[Establishment and analysis of prediction model for invasive subsolid pulmonary nodules based on radiomics].

Objective: To evaluate the best radiomic features based prediction model for identifying the histopathological subtypes of invasive adenocarcinoma or noninvasive pulmonary nodules appearing as subsolid nodules. Methods: A total of 352 patients (108 males and 244 females, median age was [M(Q1,Q3)]57 (50,65), underwent high-resolution chest CT and appearing as subsolid nodules and further treated by surgical resection whose subsequently pathological results were classified as atypical adenomatous hyperplasia (AAH), carcinoma in situ (AIS), microinvasive carcinoma (MIA), invasive adenocarcinoma (IA), from January 2015 to September 2019, in Radiology Department of Zhongda Hospital Affiliated to Southeast University and Jinling Hospital, Medical School of Nanjing University were retrospectively collected. They were divided into non-invasive group (n=233) and invasive group (n=119) according to pathological findings. According to the ratio of training set: internal test set: external test set, which is about 3∶1∶1,the patients in Zhongda Hospital Affiliated to Southeast University were randomly divided into training set (n=215, non-IA∶IA 155∶60) and internal test set(n=69, non-IA∶IA 52∶17), meanwhile a certain number of patients in Jinling Hospital, Medical School of Nanjing University(n=68, non-IA∶IA 26∶42)were randomly selected as an independent external test set. Particular quantitative parameters of the nodules, radiomic features, morphological characteristics, clinical data, and serum tumor markers were recorded. Radiomic label was constructed using LASSO regression method. The morphological model, CT model and comprehensive model were constructed by binary logistic regression and were verified in test sets, respectively. Results: Shape_MinorAxis(Gradient),Glszm_ZoneEntropy(LBP) were selected as the two most significant features based on training set. Radiomic tag=1.065 75×Shape_MinorAxis(Gradient)+0.030 58×Glszm_ZoneEntropy(LBP). Comparing the prediction performance of all models in each data cohort, the CT model (Ln(P/1-P)=-2.417 11+1.031 60×Radimic tag+1.203 06×Diameter+1.614 21×(Pleural indentation sign = Y) constructed by radiomic label, pleural depression, and quantitative parameters (diameter, average density) was much better than other models and was chosen as the optimal model, with an AUC of CT models in training cohort and test cohort was 0.954 (95%CI: 0.927-0.981), 0.865 (95%CI:0.764-0.966), better than morphological model 0.857 (95%CI:0.796-0.918), 0.818(95%CI: 0.686-0.949) and comprehensive model 0.951(95%CI: 0.921-0.981), 0.856(95%CI: 0.730-0.982), respectively. Conclusion: The integrative CT model has a better prediction efficiency for identifying invasive or noninvasive nodules appearing as subsolid nodules.

[Effectiveness of TRB3 on human hepatocellular carcinoma cells proliferation, apoptosis and migration].

Objective: To explore the regulatory role and mechanism of tribbles pseudokinase 3 (TRB3) on hepatocarcinoma (HCC) cells proliferation, apoptosis and migration. Methods: Immunohistochemistry and Western blot were used to detect TRB3 expression in cancerous and adjacent cancerous liver tissues of HCC patients. TRB3 expression was detected in vitro in HepG2 and Huh7 hepatocarcinoma cell lines. Simultaneously, CCK8 and EdU were used to detect cell proliferation after TRB3 targeted inhibition with small interfering RNA. CCK8 and EdU were used to detect cell proliferation. Flow cytometry assay was used to detect apoptosis. Transwell assay was used to evaluate migration ability. Simultaneously, Western blot was used to detect changes in apoptosis, migration-related proteins and AKT phosphorylation activity. The mean comparison between the two groups was performed by t-test, and the comparison between multiple groups was performed by one-way analysis of variance. Results: Western blot showed that the expression of TRB3 was significantly up-regulated in HCC tissues. Compared with normal liver tissues adjacent to cancer, the relative expression levels were 0.78 ± 0.12 and 0.29 ± 0.09, respectively, P < 0.01, and the difference was statistically significant. After interfering siRNA inhibited TRB3, CCK8 and EdU tests showed that the proliferation activity of HepG2 and Huh7 cells were significantly weakened (P < 0.05). Flow cytometry results showed that the apoptotic proportions of HepG2 and Huh7 cells was significantly increased (P < 0.01). Western blot also showed that the expression of apoptosis regulatory proteins BAX and BIM were significantly increased (P < 0.01). Transwell assay results showed that the migration ability of HepG2 and Huh7 cells was decreased (P < 0.05), and the expression of migration regulatory proteins MMP4 and MMP9 was also significantly down-regulated. Western blot results showed that the AKT phosphorylation level was significantly increased. Conclusion: TRB3 regulates hepatocarcinoma cells proliferation, apoptosis and migration by inhibiting the AKT phosphorylation activity. Therefore, TRB3 may be a potential target site for the liver cancer treatment.

[miR-29c-3p targeted dishevelled 2 on osteogenesis differentiation of rat bone marrow mesenchymal stem cells in high-fat environment].

Objective: To study the different expression of 4 microRNA (miRNA, miR) during the osteogenesis differentiation of bone marrow mesenchymal stem cell (BMSC) cultured in high-fat or normal environment and to explore the relationship of these miRNAs with disheveled 2 during osteogenesis differentiation. Methods: BMSC were cultured with 2 ml normal osteogenic induction (control group) and high-fat osteogenic induction (high-fat group) respectively. On the 3rd, 5th, 7th,14th, 21st day, quantitative real-time PCR (qPCR) was used to analyze expression levels of four miRNAs (miR-21-5p, miR-29c-3p, miR-138-5p and miR-351-5p), mRNA of disheveled 2, osteogenic related factors such as alkaline phosphatase (ALP), Runt-related transcription gene 2 (Runx2). And the protein was detected by Western blotting. After BMSC were transfected by 50 µl 50 nmol/L miRNA mimics/inhibitors/negative controls respectively, BMSC were put on osteogenic induction, on the 1st, 3rd, 5th, 7th day, ALP activity was detected. On the 7th day, ALP staining was to observe the degree of osteogenesis differentiation, and Western blotting was adopted to analyze the expression of dishevelled 2 and other osteogenic related factors, while qPCR was used to analyze the expression of disheveled 2 mRNA. After 293T cells were co-transfected with disheveled 2 wild-type/mutant firefly luciferase reporter plasmid with either negative control (NC) or a mimic of these four miRNAs respectively for 48 h, luciferase activities were measured. Results: On the 21th day, the expressions of miR-21-5p, miR-29c-3p, miR-138-5p and miR-351-5p in high-fat groups were higher by 20%, 60%, 340% and 4 420% respectively than those in control groups (P<0.05). The expression of ALP and Runx2 in BMSC decreased after BMSC transfected miR-21-5p and miR-29c-3p mimics, while increased after transfected miR-21-5p and miR-29c-3p inhibitors. The expression of disheveled 2 decreased by 35% after transfected by miR-29c-3p mimic, while it increased by 269% after transfected by miR-29c-3p inhibitor (P<0.05). Transfection of the miR-29c-3p mimics significantly decreased the luciferase activity of wild-type 3'-UTR compared with NC control (P<0.05). There were no statistical significances among other groups. Conclusions: miRNAs had better expression during osteogenesis differentiation of BMSC in high-fat environment; miR-29c-3p could negatively regulate the osteogenesis differentiation of BMSC by targets on dishevelled 2.

Effect of IFN-λ2 on combined allergic rhinitis with nasal polyps.

OBJECTIVE: This study sought to investigate the expression of interferon-λ2 (IFN-λ2) in patients with combined allergic rhinitis and nasal polyps (AR+NP), analyze the correlation between IFN-λ2 and tryptase, interleukin 10 (IL-10), and interleukin 12 (IL-12), and identify its peripheral blood cell origins. PATIENTS AND METHODS: ELISA kits were used to investigate plasma levels of IFN-λ2, tryptase, IL-10, and IL-12 in AR+NP patients and healthy controls (HC). Flow cytometry analysis was carried out to detect IFN-λ2 expression in peripheral blood leukocytes. Immunocytochemical staining was performed to detect nasal polyp IFN-λ2 expression in AR+NP patients. RESULTS: Elevated plasma IFN-λ2 levels and positive correlations between plasma IFN-λ2 and tryptase levels in AR+NP patients indicated that IFN-λ2 likely contributes to AR+NP pathogenesis. IFN-λ2 expression was upregulated in cytotoxic T cells and eosinophils in AR+NP patients. Nasal polyp mast cells and macrophages in AR+NP patients expressed IFN-λ2. CONCLUSIONS: The close correlation between IFN-λ2 expression and AR+NP may provide experimental evidence for a possible effect of IFN-λ2 against the allergic inflammatory reaction. Therefore, IFN-λ2 actions may have a potential utility for the treatment and prevention of AR+AP.

Correlation between methylation of the p16 promoter and cervical cancer incidence.

OBJECTIVE: To study the methylation of the promoter of the p16 gene in cervical cancer patients and explore the correlation between methylation and the incidence of cervical cancer. PATIENTS AND METHODS: We recruited 78 patients with cervical cancer and 48 healthy individuals. The methylation-specific PCR was used to detect the methylation status in the promoter of the p16 gene. The mRNA expression of p16 was studied by quantitative fluorescence PCR. The protein expression of p16 was monitored by Enzyme-linked immunosorbent assay (ELISA) and Western blot. Immunohistochemistry was applied to detect the expression and distribution of p16 in cervical tissues. RESULTS: The methylation sequencing results showed that samples from cervical cancer patients had a methylation rate of 78.52% in the p16 gene promoter region compared with a much lower rate of 9.8% in the control group (9.8%). Quantitative fluorescence PCR indicated that the p16 mRNA expression was significantly reduced in cervical cancer patients compared with controls. ELISA and Western blot results showed that expression of the p16 protein in cancer tissue was 0.81 ± 0.12 µg/l, whereas in the healthy controls it was 3.21 ± 0.24 µg/l. Immunohistochemical results showed that the p16 protein was mainly present in the cytoplasm. The rate of p16 positive cells in the healthy cervical tissue 83.29% was higher than in cervical cancer 10.18%. CONCLUSIONS: The methylation of the p16 gene promoter could significantly reduce p16 expression, losing its tumor suppressor activity and promoting the development of cervical cancer.

Determination of the energy value of corn distillers dried grains with solubles containing different oil levels when fed to growing pigs.

This experiment used indirect calorimetry to determine the net energy (NE) content of five corn distillers dried grains with solubles (corn DDGS) containing different oil levels and to compare the NE obtained using indirect calorimetry with that calculated using previously published prediction equations. There were two samples of high-oil DDGS, one sample of medium-oil DDGS and two samples of low-oil DDGS. Twelve barrows (initial BW of 32.8 ± 2.0 kg) were used in a repeated 3 × 6 Youden square design with three periods and six diets. The diets were comprised of a corn-soybean meal basal diet and five diets containing 29.25% of one of the corn DDGS added at the expense of corn and soybean meal. During each period, the pigs were individually housed in metabolism crates for 16 days which included 7 days for adaption to feed and environmental conditions. On day 8, the pigs were transferred to respiration chambers and fed one of the six diets at 2300 kJ ME/kg BW0.6 /day. Faeces and urine were collected from day 9 to 13 and heat production (HP) was also measured. From day 14 to 15, the pigs were fed 893 kJ ME/kg BW0.6 /day to allow them to adapt from the fed to the fasted state. On the last day of each period (day 16), the pigs were fasted and fasting HP was measured. The digestible energy value was 16.0, 17.1 and 15.3 MJ/kg DM, the metabolizable energy value was 14.6, 15.5 and 13.7 MJ/kg DM and the NE value was 10.7, 11.0 and 9.4 MJ/kg DM, for the high-oil, medium-oil and low-oil corn DDGS, respectively. The NE obtained with indirect calorimetry in the present study did not differ from values calculated using previously published prediction equations.

The effect of three-dimensional conformal radiotherapy on locally recurrent nasopharyngeal carcinoma and on the expression of succinate dehydrogenase B.

OBJECTIVE: Investigate the effect of three-dimensional conformal radiotherapy (3DCRT) on locally recurrent nasopharyngeal carcinoma (NPC) on the expression of succinate dehydrogenase B (SDHB). PATIENTS AND METHODS: Eighty-six patients diagnosed with locally recurrent NPC in our hospital were selected and divided into the control group (43 cases) and observation group (43 cases). Conventional two-dimensional radiotherapy was applied in the control group, and 3DCRT was adopted in the observation group. The curative effect of both groups was compared. RESULTS: The effective rate and the degree of alleviation of the observation group were higher than those of the control group, and the differences were statistically significant (p<0.05). There were no differences in the occurrence rate of complications from radiotherapy between the two groups (p>0.05). The survival rate and median survival time of the observation group were significantly higher than those of the control group (p<0.05). The positive expression rate of SDHB in the observation group after radiotherapy was significantly higher than that of the control group (p<0.05), and the median survival time of patients with positive expression of SDHB was significantly higher than patients with negative expression (p<0.05). CONCLUSIONS: 3DCRT applied for treatment of locally recurrent NPC was safe and effective. It also improved the positive expression rate of SDHB, which was associated with increased survival time.

[Clinical and anatomic study of preserving parathyroid specific adipose attachments in total thyroidectomy].

Objective: To discuss the anatomical characteristic and important role of specific adipose attachments in preserving parathyroid function in total thyroidectomy. Methods: Parathyroid glands of 91 cases underwent total thyroidectomy in Department of General Surgery, Beijing Hospital from January to November 2015 were observed prospectively. There were 19 male and 72 female patients, aging from 25 to 74 years with an average age of (52±12) years. Preoperative ultrasound examination, analysis of intraoperative high definition images, and postoperative pathological examination were used to detect the origins of the parathyroid micro vascular structures and the characteristics of parathyroid specific adipose attachments. Parathyroid specific adipose attachments preserving technique was used in all procedures. The results of parathyroid hormone (PTH), serum calcium and phosphorus were compared pre- and 1-month post-operatively. Paired t test was statistically used to analyze data. Results: Parathyroid micro vascular vessels were closely attached to parathyroid, and they were mainly originated from inside and (or) outside thyroid. Twenty patients received intraoperative high definition images analysis, 62 parathyroids were detected, in which 48 parathyroids (77.4%) had its specific adipose attachments. Lymphatic tissues could be distinguished from adipose tissue using carbon nanoparticles lymphatic tracer technique, which resulted in better preservation of parathyroid specific adipose attachments. There was no significant difference in PTH ((39±17) ng/L vs. (30±16) ng/L), serum calcium ((2.23±0.10) mmol/L vs. (2.20±0.14) mmol/L) and phosphorus ((1.27±0.20) mmol/L vs.(1.26±0.25) mmol/L) pre- and 1-month post-operatively (P>0.05). Conclusions: Preservation of parathyroid specific adipose attachments in total thyroidectomy could result in better protection of parathyroid micro vascular structure and function. It could be benefit to preservation of parathyroid in situ and its function recovery, thus may reduce the incidence of permanent postoperative hypoparathyroidism.

Comparison of Pipelle sampler with conventional dilatation and curettage (D&C) for Chinese endometrial biopsy.

The aim of this study is to investigate the accuracy and adequacy of the Pipelle endometrial sampler for endometrial biopsy as compared with those of conventional dilatation and curettage (D&C). A total of 245 patients subject to endometrial biopsy were included in this study. We have shown that the failure rates with D&C and Pipelle were 7.75% and 8.98%, respectively, without statistical difference. Additionally, the obtained specimen quality and accurate diagnosis of various diseases using the two methods had no significant statistical differences. Furthermore, patients experienced less pain when Pipelle sampler was used than D&C. Therefore, Pipelle sampler is effective in obtaining adequate endometrial tissue for histodiagnosis, and is applicable in most of the cases for Chinese endometrial biopsy.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report.

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Superficial parotid lobe-sparing delineation approach: a better method of dose optimization to protect the parotid gland in intensity-modulated radiotherapy for nasopharyngeal carcinoma.

PURPOSE: We used a superficial parotid lobe-sparing delineation approach for dose optimization with better protection for the parotid glands in intensity-modulated radiotherapy (imrt) for nasopharyngeal carcinoma (npc) patients. METHODS: Compared with traditional contouring of the entire parotid glands as organs at risk (oars) in imrt for npc, we used a superficial parotid lobe-sparing delineation approach of contouring the superficial parotid lobes as oars. Changes in dose to the parotid glands, the targets, and other oars were evaluated. RESULTS: The mean dose to the parotid glands overall decreased by more than 4 Gy in the test plans. Impressively, the mean dose to the superficial parotid lobes in the test plans was not more than 30 Gy, regardless of clinical stage. In T1-3 npc patients, the dose distributions for targets were not significantly different in the control plans and the test plans. However, for some T4 patients, the dose distributions for targets and brainstem in the test plans could not meet clinical requirements. CONCLUSIONS: The superficial parotid lobe-sparing delineation approach can significantly lower the mean dose to the entire parotid and to the superficial parotid lobe in T1-3 npc patients, which would be expected to result in less xerostomia and better quality of life for those patients.

Effects of frying and boiling on the formation of heterocyclic amines in braised chicken.

Braised chicken is a traditional ready-to-eat poultry product produced by frying chicken coated with maltose or honey and then boiling it in a soup that is circularly used. This study examined the effects of the frying time, honey concentration, boiling time, and cycle times of the soup on the formation of heterocyclic amines (HA), a class of mutagenic/carcinogenic compounds generated in heated muscle meat. Nine HA in chicken and recycled soups were analyzed by HPLC with UV and fluorescence detection. 1-Methyl-9H-pyrido[3,4-b]indole (Harman), 9H-pyrido[3,4-b]indole (Norharman), and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) were detected in most samples, and the amount of each HA increased with the frying or boiling time. Chicken skin was found to have higher HA content than chicken meat. More HA were detected in the soup than in the chicken, in most cases. 2-Amino-3-methylimidazo[4,5-f]quinoline and 2-amino-3,4,8-trimethylimidazoquinoxaline (4,8-DiMeIQx) were also detected in chicken and soup circularly boiled 20 times, and the total amount of HA reached 68.80 and 96.98 ng/g in chicken and soup, respectively.

Correlation of tumor relapse and elevated expression of survivin and vascular endothelial growth factor in superficial bladder transitional cell carcinoma.

Survivin and vascular endothelial growth factor (VEGF) are newly discovered tumor markers closely correlated with bladder cancer. We analyzed the expression of survivin and VEGF in paraffin-embedded tumor tissues from 78 patients with bladder transitional cell carcinoma (BTCC) using an immunohistochemistry method. Normal bladder mucosae from 10 non-BTCC cases were also included as a control group. All patients were closely followed up for tumor recurrence after undergoing transurethral resection of bladder tumor procedures. The positive expression rates of survivin and VEGF in superficial BTCC were 66.7% (52/78) and 69.2% (54/78), respectively, which were significantly higher than those in the control group, 0% (0/10). A positive correlation was found between survivin and VEGF expression (r = 0.283, P < 0.01). Thirty-two of 78 patients (41.0%) displayed recurrence during follow-up (median: 47; range: 7-62 months). The tumor recurrence rate in survivin(+) patients was 53.8% (28/52), which was significantly higher than that in survivin(-) patients [15.4% (4/26); P < 0.05]. The recurrence rate in VEGF(+)/ VEGF(-) patients was 50.0% (27/54) and 20.8% (5/24), respectively (P < 0.05). The sensitivity for predicting the relapse of superficial BTCC was 87.5% in the survivin(+) group, 84.4% in the VEGF(+) group, and 78.1% in the survivin(+)/VEGF(+) group, and the specificity was 47.8, 41.3, and 65.2%, respectively. Survivin and VEGF interact and jointly regulate the biological behavior of bladder cancer. Our results suggest that overexpression of survivin and VEGF accompany a higher risk of BTCC recurrence, making survivin and VEGF biomarkers for predicting the relapse of bladder cancer.

Susceptibility-weighted imaging in the diagnosis of early basal ganglia germinoma.

BACKGROUND AND PURPOSE: Germinomas originating from the basal ganglia (BG) are rare. Early diagnosis is important for favorable prognosis, but it is difficult due to the slow clinical course and subtle changes on neuroimaging. The purpose of this study was to evaluate the usefulness of susceptibility-weighted imaging (SWI) in the diagnosis of early BG germinoma. MATERIALS AND METHODS: From 2006 to 2008, 6 BG germinomas were diagnosed in children at our institution by pathology. Conventional MR imaging and SWI were available in all cases. Clinical, neuroradiologic, and follow-up features were retrospectively studied. RESULTS: Three cases were classified as early BG germinomas. Conventional MR imaging demonstrated that the tumor size was <10 mm in the largest diameter. The tumors were invisible or showed slight hyperintensity on T1-weighted images (T1WI) and patchy slight hyperintensity on T2-weighted images (T2WI) without mass effect or enhancement. On SWI, the tumors appeared as obvious hypointensity in the globus pallidus and putamen, and the size was larger than that on conventional T1WI and T2WI. The other 3 cases with tumor size >10 mm in largest diameter were classified as late BG germinomas, with tumor necrosis, fluid-fluid levels, and perifocal edema, including 1 case with subependymal spread. On SWI, only the solid portion of the tumors showed hypointensity. No recurrence was noted on follow-up. CONCLUSIONS: SWI appears to be more sensitive in detecting early BG germinomas than conventional MR imaging. This capability may prove to be useful in future attempts to characterize early BG germinomas.

Serum cytokine levels are altered in patients with West syndrome.

The objective of this study is to explore the neuroimmunomodulator effect of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha and interferon (IFN)-alpha in West syndrome (WS). Twenty-three cases of WS (13 males and 10 females, aged 4-14 months old) who first visited and consisted from 10 cryptogenic and 13 symptomatic, were enrolled in this study. Double-antibody sandwich enzyme-linked immunosorbent assay was used to measure serum IL-2, TNF-alpha and IFN-alpha levels in 23 patients with WS and the data were compared to those of 15 healthy infants who were matched with regard to age and sex. Levels of all three cytokines were significantly higher in both cryptogenic and symptomatic WS groups than the control group. Serum IL-2 levels in symptomatic WS were significantly higher than that in cryptogenic WS. There was a positive correlation between IL-2 and TNF-alpha in both cryptogenic and symptomatic WS groups. The immune systems of patients with WS are in an activated state. An imbalance in cytokine levels may be involved in the immunopathology of WS.

[Expression of CD44 variant exon 6 in lung cancers].

Immunohistochemical staining was carried out on 79 samples of lung cancers using anti-CD44v6 antibody. Strong positivity for CD44v6 was observed in the basal cells of bronchial epithelium, squamous metaplasia, and type II pneumocytes. The expression of CD44v6 in primary lesions of non-small cell lung cancers and small cell lung cancers was 67.6% (48/71) and 0% (0/8) respectively, while the expression of CD44v6 in metastases of lymph nodes was 57.6% (19/33) and 0% (0/5), respectively. It is suggest that expression of CD44v6 is correlated with histologic type, differentiation and metastasis of lung cancer.

Maternal smoking and preeclampsia.

OBJECTIVE: To study the relationship between maternal smoking and preeclampsia and whether this association differs between primiparous and multiparous women. STUDY DESIGN: We conducted a population-based, retrospective, cohort study of 58,216 singleton pregnancies from northern and central Alberta, Canada, between 1995 and 1997. Multivariate logistic regression was used to control for maternal alcohol consumption, drug dependence, maternal age, maternal weight, prior intrauterine growth restriction and other confounders. RESULTS: Maternal smoking was associated with a significantly reduced overall risk of preeclampsia (adjusted odds ratio [aOR]: .61; 95% confidence interval [CI]: .50-.75; P < .01). Stratified analyses showed that in primiparous pregnancies, maternal smoking was associated with a significantly decreased risk (aOR: .63; 95% CI: .50-.80; P < .01); in multiparous women, maternal smoking was not associated with a statistically significant decreased risk of preeclampsia (aOR: 0.72; 95% CI: .51-1.02; P > .05). CONCLUSION: Maternal smoking is protective against preeclampsia. Understanding the underlying biologic mechanisms of this protective effect may advance our knowledge of the pathogenesis of preeclampsia.

Preconditioning in rat hearts is independent of mitochondrial F1F0 ATPase inhibition.

Mitochondrial F1F0 adenosinetriphosphatase (ATPase) is responsible for the majority of ATP synthesis during normoxic conditions, but under ischemic conditions it accounts for significant ATP hydrolysis. A previous study showed that preconditioning in isolated rat hearts is mediated by inhibition of this ATPase during ischemia. We tested this hypothesis in our isolated rat heart model of preconditioning. Preconditioning was accomplished by three 5-min periods of global ischemia separated by 5 min of reperfusion. This was followed by 20 min of global ischemia and 30 min of reperfusion. Preconditioning significantly enhanced reperfusion contractile function and reduced lactate dehydrogenase release but paradoxically reduced the time to onset of contracture during global ischemia. Myocardial ATP was depleted at a faster rate during the prolonged ischemia in preconditioned than in sham-treated hearts, which is consistent with the reduced time to contracture. ATP during reperfusion was repleted more rapidly in preconditioned hearts, which is consistent with their enhanced contractile function. Preconditioning significantly reduced lactate accumulation during the prolonged ischemia. We were not able to demonstrate that mitochondrial F1F0 ATPase (measured in submitochondrial particles) was inhibited by preconditioning before or during the prolonged ischemia. The mitochondrial ATPase inhibitor oligomycin significantly conserved ATP during ischemia and increased the time to the onset of contracture, which is consistent with inhibition of the mitochondrial ATPase. Our results show that preconditioning in rat hearts can be independent of mitochondrial ATPase inhibition as well as ATP conservation.