Response of Vicia faba to short-term uranium exposure: chelating and antioxidant system changes in roots.

Uranium (U) phytotoxicity is an inherently difficult problem in the phytoremediation of U-contaminated environments. Plant chelating and antioxidant systems play an authoritative role in resistance to abiotic stress. To reveal the toxicity of U, the changes of chelating system, osmoregulatory substances and antioxidant systems in Vicia faba roots were studied after short-term (24 h) U exposure. The results indicated that the development of lateral roots and root activity of V. faba were significantly inhibited with U accumulation. Compared with the control, plant chelating systems showed significant positive effects after U exposure (15 - 25 µM). Osmoregulatory substances (proline and soluble protein) increasingly accumulated in roots with increasing U concentration, and O2- and H2O2 rapidly accumulated after U exposure (15 - 25 µM). Thus, the contents of malondialdehyde (MDA), a marker of lipid peroxidation, were also significantly increased. Antioxidant systems were activated after U exposure but were inhibited at higher U concentrations (15 - 25 µM). In summary, although the chelating, osmotic regulation and antioxidant systems in V. faba were activated after short-term U exposure, the antioxidases (CAT, SOD and POD) were inhibited at higher U concentrations (15 - 25 µM). Therefore, the root cells were severely damaged by peroxidation, which eventually resulted in inhibited activity and arrested root development.

Metastasis-Associated Protein 1 Deficiency Results in Compromised Pulmonary Alveolar Capillary Angiogenesis in Mice.

BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry. The morphological changes were investigated during pulmonary alveolar capillary formation. The heart weight/body weight (HW/BW) ratio and the size of the right ventricular wall cardiomyocytes were also measured. Regulation of MTA1 on HIF-1α was determined in vitro. RESULTS MTA1 deficiency reduced the number of pulmonary alveolar capillaries compared to the wild-type mice. MTA1-KO mice exhibited a decreased expression of HIF-1α and VEGF in the lungs. The retarded growth of the MTA1-KO mice was also noticed during the first week after birth. Accordingly, MTA1 deficiency resulted in increased infant mortality. In surviving adult mice, MTA1 deficiency induced myocardial hypertrophy, highlighted by an increased heart weight/body weight ratio and larger cardiomyocytes. In cultured cells, HIF-1α and VEGF levels were significantly upregulated upon MTA1 overexpression, suggesting a close relationship between all 3 molecules. CONCLUSIONS MTA1 participates in the formation of pulmonary capillaries via stabilization of HIF-1α. This finding sheds new light on the function of MTA1 in lung development, opening new avenues for the diagnosis/treatment of related pulmonary diseases.

Elevated growth differentiation factor 15 expression predicts poor prognosis in epithelial ovarian cancer patients.

The purpose of this study was to determine the expression of growth differentiation factor 15 (GDF15) and explore its clinical significance in epithelial ovarian cancer (EOC) patients. The expression of GDF15 in EOC tissues and serum samples was evaluated using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. The association of GDF15 expression with clinicopathologic parameters was analyzed. Survival time was assessed using the Kaplan-Meier technique and Cox regression model. Both in EOC tissues and serum, high GDF15 levels were obviously related with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, ascites, and chemoresistance. Kaplan-Meier analysis indicated that EOC patients with high GDF15 expression showed poorer progression-free survival (PFS) and overall survival (OS). Multivariate analysis demonstrated that GDF15 expression was an independent predictor of PFS in EOC patients. Our study shows that elevated GDF15 expression was associated with poor prognosis in EOC patients. We suggest that GDF15 is a novel biomarker for the early detection of EOC, prediction of the response to chemotherapy, and screening for recurrence in EOC patients.

The 6-item Kessler psychological distress scale to survey serious mental illness among Chinese undergraduates: Psychometric properties and prevalence estimate.

OBJECTIVE: To evaluate the psychometric properties of the 6-item Kessler psychological distress scale (K6) in screening for serious mental illness (SMI) among undergraduates in a major comprehensive university in China. METHOD: The K6 was self-completed by 8289 randomly sampled participants. A group of them (n=222) were re-assessed using K6 and interviewed using the Chinese version of Composite International Diagnostic Interview 3.1 (CIDI-3.1). RESULTS: The test-retest reliability of the K6 scale was 0.79, the Cronbach's alpha was 0.84, and its area under the receiver operating curve (AUC) for diagnosing CIDI-3.1 SMI was 0.85 (95% CI=0.80-0.90). For the optimal cut-off of K6 (12/13), the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and classification accuracy (AC) were 0.83, 0.79, 0.60, 0.93, and 0.80, respectively. The 12-month prevalence of SMI was estimated as 3.97% using this optimal cut-off. Binary logistic regression analysis (including gender, ethnicity, grade, number of siblings and family residency location) showed that only family residency location in rural areas compared to urban areas was significantly associated with more SMI. CONCLUSIONS: This study documented the value of using the K6 for detecting SMI in Chinese undergraduate populations and supported its cross-cultural reliability and validity.

Contrast-enhanced MRI in preoperative assessment of myometrial and cervical invasion, and lymph node metastasis: diagnostic value and error analysis in endometrial carcinoma.

OBJECTIVE: To determine the ability of contrast-enhanced magnetic resonance imaging to predict myometrial invasion, cervical invasion, and pelvic lymph node metastasis in endometrial carcinoma and to analyze factors that lead to errors in this identification. DESIGN: A retrospective study. SETTING: University general hospital. POPULATION: A total of 167 women diagnosed with endometrial carcinoma. METHODS: All patients received a preoperative contrast-enhanced magnetic resonance imaging scan. Histopathological findings were used as the definitive diagnosis. MAIN OUTCOME MEASURES: The results were compared with histopathological findings, factors that make accurate assessment of myometrial invasion, cervical invasion, and pelvic lymph node metastasis difficult by contrast-enhanced magnetic resonance imaging were analyzed. RESULTS: The sensitivity, specificity, diagnostic accuracy, positive predictive values, and negative predictive values of contrast-enhanced magnetic resonance imaging were 90.9, 91.8, 91.6, 73.2 and 97.6%, respectively, for identifying deep myometrial invasion; 84.2, 96.0, 94.6, 72.7 and 97.9%, respectively, for identifying cervical invasion; and 45.0, 91.2, 85.6, 40.9 and 92.4%, respectively, for identifying pelvic lymph node metastasis. The main causes of error in contrast-enhanced magnetic resonance imaging were myomas, cornual lesions, deep myometrial invasion, large tumor size, non-endometrioid tumor type, and lower tumor grade. CONCLUSION: Contrast-enhanced magnetic resonance imaging has a high accuracy and a low tendency to produce false-negative predictive values. Gynecological oncologists should combine the imaging data and clinical information to make therapeutic decisions and avoid diagnostic errors.

Performance of ChatGPT on the pharmacist licensing examination in Taiwan.

BACKGROUND: ChatGPT is an artificial intelligence model trained for conversations. ChatGPT has been widely applied in general medical education and cardiology, but its application in pharmacy has been lacking. This study examined the accuracy of ChatGPT on the Taiwanese Pharmacist Licensing Examination and investigated its potential role in pharmacy education. METHODS: ChatGPT was used on the first Taiwanese Pharmacist Licensing Examination in 2023 in Mandarin and English. The questions were entered manually one by one. Graphical questions, chemical formulae, and tables were excluded. Textual questions were scored according to the number of correct answers. Chart question scores were determined by multiplying the number and the correct rate of text questions. This study was conducted from March 5 to March 10, 2023, by using ChatGPT 3.5. RESULTS: The correct rate of ChatGPT in Chinese and English questions was 54.4% and 56.9% in the first stage, and 53.8% and 67.6% in the second stage. On the Chinese test, only pharmacology and pharmacochemistry sections received passing scores. The English test scores were higher than the Chinese test scores across all subjects and were significantly higher in dispensing pharmacy and clinical pharmacy as well as therapeutics. CONCLUSION: ChatGPT 3.5 failed the Taiwanese Pharmacist Licensing Examination. Although it is not able to pass the examination, it can be improved quickly through deep learning. It reminds us that we should not only use multiple-choice questions to assess a pharmacist's ability, but also use more variety of evaluations in the future. Pharmacy education should be changed in line with the examination, and students must be able to use AI technology for self-learning. More importantly, we need to help students develop humanistic qualities and strengthen their ability to interact with patients, so that they can become warm-hearted healthcare professionals.

Potentially inappropriate medication in long-term care wards of a veteran hospital in Taiwan: Investigation using a spreadsheet-based rapid assessment tool.

BACKGROUND: Multimorbidity and polypharmacy increase in the aging population and are accompanied by the use of potentially inappropriate medications (PIMs) and adverse drug events (ADEs). This study developed a rapid assessment tool to investigate PIM use among patients in long-term care wards. METHODS: We retrospectively collected the data of patients in long-term care wards of a veteran hospital in Taiwan between July 2019 and June 2020. The patients with chronic diseases and medications were selected. The data, including gender, age, diagnosis, and medications, were deidentified. Nonchronic disease diagnosis and short-term and topical use medications were excluded. We used Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA) and the 2019 version of the Beers Criteria to establish a rapid assessment tool. The correlations between the prevalence of PIM use and age, the number of diagnoses, and the number of medications were analyzed using SPSS version 23. RESULTS: A total of 176 patients were included in this study, of which 76.7% (n = 135) were male and 23.3% (n = 41) were female. The average age of men was 82.1 years and that of women was 83.4 years. The average number of diagnoses for men was 5.5, and that for women was 7.3. The average number of medications for men was 5.8, and that for women was 6.5. The prevalence of PIM use was 59.1% (n = 104). Logistic regression revealed that the prevalence of PIM use may be associated with the number of medications ( p < 0.001; odds ratio = 1.378). Decision tree analysis revealed that patients who simultaneously used more than four medications exhibited a higher risk of PIM. CONCLUSION: PIM use is a key factor causing ADEs among older adults. Therefore, comprehensive assessment of PIM use is necessary. This study designed a rapid assessment tool to simultaneously integrate and evaluate medications. Future studies may investigate the effectiveness of the proposed assessment tool.

ChatGPT failed Taiwan's Family Medicine Board Exam.

BACKGROUND: Chat Generative Pre-trained Transformer (ChatGPT), OpenAI Limited Partnership, San Francisco, CA, USA is an artificial intelligence language model gaining popularity because of its large database and ability to interpret and respond to various queries. Although it has been tested by researchers in different fields, its performance varies depending on the domain. We aimed to further test its ability in the medical field. METHODS: We used questions from Taiwan's 2022 Family Medicine Board Exam, which combined both Chinese and English and covered various question types, including reverse questions and multiple-choice questions, and mainly focused on general medical knowledge. We pasted each question into ChatGPT and recorded its response, comparing it to the correct answer provided by the exam board. We used SAS 9.4 (Cary, North Carolina, USA) and Excel to calculate the accuracy rates for each question type. RESULTS: ChatGPT answered 52 questions out of 125 correctly, with an accuracy rate of 41.6%. The questions' length did not affect the accuracy rates. These were 45.5%, 33.3%, 58.3%, 50.0%, and 43.5% for negative-phrase questions, multiple-choice questions, mutually exclusive options, case scenario questions, and Taiwan's local policy-related questions, with no statistical difference observed. CONCLUSION: ChatGPT's accuracy rate was not good enough for Taiwan's Family Medicine Board Exam. Possible reasons include the difficulty level of the specialist exam and the relatively weak database of traditional Chinese language resources. However, ChatGPT performed acceptably in negative-phrase questions, mutually exclusive questions, and case scenario questions, and it can be a helpful tool for learning and exam preparation. Future research can explore ways to improve ChatGPT's accuracy rate for specialized exams and other domains.

[Clinicalpathological characteristics of Lynch syndrome related epithelial ovarian cancer].

OBJECTIVE: To explore the clinical pathological characteristics of Lynch syndrome associated ovarian cancer. METHODS: Totally 260 cases ovarian cancer patients were admitted to Tianjin Medical University General Hospital during Jan. 2004 and Jan. 2011, among which 10 patients (LS group) belonged to Lynch syndrome associated ovarian cancer according to Amsterdam II criteria. One hundred ovarian cancer patients without any family cancer history were enrolled randomizely as control group (sporadic group). RESULTS: Lynch syndrome associated ovarian cancer accounted for 3.8% (10/260), the incidence rate of ovarian cancer for female family members of Lynch syndrome was 8.7% (10/115). Mean age at time of diagnosis in LS group was (46 ± 7) years, significantly earlier than that in sporadic group [(56 ± 11) years, P < 0.05]. There was no statistical difference between two groups in histological type or International Federation of Gynecology and Obstetrics (FIGO) stage (P > 0.05). Most of the tissue differentiation in LS group were well or moderate differentiated, there was statistical difference between the two groups (9/10 vs. 55%, P < 0.05). The 3-year and 5-year survival rate in LS group were 87.5% and 52.5% respectively, compared with 55.4%and 22.7% in sporadic group (all P < 0.05). CONCLUSION: Compared with sporadic ovarian cancer, Lynch syndrome associated ovarian cancer is more likely present as the clinical pathological characteristics of early age of onset, serous adenocarcinoma, lower grade and better prognosis.

Primary epithelioid hemangioendothelioma in the clival region: a case report and literature review.

Epithelioid hemangioendothelioma (EHE) is a rare and low-grade vascular tumor, which usually occurs in the soft tissue, liver, breast, lung and skeleton. Here we submit a case with EHE of the clival region. A 58-year-old woman was admitted with a medical history of 3 months headache and 1 month visual deterioration. MRI revealed a well-circumscribed mass of 4.0 cm × 3.0 cm with bony invasion. The tumor was subtotally removed in a piecemeal fashion. Histologically, the tumor was composed of epithelioid cells with eosinophilic cytoplasm and intracytoplasmic vacuoles. Immunohistochemically, the tumor cells were positive for the markers CD31, CD34, factor VIII and vimentin. The pathological result was interpretated as EHE of the clival region. EHE is an uncommon vascular tumor, which is rarely seen in the clival region. Definitive diagnosis depends on histopathologic and immunohistochemical features.

Malignant solitary fibrous tumor arising from the pineal region: case study and literature review.

We report a case of malignant solitary fibrous tumor involving the pineal region in a 49-year-old woman. The patient presented with headache, slowly progressive weakness of the right lower extremities and upgaze palsy over the past year. Histologically, the tumor was composed of moderately hypercellular proliferated spindle cells with eosinophilic collagen bands. These cells were diffusely and strongly immunoreactive with CD34, CD99, and vimentin, but were negative with epithelial membrane antigen, S-100 protein, Bcl-2, smooth muscle actin, cytokeratin and glial fibrillary antigenic protein. MIB-1 labeling indices and mitosis rates were 7.3 +/- 1.8% and 5 per 10 high power fields, respectively. Ultrastructural examination revealed that the neoplastic cells had features of fibroblastic differentiation. Differential diagnoses included fibrous meningioma and hemangiopericytoma. The present case provides one unique example of a rare entity to the already diverse spectrum of the pineal region neoplasms encountered in neuropathology.

Large pelvic mass arising from the cervical stump: A case report.

BACKGROUND: A large cervical cyst with a cervical high-grade squamous intraepithelial lesion arising from the cervical stump is rare. After supracervical hysterectomy, there is a risk of various lesions occurring in the cervical stump. We review the types and characteristics of cervical stump lesions and compare total hysterectomy with subtotal hysterectomy. Gynecologists should choose the most suitable surgical method based on both the patient's condition and wishes. If the cervix is retained, patients require a close follow-up. CASE SUMMARY: A 57-year-old woman was admitted to the Gynecology Department for a large pelvic mass. Her chief complaint was abdominal distention for two months. She had undergone subtotal supracervical hysterectomy for leiomyoma 14 years prior. Abdominal ultrasonography detected a 9.1 cm × 8.5 cm × 8.4 cm anechoic mass with silvery fluid in the pelvic cavity and high-risk human papilloma virus 53 (HPV53) was positive. The admission diagnosis we first considered was a pelvic mass mimicking carcinoma of the cervical stump. We performed a laparotomy and a rapid frozen biopsy was suggestive of a fibrous cyst wall coated with a high squamous intraepithelial lesion. The pelvic mass was removed, and a bilateral adnexectomy was implemented. Final pathology confirmed that the pelvic mass was a large inflammatory cyst with a cervical high-grade squamous intraepithelial lesion. After successful intervention, the patient was discharged one week after surgery and there was no recurrence of the vaginal stump at 43 mo. CONCLUSION: When addressing benign uterine diseases, gynecologists should pay adequate attention to retaining the cervix. If the cervix is retained, patients require a close follow-up.

Blockade of Discoidin Domain Receptor 2 as a Strategy for Reducing Inflammation and Joint Destruction in Rheumatoid Arthritis Via Altered Interleukin-15 and Dkk-1 Signaling in Fibroblast-Like Synoviocytes.

OBJECTIVE: This study was undertaken to uncover the pathophysiologic role of discoidin domain receptor 2 (DDR-2), a putative fibrillar collagen receptor, in inflammation promotion and joint destruction in rheumatoid arthritis (RA). METHODS: In synovial tissue from patients with RA and from mice with collagen antibody-induced arthritis (CAIA) (using Ddr2-/- and DBA/1 mice), gene and protein expression levels of DDR-2, interleukin-15 (IL-15), and Dkk-1 were measured by quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Gene knockdown of DDR2 in human RA fibroblast-like synoviocytes (FLS) was conducted via small interfering RNA. Interaction between the long noncoding RNA H19 and microRNA 103a (miR-103a) was assessed in RA FLS using RNA pulldown assays. Cellular localization of H19 was examined using fluorescence in situ hybridization assays. Chromatin immunoprecipitation and dual luciferase reporter assays were applied to verify H19 transcriptional and posttranscriptional regulation by miR-103a. RESULTS: DDR2 messenger RNA (mRNA) expression was significantly associated with the levels of IL-15 and Dkk-1 mRNA in the synovial tissue of RA patients (r2 = 0.2022-0.3293, all P < 0.05; n = 33) and with the serum levels of IL-15 and Dkk-1 in mice with CAIA (P < 0.05). In human RA FLS, activated DDR-2 induced the expression of H19 through c-Myc. Moreover, H19 directly interacted with and promoted the degradation of miR-103a. CONCLUSION: These results indicate a novel role for activated DDR-2 in RA FLS, showing that DDR-2 is responsible for regulating the expression of IL-15 and Dkk-1 in RA FLS and is involved in the promotion of inflammation and joint destruction during pathophysiologic development of RA. Moreover, DDR-2 inhibition, acting through the H19-miR-103a axis, leads to reductions in the inflammatory reaction and severity of joint destruction in mice with CAIA, suggesting that inhibition of DDR-2 may be a potential therapeutic strategy for RA.

[Blocking of Notch signaling decreased scar formation in rabbit ear hypertrophic scar model].

OBJECTIVE: To investigate the effects of Notch signaling on scars in a rabbit ear model of hypertrophic scarring. METHODS: The hypertrophic scar of rabbits' ears was reproduced. The left rabbit's ear wounds as the N-[N-(3,5-difluorophenacetyl-L-alanyl)]-(S)-phenylglycine t-butyl ester (DAPT) treated group were treated intradermally with the gamma-secretase inhibitor DAPT to inhibit the activation of Notch at 1, 3, 7 and 14 day time points. The right ears as the control group were treated with normal saline at the same time points. Experimental and control wounds were harvested on days 14, 21, 28 and 35 post wounding, and then examined histologically to quantify hypertrophic index and fibroblasts. The expression of epidermal differentiation markers-keratin 14 (K14), keratin 19 (K19), Involucrin and Notch downstream molecules-P21, P63 were examined and analyzed with immunohistochemistry staining. RESULTS: Both hypertrophic index (1.93 +/- 0.32, 1.82 +/- 0.36, 1.79 +/- 0.25) and number of fibroblasts [(4.08 +/- 0.88), (3.30 +/- 0.53), (3.19 +/- 0.73) x 10(3)/mm(2)] in the DAPT treated group were significantly reduced on days 21, 28 and 35, compared with the control group [2.56 +/- 0.29, 2.61 +/- 0.30, 2.58 +/- 0.39, and (5.45 +/- 0.99), (4.80 +/- 1.13), (4.43 +/- 1.17) x 10(3)/mm(2), all P < 0.01)]. The K19, K14 and P63 increased their expression in the DAPT treated group (28.6% +/- 5.7%, 53.1% +/- 4.5%, 57.0% +/- 5.8%) relative to the control group (10.1% +/- 2.8%, 30.8% +/- 4.9%, 16.5% +/- 2.2%, all P < 0.01) on day 14 post wounding, while the Involucrin and P21 decreased their expression in the DAPT treated group (12.3% +/- 1.9%, 11.0% +/- 1.7%) relative to the control group (29.3% +/- 4.6%, 44.3% +/- 3.5%, both P < 0.01). CONCLUSION: Inactivation of Notch signaling will inhibit scar epidermis to over-differentiation, and thereby inhibit proliferation of hypertrophic scars in the rabbit ears.

Activation of the NF-κB Pathway and Heterozygous Deletion of TNFAIP3 (A20) Confer Superior Survival in Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

OBJECTIVES: To investigate the role of TNFAIP3 deletions and NF-κB activation in extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type. METHODS: In total, 138 patients with ENKTCL were included. Activation of NF-κB pathway and expression of TNFAIP3 (A20) were examined by immunohistochemistry. TNFAIP3 was analyzed for deletions using FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for investigating neoplasms), for mutations using Sanger sequencing, and for promoter methylation using methylation-specific sequencing. RESULTS: NF-κB pathway activation was observed in 31.2% of cases (43/138), TNFAIP3 expression was negative in 15.2% of cases (21/138), and heterozygous TNFAIP3 deletion was observed in 35% of cases (35/100). TNFAIP3 exons 2 to 9 mutations and promoter methylation were not observed. Kaplan-Meier analysis showed patients with NF-κB pathway activation or TNFAIP3 heterozygous deletion to have a longer overall survival. CONCLUSIONS: Our study demonstrated that NF-κB activation and TNFAIP3 heterozygous deletion confer superior survival in patients with ENKTCL.

[Clinicopathological characteristics in hereditary nonpolyposis colorectal carcinoma-associated endometrial carcinoma].

OBJECTIVE: To study clinicopathological characteristics of hereditary nonpolyposis colorectal carcinoma (HNPCC)-associated endometrial carcinoma (EC). METHODS: Totally 421 EC patients admitted to General Hospital of Tianjin Medical University from 1981 to 2006 were divided into three groups: group A: sporadic EC; group B: familial aggregation of EC; group C: HNPCC-associated EC. RESULTS: HNPCC-associated EC accounted for 6.4% (27/421). Mean age at time of diagnosis was 49.7 years in group C, earlier than 56.3 years in group A (P = 0.004) and 55.2 years in group B (P = 0.035). There were 33.3% (9/27) patients with multiple primary carcinomas in group C. It was higher than 14.3% (9/63) in group B and 5.1% (17/331) in group A respectively (P = 0.038, P < 0.01). There was no difference among the three groups in histological type or menopausal status (P > 0.05). The numbers of patients with low grade EC in group C (70.4%, 19/27) and group B (61.35, 38/62) were more than that in Group A (P = 0.013, P = 0.023). Prognosis for group C was better than that in group A (P = 0.021), and 5- and 10-year survival rate in groups A, B and C was 80%, 70%; 88%, 85%; and 96%, 96% respectively. CONCLUSIONS: Mean age at time of diagnosis is earlier in HNPCC-associated EC than that in sporadic EC; patients with HNPCC-associated EC are more frequently complicated with multiple primary carcinomas and of low grade; prognosis is better.

[Expression and activation of insulin receptor substrate-1 in endometrial carcinoma].

OBJECTIVE: To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. METHODS: Sixty-three endometrial carcinoma (EC) patients, 21 endometrial atypical hyperplasia (AHE) patients and 22 normal control (NE) entered this study. Their clinical information were collected. Fasting serum C-peptide concentration was measured. Expression of IRS-1 in endometrium was examined by RT-PCR and western blot. Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1. RESULTS: C-peptide concentration in EC group was higher than that in NE group [(3.2 +/- 1.1) vs (2.5 +/- 0.7) microg/L, P=0.007]. There were no significant differences in IRS-1 mRNA and protein expression among the three groups. Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. IRS-1 activation in AHE group was also higher than normal control (P=0.045). IRS-1 activation in endometrioid carcinoma [(69 +/- 33) %] was higher than that in other histological types [(34 +/- 31)%; t=2.300, P=0.025]. IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. IRS-1 activation in endometrium was positively correlated with fasting serum C-peptide concentration (r=0.491, P=0.001). CONCLUSIONS: There is excessive activation of IRS-1 in endometrial carcinoma and atypical hyperplasia. Activation of IRS-1 in endometrial carcinoma is related with poor clinical-pathologic features and may be a prognostic predictor for this tumor. Over-activation of IRS-1 may be an intermediate event linking the hyperinsulinemia and endometrial carcinoma.

[Research on application of modified polyethylene glycol hydrogels in the construction of tissue engineered heart valve].

OBJECTIVE: To explore the effect of the polyethylene glycol (PEG)-hydrogels to enhance the seeding-cells adhesion to the biomaterial scaffolds. METHODS: Sixteen porcine aortic valves were decellularized with Triton X-100 and trypsin, then divided into A and B group, eight in each group. Group A: the donor goat's autologous bone marrow mesenchymal stem cells (BMSCs) Selected as the seeding-cells were encapsulated into the modified PEG-hydrogels to complete the process of the cells attaching to the acellular porcine aortic valves. Non-PEG but reservation of BMSCs was modified in Group B. After static culture for 7 d, the mono semilunar tissue engineering heart valve (TEHV) were implanted respectively into each donor goat's abdominal aortas. Gross and histology examination, ultrasonic scanning, electron microscopy observation and biomechanics detection were performed at 16 weeks after operation. The 8 native goat aortic valves from the donor goats were selected at the same time as control group (Group C). RESULTS: There were much more improvements compared Group A to Group B (P < 0.05) in tensile strength [(12.9 +/- 1.3) MPa vs. (8.8 +/- 0.4) MPa], ratio of re-endothelial (84.6% vs. 14.8%) and mural thrombosis (0/8 vs. 8/8). The data illustrated the critical importance of BMSCs differentiation to endothelial and myofibroblast for remodeling into native tissue in microenvironment in vivo. CONCLUSIONS: It is feasible to reconstruct TEHV efficiently by combining modified PEG-hydrogels with acellular biomaterial scaffold and autologous MSCs cells. It can improve the integration of the seeding-cells and scaffold. It can also protect the growth and differentiation of the BMSCs in the systemic circulation effectively.