Phthalate esters have been used as the plasticizers for about 80 years. As a kind of environmental hormone and universal pollutants, they are found widely in air dust, industrial waste water, river, soil and solid waste, moreover, they have been detected in food, drinking water and body fluid. In this paper, the new progresses of the effects of phthalate esters on the rodents and human, including reproductive toxicity and liver toxicity, were summarized and the short-term, quick and accumulative actions of phthalates mono-esters, metabolite of phthalate esters, on the rodents and human body were also reviewed.

Phthalate esters are commonly used as plasticizers in many products.They have become widely spread in the environment.Several animal studies have showed that phthalate esters possess endocrine disrupting effects.Phthalate esters have been found in body fluid such as urine,blood and semen.As the base of internal exposure assessment,metabolism of phthalate esters was reviewed in the paper.The main metabolism pathways for phthalate esters and their metabolites in urine were summarized and the levels of metabolites of phthalate esters in different people were compared.

Objective To investigate the pollution of phthalate ester in indoor environment. Methods Settled dust samples from 10 households, 10 offices and 10 student dormitories in Beijing were collected. Seven kinds of phthalate esters in these samples were determined with solid phase extraction-high performance liquid chromatography (SPE-HPLC) .Dates were analyzed statistically by nonparametric tests. Results The main phthalate esters in dust were di (2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and dicyclohexyl phthalate (DCHP). Of phthalate esters, DEHP with the range of 28-6 073 mg/kg had the highest concentration in indoor dust. The total level of phthalate esters in households was the highest, offices followed, student dormitories was the last. The Kurskal-Wallis H test showed that the concentrations of BBP, DEHP and DCHP in dust were significantly different in 3 types of rooms (P

Phthalate esters widely exist in the environment. It has been demonstrated that they are harmful to human bodies. Phthalate mono-esters are the first metabolite of phthalate esters. In general,biotransformation or metabolism of xenobiotics most frequently result in detoxification of the chemical and facilitates excretion from the body. However,this may not be the case for phthalates. In the present paper,metabolism of phthalate esters and the toxicity of the phthalate mono-esters were reviewed,not only the effect of their mutagenesis,teratogenesis and carcinogenesis,but also their toxicity on reproduction,development,hormones,nuclear receptor,inflammation and obesity were included.

Objective To investigate the clinical features of systemic sclerosis( SSc)patients with pulmonary hypertension(PAH)ane its treatment approach ane prognosis. Methods The clinical information of 16 SSc patients with PAH(PAH group)were recoreee. Seventy-four SSc without PAH were servee as no-PAH group. Patients in PAH group were given the basic therapy inclueing oxygen therapy,anticoagulants,careiac, eiuretic,anti-rheumatic,pulmonary vasoeilator therapy. Results The rate of antinuclear antiboey in PAH ane non-PAH group were 87. 5%(14 / 16)ane 75. 7%(56 / 74),ane the eifference was statistically significant(P= 0. 508). Serum albumin,erythrocyte seeimentation rate at 1 h in PAH group were(32. 6 ± 4. 6)g/ L ane (48. 4 ± 29. 4)mm/ 1 h. The rate of acral lesion proteinuria,hematuria,ECG abnormal rate were 62. 5%(10 / 16),62. 5%(10 / 16),43. 8%(7 / 16),62. 5%(10 / 16)respectively in PAH group. Serum albumin, erythrocyte seeimentation rate at 1 h in PAH group were(35. 6 ± 5. 0)g/ L ane(31. 3 ± 26. 3)mm/ 1 h in non-PAH group. The rate of acral lesions,proteinuria,hematuria,ECG abnormal rate were 31. 1%(23 / 74),27. 0%(20 / 74),12. 2%(9 / 74),9. 5%( 7 / 74 ) respectively in non-PAH group. The eifferences were significant between in terms of all above ineices(P = 0. 033,0. 041,0. 018,0. 006,0. 003,0. 000). During follow-up,the eisease was in stable in 74 case of non-PAH. Among 16 case with PAH,1 mile case was lost,1 case with severe PAH eiee of severe pneumonia,pulmonary hypertension,right ventricular failure,respiratory failure,3 mile patient with PAH were with eevelopment of primary eisease ane the rest 11 cases of PAH patients were with lower interstitial lung eisease than that of the previous eetectee by chest HRCT. Oppler echocareiography measurement of pulmonary artery systolic pressure was(48. 9 ± 2. 4)mmHg before treatment ane then reeucee to(31. 5 ± 4. 5)mmHg in rest 11 cases(t = 22. 27;P = 0. 001)measuree by Doppler echocareiography. Careiac function was improvee euring followee up ane no other aeverse reactions were seen. Conclusion SSc patients merge multiple PAH show it associate with other organ eamage,ane has a poor prognosis. Early careiac Doppler ultrasoune shoule be performee in oreer to get early eiagnosis ane treatment. Treatment approaches shoule be targetee at the primary eisease ane incentives such as pulmonary besiee oxygen therapy,eiuretics,careiac ane anticoagulant erugs in oreer to improve prognosis.

Objective To examine the effects and mechanisms of siRNA targeting aquaporin 4 (AQP 4) in combination with hyperbaric oxygen therapy(HBO) on cerebral edema and apoptosis in the brain tissue of rats after hemorrhage.Methods Rats were randomly divided into four groups,the control group,the hyperbaric oxygen group,the AQP-4 siRNA group and the combination therapy group (24 rats).Thrombin Ⅶ was injected into the caudate nucleus to establish the hemorrhage model.Construction of siRNA targeting aquaporin 4 was conducted.The mRNA expression of AQP-4 was detected by RT-PCR at day 3.Changes in brain moisture and blood-brain barrier perme ability were measured by a wet/dry weight method and Evans blue fluorometry.The nerve cell apoptosis rate was analyzed by Annexin V andTdT-mediated dUTP-biotin nick end labeling (TUNEL).The expression of proteins including AQP-4,MMP-2,MMP-9,Bcl-2 and caspase-3 was detected by Western Blotting.All the animals were given a score for their nerve function at day 3.Results AQP-4 siRNA treatment obtained better effects than HBO in decreasing the brain edema leveland silencing AQP-4 mRNA(P＜0.05)while,the combination therapy group achieved the best results(P＜ 0.05).Compared with the control group,the percentage of apoptotic cells decreased in all the three treatment groups,with the most marked decrease observed in the combination treatment group(4.24± 0.04)％(F=13.76,P=0.001).The expression of AQP-4,MMP-2,MMP-9 and caspase-3 was lower (P＜0.05) and the expression of Bcl-2 was higher(P＜0.01)in the combination treatment group than in the other three groups.Compared with the control group,all the other three groups received better scores on nerve function defect evaluation at day 3 after hemorrhage(P＜0.05),with the combination treatment group again achieving the most favorable score (4.7 ± 1.1) (F=7.21,P =0.013).Conclusions Targeted siRNA interference combined with hyperbaric oxygen can effectively reduce cerebral edema after cerebral hemorrhage,inhibit neuronal apoptosis and promote neuron function recovery.The underlying mechanisms may be related to down-regulation of AQP-4,MMP 2,MMP-9 and caspase-3 expression and up-regulation of Bcl-2 expression.

Objective: To assess clinical features and treatment outcomes in immunocompetent patients with primary central nervous system lymphoma (PCNSL). Methods: Sixty-two patients with PCNSL who attended Guangdong General Hospital between January 1998 and January 2012 were included. Survival curves were estimated using Kaplan-Meier survival methodology and statistical significance of continuous was assessed via the Cox proportional hazard model. Results: The median age of the patient cohort was 56 years, and the male to female ratio was 1.14∶1.00. The common presentations were increased intracranial pressure symptoms and neuron damage. Performance status of 54 (54/62, 87.1%) patients were the international prognostic index (IPI) 0-2. Diffuse large B-cell lymphoma (57/62, 91.9%) was most common, and the rest were T-cell lymphoma (4/62,6.4%) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (1/62, 1.6%). In the series, 32 patients (32/62, 51.6%) had multiple lesions. Involvement of deep structures was found in 30 (30/62, 48.4%) patients. An elevated serum LDH level was detected in 19 (19/62, 30.6%) patients and the Ki-67 index was ≥90% in 38 (38/62, 61.3%) patients. Univariate analysis showed patients who were female, age<60 years, had WHO Eastern Cooperative Oncology Group performance status grade 0-2, single lesion, absence of deep structures involvement and normal LDH level showed better 2-year survival rate and longer median survival time. Significance was only seen in the normal LDH level group. Multivariate Cox regression analysis revealed that radical surgery only and Rituximab+ high-dose of methotrexate+ whole brain radiation therapy (WBRT) were independent prognostic indicators in PCNSL patients (P<0.05). Conclusions PCNSL is a rare but aggressive tumor with poor prognosis. Patients treated with high-dose of methotrexate combining with rituximab, followed by WBRT have a better prognosis and longer survival time, and thus these could probably be a promising treatment.

Objective:To investigate the effect of hyperbaric oxygen combined with RNA interference (RNAi) technology targeting aquaporin-4 (AQP-4) on improving cognitive function in rats with traumatic brain injury (TBI), and to explore its mechanism.Methods:Totally 112 adult male SD rats were randomly divided into four groups: control group, hyperbaric oxygen(HBO) group, AQP-4 RNAi group and combined treatment group, with 28 rats in each group.The TBI model of rat was established by hydraulic percussion and siRNA targeting aquaporin 4 was constructed. Rats were given corresponding intervention according to their groups.Then the modified neurological severity scores(mNSS)was evaluated on the 7th day and 21th day after operation. Morris water maze test was carried out from the 21st day to 25th day after operation and the percentage of target quadrant and daily escape latency were recorded.The changes of the brain permeability of blood-brain barrier and moisture in brain tissues were measured by Evans blue fluorometry and a wet-dry-weighing technique respectively. The protein expression levels of AQP-4, Caspase-3, Bcl-2, MMP-2 and MMP-9 were detected by Western blot method. The mRNA expression of AQP-4 in TBI brain tissue was measured by RT-PCR method, and the apoptosis rate of TBI brain cells was detected by TUNEL and AnnexinV methods on the 7th day after operation. SPSS 23.0 and Graphpad Prism 7.0 softwares were used for data analysis.One-way ANOVA was used for inter group comparison.Repeated measurement ANOVA was used for Morris results, and the LSD- t test was used for pairwise comparisons. Results:The results of mNSS showed that there were significant differences among the groups on the 7th day and 21st day after operation ( F=4.89, 7.59, both P<0.05). The scores of each treatment group were lower than that of the control group, and the effect of the combined treatment group was the best (7th day: t=3.98, -7.75, both P<0.05; 21st day: t=47.82, 7.94, both P<0.05). The results of Morris water maze test showed that the time and group interaction of rats in the target quadrant residence time and escape latency were not statistically significant( F=1.83, 8.42, both P>0.05). The escape latency and the percentage of stay in the target quadrant in the combined treatment group were better than those in other groups on the 24th and 25th day after operation (all P<0.05). Evans blue staining showed that the contents of Evans blue in AQP-4 RNAi group, hyperbaric oxygen group and combined treatment group were lower than that in the control group(all P<0.05), and that in the combined treatment group was the lowest( t=6.19, P<0.05). The results of dry-wet specific gravity method showed that the water content of brain tissue in the combined treatment group((68.15±1.52)%) was the lowest, and that in the AQP-4 RNAi group((76.71±1.06)%) was lower than that in the HBO group ((80.23±1.43)%)( t=4.38, P<0.05). The results of Western blot showed that the protein levels of AQP-4, Caspase-3, MMP-2 and MMP-9 in the combined treatment group were significantly lower than those in other groups(all P<0.05), while the expression of Bcl-2 was increased in the combined treatment group( P<0.05). RT-PCR results (gray value ratio) showed that AQP-4 mRNA levels in AQP-4 RNAi group(0.61±0.21), HBO group (0.83±0.12), combined treatment group(0.22±0.05) and CON group (1.31 ± 0.25) were significantly different( F=175.05, P<0.05), while the AQP-4 mRNA levels decreased in AQP-4 RNAi group which was better than that in hyperbaric oxygen group ( t=5.25, P<0.05). The decrease was the most obvious in the combined treatment group ( t=58.94, P<0.05). The results of TUNEL and AnnexinV showed that the treatment groups were more effective than the control group in inhibiting neuronal apoptosis, especially in the combined treatment group ( P<0.01). Conclusion:The combination of targeted AQP-4 RNAi and hyperbaric oxgen can effectively promote the recovery of neurological and cognitive function, and the mechanism may be related to protecting the integrity of blood-brain barrier, alleviating brain edema and inhibiting apoptosis of nerve cells after TBI.

Objective:To investigate the effects of gene silencing inducible cyclooxygenase-2 (COX-2) combined with hyperbaric oxygen (HBO) on neuronal cell edema, apoptosis, autophagy and neural functional recovery in rats with intracerebral hemorrhage.Methods:SPF-grade adult male SD rats ( n=96) were used to establish a cerebral hemorrhage model through stereotactic injection of thrombin VII into the caudate nucleus. They were randomized (random number) into 4 groups ( n=24/group): control group, hyperbaric oxygen (HBO) group, COX-2 RNAi group and combined group (COX-2 RNAi+HBO). The siRNA plasmid targeting silencing COX-2 gene expression was constructed. After group treatment, the four rats were randomly selected from each group for testing in each category. Postoperative day 1, 7, and 14 were assessed using the modified neurological severity score (mNSS) for evaluating neurofunctional deficits. On the 7th day, the water content of the brain tissue was measured using the dry/wet weight method. The blood-brain barrier permeability was assessed using the Evans method. Annexin V and TUNEL assays were employed to assess the apoptotic rate of neural cells. The mRNA expression level of COX-2 in brain tissue was determined using the RT-PCR method. The protein expression levels of Beclin-1, COX-2, aquaporin 4 (AQP-4), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, hypoxia-inducible factor-1α (HIF-1α) and matrix metalloprotein-2/9 (MMP-2/9) were detected by Western blot (WB). SPSS software was used for data analysis. One-way ANOVA was used for inter group comparisons and LSD- t test was used for further pairwise comparison. Results:The SD rat intracerebral hemorrhage model and plasmid construction were successfully achieved. The mNSS scores were significantly decreased in COX-2 RNAi, HBO and combined groups compared with control group on the 7th day and 14th day (all P<0.01), especially in combined group ( P<0.01). The contents of Evans blue and the water content of brain tissue of all treatment groups were significantly lower than those in control group (all P<0.05), especially in combined group ( P<0.01). The apoptotic rate of neural cells decreased in all treatment groups compared with the control group (all P<0.05), and the combined group decreased the most ( P<0.01). The mRNA expression levels of COX-2 were significantly decreased in all treatment groups compared with the control group (all P<0.01), and combined group silenced COX-2 expression most obviously ( P<0.05). The results of WB showed that the protein expression levels of Beclin-1, COX-2, AQP-4, Caspase-3, HIF-1α, MMP-2/9 were significantly lower than control group (all P<0.05), while the expression of Bcl-2 was increased in all treatment groups (all P<0.01). Among them, the combined group exhibited the most pronounced trend ( P<0.01). Conclusions:Gene silencing of COX-2 in combination with hyperbaric oxygen therapy can effectively restore neurological function in rats with cerebral hemorrhage. The mechanism may be associated with reduced blood-brain barrier permeability, alleviated brain edema, and inhibition of neuronal apoptosis and autophagy.