[Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients].

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

[A panel study on the association of organophosphate ester flame retardant exposure with thyroid function related hormones in healthy older adults].

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) µIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

[The characteristics and citation analysis of the publications in the National Medical Journal of China from 2017 to 2019].

Objective: To analyze the characteristics and citation of National Medical Journal of China (NMJC) from 2017 to 2019, and provide reference for the development of the journal. Methods: All the literature published in NMJC during the period 2017 to 2019 was selected as the research objects, and the citation frequency data in Chinese core periodicals of science and technology from January 2018 to December 2021 were obtained through Institute of Scientific and Technical Information of China. The main indicators included the citation rate of published articles, average citation frequency of articles, citation status of individual papers, high citation authors and their affiliations from 2017 to 2019. Results: A total of 2 694 articles were published in 21 columns of NMJC from 2017 to 2019. The total number of published pages was 11 689, and the average number of articles was 4.34 pages. The total number of cited papers was 1 849, accounting for 68.63%. Among them, 845 papers were not cited, accounting for 31.37%. The total citation times was 6 578, with an average citation of 2.44 times. The highest citation frequency of a single paper was 217 times. A total of 54.27% articles obtained fund support, and the cited rate (72.78%) was slightly higher than that of articles without fund support (63.72%). Standard and specification articles were cited 1 817 times, with a citation rate of 96.67%, and 66 articles were cited more than 10 times. The columns with more than 30 articles but all cited less than 1 time included case report and difficult case analysis. The first author was from 31 provinces (autonomous regions, municipalities directly under the Central Government) in China. There were 21 corresponding authors whose papers have been cited more than 30 times, and 18 of them were from major hospitals and science academies in Beijing. Conclusions: NMJC has a wide coverage of contributions and strong academic influence during the period 2017 to 2019. The cited frequency of standard and specification articles is high, while case report and difficult case analysis evaluation column articles have very low cited frequencies. Therefore, NMJC should further adjust column setting, improve the academic quality, reduce the number of zero cited papers, and thus enhance the influence of the magazine.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

[Clinical phenotype and genetic analysis of patients with left ventricular noncompaction caused by the biallelic mutation of MYBPC3 and MYH7].

Objective: To explore the relationship between pathogenic gene, mutation and phenotype of left ventricular noncompaction (LVNC) patients and their family members. Methods: The subjects were the proband with LVNC and her family members. The medical history including electrocardiogram, echocardiography and cardiac magnetic resonance examination of the proband and family members were collected. Whole exome sequencing of the proband was performed, bioinformatics analysis focused on the genes related to hereditary cardiomyopathy. Candidate pathogenic sites were validated by Sanger sequencing. The clinical interpretation of sequence variants were classified according to American College of Medical Genetics and Genomics (ACMG) guidelines. Results: The proband carried a heterozygous variation of the MYBPC3 gene c.C2827T and the MYH7 gene c.G2221C. The proband's sister carried heterozygous variation of MYBPC3 gene c.C2827T. According to the ACMG guidelines, the variant was determined to be pathogenic. Conclusion: The missense variant of MYBPC3 gene c.C2827T and MYH7 gene c.G2221C are identified from the proband with LVNC and her family member, which provides a genetic basis for clinical diagnosis and genetic counseling of the patients and the family members with LVNC.

[Analysis of the relationship between syncope and poor prognosis in patients with acute pulmonary embolism and related factors].

Objective: To explore the association between syncope and poor prognosis and related factors of syncope in patients with acute pulmonary embolism (APE). Methods: A total of 740 patients with first diagnosed APE treated in West China Hospital of Sichuan University from September 1, 2016 to December 30, 2019 were enrolled. The basic information and clinical information (including clinical manifestations, complications, auxiliary examination, treatment and prognosis, etc.) of the patients were obtained from inpatient medical records. The patients were divided into the syncope group and the non-syncope group according to whether they had syncope or not. The basic and clinical conditions of the two groups were compared, and the factors related to syncope in APE patients were analyzed by multiple logistic regression model. Results: The proportion of APE patients with syncope was 12.6% (93/740). Age was (59±16) years in the syncope group (93 cases) and (59±17) years in the non-syncope group (647 cases), with 57.0% (53/93) and 60.4% (391/647) males, respectively. The body mass index, in-hospital mortality, proportions with high risk APE and mechanical ventilation of the syncope group were higher than those of the non-syncope group [(24.5±4.0) kg/m2 vs (23.3±3.8) kg/m2, 16.1% vs 7.7%, 4.4% vs 1.3% and 9.7% vs 2.5%, respectively]. The length of hospital stay [M (Q1, Q3)] of the syncope group was longer than that of the non-syncope group [15 (10, 22) d vs 14 (9, 22) d], and the proportions with chest pain and hemoptysis were lower than those of the non-syncope group (19.4% vs 36.8% and 14.0% vs 27.2%, respectively) (all P values<0.05). Multivariate logistic regression analysis showed that enlargement of the right heart [OR (95%CI): 2.46 (1.07, 5.64)] was a factor associated with syncope in APE patients. Conclusion: The proportion of APE patients with syncope is relatively high and is associated with poor prognosis, while enlargement of the right heart is associated with syncope in APE patients.

[Related factors and prognosis analysis of esophagorespiratory fistula after esophageal cancer surgery].

Objective: To explore the factors associated with the development of esophagorespiratory fistula (ERF) after esophageal cancer surgery and its relationship with patient survival. Methods: A total of 241 patients with esophageal cancer after surgery, who received postoperative sputum suction through bronchoscope from West China Hospital of Sichuan University between January and December 2021 were included. The clinical data and airway features under bronchoscope of these patients were collected. Of the 241 patients, 203 were males (84.2%) and 38 were females (15.8%), aged (63.63±8.05) years. The related factors of ERF were analyzed by multivariate logistic regression analysis, and Kaplan-meier was used to analyze the relationship between bronchoscopic specific manifestations, treatment modality and patient survival. Results: Of the 241 postoperative patients with esophageal cancer, 21 (8.7%) developed ERF. There were 39 (16.2%) patients with bronchoscopic specific manifestations, including 16 cases (6.6%) of hyperemia, 13 cases (5.4%) of congestion, and 15 cases (6.2%) of erosion. Bronchoscopic specific manifestations of tracheal mucosa (OR=13.734, 95%CI: 3.535-29.074, P<0.001) and thoracotomy (OR=9.121, 95%CI 1.843-44.237, P=0.007) were independent risk factors for the development of ERF, and preoperative chemotherapy (OR=0.128, 95%CI: 0.052-0.607, P=0.006) was a protective factor in the occurrence of ERF. The median survival time was 224 (95%CI: 95-353)d in the stent-treated group (14 patients) after the onset of ERF, and the median survival time of patients in the supportive care group (7 patients) was 29 (95%CI: 8-50)d, and the survival difference was statistically significant (χ2=5.69, P=0.017). Conclusions: Bronchoscopic specific manifestations are independent risk factors for the development of ERF in postoperative patients with esophageal cancer and are useful in assessing the risk of developing ERF. After the occurrence of postoperative ERF, timely intervention by insertion of tracheal stents to seal the fistula may prolong the survival time of the patients.

[Relationship between emotional apathy and motor symptoms, sleep and cognitive function in patients with early Parkinson's disease].

Objective: To study the relationship between emotional apathy and motor symptoms, sleep, and cognitive function in patients with early Parkinson's disease (PD). Methods: One hundred and twenty-nine early PD patients who were treated in the Second Affiliated Hospital of Soochow University from June to October 2020 were included, including 82 male and 47 female patients. The emotional apathy was assessed by modified apathy rating scale (MAES). The above 129 patients were divided into 67 patients in the PD with emotional apathy group (MAES>14 points) and 62 patients in the PD without emotional apathy group (MAES≤ 14 points). Age, gender, course of disease and levodopa equivalent dose were also collected. Hoehn-Yahr stage and unified Parkinson's disease rating scale PartⅢ(UPDRS-Ⅲ), Pittsburgh Sleep Quality Index (PSQI), polysomnography, and Montreal Cognitive Assessment Scale (MoCA) were used to evaluate the motor symptoms, sleep and cognitive functions of patients with early PD, and the clinical characteristics of patients with early PD with apathywere determined. Results: Compared with PD patients without apathy, those with apathy had longer disease duration [M(Q1,Q3)][5.0 (3.0, 7.0) years vs 3.0 (2.0, 5.0) years, P=0.006] and severer motor symptoms [20.0 (10.0, 28.0) vs 14.0 (8.5, 23.0), P=0.047]. There was no significant difference in PSQI score between the two groups. Among the 33 patients who completed polysomnography, compared with PD patients without apathy (n=16), those with apathy (n=17) had a longer rapid eye movement (REM) sleep latency [150 (124, 184) min vs 87 (57, 133) min, P=0.035)] and more frequent periodic limb movements in the REM phase(P=0.042).The REM sleep ratio (r=0.373, P=0.042), apnea-hypopena index (AHI)(r=0.374, P=0.046) and oxygen deficit index (r=0.409, P=0.025) were positively correlated with the degree of apathy in PD patients. PD patients with apathy had relatively poorer performance in cognition assessment than those without apathy and total MoCA score was inversely correlated with the degree of apathy (r=-0.231, P=0.017). Conclusion: Early PD patients with apathy have objective sleep disorders dominated by REM sleep disorders, which can have a negative impact on cognitive function.

[Risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a multicenter retrospective study].

Objective: To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality. Results: Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (all P<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d, P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (all P<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (all P<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD. Conclusion: Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

[Effectiveness and safety of idarucizumab in the management of perioperative complications of atrial fibrillation catheter ablation in atrial fibrillation patients under dabigatran therapy].

Objective: To investigate the efficacy and safety of idarucizumab in the treatment of perioperative cardiac tamponade and thromboembolic events during catheter ablation in atrial fibrillation (AF) patients under dabigatran therapy. Methods: This study was a retrospective analysis enrolling patients under dabigatran therapy, who underwent catheter ablation for AF at Beijing Anzhen Hospital from January 2019 to December 2020 and developed perioperative cardiac tamponade or acute ischemic stroke (AIS) and received idarucizumab to reverse the anticoagulant effect of dabigatran. Patients' age, sex, renal function, coagulation test and safety events at 30 d after idarucizumab administration were collected and analyzed. The clinical presentation and prognosis were also analyzed. Results: A total of 7 patients were included, 2 (2/7) were male, mean age was (66.3±11.2) years, serum creatinine level was (66.3±13.6) µmol/L, estimated glomerular filtration rate was (89.4±11.2) ml·min-1·1.73 m-2, CHA2DS2-VASc and HAS-BLED scores were (3.2±1.9) and (1.3±1.3), respectively. Five patients (5/7) developed cardiac tamponade during the perioperative period and the time interval to the last dose of dabigatran was (6.3±2.6) h. Idarucizumab was given at (36.4±16.7) min after the definitive diagnosis of cardiac tamponade. A significant decrease of activated partial thromboplastin time was achieved after idarucizumab administration in all five cases. Pericardial puncture and drainage were applied to all patients (5/5) with cardiac tamponade, the drainage volume was (1 037.0±846.9) ml, the retention time of pericardial drainage catheter was (27.9±13.9) h, and the recovery time of anticoagulation was (28.4±13.2) h. One patient (1/5) underwent thoracotomy for hemostasis due to excessive blood loss with the aim of ensuring complete hemostasis. Bleeding occurred in 1 patient (1/5) after the first restart of anticoagulation. AIS occurred in 2 patients (2/7) after operation. One case (1/2) received intravenous thrombolysis after receiving 5.0 g idarucizumab, no hemorrhagic transformation was observed, and the recovery process was satisfactory. Another patient in this group experienced significantly prolonged onset time and 5.0 g idarucizumab was applied before intravascular thrombectomy, there was no bleeding complication in this patient after thrombectomy. At the time of discharge, the consciousness was not significantly improved, and the muscle strength of the right lower limb was recovered somehow compared with that before operation. No hypersensitivity reactions or thrombotic events occurred in these patients within 30 days of the administration of idarucizumab. Conclusion: In AF catheter ablation-associated cardiac tamponade and AIS, idarucizumab is safe and effective in rapidly reversing the anticoagulant effect of dabigatran, use of thrombectomy saves valuable time for timely hemostasis and improvement of cerebral blood circulation.

Mitochondrial DNA Heteroplasmy of Hair Shaft Using HID Ion GeneStudioTM S5 Sequencing System.

ABSTRACT: Objective To study the heteroplasmy of the whole mitochondrial genome genotyping result of hair shaft samples using HID Ion GeneStudioTM S5 Sequencing System. Methods The buccal swabs and blood of 8 unrelated individuals, and hair shaft samples from different parts of the same individual were collected. Amplification of whole mitochondrial genome was performed using Precision ID mtDNA Whole Genome Panel. Analysis and detection of whole mitochondrial genome were carried out using the HID Ion GeneStudioTM S5 Sequencing System. Results The mitochondrial DNA sequences in temporal hair shaft samples from 2 individuals showed heteroplasmy, while whole mitochondrial genome genotyping results of buccal swabs, blood, and hair samples from the other 6 unrelated individuals were consistent. A total of 119 base variations were observed from the 8 unrelated individuals. The numbers of variable sites of the individuals were 29, 40, 38, 35, 13, 36, 40 and 35, respectively. Conclusion Sequence polymorphism can be fully understood using HID Ion GeneStudioTM S5 Sequencing system.

[Study on the effect of direct anti-human globulin test positive strength on patients' red blood cell transfusion].

Objective: To investigate the effect of direct antiglobulin test (DAT) positive strength on the clinical effect of red blood cell transfusion. Methods: The clinical data was collected on blood transfusion compatibility test and clinical transfusion of patients who underwent DAT testing from January 2015 to March 2019 in the Department of Blood Transfusion, Beijing Shijitan Hospital affiliated to Capital Medical University. A retrospective cohort study method was used to analyze the correlation between the DAT positive strength and the blood match results, irregular antibody test results, bilirubin value after blood transfusion, and red blood cell transfusion effect. Results: According to the blood matching test results, the minor cross-matching results were significantly correlated with the DAT strength (r=0.58, P<0.01). The DAT strength of the antibody-screening positive patients was greater (χ(2)=126.810, P<0.01). DAT-positive strength influences the direct bilirubin, the higher the DAT-positive strength, the higher the direct bilirubin concentration of the patients (χ(2)=32.069, P<0.01). DAT-positive strength also had an effect on patients' total bilirubin value (χ(2)=17.981, P=0.001). From the effect of red blood cell transfusion, patients with a DAT positive strength of 0.5 had a lower effective rate of transfusion (28.6%). The remaining DAT strength had no relation to the effect of red blood cell transfusion, and the efficiency of blood transfusion in patients with different DAT-positive strengths (1, 2, 3, 4) was 57.0%, 60.1%, 65.6% and 60.0%, respectively. With the same DAT strength, the patient's transfusion efficiency was higher (χ(2)=41.071, P=0.009). Conclusion: Different DAT-positive strengths are correlated with the patient's minor cross-match results and bilirubin content, while the effect of red blood cell transfusion has no significant correlation with DAT-positive strength. However, with the increase of DAT positive strength, patients are more likely to have irregular antibodies.

[Analysis of genes related to hypothyroidism during pregnancy].

Objective: By comparing and analyzing the differential sites of single nucleotide polymorphisms (SNP) between pregnant women with hypothyroidism and normal controls, the possible pathogenesis of hypothyroidism during pregnancy was explored. Methods: A total of 53 pregnant women with hypothyroidism during pregnancy from January 2018 to October 2018 were enrolled. A total of 50 pregnant women who underwent concurrent delivery and matched age with the case group were selected. Whole blood scans were performed on blood samples from two groups of subjects using the Illumina ASA chip to analyze the SNP with significant differences between the two groups. The human genome database hg19_dbsnp_version150 was employed to locate related genes. The association of related genes with thyroid dysfunction and pregnancy complications were analyzed. Results: A total of 13 SNPs were found in the study: rs4668077 (P=2.87E-05) in CERS6, rs6717546 (P=5.92E-05) in UGT1A1, rs1965358(P=7.78E-05) in CASR, rs916801 (P=9.22E-05) near CXCL14, rs6886845 (P=8.67E-05)near MAT2B, rs76245053 in GRIK2 (P=2.07E-05), rs6977642 (P=2.10E-05)in HDAC9, rs6949597 (P=3.68E-05) near ATXN7L1, rs11186331 (P=2.08E-05) in HTR7, rs2415551 (P=4.53E-05) near FBXO33, rs75850124 (P=9.24E-05) and rs76519339 (P=9.24E-05)in MIR4527, rs1014971 (P=3.24E-05) near CBX6 were statistically significant in the hypothyroidism group compared with the control group. Conclusions: The related gene UGT1A1 is related to the metabolism of thyroxine in the liver. CASR, CXCL14 and CBX6 are related to reproductive ability. CXCL14, CASR, HBAC9 and CERS6 are related to metabolic syndrome, and GRIK2, HTR7 and FBOX33 are related to neuropsychiatric diseases. Abnormal serum thyroxine levels during pregnancy may be associated with abnormal metabolism of thyroxine caused by UGT1A1 mutation. Genes associated with reproduction, metabolism, and neuropsychiatric disorders suggest a pathogenic link between hypothyroidism and infertility, metabolic syndrome, and neuropsychiatric disorders.

[Analysis of adverse events of clinical blood use except for the adverse reactions of blood transfusion].

Objective: To reduce the occurrence of adverse events of clinical blood use by analyzing the clinical adverse events of blood use except for the adverse reactions of blood transfusion. Methods: A retrospective analysis was performed on 294 cases of adverse events of clinical blood use other than adverse blood transfusion reactions in Shijitan hospital from January 2014 to December 2017, and a statistical analysis was made on the types of adverse events of clinical blood use, blood transfusion related departments, and internal and surgical blood use. Results: The incidence of adverse events of clinical blood use was 10.3‰, 9.6‰, 4.2‰ and 4.6‰ in these 4 years respectively, and there were 216 cases (73.5%) of external departments, 49 cases (16.7%) of internal departments, 8 cases (2.7%) of nursing departments, and 21 cases of others(7.1%), which includes 12 cases of errand department, 4 cases of the clinical laboratory and 5 cases of transfusion department. The adverse events of clinical blood use were divided into 4 types: 71 cases (24.1%) of transfusion process problems, 36 cases (12.2%) of clinical communication between departments, 182 cases (61.9%) of clinical unreasonable transfusion and 5 others (1.8%). There were statistically significant differences in the occurrence of adverse events of different types of blood use in external and internal departments based on the property of the department, among which there were significant differences in unreasonable transfusion between them. According to the purpose of blood use, there were statistically significant differences in the occurrence of different types of adverse events between the two departments, and the incidence of different types of external departments were higher than that of internal departments. Conclusions: The incidence of adverse events of blood use in external departments is higher than that in internal departments. Reasonable transfusion should be strengthened to avoid the occurrence of adverse events of clinical blood use, so as to ensure the safety of blood transfusion.

Secalonic acid- F inhibited cell growth more effectively than 5-fluorouracil on hepatocellular carcinoma in vitro and in vivo.

Hepatocellular carcinoma (HCC), one of the most common types of liver cancer, could be treated with 5-fluorouracil (5-FU). Due to its side effects, 5-FU is more often used as the co-administration drug in clinical practice. Secalonic acid-F (SAF), isolated from a fungal strain identified in our lab as Aspergillus aculeatus, showed potent biological activities. The goal of this study was to evaluate the inhibitory effects of SAF on hepatocellular carcinoma and to compare it with that of 5-FU. Results showed that SAF effectively inhibited cell growth with a dose-dependent manner in vitro and in vivo. And the inhibitory effects of SAF were stronger than that of 5-FU. Importantly, the cytotoxicity of SAF to peripheral blood mononuclear cells (PBMC) was similar to that of 5-FU. Furthermore, this study demonstrated that SAF arrested the cell cycle at the G1 phase and induced apoptosis with a dose-dependent manner by activating caspase3 and caspase9 through a mitochondrial pathway. Consequently, SAF may be a better potential candidate compound for human cancer treatment; these results will afford more data for antitumor agent design in detail.

[Research on the correlation and regulation of bone metabolism related biochemical indexes in different gestational ages].

Objective: To investigate the correlation and metabolic characteristics of the growth hormone (GH) and other bone metabolism related biochemical markers in pregnancy women serum. Methods: Determination of GH, 25 hydroxy vitamin D(25(OH)D), osteocalcin n-terminal fragments (N-MID), total propeptide of type 1 procollagen (TP1NP) and alkaline phosphatase (ALP) levels in different gestation women serum, the experimental group involving 75 cases of early pregnancy women(11-14 weeks), 135 cases of pregnancy women(15-21 weeks), 62 cases of late pregnancy women(31-40 weeks) and 28 cases of postpartum women(1-3 days). All cases were selected from prenatal screening patients in hospital from February 2016 to February 2017. The control group involving 55 cases of physically healthy nulliparous. The indicators of GH, 25(OH)D, TPINP and N-MID were detected by electrochemiluminescence and ALP were detected by rate method. All data were processed by SPSS. Variance analysis and Pearson correlation analysis were employed. Results: Serum GH level in early pregnancy, pregnancy, late pregnancy and control group were (4.54±2.26), (9.04±3.23), (20.16±4.89), (0.55±0.49)µg/L, respectively. The difference was statistically significant (F=270.037, P<0.01). Serum GH in each group of pregnant women were more higher than those in control group (all P<0.01), and there was statistical difference in different gestational stages(all P<0.01). Serum 25 (OH)D expression in early pregnancy, pregnancy and late pregnancy were (25.60±14.48), (27.10±12.05), (25.45±9.85)nmol/L. Compared with the control group(39.93±14.88)nmol/L, the difference was statistically significant (all P<0.01). Serum TP1NP level in early pregnancy, pregnancy, late pregnancy and control group were (44.44±11.80), (48.41±20.87), (102.63±41.73), (54.73±24.07)µg/L, respectively. The difference was significantly significant (F=54.027, P<0.01) and TP1NP in late pregnancy group was obvious higher than in early pregnancy group, pregnancy group and control group apart(all P<0.01). Serum N-MID level in early pregnancy, pregnancy, late pregnancy and control group were (5.91±2.64), (7.45±2.27), (17.24±6.47), (18.52±6.95)µg/L, and the difference was significantly significant(F=55.699, P<0.01). N-MID in early and middle pregnancy group were apparent lower than that in late pregnancy and control group (all P<0.01). Serum ALP level in early pregnancy, pregnancy, late pregnancy and control group were (49.74±10.14), (77.76±26.90), (168.34±45.15), (52.81±10.33) U/L, and the difference was significantly significant(F=180.349, P<0.01). However, there was noticeable difference in ALP level between late pregnancy and other pregnant group(P<0.01 or P<0.05). The serum GH, TP1NP and N-MID in postpartum women (1-3 days) were (1.44±0.99), (73.41±34.27), (12.10±5.64) µg/L, respectively. Compare with late pregnancy groups, the difference was significantly significant(all P<0.01). The content of GH in serum of 272 cases pregnant women was positively correlated with the concentration of TP1NP, N-MID and ALP, the gestational age and body weight of pregnant women(r=0.509, 0.720, 0.862, 0.827, 0.324, all P<0.01). The content of TP1NP, N-MID and ALP were positively correlated with gestational age, respectively(r=0.603, 0.722, 0.901, all P<0.01). Moreover, TP1NP expression was positively correlated with N-MID (r=0.849, P<0.01), and there was no correlation between other indexes. Conclusions: These findings have revealed that there are different metabolic character of the GH and bone metabolism related biochemical indexes during different pregnancy period. And there is a positive correlation between gestational age and the index of GH, N-MID, TP1NP, ALP, respectively. Finally, the bone metabolism is more active and Vitamin D deficiency is severe throughout pregnancy.

[A control study of artificial oocyte activation in the same period].

Objective: To compare the fertility rate and embryo outcome between normal fertilization and the use of Calcium ionophore A23187 on the same period of the same cycle of human ovum for artificial activation. Methods: Patients who conducted the intracytoplasmic sperm injection (ICSI) cycle in vitro fertilization assisted reproductive from January 2015 to December in reproductive center of the Third Affiliated Hospital of Zhengzhou University were enrolled.The protocol of this study was approved by the ethics committee of The Third Affiliated Hospital of Zhengzhou University.The subjects must met at least one of the inclusion criteria: (1)the normal fertilization rate was less than 30% ICSI in the previous ICSI cycle; (2)no good quality embryos in a previous period of third days in ICSI; (3)patients with globozoospermia.The ovum were randomly divided into two groups, control group and artificial oocyte activation (AOA) group. In the control group, the eggs were treated with routine ICSI operation, and the AOA group was activated by A23187 after ICSI. Normal fertilization rate, cleavage rate, pregnancy and birth outcome of two groups were compared. Results: The 2PN fertilization rate in the AOA group 65.93% (60/91) was significantly higher than that in the control group 46.67% (41/89) (P<0.05). In addition, in patients who met the inclusion criteria of 1 categories (2PN≤30%), the 2PN fertilization rate was significantly higher (P<0.05) in the AOA group [79.59% (39/49)] compared with the control group [57.14% (28/49)]. In patients who met the inclusion criteria of 3 categories (globozoospermia), the 2PN fertilization rate was significantly higher (P<0.05) in the AOA group [75% (6/8)] compared with the control group [0% (0/5)]. Conclusions: The use of calcium ionophore A23187 assisted activation could be helpful to improve the normal fertilization rate of ICSI. But the effects of early embryonic development and the safety of generation need to be further studied.