cardiac injury including creatinine kinase (CK), CK iso-enzyme (CK-MB), cardiac troponin I (cTNI) and brain natriuretic peptide (BNP) were assessed. Electrocardiogram (ECG) and echocardiography (ECHO) were also performed. RESULTS: Half of patients manifested with cardiovascular complications, with hypotension (47.5%) and heart failure (40.0%) the most prevalent. CK, CK-MB and cTNI showed marked increase with H7N9 virus infection but significantly decreased after H7N9 viral tests turned negative. More than half of patients presented with an abnormal ECG, but most of them are benign changes. ECHO examination showed different degree of impairment of cardiac function. Pulmonary artery systolic pressure was increased in all groups. Cardiac damage was more evident in patients with higher APACHE II score. CONCLUSIONS: H7N9 virus exerts a transient impairment on the cardiovascular system. Patients with a higher APACHE II score are more susceptible to cardiac damage.

Association of polymorphisms in the MAFB gene and the risk of coronary artery disease and ischemic stroke: a case-control study.

BACKGROUND: The v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B gene (MAFB) has been associated with serum lipid levels in the Eurpean population, but little is known about such association in the Chinese population or in atherosclerosis-related patients. Therefore, the purpose of the present study was to assess the association of the single nucleotide polymorphisms (SNPs) in the MAFB and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese population. METHODS: A total of 1,065 unrelated patients (CAD, 525 and IS, 540) and 539 healthy controls were recruited in this study. Genotypes of the MAFB rs2902940 and rs6102059 SNPs were determined by the Snapshot technology platform. RESULTS: The rs2902940AA genotype was associated with an increased risk of CAD (adjusted OR = 1.63, 95% CI = 1.07-2.48, P = 0.023) and IS (adjusted OR = 1.69, 95% CI = 1.09-2.61, P = 0.017). The rs2902940GA/AA genotypes were also associated with an increased risk of CAD (adjusted OR = 1.56, 95% CI = 1.04-2.32, P = 0.030 for GA/AA vs. GG) and IS (adjusted OR = 1.72, 95% CI = 1.14-2.60, P = 0.010 for GA/AA vs. GG). Significant interactions were observed only in those with higher body mass index (BMI), hypertension and diabetes (P < 0.05). The subjects with rs2902940GA/AA genotypes in controls had lower serum ApoAI levels than the subjects with GG genotype (P = 0.024). CONCLUSIONS: The rs2902940A allele carriers in the MAFB conferred a decreased serum ApoAI level in controls and an increased risk of CAD and IS. The rs2902940GA/AA genotypes interacted with higher BMI, hypertension and diabetes to contribute the risk of CAD and IS.

A case report-application of pericardial effusion cytology and next-generation sequencing technology: quick and secure diagnosis of primary effusion lymphoma.

Background: Primary effusion lymphoma (PEL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that usually involves the pleura, pericardium, and peritoneum without an obvious tumour mass, with multiple plasma effusions as its main clinical feature. We report a case of a massive pericardial effusion in an elderly male with a final diagnosis of PEL. Case summary: A 70-year-old male patient was admitted to hospital with symptoms of chest tightness, shortness of breath, fatigue, loss of appetite, and cough with phlegm after a pericardial effusion had been found for 5 months. The next-generation sequencing of pericardial effusion found human herpesvirus type 8 (HHV-8) infection, and further cytomorphological and immunohistochemical examination were done. According to the patient's HHV-8 infection, the pathological features of heterogeneous B cells with plasmablastic differentiation and the immunohistochemical characteristics of PEL, the final diagnosis was made as human immunodeficiency virus-negative PEL. Discussion: The diversity and non-specificity of PEL symptoms, as well as its rarity, make it difficult to diagnose. In this case, we used the next-generation sequencing technology to screen the pathogen of the patient's pericardial effusion and carried out morphological and immunohistochemical examination of the cells in the pericardial effusion, which provided a clinically operable diagnosis for an uncommon disease, enabling us to make a clear diagnosis faster and start treatment in time.

ANGPTL4 variants and their haplotypes are associated with serum lipid levels, the risk of coronary artery disease and ischemic stroke and atorvastatin cholesterol-lowering responses.

BACKGROUND: This study aimed to assess the association between the angiopoietin-like protein 4 gene (ANGPTL4) single nucleotide polymorphisms (SNPs) and serum lipid levels, the risk of coronary artery disease (CAD) and ischemic stroke (IS), and response to atorvastatin therapy in a Southern Chinese Han population. METHODS: Genotypes of the ANGPTL4 rs4076317, rs7255436, rs1044250 and rs2967605 SNPs in 1,654 unrelated subjects (CAD, 568; IS, 537; and controls, 549) were determined by the Snapshot technology. Another group of 724 hyperlipidemic patients was selected and treated with atorvastatin calcium tablet 20 mg/day for 8 weeks. RESULTS: The rs2967605 CT/TT genotypes were associated with a decreased risk of CAD (adjusted OR = 0.68, 95% CI = 0.47-0.99, P = 0.043 for CT/TT vs. CC) and IS (adjusted OR = 0.55, 95% CI = 0.38-0.80, P = 0.020 for CT/TT vs. CC). There was no significant association between the four SNPs and angiographic severity of CAD. The subjects with the rs4076317 CG/CC genotypes in controls had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels than the subjects with the GG genotype (P < 0.001; a P < 0.0018 was regarded statistically significant by the Bonferroni correction). The subjects with rs4076317CG/GG genotypes had lower TC and LDL-C levels than the subjects with CC genotype after atorvastatin treatment (P < 0.001). CONCLUSIONS: The observed associations suggest that the ANGPTL4 variants have a potential role on serum lipid levels and atherosclerosis-related diseases in the Chinese Han population, especially the ANGPTL4 rs4076317 and rs2967605 SNPs.

Polymorphisms in the GCKR are associated with serum lipid traits, the risk of coronary artery disease and ischemic stroke.

The present study was to determine the association of two single nucleotide polymorphisms (SNPs) in the glucokinase regulator gene (GCKR) and serum lipid levels, and the risk of coronary artery disease (CAD) and ischemic stroke (IS). Genotypes of the GCKR rs1260326 and rs8179206 in 1736 unrelated subjects (CAD, 584; IS, 555; and healthy controls; 597) were determined by the Snapshot technology platform. The genotypic and allelic frequencies of rs1260326 and rs8179206 were not different among the three groups (P > 0.05). The subjects with rs1260326TT genotype had higher serum low-density lipoprotein cholesterol (LDL-C) levels in controls, and higher triglyceride (TG) levels in CAD patients than the subjects with CC and CT genotypes after adjustment for age, sex, body mass index, blood pressure, alcohol consumption, and cigarette smoking (P < 0.05). The rs1260326TT genotype was also associated with decreased risk of IS in females (OR = 0.37, 95% CI: 0.18-0.76, P = 0.007). The present study shows that the GCKR rs1260326TT genotype is associated with high LDL-C in controls, high TG levels in CAD patients, and a decreased risk of IS in females.

Association of variants in CELSR2-PSRC1-SORT1 with risk of serum lipid traits, coronary artery disease and ischemic stroke.

Recent genome-wide association studies (GWAS) have identified genetic variants associated with coronary artery disease (CAD), ischemic stroke (IS) and serum lipid traits in different ethnic groups. Some loci were found to affect the risk of CAD and IS. However, there were no data in the southern Chinese populations. Our study was to assess the association of CELSR2-PSRC1-SORT1 rs599839, rs464218 and rs6698443 SNPs and serum lipid levels and the risk of CAD and IS. The genotypes of 3 SNPs were detected in 561 CAD and 527 IS patients, and in 590 healthy controls. The genotypic and allelic frequencies of the rs599839 SNP were different between the controls and IS patients (P < 0.05). The minor G alleles of rs599839 and rs464218 SNPs were associated with higher high-density lipoprotein cholesterol concentrations in CAD and IS patients (P < 0.05); respectively. No association was found between the SNPs of rs599839, rs464218 and rs6698843 at the CELSR2-PSRC1-SORT1 and the risk of CAD or IS. These results will be replicated in the other Chinese populations.

Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke.

Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS.

Precision medicine in breast cancer research / 复旦学报（医学版）

Breast cancer is the most common malignant tumor in women,and its incidence has increased in recent years in China.Evidence-based medicine has made great achievements in systemetic treatment of breast cancer,which laid the foundation for standardized treatment of breast cancer.Additionally,precision medicine provides more refined,individualized treatment for breast cancer patients.Breast cancer research in multiomic analysis,ctDNA,intratumour heterogeneity and interaction between tumor and microenvironment has broad prospects.

Clinical efficacy and safety of intra-arterial chemotherapy for the treatment of young infants with retinoblastoma / 眼科新进展

Objective To assess the safety and efficacy of intra-arterial chemotherapy (IAC) for the treatment of young infants (≤ 6 months) with retinoblastoma (RB).Methods Together 21 (24 eyes) young infants (≤6 months) with RB who received IAC were included from January 2013 to February 2017 in this study and the clinical data were retrospectively analyzed.According to the international stages for intraocular retinoblastoma,stage B appeared in 4 eyes,stage D in 13 eyes,and stage E in 7 eyes.And there were two kinds of administration for chemotherapy,including perfusion chemotherapy of melphalan (≤ 0.5 mg · kg-1) combined carboplatin (20 mg) on the first and third IAC procedures,and melphalan (≤ 0.5 mg · kg-1) combined with topotecan (0.5-1.0 mg) on the second and fourth IAC procedures,and the dose of melphalan was appropriately adjusted according to the tumor changes and the response of the child after the previous IAC.Then main outcome measures include successful rate for procedures,ocular preservation rate,local and systemic complications and the time and dose of radiation exposure during IAC were evaluated.Results Of the 70 IAC procedures performed on 24 eyes,69 procedures (98.6％) were successful,and 1 was failed due to ophthalmic spasm.IAC ranged from 2 to 4 cycles with mean 3.3 cycles.After IAC procedures,17 eyes presented fish-like changes or calcification or scar formation,and the overall ocular preservation rate was 70.8％,and the other 7 eyes (29.2％) underwent enucleation of the eyeballs due to fundus hemorrhage in 3 eyes and extensive vitreous implantation in 4 eyes.Postoperative adverse reactions included eyelid oedema in 8 patients,fundus hemorrhage in 3 eyes,ocular arteriospasm in 1 patients and bone marrow suppression in 9 patients.The mean irradiation time was 3.2-32.4 (6.3 ± 1.2) min for one IAC procedure and the mean irradiation dose was 5-153 (51.9 ±9.2)mGy.The cumulative irradiation time was 6.6-53.1 (19.2 ±0.9)min for each patient of IAC cycles and the cumulative irradiation dose was 41-281 (157.3 ± 13.1) mGy.Conclusion IAC is safe and effective for the treatment of young infants (≤≤ 6 months) with RB,and the irradiation dose in IAC is lower than the threshold dose that can cruise lens tissue reactions.