Difference in proinflammatory cytokines produced by monocytes between patients with major depressive disorder and healthy controls.

BACKGROUND: Immune activation and suppression in patients with major depressive disorders (MDD) have been both reported in different studies. We assume that these findings may indicate innate immunological tolerance in MDD, with subclinical elevated level of proinflammatory cytokines and the decrease in innate immune response while encountering pathogens. METHODS: Peripheral monocytes of 50 untreated patients with MDD and 40 healthy controls were isolated and cultured, with or without 10 ng/ml lipopolysacchride (LPS) for 6 h (6 h, LPS+/-), and with LPS for 18 h (18, LPS+). The cell culture supernatants were collected to measure concentrations of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 beta (IL-1ß). RESULTS: The baseline concentrations of IL-6 and IL-1ß (6 h, LPS-) were significantly higher in the MDD group than those in the control group. There was no significant difference of TNF-α between the two groups. The fold changes of LPS-induced secretion of IL-6 and TNF-α from monocytes cultured for 6 and 18 h were all lower in the patient groups, and that was true for IL-1ß as monocytes cultured for 18 h. LIMITATIONS: Given the gap between the results of in vitro experiments and the actual response that happens in vivo when the immune system encounters pathogens from the external world, future research should include in vivo methods to test the results of the current study. CONCLUSIONS: Patients with MDD may have subclinical inflammation during a depressive episode, and the reduced response to LPS in monocytes indicates innate immunological tolerance.

Effects of the phthalate exposure during three gestation periods on birth weight and their gender differences: A birth cohort study in China.

Phthalate has been widely used as a type of plasticiser in various consuming products in daily life. Recent studies have suggested that prenatal phthalate exposure may have adverse effects on fetal development. We aimed to identify the effects of in utero phthalate exposure on birth weight (BW). We evaluated a birth cohort comprising 3474 pregnant women and their single infants; 3103, 2975 and 2838 urine samples were collected in the first, second and third trimesters, respectively. Phthalate metabolites included monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEHHP), and mono-(2-ethyl-5-hydroxylhexyl) phthalate (MEOHP), which were analysed in the urine by using high performance liquid chromatography-tandem mass spectrometry. Mixed linear model was used in the statistical analysis. Generally, MMP and MEP exposure during pregnancy was associated with decreased birth weight of infants (MMP, ß=-12.192, p=0.009; MEP, ß=-11.876, p=0.014). Hierarchical analysis found that MMP and MEOHP exposure was associated with decreased infants' birth weight only in low birth weight groups (MMP, ß=-42.538, p=0.005; MEOHP, ß=-63.224, p=0.008); MEHP and MEHHP exposure was associated with decreased infants' birth weight in both low birth weight group (MEHP, ß=-42.348, p=0.035; MEHHP, ß=-50.485, p=0.006) and high birth weight group (MEHP, ß=-16.580, p=0.034; MEHHP, ß=-18.009, p=0.040), MBP and MEHP exposure were associated with increased infants' birth weight in male NBW group (MBP, ß=10.438, p=0.039; MEHP, ß=13.223, p=0.017). Moreover, the effect has sex difference. The reduction of birth weight associated with MEHP and MEOHP exposure was stronger in male infants, while MMP and MEP exposure was more significant in female infants.

Urinary concentrations of phthalate metabolites in early pregnancy associated with clinical pregnancy loss in Chinese women.

Limited evidence revealed conflicting results on relationship between phthalate exposure and clinical pregnancy loss (gestational weeks >6). A prospective cohort study in Chinese pregnant women (n = 3220) was conducted to investigate the association between urinary phthalate metabolites and clinical pregnancy loss (gestational weeks 6 to 27; n = 109). Morning urine samples during gestational weeks 5 to 14 (mean 10.42) were collected to measure monomethyl phthalate (MMP), monoethyl phthalate (MEP), monobutyl phthalate (MBP), monobenzyl phthalate (MBzP), mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). The concentrations of low- and high-molecular weight phthalate metabolites (ΣLMWP <250 Da and ΣHMWP >250 Da) were calculated. Adjusted logistic regression models showed increased risks of clinical pregnancy loss in women with higher creatinine- normalized concentrations of MEP, MBP, MEOHP, MEHHP, ΣLMWP and ΣHMWP. Stratified analysis by gestational weeks (10 weeks) of miscarriage indicated positive associations of MEP, MEOHP, MEHHP and ΣHMWP with embryonic loss (during gestational weeks 6 to 10). The only association of foetal loss (during gestational weeks 11 to 27) was observed with MEHHP. Our findings suggested that Chinese women who were exposed to phthalates during early pregnancy had an increased risk of clinical pregnancy loss, especially embryonic loss.

Cumulative risk assessment of phthalates associated with birth outcomes in pregnant Chinese women: A prospective cohort study.

A prospective cohort study of a Chinese population of mother-neonate pairs (n = 3103) was conducted to investigate the relationship between the cumulative hazard index (HI) of combined diethyl phthalate (DEP), dibutyl phthalate (DBP), dibenzyl phthalate (BBzP) and di(2-ethylhexyl) phthalate (DEHP) exposure and birth outcomes. The estimated HI for phthalates was based on phthalate metabolite concentrations in urine collected between 5th and 14th gestational weeks. The median HI values according to the European Food Safety Authority tolerable daily intake (HITDI) and U.S. Environmental Protection Agency reference dose (HIRfD) were 0.358 and 0.187, respectively. A total of 16.3% and 1.9% of the women exhibited HITDI and HIRfD exceeding the value of one, respectively. In unadjusted models, the categories (low < P25, median P25-P50, high > P75) of HITDI were associated with decreased birth weight (ß = -26.34 g, p = 0.021) and head circumference (ß = -0.09 cm, p = 0.029), whereas those for HIRfD were negatively associated with birth weight (ß = -31.74 g, p = 0.005), birth length (ß = -0.11 cm, p = 0.032), head circumference (ß = -0.13 cm, p = 0.003) and chest circumference (ß = -0.10 cm, p = 0.021) in all neonates. Adjustment for potential confounders revealed that HIRfD was inversely associated with head circumference (ß = -0.10 cm, p = 0.020). Stratification by gender indicated that HIRfD was associated with decreased birth length (ß = -0.17 cm, p = 0.041) in infant boys and HITDI was associated with decreased birth weight (ß = -33.12 g, p = 0.036) and head circumference (ß = -0.13 cm, p = 0.027) in girls. This is the first study on the cumulative risk assessment of phthalate exposures in pregnant Chinese women. We found that the HI values of multiple phthalate co-exposure were sex-specifically related to birth outcomes.

Maternal phthalate exposure during the first trimester and serum thyroid hormones in pregnant women and their newborns.

Animal and human studies have suggested that phthalate alters thyroid hormone concentrations. This study investigated the associations between phthalate exposure during the first trimester and thyroid hormones in pregnant women and their newborns. Pregnant women were enrolled from the prospective Ma'anshan Birth Cohort study in China. A standard questionnaire was completed by the women at the first antenatal visit. Seven phthalate metabolites were measured in one-spot urine at enrolment (10.0 ± 2.1 gestational weeks), as were thyroid hormone levels in maternal and cord sera. Multivariable linear regression showed that 1-standard deviation (SD) increase in natural log (ln)-transformed mono(2-ethylhexyl) phthalate (MEHP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with 0.163 µg/dL (p = 0.001) and 0.173 µg/dL (p = 0.001) decreases in maternal total thyroxine (TT4). Both MEHP and MEHHP were negatively associated with maternal free thyroxine (FT4; ß: -0.013, p < 0.001 and ß: -0.011, p = 0.001, respectively) and positively associated with maternal thyroid-stimulating hormone (ß: 0.101, p < 0.001; ß: 0.132, p < 0.001, respectively). An inverse association was observed between monobenzyl phthalate and maternal TT4 and FT4. A 1-SD increase in ln-transformed monoethyl phthalate was inversely associated with maternal TT4 (ß: -0.151, p = 0.002). By contrast, the concentrations of phthalate metabolites in urine were not associated with those of thyroid hormone in cord serum. Our analysis suggested that phthalate exposure during the first trimester disrupts maternal thyroid hormone levels.

[Causation between occupational prolonged standing time during progestation and pregnancy related complications].

OBJECTIVE: To describe the epidemiological characteristics of profession related long-standing behavior during preconception and progestation, and to probe the relationship between prolonged standing jobs and the common pregnancy related complications among pregnant women, in Ma' anshan city,Anhui province. METHODS: In this cohort study, subjects who had their first antenatal examination at Ma' anshan Maternal and Child Care Centers were recruited under informed consent, from October 2008 to October 2010. All the information were collected through questionnaires in the first, second and third trimesters respectively. Three questionnaires were filled in by subjects under the guidance of healthcare takers. RESULTS: In the study, the 75(th) percentile of prolonged-standing times were 4.0 h/d and 3.0 h/d respectively in preconception and progestation. The characteristics of pregnant women with low social/economic status, prone to be involved in stand-long occupation. Results in logistic regression analysis, prolonged-standing jobs during preconception was the risk factor of pregnancy-induced hypertension and severe anemia. The adjusted odds ratios were 2.05 (95%CI:1.26-3.31) and 1.38(95%CI:1.03-1.85)respectively. CONCLUSION: Prolonged standing jobs appeared to be common occupational exposure to and risks of both pregnant woman and their fetus. Exposure to these kinds of jobs during preconception could increase the risk of pregnancy-induced hypertension and severe anemia. In order to promote maternal health programs, all the related occupational risk factors should be valued and avoided during preconception and pregnancy.

[Relationship between folic acid supplements during peri-conceptional period and the adverse pregnancy outcomes: a cohort study].

OBJECTIVE: To examine the association between folic acid supplements during peri-conception and the related adverse birth outcome. METHODS: Pregnant women who received first prenatal care at 4 municipal-level medical institutions in Maanshan, from Oct. 2008 to Oct. 2010 were selected as the target population. All participants were asked to complete a self-administered questionnaire which including data on demographic characteristics, interval, complications and frequency of taking folic acid etc., during pregnancy. The follow-up-records after delivery would include factors as: fetal weight, height, circumference of head, chest circumference of the neonates. Finally, 4448 valid questionnaires were gathered, including 190 premature, 147 small for gestational age and 104 low birth weight babies. Descriptive statistics and logistic regression models were used for data analysis. RESULTS: Data showed that the weight, height and head circumference of the fetal at birth among pregnant women who had taken supplementary standard folic acid during peri-conception period or only during the first trimester, were all better than those pregnant women who had not taken the standard folic acid supplements. After adjustment for potential confounders as gestational weeks, maternal age, mather's education level, results from the logistic regression showed that intake of standard folic acid supplements appeared a protective factor for those babies who were smaller than the gestational age (RR = 0.45, 95%CI: 0.24 - 0.86), at premature delivery (RR = 0.52, 95%CI: 0.32 - 0.87) or with low birth weight (RR = 0.39, 95%CI: 0.19 - 0.80). However, data from this study showed that provision of folic acid supplements to the pre-pregnant or at first trimester alone did not make obvious impact on those babies as prematured, small for gestational age and at low birth weight. CONCLUSION: Standardized provision of folic acid supplements during peri-conceptional period could improve the outcomes of birth.

The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy.

The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam radiotherapy (CRT). We performed a prospective, controlled and non-randomized study on 120 patients with advanced PCa after HT who received HIFU, CRT, HIFU+LRT and HT alone, respectively. CT/MR imaging showed the primary tumours and pelvic lymph node metastases visibly shrank or even disappeared after HIFU+LRT treatment. There were significant differences among four groups with regard to overall survival (OS) and disease-specific survival (DSS) curves (P = 0.018 and 0.015). Further comparison between each pair of groups suggested that the long-term DSS of the HIFU+LRT group was higher than those of the other three groups, but there was no significant difference between the HIFU+LRT group and the CRT group. Multivariable Cox's proportional hazard model showed that both HIFU+LRT and CRT were independently associated with DSS (P = 0.001 and 0.035) and had protective effects with regard to the risk of death. Compared with CRT, HIFU+LRT significantly decreased incidences of radiation-related late gastrointestinal (GI) and genitourinary (GU) toxicity grade ≥ II. In conclusion, long-term survival of patients with advanced PCa benefited from strengthening local control of primary tumour and regional lymph node metastases after HT. As an alternative to CRT, HIFU+LRT showed good efficacy and better safety.

[A prospective study on the current status of repeated injuries and its risk factors in middle school and college students].

OBJECTIVE: To examine the epidemiological features and relative risk factors of repeated injuries among middle, high and college students in Ma'anshan city of Anhui province. METHODS: A prospective study on repeated injuries for 1-year follow-up period was carried out among 1494 students from 3 middle schools or colleges. Risk factors for repeated injuries were analyzed with multivariate logistic regression model. RESULTS: 799 students suffered 1639 episodes of injuries, with an incidence rate of 53.48%. The repeated group consisted of 200 students who suffered 854 injuries, accounted for 52.10% among the total injuries. RESULTS: from Multi-normal logistic regression analysis showed that male, number of family members of 4 or over, extraversion of character trait, and upper quartile of self-rating anxiety symptoms were the risk factors for the occurrence of repeated injuries. Moderate or well-of family income, mothers with senior high school education, and upper quartile of self-rating depression symptoms were protective factors for repeated injuries. CONCLUSION: Socio-demographic factors and emotional status may predict the occurrence of repeated injuries that called for further study.

[An association study of brain-derived neurotrophic factor gene polymorphism in bipolar disorders].

OBJECTIVE: To investigate the association between brain-derived neurotrophic factor (BDNF) gene polymorphism and bipolar disorder. METHODS: Single nucleotide polymorphisms rs6265 and rs11030101 in BDNF gene were detected and compared between 228 patients with bipolar disorder and 361 healthy controls. RESULTS: The genotypes, alleles and combinative genotype of BDNF gene single nucleotide polymorphism rs6265 and rs11030101 did not show significant differences between two groups. There were also no significant differences in genotypes and combinative genotypes between diagnostic subtypes, genders and on-set age of bipolar disorder and controls. CONCLUSION: This study did not found that BDNF gene single nucleotide polymorphism rs6265 and rs11030101 are associated with bipolar disorders.

[Influence of retrospective time period on reliability of epidemiological survey to injuries].

OBJECTIVE: To analyze the influence of different recall time periods on epidemiological survey of injuries among children and adolescents. METHODS: A study on injuries for 12 months follow-up period was actively surveyed among 4523 pupils selected by cluster sampling from 12 kindergartens, 1 elementary school, 1 junior high school, 1 senior high school and 1 college in Maanshan city in November, 2007 to November, 2008. Injury events were actively surveyed by school doctors or class health workers simultaneously. Participants were divided into three groups, the first group including self-reported injuries by 3-months interval, the second group with self-recalled injuries by 6-months interval and the third group with self-reported injuries in the past 12 months. Validity and reliability of injuries between surveillance injuries and retrospective injuries were compared. RESULTS: The overall rate of injury events was 74.2% and injury events and rate was higher in boys than that in girls (P < 0.01), In total, 6350 injury events were registered for the survey. Compare with surveillance findings, the injury rate declined 0.02% and the number of injuries had a 19 person/time reduction from the retrospective injuries by 3-months interval. The injury rate declined 0.02% and number of injuries reduced 58 person/times from the survey of retrospective injuries by 6-month interval. The rate of injuries declined 8.8% and frequencies had a 505 reduction from data of self-reported injuries in the past 12 months. The largest declines were found for the 3 to 6 year-old age group and for minor injuries. CONCLUSION: The 12-month recall period on underestimate injury rates was compared to the 3-month recall periods and 6-month recall periods. Recall periods of 6 months were recommended to be used in injury survey in children and adolescents.

[Surgical treatment of pronation and supination external rotation trimalleolar fractures].

OBJECTIVE: To explore the operative method and its clinical effects of pronation and supination external rotation trimalleolar fractures. METHODS: From March 2000 to July 2006,42 patients of the pronation and supination external rotation trimalleolar fractures treated with open reduction and internal fixation. Thirty-one were males and 11 were females,with an average age of 40.5 years (from 19 to 76 years). Four cases were open fractures and 38 cases close fractures. The fractures were classified as pronation-external rotation (grade IV) injury in 18 cases and supination-external rotation (grade IV)in 24 cases according to the system of Lauge-Hansen. The time of injury to operation was 2 hours to 27 days. The medial, lateral and posterior malleolus were exposed by standard anteromedial and Gatellier-Chastang approaches. The reduction and internal fixation started with the posterior,then the medial and the lateral malleolus and distal tibiofibular syndesmosis in sequence. The anteroposterior, lateral and mostise X-ray films were taken after operation. RESULTS: All the patients were followed up for an average time of 13.5 months(from 6 to 24 months). The time of union was from 12 to 16 weeks. The results were excellent in 20,good in 16, fair in 4 and poor in 2 cases according to Baird-Jackson ankle scoring system based on pain, stability, walking ability,range of motion and radiological manifestations. The excellent and good rate was 85.7%. There were no infection,malunion and nonunion of the fractures except that the inserted screw to distal tibiofibular syndesmosis was broken in 1 case. CONCLUSION: The key of operative treatment is to restore the anatomy of ankle and to regain the ankle function maximally.

[An experimental study on high intensity focused ultrasound combined with mitomycin treatment of bladder tumor].

OBJECTIVE: To study the therapeutic effect and synergistic inhibition effect of high intensity focused ultrasound in combination with mitomycin on T739 mice bladder tumor. METHODS: BTT739 tumor-bearing mice receiving HIFU and/or mitomycin in two weeks, were divided into control group, low dose chemotherapy group, high dose chemotherapy group, HIFU group and HIFU combined chemotherapy group. The growth of mice tumor volume was observed in two weeks, by which we counted tumor volume doubling time and performed the growth curve. All specimens were analysed histologically. RESULTS: HIFU combined mitomycin has significant synergistic inhibition effect. Tumor tissue damage such as huge coagulation necrosis was observed using light microscopy. However, there were still some remaining alive cells. The apoptosis of tumor cell in HIFU group and HIFU combined chemotherapy group obviously increased in comparison with other groups. CONCLUSIONS: HIFU group, HIFU combined chemotherapy group can distinctively inhibit tumor growth; HIFU combined with mitomycin has notable synergistic inhibitory effect. HIFU may induce the apoptosis of tumor cell.