This study was aimed to investigate the effect of multikinase inhibitor sorafenib on the proliferation and apoptosis of U937 cells and its possible mechanism. U937 cells were treated with different concentrations of sorafenib for 48 hours. Cell viability was determined by Cell Counting Kit-8; cell apoptosis and cell ratio in cell cycle were detected by flow cytometry with Annexin V/PI staining and PI staining respectively; expressions of GSK-3β, β-catenin and cyclin-D1 were assayed by Western blot. The results showed that the proliferation of U937 cells was inhibited by sorafenib in a dose-dependent manner (p < 0.05). Sorafenib induced cell apoptosis and cell cycle G(1)/G(0) arrest. Compared with results of Western blot before treatment, expression of inactivated GSK-3β, β-catenin and Cyclin-D1 down-regulated in a dose-dependent manner after treatment with sorafenib, this same changes were observed after up-regulation of inactivated GSK-3β by LiCl (p < 0.05). It is concluded that sorafenib inhibits the proliferation of U937 cells and induces cell apoptosis through reducing negative regulation of WNT signal pathway on inactivated GSK-3β and down-regulating β-catenin and cyclin-D1 level, which result in U937 cell cycle G(1)/G(0) arrest.
Apoptosis ; drug effects ; Benzenesulfonates ; pharmacology ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Humans ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; pharmacology ; U937 Cells ; Wnt Signaling Pathway ; beta Catenin ; metabolism

OBJECTIVETo study the clinical features and histopathology of the neuroendocrine carcinoma (NEC) of the breast.

METHODSTwenty-two cases of NEC of the breast were analysed by morphology and immunohistochemistry using synaptophysin, chromogranin A, NSE, CD56, estrogen receptor (ER), progesterone receptor (PR), HER2, EGFR, CK5/6, CK14, p63, E-cadherin, p120, p53 and Ki-67 staining. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH) for cases with HER2 protein expression 2+. The diagnosis of breast NEC relies on the expression of neuroendocrine markers expression in more than 50% of tumor cells, and no evidence of neuroendocrine carcinoma in any other parts of the body at the same time.

RESULTSThe patients aged from 31 to 96 years (mean 65.2 years), and all were female but one. Amongst the 22 patients studied, the NECs were in the left breast in 15 cases (68.2%) and in the right breast in seven cases (31.8%); the tumor size was 0.5 to 5.5 cm (mean 2.7 cm). Lymph node metastasis was found in six cases. Basing on the morphologic features, these 22 cases were categorized into six subtypes including nine cases of solid cohesive, six of mucinous, three of solid papillary, two of small cell, one of large cell and one of alveolar variants. Immunohistochemically, the expression rate of markers was 100% (22/22) for synaptophysin, 12/13 for NSE, 54.5% (12/22) for chromogranin A, and 5/16 for CD56. Also, 90.5% (19 of 21) of cases expressed ER, 81.0% (17 of 21) of cases expressed PR, and none expressed EGFR, CK5/6, CK14 and p63. HER2 protein over-expression (3+) and gene amplification was not detected in any case. All cases (19/19) were positive for membrane staining for E-cadherin and p120. p53 expression was seen in 6 of 17 cases. Ki-67 labeling index was less than 3% in 9.5% (2/21) of the cases, 3% to 20% in 66.7% (14/21) of the cases and more than 20% in 23.8% (5/21) of the cases. Both cases of HER2 (2+) did not show gene amplification by FISH. On the basis of immunophenotypes, most of the breast NECs were of the luminal molecular subtype, but not HER2-overexpression or basal-like subtypes.

CONCLUSIONSNEC of breast more likely occurs in elderly patients and in the left breast than the right breast. The most common morphology is the solid cohesive subtype, followed by the mucinous variant.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; classification ; metabolism ; pathology ; surgery ; Breast Neoplasms, Male ; classification ; metabolism ; pathology ; surgery ; Cadherins ; metabolism ; Carcinoma, Neuroendocrine ; classification ; metabolism ; pathology ; surgery ; Chromogranins ; metabolism ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Mastectomy ; methods ; Middle Aged ; Phosphopyruvate Hydratase ; metabolism ; Prognosis ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Synaptophysin ; metabolism

OBJECTIVE: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT) to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiple medical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, and prognostic factors of this disease and reviewed related literature. METHODS: Pathological reports of 16,001 patients with primary ovarian cancer who were treated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients with MT of MCT to SCC were identified. RESULTS: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age of patients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40 cm). We analyzed the patients in our study and those in the literature and determined that early identification and complete surgical resection of the tumor are essential for long-term survival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be used to treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTs are suitable indicators predicting the risk of MT of MCT to SCC. CONCLUSION: Similar to general epithelial ovarian cancers, the early detection of MT of MCT to SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should be evaluated to exclude potential MT to SCC.
Carcinoma, Squamous Cell* ; Cell Transformation, Neoplastic ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Epithelial Cells* ; Humans ; Incidence ; Ovarian Neoplasms ; Taiwan ; Teratoma*

OBJECTIVETo measure lutein, zeaxanthin and β-carotene level in foods commonly consumed in Beijing, and compare the content difference between raw and cooked food.

METHODSForty-six commonly consumed foods of 8 classes were collected in Haidian district of Beijing from September to October in 2009. A high performance liquid chromatography method was used to determine the content of lutein, zeaxanthin and β-carotene in both raw and cooked samples.

RESULTSLutein was abundant in cucurbitaceous and solanaceous, allium and nuts, especially in Chinese chive (18 226.9 µg/100 g) and pumpkin (13 265.2 µg/100 g). Major sources of zeaxanthin included round pumpkin, green garlic shoot, corn and eggs, whose level of zeaxanthin were 444.6, 283.5, 279.7, 118.6 - 377.9 µg/100 g, respectively. Zeaxanthin level of those cooked foods changed to 483.9, 239.3, 279.1, 149.5 - 594.7 µg/100 g, respectively. The zeaxanthin level of cooked Chinese chive reached 1081.2 µg/100 g, while we did not detect any zeaxanthin in raw Chinese chive. β-carotene was present in a wide variety of vegetables and fruits. Carrot (17 234.3 µg/100 g) was a good source of β-carotene, while its level in cooked carrot was 17 013.5 µg/100 g.

CONCLUSIONConsuming the proper kinds of foods and changing the method of food processing were beneficial to increase the intake of lutein, zeaxanthin and β-carotene.

China ; Cooking ; Food ; Food Analysis ; Lutein ; analysis ; Xanthophylls ; analysis ; Zeaxanthins ; beta Carotene ; analysis

OBJECTIVETo investigate the correlative factors affecting the IIEF-5 scores of the patient with type 2 diabetic mellitus (T2DM).

METHODSA total of 149 T2DM patients were investigated for the relationships between their IIEF-5 score and such factors as age, body mass index (BMI), fasting plasma glucose (FPG), 2hPG, insulin (INS), GHbA1c, C-peptide, nitric oxide (NO), testosterone (T), estradiol (E2), the ratio of testosterone to estradiol (T/E), erythrocyte aldose reductase (AR), drinking, smoking, concomitant diseases, complications and medication.

RESULTSThe scores of the groups of smoking, complication, medication and concomitant disease were significantly lower than those of the controls. There was significant negative correlation between IIEF-5 scores and age, BMI, FPG, 2hPG, INS, GHbA1c and AR (P < 0.05), and significant positive correlation between IIEF-5 scores and NO (P < 0.05). But there was no correlation between drinking, T, E2 and T/E2 (P > 0.05).

CONCLUSIONMany factors may affect the IIEF-5 scores of T2DM patients.

Adult ; Age Factors ; Aged ; Aldehyde Reductase ; blood ; Body Mass Index ; Diabetes Mellitus, Type 2 ; epidemiology ; physiopathology ; Erectile Dysfunction ; epidemiology ; Factor Analysis, Statistical ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Nitric Oxide ; blood ; Penile Erection ; physiology ; Regression Analysis ; Surveys and Questionnaires

Objective To study the infection status and the molecular characteristics of Vibrio parahaemolyticus isolated from diarrheal patients in Shenzhen, in 2007 to 2008 and to provide evidence for the prevention and control of diarrheal diseases caused by Vibrio parahaemolyticus. Methods More than 80 fecal specimens from four sentinel surveillance hospitals were collected and cultured each month. A total of 361 isolates of Vibrio parahaemolyticus were sero-typed and examined by real-time PCR for the presence of two major virulence genes, tdh and trh. Of 361 strains, 60 O3: K6 strains isolated from six suspected outbreaks in August, 2007 and in September, 2008 were typed by pulsed-field gel electrophoresis (PFGE). Results 4384 stool samples were detected in four sentinel surveillance hospitals and with 361 Vibrio parahaemolyticus strains isolated that belonged to 28 serotypes. Serotype O3:K6, O4:K8 and O1:KUT accounted for 67.90%, 7.50% and 6.10%, respectively. Of 361 strains, 337 strains belonged to tdh + trh- , 11 strains were tdh-trh- and 13 strains were tdh + trh +. The most prevalent serotype which caused diarrheal diseases was tdh + trh-in Shenzhen. The 60 isolates were discriminated into twenty different PFGE patterns, which belonged to three clones. Among the 60 isolates, most of the PFGE patterns of isolates from the suspected outbreak locations were identical and some strains isolated from different year were different. Conclusion Vibrio parahaemolyticus isolates in Shenzhen were dominated by O3:K6 strains. Most of these isolates carried tdh gene and few carried trh gene. Meanwhile, the identical patterns of isolates from 6 suspected outbreaks locations demonstrated that Vibrio parahaemolyticus outbreaks occurred in July 2007 and in September 2008 in Shenzhen. However, the dominated strains' PFGE patterns were different each year, indicating that the sources of Vibrio parahaemolyticus had a multiplex nature and the multiplex sources such as water, sea food and pickled products should be integrated monitored. Laboratory based surveillance of diarrheal diseases could contribute in establishing early warning system for the better prevention and control of diarrheal diseases.

OBJECTIVEThe aim of this study was to establish a standard protocol for detection of EGFR mutations in cytologic specimens.

METHODS287 cytologic samples were collected from the patients who were suspected of having lung cancer at six hospitals in Beijing. A detection protocol for EGFR mutations was designed. Two comparative experiments were carried out for the coincidence in EGFR mutation rates between direct sequencing (Seq) and amplification refractory mutation system (ARMS) methods, and between 40 matched cytologic samples with formaldehyde-fixed paraffin embedded (FFPE) cytologic blocks and cytospin slides.

RESULTSTumor cells were found in 236 out of 287 cases (82.2%, 236/287) . Among them, there were 31 cases (13.1%, 31/236) of low tumor cell content samples and 205 cases (86.9%, 205/236) of high tumor cell content samples. 180 cases in the high tumor cell content samples (87.8%, 180/205) were diagnosed to be consistent with NSCLC. 25 out of 194 cases were ruled out or indefinite to be diagnosed as NSCLC by immunohistochemistry. By direct sequencing, the mutation rate of EGFR was 27.8% (50/180) in NSCLC samples and 28.2% (50/177) in adenocarcinoma samples (high tumor content samples) . By ARMS, the mutation rate of EGFR was 45.6% (82/180) in NSCLC samples and 46.3% (82/177) in adenocarcinoma samples (high tumor content samples). The EGFR mutation rate in low tumor content samples was 38.7% (12/31) , there was no significant difference in EGFR mutation rates between the groups of low tumor cell content samples and high tumor cell content samples (P = 0.12). The concordance rate of EGFR mutation rates was 100% between scraping tumor cells from slides samples and from FFEP blocks in the 40 matched samples. Forty-eight out of 180 definitive NSCLC patients received Gefitinib therapy. The FPS was 12 months in the gefitinib-treated ARMS⁺ group and 2 months in the ARMS⁻ group (P < 0.001), and the OS was 19 months in the gefitinib-treated ARMS⁺ group and 7 months in the ARMS⁻ group (P = 0.003), but no significant differences were found in the efficacy (PFS and OS) of Gefitinib between Seq⁺ and Seq⁻ groups (P = 0.227, P = 0.510, respectively), and Seq⁺/ARMS⁺ and Seq⁻/ARMS⁺ groups (P = 0.354, P = 0.334, respectively).

CONCLUSIONSThe detection protocol for EGFR mutations in cytological specimens introduced in this study is tested to be reliable and feasible. Pathological evaluation and immunohistochemistry are important in the detection procedure of EGFR mutations in cytologic specimens. High sensitivity methods should be selected for detection of EGFR mutations in cytologic samples.

Adenocarcinoma ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; Humans ; Lung Neoplasms ; diagnosis ; epidemiology ; metabolism ; Mutation ; Mutation Rate ; Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; genetics ; metabolism

OBJECTIVESTo investigate the effects of astilbin on the expressions of TNF alpha and IL-10 during liver warm ischemia-reperfusion injury.

METHODSC57BL/ 6 mice were randomly divided into 4 groups (n = 8): sham-operated group (Sham), model control group(I/R), low dosage of astilbin treatment group (10 mg/kg) and high dosage of astilbin (40 mg/kg) treatment group. The treatment group mice were intraperitoneally injected with 10 or 40 mg/kg astilbin 24 hours and one hour before Ischemia, the hepatic ischemia-reperfusion model were thus established. After jn90 of min ischemia and 6 h reperfusion of the partial hepatic lobe, the expressions of TNF alpha and IL-10 in liver tissues collected from the experimental groups were detected by Western blot and semiquantitative RT-PCR.

RESULTSThe expression of TNF alpha protein in liver tissues gradually decreased in treatment groups (low and high dosages of astilbin treatment groups) as compared to the I/R model control group. Similar results were observed in the mRNA expressions of these genes as determined by semiquantitative RT-PCR (P less than 0.05 for low dosage group; P less than 0.01 for high dosage group). Compared with the I/R model control group, the expression of IL-10 was increased in both treatment groups (low dosage group P less than 0.05; large dosage group P less than 0.01).

CONCLUSIONTreatment with astilbin decreases TNF alpha expression but induces IL-10 expression in liver during warm ischemia-reperfusion injury.

Animals ; Flavonols ; pharmacology ; Interleukin-10 ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury ; etiology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism ; Warm Ischemia

Aim To investigate the alteration of volt-age-depending potassium channel(KV) current in pul-monary arterial smooth muscle cells(PASMCs) of pul-monary hypertension (PH) rats, and the effect of tet-raethylammonium (TEA,a blocker of KV) on potassi-um channel current in different PH models. Methods The whole-cell patch clamp techniques were applied to record the KVcurrents from PASMCs cultured with Ham's F-12 (1% FBS). Furthermore, the effects of TEA on the KVcurrents were examined in different PH models. Results The whole-cell KVcurrents were ob-viously inhibited in PASMCs of chronic hypoxia (CH)and monocrotaline (MCT)-treated rats. TEA signifi-cantly decreased the whole-cell KVcurrents in PASMCs of control and PH rats,and the inhibitory effect of TEA was dramatically reduced in PH group. Conclusions The degree of the voltage-dependent potassium chan-nels opening is significantly inhibited in PASMCs of CH and MCT-treated rats,accordingly,the TEA-sen-sitive KVcurrents obviously decrease.

OBJECTIVE: To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency. METHODS: A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure. RESULTS: The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant. CONCLUSION The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.
Humans ; Male ; Female ; Pedigree ; Factor XII/genetics* ; Mutation ; East Asian People ; Heterozygote ; Mothers ; Factor XII Deficiency/genetics*