[The possible mechanisms of simvastatin on apoptosis of lung adenocarcinoma cells].

Objective: To explore the possible mechanisms of simvastatin-induced apoptosis in lung adenocarcinoma cells. Methods: The experiment was divided into control group (vehicle treated A549 cells), different concentrations (10, 20, 40, 80 mg/L) simvastatin group (simvastatin treated with different concentrations of A549 cells), aspartate specific proteinase (caspase) inhibitor (Z-VAD-FMK) group (50 µmol/L Z-VAD-FMK treated A549 cells), 40 mg/L simvastatin combined with Z-VAD-FMK group (40 mg/L simvastatin combined with 50 µmol/L Z-VAD-FMK co-treated A549 cells), interleukin-6 (IL-6) group (IL-6 acts on A549 cells) and different concentrations (10, 20, 40 mg/L) simvastatin combined with IL-6 group (simvastatin combined with IL-6 act on A549 cells). Cell counting kit-8 (CCK8) method was used to detect the effect on survival rate of lung adenocarcinoma A549 cells; Flow cytometry was used to detect the effect of simvastatin on A549 cell cycle; Mitochondrial membrane potential-1 (JC-1) fluorescent probe was wsed to detect the effect of simvastatin on mitochondrial membrane potential (MMP); Flow-type phosphatidl serine protein antibody Annexin V/propidium iodide (Annexin V-FITC/PI) double staining method was used to detect the effect of simvastatin on A549 cell apoptosis; CCK8 method was used to detect the effect of Z-VAD-FMK on the survival rate of A549 cells; TdT-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling (TUNEL) method was used to detect the effect of Z-VAD-FMK on simvastatin-induced apoptosis in A549 cells; Western blot method was used to detect the effect of simvastatin on the expression levels of Janus kinase 2 and activation of signal transducers and activators of transcription 3 (JAK2/STAT3) pathway-related proteins phosphorylated JAK2 (p-JAK2), JAK2, phosphorylated STAT3 (p-STAT3), and STAT3 before and after the activator IL-6 of JAK2/STAT3 pathway acted on A549 cells. Results: The survival rates of A549 cells in the 20-80 mg/L simvastatin-treated groups were significantly lower than that in the control group (all P<0.05), and gradually decreased with the increase of the concentration of the simvastatin and the extension of the action time. The cells in the G(0)/G(1) phase of the simvastatin group were significantly higher than those in the control group, and the cells in the G(2)/M phase were significantly lower than those in the control group (all P<0.01). The MMP of the treatment group with different concentrations of simvastatin was significantly lower than that of the control group (all P<0.05). The apoptosis rate of the 20 mg/L and 40 mg/L simvastatin-treated group was significantly higher than that of the control group (both P<0.01). The cell survival rate of the 40 mg/L simvastatin group and the 40 mg/L simvastatin combined with Z-VAD-FMK group were (52.2±2.7)% and (57.5±3.8)%, respectively, were lower than that of the control group (100.0±2.7)% (both P<0.01). But the difference between 40 mg/L simvastatin group and the simvastatin combined with Z-VAD-FMK group was not statistically significant (P>0.05). The cell numbers with positive fluorescent staining in the 40 mg/L simvastatin group were significantly more than those in the control group, but the cell numbers with positive fluorescent staining in the 40 mg/L simvastatin combined with Z-VAD-FMK group had no statistical significance compared with the simvastatin group (P>0.05). The specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in the simvastatin-treated group (20, 40 mg/L) were significantly lower than that in the control group, respectively (both P<0.05). The specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in IL-6 group were significantly higher than those in control group (both P<0.05), the specific value of p-JAK2/JAK2 and p-STAT3/STAT3 protein relative expressions in simvastatin (20, 40 mg/L) combined with IL-6 groups were lower than those in IL-6 group (all P<0.05), respectively. Conclusion: Simvastatin can induce the apoptosis of A549 cells through a non-caspase-dependent mitochondrial apoptosis pathway, which may be achieved by inhibiting the JAK2/STAT3 pathway.

[Identification of a novel mutation of SLC26A4 gene with enlarged vestibular aqueduct syndrome].

Objective:To explore the mutation spectrum of SLC26A4 in Chinese patients with enlarged vestibular aqueduct syndrome.Method:Genomic DNA samples were extracted from peripheral blood of the cochlear implant recipients associated with enlarged vestibular aqueduct syndrome. The SLC26A4 mutations were analyzed by direct sequencing.Result:A novel missense mutation(347G>A) of SLC26A4 gene was found in a male patient,which led to a substitution of codon 116 from glycine to asparagic acid. This mutation was not observed among 60 normal controls.Conclusion:The 347G>A of SLC26A4 gene was a novel pathologic mutation,contributing to the mutation spectrum of SLC26A4 of enlarged vestibular aqueduct syndrome.

[Anaplastic carcinoma of the thyroid: an analysis of 33 cases].

Thirty-three patients with anaplastic carcinoma of the thyroid were treated during the past 30 years with 27 cases of simple anaplastic carcinoma and the other 6 found also with some differentiated carcinoma component. survival rate of 3.5 and 10 years were 35.5%, 36.7% and 29.6%, respectively. The survival rate of patients younger than 45 years were higher than older, and of those with tumor size less than 4cm in diameter were better than that with larger size. Patients received radical surgery plus adjuvant therapy had better survival rate, and patients with differentiated carcinoma component had better survival rate. This study suggested that surgical treatment plus adjuvant therapy is the treatment of choice in anaplastic carcinoma of the thyroid, and the extent of the operation must be dependent on the size of primary tumor.

A novel enzymatic decarboxylation of oxalic acid by the lignin peroxidase system of white-rot fungus Phanerochaete chrysosporium.

Oxidation of veratryl alcohol by lignin peroxidase (LiP) was potently inhibited by oxalic acid. The inhibition analysis with Lineweaver-Burk plots clearly showed that the type of inhibition is non-competitive. The enzymatic oxidation of veratryl alcohol in the presence of 14C-oxalic acid yielded radioactive carbon dioxide. The results indicate that the apparent inhibition of LiP is caused by reduction of the veratryl alcohol cation radical intermediate back to the substrate level by oxalate, which is concomitantly oxidized to carbon dioxide.

[Salvage surgery for cervical residual and recurrent lesions of nasopharyngeal carcinoma after radiotherapy].

Recently, in spite of the great progress made in the radiotherapy for NPC, there remains 10 approximately 20% of patients who would die of their cervical lesions, either residual or recurrent after irradiation. It is well known that the skin of the neck can not tolerate too high a dose of radiation and the cervical metastatic lymph nodes of NPC may be less sensitive to radiation than the primary. From April 1977 to March 1987, 79 NPC patients with persistent cervical lymph node metastasis after irradiation were treated by salvage surgery (31 residual and 48 recurrent cancers). Most of the lesions were located in the upper neck (64 cases) and a few along the margin of previous radiation field, such as submaxillary or posterior cervical triangle. Of the 69 patients treated by salvage neck dissection, 38 were confirmed pathologically to have soft tissues involvement, such as sternocleidomastoid, digastric, splenius, and levator scapular muscles, and 2 had hypoglossus nerve and carotid sheath involvement. The authors emphasized that all the involved tissues, such as skin, muscle, nerve or jugular vein should be resected completely. If the neck defect could not be closed primarily, the pectoral major myocutaneous flap (7 cases) or lateral trapezius myocutaneous flap (3 cases) were used for repair. There were no postoperative complications. 32 patients were followed over 3 years with a 3-year survival rate of 34% (11/32). 43 were followed less than 3 years. 31 were alive and 12 were dead.(ABSTRACT TRUNCATED AT 250 WORDS)

The infrahyoid myocutaneous flap for reconstruction after resection of head and neck cancer.

From May 1979 to August 1984, 112 infrahyoid myocutaneous flaps (IHMCFs) were used for reconstruction of the tongue after resection of lingual carcinoma (67 flaps in 63 consecutive cases) and for repair of defects after resection of carcinomas of buccal mucosa (23 cases), floor of mouth (8 cases), parotid gland (7 cases), and other malignancies (7 cases). Ten IHMCFs were extended to Ludwig's angle for repairing the open defect of the cheek or combined defect in the buccal mucosa and hard palate. The donor sites of 76 IHMCFs could be sutured primarily. The flap was successful in 90% of the cases (101 of 112 cases). Postoperatively, 94% of the cases (60 of 64 cases) of reconstructed tongue had good deglutition and 78% of the cases (50 of 64 cases) gave satisfactory enunciation. IHMCF is a new, versatile, reliable, and convenient flap suitable for repairing the defects in and around the oral cavity, particularly in the tongue, even in aged and weak patients.