Association of thyroid disease and risk of fatty liver disease: an exposure-wide Mendelian randomization study.

OBJECTIVE: Previous studies have often observed a possible association between thyroid and fatty liver diseases. The pathogenesis of both diseases is complex, with many confounding factors and controversies. We used a two-sample Mendelian randomization (MR) analysis to test the causality between thyroid disease and the risk of developing fatty liver disease. MATERIALS AND METHODS: All data were obtained from the genome-wide association studies (GWAS) Catalog database. Thyroid disorders include hypothyroidism, hyperthyroidism, autoimmune thyroiditis, and Hashimoto's thyroiditis. Fatty liver diseases include alcoholic fatty liver disease and non-alcoholic fatty liver disease (NAFLD). The inverse variance weighting (IVW) method was used for MR analysis, and sensitivity analysis was further performed to test its robustness. RESULTS: We discovered no causal relationship between thyroid disease and alcoholic fatty liver disease after excluding weak instrumental variables (IVs). Hyperthyroidism and hypothyroidism had a significant causal relationship with NAFLD. Hypothyroidism increased the risk of NAFLD using the IVW method (OR=7.62, 95% CI: 2.61-22.25, p<0.001). MR-Egger regression did not suggest potential evidence of directional pleiotropy (intercept, p=0.698). Hyperthyroidism also significantly increased the risk of NAFLD (OR=11.83, 95% CI: 2.9-22.54, p=0.026). MR-Egger regression did not suggest any potential directional pleiotropy (intercept, p=0.295). CONCLUSIONS: Hypothyroidism can significantly increase NAFLD incidence, and hyperthyroidism may be a risk factor for NAFLD.

[The association of renalase single-nucleotide polymorphisms rs2576178 and rs10887800 with hypertension in patients with obstructive sleep apnea].

Objective: To evaluate the associations between the renalase single-nucleotide polymorphisms rs2576178 and rs10887800 and the risk of hypertension in OSA patients. Methods: A total of 3, 570 male OSA subjects diagnosed via standard polysomnography were included in this retrospective study. We recorded anthropometric, genomic, and polysomnographic parameters and blood pressure levels. All subjects were divided into four groups based on quartiles of the apnea-hypopnea index (AHI). The relationships between rs2576178 and rs10887800 and the risk of hypertension were evaluated using the binary logistic regression, and haplotype analysis. Results: In the bottom AHI quartile, rs10887800 was significantly associated with the risk of hypertension according to the dominant model [odds ratio(OR)=0.691, 95% confidence interval (CI)=0.483-0.990, P=0.044] even after adjustment for age, sex, and the body mass index. The G-A haplotype was associated with a co-effect of the two SNPs, namely, the risk of hypertension decreased (OR=0.879, 95%CI=0.784-0.986, P=0.028). Conclusions: We find no association between single rs2576178 or rs10887800 variants with the risk of hypertension in our OSA population. But, the synergistic effect of the two polymorphisms is associated with the risk of hypertension in OSA patients.

[Factors affecting BK polyomavirus infection after kidney transplantation in post-school children and a predictive infection model].

Objective: To analyze high-risk factors affecting BK polyomavirus (BKPyV) infection and to construct a prediction model for BKPyV infection in children after renal transplantation. Methods: The clinical data of 332 children who received allogeneic kidney transplantation in the First Affiliated Hospital of Zhengzhou University from January 2014 to March 2022 were retrospectively collected. According to the BKPyV load level, the dynamic change process of lymphocytes at different time points were analyzed. The factors that have potential influence on BKPyV infection were screened by Cox regression analysis, and the receiver operating characteristic curve (ROC) was used to evaluate the sensitivity and specificity of the predictive model of infection. Results: Among the 332 children, there were 215 males and 117 females; the age of transplantation was (12.2±3.9) years old; 37 cases were preschool (1-5 years old), and 295 cases were post-school age (6-18 years old). BKPyV load in 224 urine samples and 30 blood samples of children were detected. There were 9 cases of BKPyV-associated viruria and 3 cases of BKPyV associated viremia in pre-school children, 76 cases BKPyV associated viruria and 14 cases of BKPyV associated viremia in post-school children. Multivariate Cox regression analysis showed that higher body mass index (BMI) (HR=1.105, 95%CI: 1.020-1.197), antithyroglobulin (ATG) application (HR=2.196, 95%CI: 1.335-3.613), and higher tacrolimus concentration (HR=2.484, 95%CI: 1.298-4.753), higher natural killer (NK) lymphocyte count (HR=1.193, 95%CI: 1.009-1.411), higher CD14++CD16-cell count (HR=1.096, 95%CI: 1.024-1.173) were independent risk factors for BKPyV associated viruria in post-school children. Delayed graft function (DGF) (HR=4.993, 95%CI: 1.555-16.038), Acute rejection (AR) (HR=6.021, 95%CI: 1.930-18.787), higher CD14++CD16-cell count (HR=1.227, 95%CI: 1.081-1.392) were independent risk factors for BKPyV associated viremia in post-school children. The results of ROC curve analysis showed that combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, and CD14++CD16-cell count predicted the occurrence of BKPyV associated viruria in post-school children after kidney transplantation at 0.5, 1, 2, and 5 years with area under curve (AUC) of 0.712 (95%CI: 0.626-0.798), 0.708 (95%CI: 0.612-0.804), 0.754 (95%CI: 0.668-0.840) and 0.767 (95%CI: 0.685-0.849). The sensitivity and specificity of the model were 64.9%, 61.4%, 61.6%, 55.8% and 70.9%, 72.4%, 76.0%, 84.0%, respectively. Combined with DGF, AR, and CD14++CD16-cell counts predicted the occurrence of BKPyV-associated viremia at 0.5, 1, 2, and 5 years after renal transplantation in post-school children with AUC of 0.791 (95%CI: 0.631-0.951), 0.744 (95%CI: 0.547-0.936), 0.786 (95%CI: 0.629-0.946) and 0.812 (95%CI: 0.672-0.948). The sensitivity and specificity of the model were 76.1%, 67.1%, 75.0%, 77.9% and 88.9%, 89.0%, 89.9%, 88.0%, respectively. Conclusions: The postoperative CD14++CD16-cell level can be used as an independent predictor of BKPyV infection in post-school children after renal transplantation. Combined BMI, immune induction drugs, tacrolimus concentration, NK cell count, CD14++CD16-cell count and combined DGF, AR, CD14++CD16-cell count show good fitting effect in predicting the occurrence of BKPyV-associated viruria and viremia after transplantation in post-school children respectively.

[Risks to predict blood loss and cranial nerve injury in carotid body paraganglioma resection].

Objective: To investigate clinical and imaging parameters to predict blood loss and cranial nerve injury (CNI) following carotid body paraganglioma (CBP) resection. Methods: A retrospective examination of clinical and imaging data was conducted on 63 patients who underwent CBP resection at Xiangya Hospital of Central South University from January 2016 to December 2022, including 23 males and 40 females, aged 26-87 years old. Three imaging parameters including tumor volume, the angle of contact with the internal carotid artery (ICA), and the distance to the base of skull (DTBOS) were gauged using the IMEDPACS software on CTA and MR imaging. The predictive efficacies of age, gender, Shamblin classification, and three imaging parameters for blood loss and CNI following surgery were analysed. Logistic composite parameter models were constructed and their predictive validity was assessed. Results: Multivariate logistic regression analysis underscored that only tumor volume (OR=1.381,95%CI:1.167-1.507,P=0.001) showed significant statistical correlations with blood loss following surgery. Area under curve (AUC) values of 0.910 for receiver operating characteristic (ROC) curves showed a sensitivity of 1.000 and a specificity of 0.694. Tumor volume (OR=1.126,95%CI:1.030-1.231, P=0.002) and DTBOS (OR=0.225,95%CI:0.081-0.630,P=0.005) were significantly associated with postoperative CNI. The analysis of logistic composite model showed AUC values for tumor volume, DTBOS and combination of the two parameters were 0.858, 0.788, and 0.872, respectively. The model for combination of tumor volume and DTBOS also proved superior in predicting postoperative CNI (Z=3.106, P<0.001), with a sensitivity of 0.833 and a specificity of 0.769. Conclusions: Tumor volume and DTBOS emerged as effective predictors for blood loss and/or CNI in patients with CBP resection. Moreover, the logistic composite parameter model outclassed single-parameter models in terms of their predictive clinical value.

[Analysis of prognostic factors of pediatric kidney transplantation].

Objective: To evaluate the short-and mid-term efficacy of pediatric kidney transplantation and the risk factors for kidney graft and recipient. Methods: The baseline data and postoperative complications of pediatric donors and recipients of 284 kidney transplants were retrospectively analyzed in the Department of Kidney Transplantation in the First Affiliated Hospital of Zhengzhou University from August 2010 to May 2021 and all subjects were followed up until December 31, 2021. According to the survival status of donors and recipients, they were divided into the graft-loss group and the graft-survival group, and the recipient death group and survival group, respectively. Univariate comparison between groups was performed by Log-rank test, and Cox proportional risk model was used to explore the independent risk factors for the graft and recipient survival. Results: Among the 284 children recipients, 184 cases (64.8%) were male and 100 cases(35.2%) were female, and 19 cases (6.7%) were living relative donor renal transplantation, 19 cases (6.7%) were preemptive transplantation, and 8 cases were secondary transplantation. The age of 284 recipients at the time of transplantation was 13.0 (9.0, 15.0) years, among whom 29 cases aged 0-6 years, 96 cases aged 7-11 years old, and 159 cases aged 12-18 years. The 1, 3, and 5 year survival rates were 92.3%, 88.9% and 84.8% for the kidney grafts, and were 97.1%, 95.6% and 94.4% for the recipients, respectively. Multivariate analysis showed postoperative acute rejection (HR=3.14, 95%CI 1.38-7.15, P=0.006) and perioperative vascular complications (HR=4.73, 95%CI 2.03-11.06, P<0.001) were independent risk factors for the survival of kidney graft. Postoperative infection (HR=14.23, 95%CI 3.45-58.72, P<0.001) was an independent risk factor for the postoperative mortality of recipients. Conclusions: Pediatric kidney transplantation shows a good short-and mid-term prognosis. Postoperative acute rejection and perioperative vascular complications are the risk factors for the survival of kidney graft, and postoperative infection is the risk factor affecting the survival of recipient.

[Study on mental health status of pregnant women and its influencing factors in the third trimester].

Objective: To understand the mental health status of pregnant women in the third trimester of pregnancy, and explore the influencing factors. Methods: The general demographic information and pregnancy information of 575 pregnant women in the Chinese Pregnant Women Cohort Study were collected. The mental health status of pregnant women in the third trimester was investigated by using Edinburgh Postpartum Depression Scale, Self-Rating Anxiety Scale and University of California at Los Angeles. Multivariate unconditional logistic regression was used to analyze the influencing factors for mental health of pregnant women. Results: In the third trimester of pregnancy, the incidence of depression was 16.52%, the incidence of anxiety was 11.13%, and the incidence of feeling loneliness was 26.26%. Logistic regression analysis showed that compared with those with education level of junior high school below, those with education level of college or bachelor's degree (OR=0.418, 95%CI: 0.184-0.950) and master's degree or above (OR=0.116, 95%CI: 0.027-0.503) were less likely to feel loneliness. Pregnant women with higher annual family income (10 000 RMB yuan) were less likely to suffer from depression (≥20 vs. <10: OR=0.527, 95%CI: 0.279-0.998), anxiety (10-20 vs. <10: OR=0.363, 95%CI: 0.180-0.731; ≥20 vs. <10: OR=0.271, 95%CI: 0.132-0.554) and feeling loneliness (≥20 vs. <10: OR=0.477, 95%CI: 0.276-0.826). Conclusions: The education level and family income have impacts on the mental health status of pregnant women in the third trimester. Medical staff should give targeted psychological advice to pregnant women to improve their mental health status.

Frequent loss of CD10 expression in follicular lymphoma with leukaemic presentation.

INTRODUCTION: Follicular lymphoma (FL) is usually a nodal lymphoma expressing CD10, rarely with leukaemic presentation (FL-LP). MATERIALS AND METHODS: We searched for FL-LP in our institution from 2000 to 2018 and characterised the neoplastic cells by flow cytometry, immunohistochemistry and fluorescence in situ hybridization. Thirteen (6.1%) of 212 FL cases were FL-LP, all de novo neoplasms. The leukaemic cells were small in 12 cases and large in one. All had concurrent FL, mostly (92%; 12/13) low-grade. The single case with large leukaemic cells had a concurrent primary splenic low-grade FL and a double-hit large B-cell lymphoma in the marrow. RESULTS: CD10 was expressed in the leukaemic cells in 38% (5/13) cases by flow cytometry and in 77% (10/13) cases in tumours (p= 0.0471). IGH/BCL2 reciprocal translocation was identified in 85% (11/13) cases. Most patients were treated with chemotherapy. In a median follow-up time of 36 months, nine patients were in complete remission. The 2- and 5-year survival rates were at 100% and 83%, respectively. In this study, we characterised a series of de novo FL-LP in Taiwan. All patients had concurrent nodal and/or tissue tumours, which might suggest that these patients seek medical help too late. CONCLUSION: The lower CD10 expression rate by flow cytometry than by immunohistochemistry might be due to different epitopes for these assays. Alternatively, loss of CD10 expression might play a role in the pathogenesis of leukaemic change. The clinical course of FL-LP could be aggressive, but a significant proportion of the patients obtained complete remission with chemotherapy.

[Associations between physical activities and gestational diabetes mellitus in the first trimester of pregnancy].

Objective: To prospectively explore the associations between total and different types of physical activities and gestational diabetes mellitus (GDM) in the first trimester of pregnant women, in Beijing. Methods: Data of 909 participants from the Chinese Pregnant Women Cohort study were extracted and studied. Four types of physical activities, including household/care-giving, occupational, sports/exercise and outdoor ways of transportation (walking/cycling/E-biking) in early pregnancy were studied by using the pregnancy physical activity questionnaire (PPAQ). All the participants were followed up and related data on GDM collected. Logistic regressions were conducted for data analysis on the associations of interests. Results: A total of 206 pregnant women (22.7%) were diagnosed with GDM. After adjusting for age, pre-pregnancy BMI, family history of diabetes and other types of physical activities, results from the logistic regression showed that women with moderate level of household/care-giving activities were with the lower odds on GDM (OR=0.654, 95%CI: 0.436-0.980). Women who had met the guideline of exercise were less likely to have GDM (OR=0.518, 95%CI: 0.287-0.934). There was no significant association appeared between total physical, occupational and outdoor ways of transportation (walking/cycling/E-biking) activities with GDM. Conclusions: Sports/exercise and household/care-giving activities in early pregnancy appeared important on GDM prevention. Pregnant women are encouraged to wisely arranging their sports/exercise activities and engaging in moderate household/care-giving activities in the first trimester of pregnancy, to prevent GDM.

[Effects of changes in physical activities on depressive symptoms during pregnancy: a cohort study].

Objective: To investigate the effect of changes in physical activities on depressive symptoms in the second trimester of pregnancy. Methods: Data from the Chinese Pregnant Women Cohort Study, from July 25, 2017 to November 26, 2018, were used. Women who had effectively completed the survey of physical activity and depressive symptoms in the first and second trimesters of pregnancy, were recruited. Both International Physical Activity Questionnaire-short and Edinburgh Postnatal Depression Scale were used, respectively. Pregnant women who had completed two surveys were included in our study and were divided into two groups according to the depressive symptoms, measured at the baseline. Among the pregnant women without depressive symptoms at the baseline, logistic regression was used to analyze the effects of changes in physical activity on the prevention of depressive symptoms. Effect on the reduction of depressive symptoms was analyzed, using the same method. Results: The prevalence rates of depressive symptoms were 23.83% and 20.57% in the baseline and second trimester, respectively. After adjusting for age, education level, occupation, family annual income and pre-pregnancy BMI, data from the logistic regression showed that women without depressive symptoms and with increased and adequate physical activities in the baseline, were with lower risks to develop depressive symptoms in the second trimester (OR=0.479, 95%CI: 0.335-0.684;OR=0.566, 95%CI: 0.394-0.815). Among women with depressive symptoms in the baseline survey, association between physical activity and depressive symptoms was not statistically significant (P>0.05). Conclusions: Increased and adequate physical activities showed preventive effects on depressive symptoms during pregnancy, but the remission effect was not obvious in women with depressive symptoms. Pregnant women should be encouraged to increase their physical activities while screening programs should also be carried out to reduce the depressive symptoms during pregnancy.

[Factors associated with sleep quality during first and second trimester in Chinese pregnant woman].

Objective: To investigate sleep quality in pregnant women during their first and second trimester and to identify risk factors. Methods: Data was from the Chinese Pregnant Women Cohort Study. A total of 3 618 pregnant women were included, with the exclusion 346 women who had missing information. Sociodemographic, health-related behavior, depression and sleep quality information were collected and analyzed. Logistic regression analysis were used to explore the influencing factors of sleep quality in pregnant women. Results: Among the 3 618 pregnant woman 28.2% had poor sleep quality in their first trimester and 28.7% in the second trimester. 15.2% pregnant women had progressively worse sleep and 13.0% had persistently poor sleep had pregnant women were generally suffered from poor sleep quality, difficulty falling asleep, sleep disorders and daily fatigue. Regular diet (OR=0.75, 95%CI: 0.62-0.92) and work (OR=0.84,95%CI: 0.71-0.99) in the first trimester were protective factors of sleep quality in pregnant women. Age ≥30 year old (OR=1.19, 95%CI: 1.03-1.37), passive smoking (OR=1.18, 95%CI: 1.02-1.36) and depression (OR=2.25, 95%CI: 1.95-2.61) in the first trimester were risk factors. Conclusions: The rate of poor sleep quality are high among Chinese pregnant woman during their first and second trimester. The risk factors of sleep quality are multiple. Regular diet and work, reduction of tobacco exposure, alleviation of depression symptom may help improve sleep quality among pregnant women.

[Effect and mechanism of cardiac adipose triglyceride lipase overexpression on burn-induced cardiac injury].

Objective: To explore the effect and potential mechanism of cardiac adipose triglyceride lipase (ATGL) overexpression on burn-induced cardiac injury. Methods: Eight-week-old C57BL/6J mice with cardiac ATGL overexpression driven by the myosin heavy chain (MHC) promoter (MHC-ATGL burn group) and wild-type (wild-type burn group) mice were randomly chose to the following experiments with burn injury after 24 h (n=8/group), MHC-ATGL mice and wild-type mice with corresponded age and sex were included as control. Cardiac ATGL protein expression, serum levels of cardiac troponin T and cardiac kinase-MB (CK-MB), cardiac free fatty acid and reactive oxygen species were detected. The wild-type and MHC-ATGL burn groups were not only compared with their corresponded control groups, but also compared between each other. Results: The hair color and development were shown little difference between each group. ATGL protein expression is elevated in wild-type burn group (1.00±0.68 vs 3.09±0.93, P=0.023) and decreased in MHC-ATGL burn group (17.84±2.41 vs 10.36±2.22, P<0.001), while ATGL protein expression is still increased in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Serum levels of cardiac troponin T and CK-MB were both elevated in wild-type burn group and MHC-ATGL burn group [(0.456±0.131) vs (0.076±0.019) µg/L and (0.219±0.089) vs (0.060±0.019) µg/L, (1 421±162) vs (221±67) U/L and (761±142) vs (221±41) U/L] (all P<0.001), while serum levels of cardiac troponin T and CK-MB was still decreased in MHC-ATGL burn group compared with wild-type burn group (P<0.001). In addition, cardiac free fatty acid was increased in wild-type burn group and little difference was found in MHC-ATGL burn group [(2.54±0.51) vs (0.46±0.27) mmol/L, P<0.001, and (0.81±0.38) vs (0.59±0.25) mmol/L, P=0.251], while cardiac free fatty acid was significant reduction in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Levels of cardiac reactive oxygen species was both elevated in wild-type burn group and MHC-ATGL burn group [(1.89±0.23) vs (1.00±0.18) and (1.38±0.17) vs (0.95±0.13)] (both P<0.001), while levels of cardiac reactive oxygen was reduction in MHC-ATGL burn group compared with wild-type burn group (P<0.001). Conclusion: Cardiac ATGL overexpression may protect against burn-induced cardiac injury through reducing free fatty acid and reactive oxygen species production.

[Effects of sodium butyrate on intestinal barrier of severe scald mice and the related mechanism].

Objective: To investigate the effects of sodium butyrate on intestinal barrier of the severe scald mice and the related mechanism. Methods: Eighteen C57BL/6 female mice, aged eight to twelve weeks, were divided into sham scald group, pure scald group, and scald+ sodium butyrate group according to random number table, with 6 mice in each group. Back of each mouse in pure scald group and scald+ sodium butyrate group were immersed into 90 ℃ water for 9 s, causing full-thickness scald of 30% total body surface area, while back of each mouse in sham scald group were immersed into 37 ℃ water for 9 s, causing sham injury. All of the mice in 3 groups were intraperitoneally injected with 1 mL sterile lactated Ringer's solution immediately after injury. Besides, mice in scald+ sodium butyrate group were intraperitoneally injected with 300 mg/kg sodium butyrate at 30 min before injury and immediately after injury, while mice in sham scald group and pure scald group were intraperitoneally injected with the same volume of sterile phosphate buffer solution. At post injury hour (PIH) 24, portal vein of mice in 3 groups was harvested, intestinal permeability was measured by fluorescin isothiocyanate-dextran fluorescence probe tracing method, then lileal tissue of mice in 3 groups was harvested, protein expressions of zonula occludens l (ZO-1), occludin, claudin-1, claudin-2, nucleotide-binding oligomerization domain-containing protein-like receptor family pyrin domain containing 3 (NLRP3), interleukin-1ß (IL-1ß), and IL-18 were detected by Western blotting, and distribution of ZO-1 in intestinal mucosa was observed by indirect immunofluorescence. Data were processed with one-way analysis of variance, least-significant difference test, and Bonferroni correction. Results: (1) At PIH 24, the intestinal permeability of mice in sham scald group, pure scald group, and scald+ sodium butyrate group was 0.88±0.19, 2.62±0.48, 1.23±0.16, respectively. Compared with that in sham scald group, the intestinal permeability of mice in pure scald group was significantly elevated (P<0.01), while the intestinal permeability of mice in scald+ sodium butyrate group showed no obvious change (P>0.05). Compared with that in pure scald group, the intestinal permeability of mice in scald+ sodium butyrate group was significantly decreased (P<0.01). (2) At PIH 24, compared with those in sham scald group, the protein expressions of ZO-1, occludin, and claudin-1 of mice in pure scald group and scald+ sodium butyrate group were significantly decreased (P<0.05), while the protein expression of claudin-2 was significantly increased (P<0.05). At PIH 24, compared with those of pure scald group, the protein expressions of ZO-1 and occludin of mice in scald+ sodium butyrate group were significantly elevated (P<0.05), while the protein expression of claudin-2 was significantly decreased (P<0.05), the protein expression of claudin-1 showed no significant difference (P>0.05). (3) At PIH 24, compared with those in sham scald group, the protein expressions of NLRP3, IL-1ß, and IL-18 of mice in pure scald group and scald+ sodium butyrate group were significantly increased (P<0.05). Compared with those of pure scald group, the protein expressions of NLRP3, IL-1ß, and IL-18 of mice in scald+ sodium butyrate group were significantly decreased (P<0.05). (4) At PIH 24, ZO-1 in intestinal mucosa of mice in sham scald group was distributed smoothly, continuously and homogeneously along the membrane. ZO-1 in intestinal mucosa of mice in pure scald group was distributed unsmoothly with breaks. The distribution of ZO-1 in intestinal mucosa of mice in scald+ sodium butyrate group was ameliorated compared with that in pure scald group. Conclusions: Sodium butyrate can inhibit the activation of NLRP3 inflammasome and decrease the production of IL-1ß and IL-18 in intestinal mucosa of severe scald mice, which protects the intestinal barrier function by alleviating the alteration of tight junction protein expression and localization.

[Risk factors for preterm birth, low birth weight and small for gestational age: a prospective cohort study].

Objective: To study the relationship between exposure factors in early pregnancy and preterm birth (PB), low birth weight (LBW) and small for gestational age (SGA) of neonates. Methods: A total of 3 172 pregnant women who were enrolled in the project of Chinese Pregnant Women Cohort Study-Peking Union Medical College (CPWCS-PUMC) from July 25, 2017 to July 24, 2018 and delivered before December 31, 2018 were selected as subjects in this study. The relationship between exposure factors in early pregnancy and adverse outcomes of neonatal delivery was analyzed by using binary logistic regression analysis. Results: The incidence rates of PB, LBW and SGA were 4.76%, 3.53% and 5.74%, respectively. In terms of PB, the analysis results showed that the gestational weight gain (GWG) and living in northern China were protective factors, while premature rupture of membranes, gestational hypertension, dental examination or treatment within 1-3 years and family with 3-4 members were risk factors. In the respect of LBW, GWG and daily consumption of milk and dairy products were the protective factors, while premature rupture of membranes, gestational hypertension, sedentary working time more than 6 hours, dental examination or treatment within 1-3 years and passive smoking were risk factors. For SGA, baby girl, passive smoking, peanut oil consumption and unsalted taste were risk factors, while folic acid supplementation was protective factor. Conclusion: The risk factors for PB, LBW and SGA were multifactorial, and relevant specific measures should be taken to reduce the occurrence of adverse neonatal outcomes.

[Significance of intestinal fatty acid binding protein in evaluation of intestinal barrier dysfunction of mice at early stage of severe burn injury].

Objective: To investigate the significance of intestinal fatty acid binding protein (IFABP) in the evaluation of intestinal barrier dysfunction of mice at the early stage of severe burn injury. Methods: Thirty-six 8-week-old C57BL/6 male mice were collected and divided into normal control group (n=6) and scald group (n=30) according to random number table. Back of each mouse in scald group was placed into hot water of 90 ℃ for 10 s, causing full-thickness scald (hereinafter refer to as burn) of 30% total body surface area, while mice in normal control group were not inflicted with burns. Six mice in normal control group were taken, and 6 mice in scald group at 1, 2, 6, 12, and 24 h post injury were taken respectively. The portal vein blood of each mouse was extracted and the plasma was separated to measure intestinal permeability with fluorescin isothiocyanate-dextran fluorescence probe tracing method and plasma IFABP content by enzyme-linked immunosorbent assay. The distal ileum tissue of mice in normal control group and scald group at each time point post injury was collected to observe the morphology of the intestinal mucosa tissue by hematoxylin-eosin staining. Data were processed with one-way analysis of variance and Student-Newman-Keuls test, and pearson correlation test was used to analyze the correlation between intestinal permeability and plasma IFABP content of burned mice. Results: (1) At 1, 2, 6, 12, and 24 h post injury, the intestinal permeability of mice in scald group was 2.7±0.8, 5.4±2.5, 7.3±4.2, 12.4±6.1, 1.4±0.7, respectively, obviously higher than 1.0±0.4 of normal control group (P<0.05 or P<0.01). The intestinal permeability of mice in scald group showed an increasing trend post injury, reaching the peak at 12 h post injury, and rapidly falling back at 24 h post injury. (2) At 1, 2, 6, 12, and 24 h post injury, the plasma IFABP content of mice in scald group was (64±11), (59±12), (76±18), (111±22), and (66±10) ng/mL, obviously higher than (35±8) ng/mL in normal control group (P<0.05 or P<0.01). The plasma IFABP content of mice in scald group showed an increasing trend post injury, reaching the peak at 12 h post injury, and rapidly decreasing at 24 h post injury. (3) Uniform thickness of mucosa, intact epithelia, regularly arranged villi, and no inflammatory cell infiltration were observed in ileum of mice in normal control group. In ileum of mice in scald group, shortened villi of mucosa with different degrees, edema of lamina propria, and infiltration of neutrophils were observed at 1 and 2 h post injury; obviously damaged and partially exfoliated ileal mucosa, disorderly arranged and broken villi, degenerated and necrotic epithelial cells, dilated central lacteal, and infiltration of lymphocytes and neutrophils were observed at 6 and 12 h post injury; the damage of ileal mucosa was alleviated, and basically intact epithelia, dilated central lacteal, and infiltration of inflammatory cells were observed at 24 h post injury. (4) There was a significantly positive correlation between the intestinal permeability and the plasma IFABP content of burned mice (r=0.841, P<0.05). Conclusions: The plasma IFABP can be used as a good biological indicator for the evaluation of intestinal barrier dysfunction of mice at the early stage of severe burn injury.

Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.

Background: Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Methods and patients: Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. Results: A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. Conclusion: ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. Clinical Trial number: www.clinicaltrials.gov (NCT 01287585).

[Effects of short chain fatty acid on barrier disruption of human intestinal epithelial cell induced by endotoxin/lipopolysaccharide and the related mechanism].

Objective: To investigate the effects of short chain fatty acid (SCFA) on barrier disruption of human intestinal epithelial cell induced by endotoxin/lipopolysaccharide (LPS) and the related mechanism. Methods: The human intestinal epithelial cell line Caco-2 was used to reproduce monolayer-cells. Cells were divided into control group, LPS group, and SCFA+ LPS group according to the random number table. Cells in control group were only routinely cultured with DMEM medium. Cells in LPS group were cultured with DMEM medium and LPS with final mass concentration of 10 µg/mL. Cells in SCFA+ LPS group were cultured with DMEM medium, LPS and SCFA (consisting of 0.5 mmol/L acetate, 0.01 mmol/L propionate, and 0.01 mmol/L butyrate) with final mass concentration of 10 µg/mL. At post culture hour (PCH) 0, 1, 2, 6, 12, and 24, transepithelial electrical resistance (TER) of cells was determined with an ohmmeter, with sample number of 72. Another portion of cells were divided and treated as above, and then Western blotting was employed to detect the protein expressions of zonula occludens 1 (ZO-1), occludin, and claudin-1 at PCH 24, with sample number of 6. Another portion of cells were divided and treated as above and then immunofluorescence was used to observe cellular morphology and distribution of ZO-1. Data were processed with analysis of variance of factorial design, one-way analysis of variance, least-significant difference test, and Bonferroni correction. Results: (1) Compared with that in control group, TER of cells in LPS group was significantly reduced from PCH 1 to 24 (P<0.01), while TER of cells in SCFA+ LPS group showed no obvious change (P>0.05). TER of cells in SCFA+ LPS group was significantly higher than that in LPS group from PCH 1 to 24 (P<0.01). (2) Compared with the protein expressions of ZO-1, occludin, and claudin-1 of cells in control group (1.25±0.10, 1.17±0.04, and 1.24±0.20), those of cells in LPS group (0.74±0.23, 0.76±0.11, and 0.77±0.11) at PCH 24 were significantly decreased (P<0.05), while those of cells in SCFA+ LPS group (1.23±0.46, 1.05±0.09, and 1.01±0.13) showed no significant differences (P>0.05). Protein expressions of occludin and claudin-1 of cells in SCFA+ LPS group were significantly higher than those in LPS group at PCH 24 (P<0.05). Protein expression of ZO-1 of cells in SCFA+ LPS group was higher than that in LPS group at PCH 24 with no significant difference (P>0.05). (3) At PCH 24, cells in control group were compact in arrangement with pebble-like appearance, and ZO-1 was distributed smoothly and continuously along the cell membrane. In LPS group, cells were sparse in arrangement with change in appearance, and ZO-1 was distributed uncontinuously along the cell membrane with curls and breaks. In SCFA+ LPS group, the appearance of cells and distribution of ZO-1 were remarkably ameliorated compared with those in LPS group. Conclusions: SCFA can alleviate the barrier disruption of human intestinal epithelial cell induced by LPS through interdicting the abnormal distribution of ZO-1 and decrease of TER and tight junction proteins' expressions.

[Study on correlation between retinal vessel morphology or ocular hemodynamic parameter and internal carotid artery stenosis].

Objective: To analyze the correlation between retinal vascular calibers, ocular blood flow parameters and internal carotid artery stenosis and to evaluate the effect of internal carotid artery stenosis on ocular blood vessels comprehensively. Methods: A retrospective case-control study. The clinical data of 141 patients who underwent head-and-neck computed tomography (CT) angiography examinations of the ICA were collected at Beijing Friendship Hospital, Capital Medical University from January 2014 to January 2016. According to diagnostic criteria, the patients were divided into four groups: the non-stenosis group, the mild stenosis group, the moderate stenosis group, and the severe stenosis andocclusion group. The retinal vascular caliber was measured in color fundus photograph by IVAN software. Color Doppler ultrasonography was used to measure the parameters of ocular blood flow, including the peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI) and pulsatility index (PI). The enumeration data were analyzed with chi-square test, the measurement data were analyzed with rank-sum test, and the correlation test was performed with spearman. Results: The gender ratio of the patients without stenosis, mild stenosis, moderate stenosis, severe stenosis and occlusion was 12/7, 31/19, 28/25, 12/7, χ2 test was not statistically significant (χ2= 0.79, P=0.85); There was no statistically significant difference between the different groups (χ2= 0.15, P=0.68), the age of four groups were (64.1±8.3), (54.3±14.3), (68.9±11.8) and (59.1±8.0) y, respectively. In the no internal carotid artery stenosis group, the arteries diameter is (164.5±15.6) µm ,the vein diameter is (245.6±20.0) µm and the arteriovenous ratio is 0.7±0.1. There is no difference among the mild stenosis group, moderate stenosis group and the severe stenosis (χ2artery caliber=6.92, Partery caliber=0.08; χ2vein diameter=4.16, Pvein diameter=0.25; χ2arteriolar-venular ratio=1.38,Parteriolar-venular ratio=0.71) . The PSV of central retinal artery in the above groups were (14.6±3.6), (34.4±13.2), (35.7±14.6), (42.3±19.0)cm/s respectively, the data were analyzed by rank-sum test and there was a significant difference (χ2=13.44, P< 0.01) ; The PSV of the posterior ciliary artery in the above groups (17.6±6.5), (15.0±4.6), (13.4±4.3) and (11.0±3.2)cm/s respectively, the data were analyzed by rank-sum test and there was a significant difference (χ2=22.71, P<0.01) , EDV were (5.90±2.2), (5.1±2.1), (4.3±1.5) and (4.3±4.8)cm/s respectively and there was a significant difference (χ2=20.36, P<0.01) .There was a correlation between retinal artery diameter, PSV and EDV of the central retinal artery, PSV and EDV of the posterior ciliary artery and the diameter of the internal carotid artery but without linear correlation. (rartery caliber=-0.23, Partery caliber=0.01; rPSV of central retinal artery= -0.29, PPSV of central retinal artery<0.01; rPSV of posteri or ciliary artery=-0.34, PPSV of posterior ciliary artery<0.01, rEDV of posterior ciliary artery=-0.35, PEDV of posterior ciliary artery<0.01). Conclusions: There was a correlation between retinal artery diameter, PSV and EDV of the central retinal artery, PSV and EDV of the posterior ciliary artery and the diameter of the internal carotid artery. PSV of the central retinal artery, PSV and EDV of the posterior ciliary artery changed significantly when the internal carotid artery stenosis existed. (Chin J Ophthalmol, 2016, 52: 905-910).

Synthesis of platinum(II) and palladium(II) complexes with 9,9-dihexyl-4,5-diazafluorene and their in vivo antitumour activity against Hep3B xenografted mice.

Two complexes dichloro(9,9-dihexyl-4,5-diazafluorene)platinum(II) (Pt-DHF) and dichloro(9,9-dihexyl-4,5-diazafluorene)palladium(II) (Pd-DHF) were synthesized and their in vivo antitumour activity was investigated using an athymic nude mice model xenografted with human Hep3B carcinoma cells. Pt-DHF- and Pd-DHF-treated groups showed significant tumour growth inhibition (with about 9-fold and 3-fold tumour growth retardation) when compared with the vehicle control group. The liver toxicology effects on the animals of the two compounds were investigated. Pt-DHF and Pd-DHF-treated groups had a lower alanine transaminase and aspartate transaminase values than those of the vehicle treated group as the animals from the vehicle control group had very heavy hepatoma burden. We assume that both complexes could be further investigated as effective antitumour agents and it is worthwhile to study their underlying working mechanism.