[Investigation of familial tendency of endometriosis].

Objective: To investigate the familial heritability of endometriosis and to compare the clinical characteristics of patients with or without a family history of endometriosis. Methods: From January 2020 to June 2022, 850 patients with endometriosis confirmed by laparotomy or laparoscopy in Peking University Third Hospital were included in this study. Clinical data were collected, family history was followed up, and the differences of clinical indicators between patients with and without family history of endometriosis were compared. Results: A total of 850 patients were enrolled, with an average age of (33.8±7.0) years old, 315 (37.1%, 315/850) patients in stage Ⅲ and 496 (58.4%, 496/850) patients in stage Ⅳ. There were 100 patients with family history of endometriosis, accounting for 11.8% (100/850). Most of the 113 relatives involved were mothers, daughters and sisters (76.1%, 86/113), 81.5% (22/27) of the second and third degree relatives were maternal relatives. The median ages of patients with and without family history of endometriosis were 30 and 33 years old respectively at the time of diagnosis. The unmarried rate of patients with family history was higher [42.0% (42/100) vs 26.3% (197/750)]. The percentage of dysmenorrhea patients with family history was higher [89.0% (89/100) vs 55.5% (416/750)]. The medians of dysmenorrhea score in patients with and without family history were 6 and 2, and the median durations of dysmenorrhea were 10 and 1 years. There were significant differences in age, marital status, percentage of dysmenorrhea, dysmenorrhea score and duration (all P<0.001). The median levels of serum cancer antigen (CA) 125 in patients with family history and patients without family history at the time of diagnosis were 57.5 and 46.9 kU/L respectively, with a statistically significant difference (P<0.05). However, there were no significant differences between the two groups in nationality, bady mass index, menarche age, menstrual cycle, menstrual period, menstrual volume, serum CA19-9 level, cyst location and size, stage, history of adverse pregnancy and childbirth, infertility, adenomyosis and deep infiltrating endometriosis (all P>0.05). By comparing the specific conditions of dysmenorrhea patients with and without family history of endometriosis, there were no significant differences between the two groups in terms of the age of onset of dysmenorrhea, duration of dysmenorrhea, primary and secondary dysmenorrhea, and progressive aggravation of dysmenorrhea (all P>0.05). The difference in the degree of dysmenorrhea in dysmenorrhea patients with family history of endometriosis was significant (P<0.001). Conclusions: The incidence of endometriosis has a familial tendency, and most of the involved relatives are the first degree relatives. Compared with patients without family history of endometriosis, endometriosis patients with family history are diagnosed at an earlier age, with higher percentage of dysmenorrhea, had more severe dysmenorrhea and higher serum CA125 level.

[Clinical risk factors of cesarean scar pregnancies].

Objective: To explore the risk factors related to cesarean scar pregnancies (CSP). Methods: Among the patients during July 2016 to June 2021 in Peking University Third Hospital, 596 cases of CSP patients were included as study group, and 1 192 cases of intrauterine pregnancy(IUP) women with history of cesarean section(s) were chosen as control group through stratified sampling according to the civil year of previous cesarean section matched with CSP group. The correlation between the general situation of patients, the history of gravidity and parity, the history of surgeries in uterine cavity and the previous cesarean section and the occurrence of CSP was explored through multivariate logistic regression analysis. Results: The current age of 596 CSP patients was (34.6±4.4) years, and that of 1 192 IUP patients was (35.6±3.6) years (P<0.001). Multivariate logistic regression analysis showed that the following factors may increase the risk of CSP: age<35 years old (OR=2.306, 95%CI: 1.774-2.998), history of medical abortion (OR=1.629, 95%CI 1.102-2.407), pregnancy interval<2 years from the last cesarean section (OR=2.147, 95%CI: 1.237-3.726), pregnancy interval ≥8 years from the last cesarean section (OR=1.474, 95%CI: 1.110-1.957), history of surgeries in uterine cavity before the last cesarean section (OR=2.558, 95%CI: 1.809-3.615), history of surgeries in uterine cavity after the last cesarean section (OR=8.020, 95%CI: 5.966-10.781), previous cesarean delivery ≥2 times (OR=14.051, 95%CI: 9.699-20.356) and history of previous cesarean sections before labor (OR=2.683, 95%CI: 1.930-3.731)(all P<0.05). Conclusions: The occurrence of CSP is related to the age of patients, the history of medical abortion, pregnancy interval, the history of surgeries in uterine cavity and the previous cesarean section, among which previous cesarean delivery ≥2 times and history of surgeries in uterine cavity after the last cesarean section are the strongly associated risk factors.

[The influence of molecular classification in the selection of postoperative adjuvant therapy in endometrial carcinoma].

Objective: To study the value of molecular classification in postoperative adjuvant therapy for endometrial carcinoma (EC). Methods: Patients with stage Ⅰ EC who underwent surgical-pathological staging surgery and molecular classification in Peking University Third Hospital from January 2020 to April 2022 were retrospectively analyzed. The influence of different molecular types of EC on postoperative adjuvant therapy were studied. Results: The age of the 196 patients was (55.1±10.2) years old, and the body mess index (BMI) was (26.0±3.9) kg/m2. Molecular classification was performed in 196 stage ⅠEC patients, identifying the 4 subgroups: POLE mutation (POLEmut, n=19, 9.7%), mismatch repair-deficient (dMMR, n=28, 14.3%), no-specific molecular profile (NSMP, n=142, 72.4%) and p53 mutation (p53abn, n=7, 3.6%). Molecular classification was one of the influencing factors on the selection of postoperative adjuvant therapy for EC patients (P=0.003). POLEmut, dMMR and NSMP subtypes were not the variables in selecting radiotherapy or combined chemo-radiotherapy postoperatively. p53abn subtype was not the influencer for radiotherapy, however, it may contribute to the selection of combined chemo-radiotherapy postoperatively (P<0.001). Conclusion: The p53abn subtype in the molecular classification is an influencing factor in the selection of combined chemo-radiotherapy for EC patients postoperatively.

High-Performance Dental Composites Based on Hierarchical Reinforcements.

Use of high-performance fibers such as poly(p-phenylene-2,6-benzobisoxazole) (PBO) improves the mechanical properties of dental fiber-reinforced composites (FRCs). However, the surfaces of high-performance fibers are relatively inert, and the interface with the resin matrix is poor. This has become a limitation restricting the performance of PBO FRCs in dentistry. Nanomaterials were introduced onto PBO fibers to construct various hierarchical reinforcements to obtain a dental FRC with higher flexural performance and optimized interface bonding. Four hierarchical reinforcements were constructed: PBO-ZnO nanoparticles (NPs), PBO-ZnO nanowires (NWs), PBO-ZnO NPs-cage silsesquioxane (POSS), and PBO-ZnO NWs-POSS. Performance following this optimized method was evaluated at macroscale and microscale levels, including measurement of the interfacial properties and mechanical properties of FRCs. The physicochemical characteristics of PBO fibers before and after modification were measured to determine the interfacial bonding mechanisms and to verify the connection between the microinterface and macromechanical properties. The cytotoxicity of the preferred PBO FRC was evaluated using the CCK8 assay. In comparison to other designs, the interfacial shear strength (IFSS) of PBO-ZnO NWs-POSS was the highest (29.31 ± 2.40 MPa). The corresponding FRC had the highest flexural strength under a static load (925.0 ± 39.2 MPa), the flexural modulus (39.39 ± 1.41 GPa) was equivalent to that of human dentin, and in vitro cytotoxicity was acceptable. The interfacial bonding mechanisms of PBO-ZnO NWs-POSS resulted from mechanical interlocking, chemical bonds, hydrogen bonds, and van der Waals forces. In summary, the PBO-ZnO NWs-POSS hierarchical reinforcement was introduced in dental FRCs and showed remarkable enhancement of the IFSS and flexural properties. We verified that the PBO-ZnO NWs-POSS hierarchical reinforcement was successful. This PBO FRC may be applied in dentistry as a new option for endodontic posts. Our study provides an interface design strategy for developing high-performance FRCs reinforced with high-performance fibers for dental applications.

[The composition of ascites lymphocytes in high-grade serous ovarian cancer and its correlation with clinical features].

Objective: To explore the composition of ascites lymphocytes in high-grade serous ovarian carcinoma (HGSOC) and its correlation with clinical features. Methods: A total of 59 newly-diagnosed HGSOC patients, aged (58±11) years old, who were treated at the Department of Obstetrics and Gynecology of Peking University Third Hospital from July 2019 to December 2020 were included, collecting ascites and peritoneal irrigation fluid respectively. Detect the proportion of T, B, NK cell and its subpopulations by flow cytometry, and analyze its correlation with the clinical characteristics of patients. Results: Among 59 patients, 48 patients (81.4%) had ascites, and 11 patients (18.6%) had no ascites. Compared with the peritoneal irrigation fluid, the CD3+T (70.2%±15.6% vs 78.1%±6.7%, P=0.014), CD8+T (38.3%±11.2% vs 47.7%±10.1%, P=0.014) and CD16-CD56bright NK [2.0% (0.8%, 3.6%) vs 4.2% (1.5%, 7.1%), P=0.026] cells were significantly decreased in the ascites, while the CD16+CD56dim NK cells was significantly increased [6.8% (2.8%, 15.7%) vs 2.6% (1.6%, 4.3%), P=0.008]. In patients with ascites volume ≥1 000 ml, CD16-CD56bright NK cells were significantly increased than those ascites volume<1 000 ml [3.1% (1.2%, 3.9%) vs 0.8% (0.4%, 2.3%), P=0.002]. Age was significantly positively correlated with the level of CD4+T cells (r=0.332, P=0.021) and the ratio of CD4+T/CD8+T (r=0.379, P=0.008) in ascites. In ascites from patients with poor response to treatment, the proportion of CD4+T cells was increased significantly than those with better response (64.7%±4.2% vs 48.3%±11.7%, P=0.002). Conclusion: The formation of ascites in newly diagnosed high-grade serous epithelial ovarian cancer patients would affect the lymphocyte composition in the abdominal cavity microenvironment, which is related to the patient's age, cancer progression and treatment response.

Long non-coding RNA LINC00152 is up-regulated in ovarian cancer tissues and regulates proliferation and cell cycle of SKOV3 cells.

OBJECTIVE: To characterize functions of long non-coding RNA (lncRNA) in the progression of epithelial ovarian cancer. PATIENTS AND METHODS: Epithelial ovarian cancer tissues and matching normal tissues were collected from two individual patients for RNA microarray analysis. Besides, twenty-two ovarian cancer samples and ten healthy ovarian epithelial tissues were collected for Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR). Microarray assay suggested that a list of cancer relating mRNAs and lncRNAs were upregulated. The identified lncRNAs were validated via RT-qPCR, which led to the identification of long intergenic non-protein coding RNA 152 (LINC00152). To determine the function of LINC00152 in ovarian cancer, we knocked down the expression of LINC00152 in epithelial ovarian cancer cell line SKOV3 with small interference RNAs (siRNAs). The effects of LIN00152 on the proliferation and cell cycle were determined by comparing the cell viability of SKOV3 cells with LIN00152 knockdown and the control cells with negative siRNA. The cell viability was assessed using Cell Counting Kit-8 (CCK-8) and flow cytometry assay. RNA microarray assay was used again in control and LINC00152 knockdown SKOV3 cells to identify downstream signaling pathways. RESULTS: Fourteen ovarian cancer relating lncRNAs were identified by RNA microarray assay. Up-regulation of LINC00152 was validated via RT-qPCR. A higher expression of LINC00152 in late cancer stage (III-IV) compared to the early stage tumors was also demonstrated. Inhibition of LINC00152 in SKOV3 cells inhibited cell proliferation and induced cell cycle arrest that involved prolonged G1 phase and shortened S phase. The microarray assay data of SKOV3 cells suggested that Cyclin-Dependent Kinase Inhibitor 1C (CDKN1C) was a potential downstream target of LINC00152. CONCLUSIONS: LINC00152 is upregulated in epithelial ovarian cancer tissues comparing to normal tissues. Knockdown of LINC00152 expression inhibits cell proliferation and induces cell cycle arrest. LINC00152 possibly interacts with Tumor Necrosis Factor (TNF) signaling pathway. CDKN1C is a potential downstream target of LINC00152.

A 15-year-long Southern blotting analysis of FMR1 to detect female carriers and for prenatal diagnosis of fragile X syndrome in Taiwan.

Here, we review the results of Southern blotting analyses of the FMR1 gene performed in our reference laboratory in Taiwan over a 15-year period. In total, 725 high-risk women with a family history of fragile X syndrome (FXS) or idiopathic intellectual disability, 3911 low-risk pregnant women without such family history, and prenatal diagnosis data for 32 foetuses from 24 carrier mothers were included. Only 2 carriers were in the low-risk group, which indicated a prevalence of 1 of 1955 women (95% confidence interval: 1/7156-1/539). A total of 100 carriers were found to be in the high-risk group, thus revealing a significantly higher frequency than the low-risk group (100/725 vs 2/3911, P<0.0001). Eight of the 14 foetuses that inherited the maternal mutant allele were verified to have a full mutation, with the smallest maternal pre-mutation allele carrying 56 CGG repeats. The overall findings confirmed that the carrier prevalence among low-risk women in Taiwan is significantly lower than that reported in western countries. Therefore, the most important step for preventing FXS in Taiwan would be to focus on high-risk women by promoting general awareness of this disease and spreading knowledge regarding the benefits of carrier screening and prenatal testing.

Gastrodin suppresses BACE1 expression under oxidative stress condition via inhibition of the PKR/eIF2α pathway in Alzheimer's disease.

The expression of ß-site APP-cleaving enzyme 1 (BACE1) is increased in the brain of late-onset sporadic Alzheimer's disease (AD) and oxidative stress may be the potential cause of this event. The phenolic glucoside gastrodin (Gas), a main component of a Chinese herbal medicine Gastrodia elata Blume, has been demonstrated to display antioxidant activity and suppresses BACE1 expression. However, the mechanisms by which Gas suppresses BACE1 expression are not clear. Morris water maze test was performed to assess the effect of Gas treatment on memory impairments in Tg2576 mice. The level of oxidative stress in the brain of Tg2576 mice was determined by measuring the superoxide dismutase (SOD) activity, catalase (CAT) activity, and the levels of malondialdehyde (MDA) and ROS. In vivo and in vitro, we detected the expression levels of BACE1, pPKRThr446, PKR, pPERKThr981, PERK, peIF2αSer51, and eIF2α using western blot analysis. We found that Gas improved learning and memory abilities of Tg2576 transgenic mice and attenuated intracellular oxidative stress in hippocampi of Tg2576 mice. We discovered that the expression levels of BACE1, activated PKR (pPKRThr446) and activated eIF2α (peIF2αSer51) were elevated in the brains of Tg2576 mice and hydrogen peroxide (H2O2)-stimulated SH-SY5Y cells. Moreover, peptide PKR inhibitor (PRI) and Gas down-regulated BACE1 expression in Tg2576 mice and H2O2-stimulated SH-SY5Y cells by inhibiting activation of PKR and eIF2α. Gas alleviates memory deficits in mice and suppresses BACE1 expression by inhibiting the protein kinase/Eukaryotic initiation factor-2α (PKR/eIF2α) pathway. The research suggested that Gas may develop as an drug candidate in neurodegenerative diseases.

Gene-gene and gene-environment interactions on IgE production in prenatal stage.

BACKGROUND: Prevalence of allergic diseases in children has increased worldwide over the past decades. Allergy sensitization may occur in fetal life. This study investigated whether gene-gene and gene-environment interactions affected cord blood IgE (CBIgE) levels. METHODS: A total of 575 cord blood DNA samples were subjected to a multiplex microarray for 384 single nucleotide polymorphisms (SNPs) in 159 allergy candidate genes. Genetic association was initially assessed by univariate and multivariate analyses. Multifactor dimensionality reduction (MDR) was used to identify gene-gene and gene-environment interactions. Environmental factors for analysis included maternal atopy, paternal atopy, parental smoking, gender, and prematurity. RESULTS: Twenty-one SNPs in 14 genes were associated with CBIgE elevation (>or =0.5 KU/l) in univariate analysis. Multivariate analysis identified eleven genes (IL13, IL17A, IL2RA, CCL17, CXCL1, PDGFRA, FGF1, HAVCR1, GNAQ, C11orf72, and ADAM33) which were significantly associated with CBIgE elevation. MDR analyses of gene-gene interactions identified IL13 interacted with IL17A and/or redox genes on CBIgE elevation with the prediction accuracy of 62.52%. Analyses of gene-environment interactions identified that maternal atopy combined with IL13, rs1800925 and CCL22, rs170359 SNPs had the highest prediction accuracy of 67.15%. All the high and low risk classifications on gene-gene and gene-environment interactions by MDR analyses could be validated by Chi-square test. CONCLUSIONS: Gene-gene (e.g. immune and redox genes) and gene-environment (e.g. maternal atopy and FGF1or redox genes) interactions on IgE production begin in prenatal stage, suggesting that prevention of IgE-mediated diseases may be made possible by control of maternal atopy and redox responses in prenatal stage.

Interaction of maternal atopy, CTLA-4 gene polymorphism and gender on antenatal immunoglobulin E production.

BACKGROUND: Genetic heritability and maternal atopy have been correlated to antenatal IgE production, but very few studies have studied gene-maternal atopy interaction on antenatal IgE production. This study investigated the interaction of CTLA-4 polymorphism with prenatal factors on the elevation of cord blood IgE (CBIgE). METHODS: Pregnant women were antenatally recruited for collection of prenatal environmental factors by a questionnaire. Umbilical cord blood samples were collected for CBIgE detection by fluorescence-linked enzyme assay and CTLA-4 polymorphism measurement by restriction fragment length polymorphism. RESULTS: A total of 1104 pregnant women initially participated in this cohort study, and 898 of them completed cord blood collection. 21.4% of the newborns had elevation of CBIgE (>or=0.5 kU/L). The CTLA-4+49A allele (P=0.021), maternal atopy (P<0.001) and gender (P=0.034), but not the CTLA-4+49G allele, -318C allele, -318T allele, parental smoking or paternal atopy, were significantly correlated with the CBIgE elevation in multivariate analysis. A dichotomous analysis of gene-maternal atopy interactions identified maternal atopy and CTLA-4+49A allele had an additive effect on the CBIgE elevation, especially prominent in male newborns; and in the absence of maternal atopy, CTLA-4+49GG genotype had a protective effect on CBIgE elevation in female newborns. CONCLUSIONS: Maternal but not paternal atopy has significant impacts on CBIgE elevation depending on gender and CTLA-4+49A/G polymorphism of newborns. Control of maternal atopy and modulation of CTLA-4 expression in the prenatal stage may be a target for the early prevention of perinatal allergy sensitization.

Comparison of clinical outcomes and spectral Doppler indices of uterine and ovarian stromal arteries in women undergoing myomectomy with or without hypogastric arterial ligation.

OBJECTIVE: To compare clinical outcomes and hemodynamic alterations of uterine and ovarian stromal arteries between patients with symptomatic myomas undergoing myomectomy preceded by arterial ligation and those undergoing myomectomy alone. METHODS: In this prospective, non-randomized comparative study, myomectomy was performed on 69 women with symptomatic myomas. Myomectomy alone was performed in 31 patients (Group I) and myomectomy with concomitant bilateral hypogastric arterial ligation was performed in 38 patients (Group II). In both groups, surgical results and clinical outcomes were evaluated by peripheral hemoglobin levels, a pictorial blood-loss assessment chart, and visual analog scales. Spectral Doppler indices of uterine and ovarian stromal arteries, including peak systolic velocity, end-diastolic velocity, pulsatility index and resistance index were performed preoperatively, and 1 day and 1 or more months postoperatively. RESULTS: Twenty-two patients in Group I and 31 patients in Group II received regular follow-up examinations for a mean follow-up period of 10.1 months. Menstrual flow, dysmenorrhea and hemoglobin levels improved significantly after surgery in both groups. Blood loss during surgery was less in Group II than it was in Group I (P=0.02). Doppler indices of uterine and ovarian stromal arteries from preoperation to mean follow-up point were not significantly different between the groups, except for a significantly lower uterine artery pulsatility index in Group II (P=0.01). CONCLUSIONS: Myomectomy with hypogastric arterial ligation for symptomatic myomas is as efficient as is myomectomy alone and reduces blood loss during surgery. Serial Doppler studies showed that hypogastric ligation does not block uterine and ovarian perfusion, and even reduces the impedance of the uterine arteries. The long-term recurrence rate after myomectomy with hypogastric arterial ligation remains to be determined.

Organ-specific toxicokinetics and dose-response of arsenic in tilapia Oreochromis mossambicus.

We appraised organ-specific toxicokinetics and dose responses of arsenic burdens in tilapia Oreochromis mossambicus. We kinetically linked an Area-under-the-curve (AUC)-based acute toxicity model and a pharmacodynamic model to derive dose-response relationships between equilibrium organ-specific arsenic concentrations and mortality effects. The AUC-based acute toxicity model was also used to derive organ-specific internal effect concentration (IEC)-time-response relationships, which can also be applied to predict a time-mortality profile. We conducted a 7-day exposure experiment to obtain toxicokinetic parameters, whereas the AUC-based acute toxicity model was verified with LC50(t) data obtained from a 7-day acute toxicity bioassay. Our results demonstrated that 96-hour LC50 and incipient LC50 for tilapia exposed to arsenic are 28.68 (95% confidence interval to 24.92 to 32.44) and 25.55 mg L(-1), respectively. Dose-response relationships followed the Hill equation, which could be expressed as organ-specific bioconcentration factors and incipient LC50. Organ-specific dose-response relationships showed that muscle, gill, and liver have a relatively steep sigmoid dose-response profile in that IEC50 were 26.6, 62.5, and 78.5 microg g(-1) dry wt (dw), respectively. Organ-specific arsenic internal lethal burdens were the highest in the gill and the lowest in the muscle in waterborne-exposed tilapia. The IEC and target-organ concentrations derived in this study can be used in site-specific risk assessment.

Polymorphism of metabolic genes and susceptibility to occupational chronic manganism.

In this study we investigated genetic polymorphisms of five metabolizing genes and their association with occupational chronic manganism. We recruited 49 patients with chronic manganism and 50 unrelated healthy control subjects who were welders and ferromanganese smelters and occupationally exposed to manganese dust and fume in the same workshops from three metallurgical industries. The controls were matched to the cases by sex, age, cigarette and alcohol intake, as well as the manganese exposure duration. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to genotype the cytochrome P450 2D6L gene (CYP2D6L) and the NAD(P)H:quinone oxidoreductase gene (NQO1). Allele-specific PCR was used to detect the cytochrome P450 1A1 gene (CYP1A1), and the glutathione-S-transferase mu and theta genes (GSTM and GSTT). The frequency of polymorphic alleles, a mutation of CYP2D6L, was significantly lower in patients with chronic manganism (16.3%) than in controls (29.0%). Individuals with the homozygote polymorphism (L/L) of CYP2D6 had a 90% decreased risk of chronic manganism compared with the wild-type (Wt/Wt) (odds ratio =0.10, 95% confidence interval = 0.01-0.82). A significant association between the CYP2D6 genotype subgroup and the latency of chronic manganese poisoning was also found. Patients who had homozygous (L/L) or heterozygous (Wt/L) mutant alleles developed manganism an average of 10 years later than those who were homozygous wildtype (Wt/Wt). However, the allele and genotype frequencies of CYP1A1 and NQO1 genes were distributed similarly in cases and controls. In addition, no difference in the frequencies of GSTM1 and GSTT1 null genotypes were observed between cases and controls. The results suggest that CYP2D6L gene polymorphism might influence susceptibility to manganese-induced neurotoxicity. However, because of limited sample size, our results should be validated in large-scale studies.

Characterization of mixing patterns in a ventilated airspace with a multiple airflow regions gamma model.

A model called the multiple airflow regions gamma model (MARGM) was developed based on a continuous distribution of residence time for predicting the mixing behavior in a ventilated airspace in that data interpretation and mean residence time calculation for a specified output concentration profile can also be evaluated. The MARGM takes the form of the two-parameter gamma distribution and accounts for different mixing types: complete mixing, no mixing (piston flow), incomplete mixing, and various combinations of the above types. In these combinations, the different mixing types simulated by the MARGM conceptually represent airflow regions in series. The mixing efficiency was introduced to characterize the extent or degree of mixing in a ventilation system. Mixing efficiency equals zero for piston flow (no mixing), unity for complete mixing, and a value in between these two extremes for incomplete mixing. The MARGM simulates the combinations of complete mixing, incomplete mixing, and piston flow. Therefore, seven models are introduced in this effort: complete mixing model, piston flow model, complete-piston flow model, complete-incomplete-piston flow model (the general model), complete-incomplete mixing model, incomplete-piston flow model, and incomplete mixing model. The applicability of models was tested by several case studies. Results show that combination models give better fitting than other simpler models. The MARGM enables building microenvironment designers reconsider the possibilities and consequences of various forms of incomplete mixing in investigating indoor air quality problems.

Modeling effects of moisture content and advection on odor causing VOCs volatilization from stored swine manure.

Two models for evaluating the contents and advection of manure moisture on odor causing volatile organic compounds (VOC-odor) volatilization from stored swine manure were studied for their ability to predict the volatilization rate (indoor air concentration) and cumulative exposure dose: a MJ-I model and a MJ-II model. Both models simulating depletion of source contaminant via volatilization and degradation based on an analytical model adapted from the behavior assessment model of Jury et al. In the MJ-I model, manure moisture movement was negligible, whereas in the MJ-II model, time-dependent indoor air concentrations was a function of constant manure moisture contents and steady-state moisture advection. Predicted indoor air concentrations and inhaled doses for the study VOC-odors of p-cresol, toluene, and p-xylene varied by up to two to three orders of magnitude depending on the manure moisture conditions. The sensitivity analysis of both models suggests that when manure moisture movement exists, simply MJ-I model is inherently not sufficient to represent a more generally volatilization process, which can even become stringent as moisture content increases. The conclusion illustrates how one needs to include a wide variety of manure moisture values in order to fully assess the complex volatilization mechanisms that are present in a real situation.

Exposure assessment model for odor causing VOCs volatilization from stored pig slurry.

A mathematical model taking into account source depletion with time and the actual thickness of manure layer was derived to evaluate indoor inhalation exposure dynamics to three selected odor causing volatile organic compounds (VOC-odors) of p-cresol, toluene, and xylene volatilization from stored pig slurry. The model assumes that pig slurry is undisturbed and the VOC-odors released in a contaminated layer and transported through a clean layer as well as a manure-air interface boundary. The model simulates time-dependent volatilization, the depletion of source contaminant via both volatilization and degradation, and could be used with a contaminated zone of finite thickness. For a given VOC-odor, the predicted total exposure and resulting manure cleanup criteria can be a large variability depending on the model whether a finite or infinite manure layer thickness was considered. Results obtained from model comparisons suggest that the model incorporating depth-varying of manure layer and contaminant source depletion is more suitable to evaluate the VOC-odor exposure dynamics in swine housing bioclimate.

Swine manure cleanup criteria calculation for odor causing volatile organic compounds based on manure-to-ventilation air exposure pathway.

A mathematical model was derived to calculate swine manure cleanup criteria for odor causing volatile organic compounds (VOCs) so that acceptable total dose would not exceeded through the inhalation of ventilation air in swine housing for workers and pigs. A hypothetical scenario was used which assumed that subsurface contaminant in swine manure diffuses through a layer of manure-air interface then is swept into the ventilated airspace via advection, where long-term inhalation of contaminant was assumed to occur. The philosophy of the transport model is to incorporate the age distribution of contaminated air and a first-order decay of contaminant sources into the diffusion model for simulation of air concentrations of VOCs and total exposure dose. A closed-form solution is presented to allow a series of numerical experiments for investigating the effects of adsorption characteristics between manure gas and manure, the mean age of contaminated air, effective diffusivity, and degradation coefficient on total dose. Swine manure cleanup criteria based on non-exceedence of the total hazardous dose corresponding to an acceptable risk from indoor inhalation of four selected VOCs of p-cresol, hexane, toluene, and xylene were calculated in a typical pig unit. The model can be used in the future to compute the relative effectiveness of VOCs filtration systems and/or altered ventilation rates on the VOC exposure problem in animal housing.

Hepatic arterial infusion chemotherapy and embolization in the treatment of primary hepatic carcinoma.

AIM: To study the effects of hepatic arterial infusion chemotherapy (HAI) or embolization (HAE) in the treatment of primary hepatic carcinoma (PHC) and the factors influencing these effects. METHODS: A retrospective analysis of 188 patients (166 males and 22 females) with PHC treated with HAI (n = 82) or HAE (n = 106) was conducted. RESULTS: In the group as a whole, the percentage of patients experiencing therapeutic outcomes was as follows: Symptomatic relief (59.6%); Tumor shrinkage (55%); A decrease in blood alpha fetoprotein (AFP) (37.8%) and overall survival rates at 0.5, 1.0, 2.0, and 3.0 years of 75.4%, 46%, 23.5% and 14.7%, respectively. The mean survival time in the entire group was 12.2 mo, and the longest survival period was 50 mo. In the HAI group the survival rates at 0.5, 1.0. 2.0 and 3.0 years of follow-up were 61.0%, 25.4%, 4.5% and 0%, respectively, with a mean survival time of 7.7 mo. In the HAE group the corresponding survival rates were 86.8%, 61.7%, 37.8% and 26.1%, respectively, with a mean survival time of 15.7 mo. Eighteen patients received secondary surgery. Factors that had a favorable effect on therapeutic outcomes were presence of no or only mild liver cirrhosis, presence of stage I or Stage II disease, presence of only a single tumor, a tumor size less than 10 cm in diameter, an absence cancerous thrombus within the portal vein or hepatic arterio venous fistula, and HAE treatment. CONCLUSION: This study helped identify the effects of HAI and HAE in patients with PHC, and identified some important factors which influence such treatment.

Elevated pressure stimulates protooncogene expression in isolated mesenteric arteries.

The aim of this study was to determine whether an increase in pressure alone is a sufficient stimulus in isolated small arteries to induce the immediate early genes that are associated with vascular wall growth. Mesenteric arteries (303-506 microm diam) were isolated from Wistar rats and subjected to static pressure of 90 mmHg (control) or 140 mmHg (hypertensive). The arteries possessed little active tone or myogenic response to pressure elevation; therefore, both sets of vessels were stretched by similar amounts, but wall stress in the hypertensive vessels was 60-80% above that of controls. After 30, 60, 180, and 360 min, the arteries were fixed in Formalin, embedded in paraffin, and sectioned for in situ hybridization. The levels of mRNA for c-fos increased in the hypertensive arteries 2.33-fold at 30 min and 6.64-fold at 60 min. mRNA for c-myc increased 5.13-fold at 60 min and 5.25-fold at 180 min. After this early response gene induction, 18S rRNA increased in hypertensive vessels: 3.35-fold at 180 min and 4.2-fold at 360 min. These changes were not the result of a nonspecific activation of total gene expression in hypertensive vessels, inasmuch as levels of mRNA for beta-actin did not differ from controls; however, hypertensive and control vessels showed increases at 60 min. These results indicate that increased pressure is a sufficient stimulus for protooncogene induction and rRNA production in vascular smooth muscle cells in the arterial wall and suggest that the mechanical signal is wall stress. Therefore, this model represents a unique tool to complement cultured cells for the study of the signaling pathways in the mechanotransduction of a pressure stimulus.