OBJECTIVE: To investigate and analyze dynamic changes of auditory function in premature babies with fetal age of less than 37 weeks who were categorized into different birth weight groups and to detect abnormalities of auditory function in these babies and to describe the early development patterns of auditory function in infancy. METHODS: Total of 252 subjects (504 ears) from neonatal ward, neonatal intensive care unit and auditory clinic in Guangzhou Children Hospital, whose fetal age were less than 37 weeks, were included in our study and received auditory function evaluation from January 2004 to February 2008. To investigate the correlation between birth weight and development and abnormality of auditory function in premature babies, all subjects were divided into four groups according to birth weight:</= 1.50 kg, 1.51 - 2.00 kg, 2.01 - 2.50 kg and > 2.5 kg. Each group was further categorized by subject's age on first auditory function evaluation in 0 - 3 months (include 3 months), 3 - 6 months (include 6 months) and above 6 months, respectively. Subjects who were evaluated more than once in different age frame would be grouped into multiple evaluation subgroups. All subjects underwent one or more objective auditory examinations including auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), tympanometry and acoustic stapedius reflex. RESULTS: A tendency of decreased wave V threshold of ABR was seen as birth weight increased, while the percentage of subjects with ABR wave V threshold </= 40 dB nHL increased as well. A tendency of decreased wave V threshold of ABR was also seen as age increased after birth, likewise the percentage of subjects with ABR wave V threshold </= 40 dB nHL increased with age after birth. For multiple evaluation subgroups, improvement rate ranged from 56.67% to 82.76% depending on subjects' birth weight. In all low birth weight (LBW) premature babies, 4 subjects and 6 ears with no wave or just wave V at maximum stimulation 103 dB nHL in ABR were diagnosed with auditory neuropathy, giving an incidence of 3.75%(by ears). CONCLUSIONS: Auditory function (including middle ear and auditory nerve system) of premature LBW improved gradually within examined age frame, as birth weight and age after birth increased. For LBW preterm who showed abnormality in auditory evaluation, a 6-month follow-up should be scheduled, babies weighted less than 1.50 kg at birth that showed abnormality in the first auditory evaluation should be re-evaluated within 2 months. Babies weighted more than 1.50 kg who showed abnormality in the first auditory evaluation should be re-evaluated within 3 months.

OBJECTIVE: To investigate the correlation between thresholds in the chirp-ABR and behavior audiogram in order to find out if it is possible to be used as an clinical application of the chirp-ABR in estimating hearing sensitivity. METHODS: Twenty-two cases with hearing loss or normal hearing were enrolled in the study. The behavior audiogram and the response thresholds of chirp ABR (including chirp ABR, L-chirp ABR and U-chirp ABR) were obtained from 35 ears. RESULTS: Twenty-two cases were of both genders. The age was between 3.3- 6.5-years-old with the average age of 4.8-years-old. Divided by the degree of hearing loss, in the 35 ears, there were 6 with normal hearing, 2 with slightly hearing loss, 4 with moderate hearing loss, 10 with severe hearing loss and 13 with profound hearing loss. The Pearson correlation coefficients were 0.939, 0.900 and 0.930, respectively, which got from the data between the average of 0.5 - 4 kHz and chirp ABR respond threshold, 0.5 kHz and L-chirp ABR, and the average of 1 - 4 kHz and U-chirp ABR. CONCLUSION: As an objective test, the response threshold of chirp-ABR and the behavior audiogram were a highly correlated with each other, but more application in more subjects is needed.

OBJECTIVE: To investigate the expressions of epidermal growth factor receptor (EGFR) in primary nasopharygeal carcinoma (NPC) and lymph node metastases. METHODS: Archived samples of primary NPC and paired lymph node metastases from 86 patients were examined immuohistochemically for the protein expression of EGFR. RESULTS: EGFR expression positivity was detected in the primary NPC and lymph node metastases at the rate of 73.3% and 60.5%, respectively, and primary and metastatic foci showed significant difference in the expression levels (P=0.001). A discrepancy of EGFR expression between the primary and metastatic foci was found in 25 patients, with a discrepancy rate of 29.1%(25/86). CONCLUSION: The difference in EGFR expression between the primary and lymph node metastastic foci of NPC needs to be evaluated when performing EGFR-targeted therapies especially in advanced NPC cases.

The role of autophagy in oncogenesis remains ambiguous, and mechanisms that induce autophagy and regulate its outcome in human cancers are poorly understood. The maternally imprinted Ras-related tumor suppressor gene aplasia Ras homolog member I (ARHI; also known as DIRAS3) is downregulated in more than 60% of ovarian cancers, and here we show that re-expression of ARHI in multiple human ovarian cancer cell lines induces autophagy by blocking PI3K signaling and inhibiting mammalian target of rapamycin (mTOR), upregulating ATG4, and colocalizing with cleaved microtubule-associated protein light chain 3 (LC3) in autophagosomes. Furthermore, ARHI is required for spontaneous and rapamycin-induced autophagy in normal and malignant cells. Although ARHI re-expression led to autophagic cell death when SKOv3 ovarian cancer cells were grown in culture, it enabled the cells to remain dormant when they were grown in mice as xenografts. When ARHI levels were reduced in dormant cells, xenografts grew rapidly. However, inhibition of ARHI-induced autophagy with chloroquine dramatically reduced regrowth of xenografted tumors upon reduction of ARHI levels, suggesting that autophagy contributed to the survival of dormant cells. Further analysis revealed that autophagic cell death was reduced when cultured human ovarian cancer cells in which ARHI had been re-expressed were treated with growth factors (IGF-1, M-CSF), angiogenic factors (VEGF, IL-8), and matrix proteins found in xenografts. Thus, ARHI can induce autophagic cell death, but can also promote tumor dormancy in the presence of factors that promote survival in the cancer microenvironment.

The role of autophagy in oncogenesis remains ambiguous, and mechanisms that induce autophagy and regulate its outcome in human cancers are poorly understood. The maternally imprinted Ras-related tumor suppressor gene aplasia Ras homolog member I (ARHI; also known as DIRAS3) is downregulated in more than 60% of ovarian cancers, and here we show that re-expression of ARHI in multiple human ovarian cancer cell lines induces autophagy by blocking PI3K signaling and inhibiting mammalian target of rapamycin (mTOR), upregulating ATG4, and colocalizing with cleaved microtubule-associated protein light chain 3 (LC3) in autophagosomes. Furthermore, ARHI is required for spontaneous and rapamycin-induced autophagy in normal and malignant cells. Although ARHI re-expression led to autophagic cell death when SKOv3 ovarian cancer cells were grown in culture, it enabled the cells to remain dormant when they were grown in mice as xenografts. When ARHI levels were reduced in dormant cells, xenografts grew rapidly. However, inhibition of ARHI-induced autophagy with chloroquine dramatically reduced regrowth of xenografted tumors upon reduction of ARHI levels, suggesting that autophagy contributed to the survival of dormant cells. Further analysis revealed that autophagic cell death was reduced when cultured human ovarian cancer cells in which ARHI had been re-expressed were treated with growth factors (IGF-1, M-CSF), angiogenic factors (VEGF, IL-8), and matrix proteins found in xenografts. Thus, ARHI can induce autophagic cell death, but can also promote tumor dormancy in the presence of factors that promote survival in the cancer microenvironment.

OBJECTIVE: To explore the clinic characteristics, audiological characteristics and location of lesions in children with retrocochlear auditory nerve impairment which, including auditory neuropathy characterized by severely abnormal results of ABR and normal results of DPOAE. METHODS: Between 2002 and 2006, eighty-six cases (165 ears) with severely abnormal ABR but normal results of DPOAE were enrolled in the study group. The mean patient age was one year and one-month-old, with a range of 8 days to 7 years. The cases with abnormal conductive function were excluded. The cases with severely abnormal ABR and normal cochlear functions as measured by DPOAE and without abnormal conductive function were selected as the cochlear lesion group. Some same age healthy children without hearing loss were subjected as normal control group. The latency and amplitude of waves I, III and V, the inter peak latency I-III was compared among the three group. RESULTS:(1) Fifty-one cases (59.3%) had a history of hypercholesterolemia during neonatal period, but 40 cases (46.51%) had a severe hypercholesterolemia and 11 cases (12.79%) had mild or moderate hypercholesterolemia. Clinical features common among the population included a history of dyskinesia [n = 40 (46.51%)], hearing and language disorder [n = 10 (11. 63%)]. Thirty-two cases (37.2%) were accompanied by cerebral palsy .(2) Among the 165 ears, absent ABRs to click stimuli presented at 103 dB was in 103 ears, only wave I was developed in 27 ears and only wave Vwas developed in 19 ears,wave I and III in 13 ears and differentiated wave I and V in 3 ears.(3) When compared to control group, the latency of wave I was prolonged and amplitude of wave I was lower in cases with only wave I developed (t =-6.75 and 2.58, P < 0.05). For for cases with only wave I and III differentiated, the latency and amplitude of wave I was the same but the latency of wave III was prolonged and amplitude of wave III was lower while interpeak latency I-III was prolonged. CONCLUSIONS: Auditory neuropathy which was characterized by severely abnormal ABR was the most common type of retrocochlear auditory nerve impairment. It was mainly due to a disorder of VIII nerve. The pathologies that affect higher levels of the auditory pathway, from the brainstem to the auditory cortex, might be the main sites of lesion in cases with only wave I developed. Superior olivary nucleus where wave III was generated and higher levels of the auditory pathway might be the main sites of lesion in cases with wave I and III differentiated. The low-amplitude wave V was not characteristics of auditory neuropathy. Cerebral cortex, brain stem auditory nucleus and VIII nerve might be damaged successively in cases with retrocochlear auditory nerve impairment induced by hypercholesterolemia.

Cancer antigen 125 (CA125) is an antigen that is elevated in the serum of women with ovarian carcinoma, but can also be detected in serum from healthy women. CA125 is expressed in 80% of human ovarian cancers, as well as in normal adult endometrium, lung, and amnion. The gene encoding human CA125 was identified as MUCIN16 (MUC16). A database search identified the orthologous mouse gene, Muc16. Reverse transcription-polymerase chain reaction and RNA in situ hybridization detected Muc16 transcripts in the surface epithelia of the upper respiratory tract, the mesothelia lining body cavities and the internal organs, as well as male and female reproductive organs, and the amnion. Antibodies raised against human MUC16 do not recognize mouse MUC16. Therefore, a rabbit anti-mouse polyclonal antibody against recombinant mouse MUC16 was generated. Immunohistochemistry using this anti-mouse MUC16 antibody revealed expression in the luminal epithelia of the trachea, the epithelia of the secretory glands in the oral cavity, the surface of the olfactory epithelia, as well as mesothelial cells lining body cavities (i.e., pleural, peritoneal, and pelvic cavities), and male and female reproductive organs. In addition, MUC16 protein was detected in other cell types, such as the surface epithelia of the cochlear duct and chief cells of the stomach, suggesting multiple roles for MUC16. In mouse serous epithelial ovarian cancer, MUC16 protein was detected at the apical surface of well-differentiated tumors, but not poorly differentiated tumors. These findings document the presence of MUC16 in murine ovarian cancer and in normal tissues and provide a foundation for future functional studies.

Platelet and leucocyte activity are important in the acute development of thrombosis and in the pathogenesis of ischaemic vascular disease. Dan Shen Di Wan (DS, Cardiotonic Pill or Dantonic(R) Pill) is one of the most commonly used Chinese herbal formulations for treating patients with atherosclerotic disease in China and several Asian countries. We studied the effect of DS on platelet and leucocyte function and compared the effects with conventional antiplatelet agents, cangrelor (ADP P2Y(12) receptor antagonist) and aspirin (acetyl salicylic acid, ASA). Measurements were made by platelet aggregation (%) and activation (CD62P %), platelet-monocyte conjugate formation (P/M, CD42a median fluorescence, mf), platelet-neutrophil conjugate formation (P/N, mf), and leucocyte activation (CD11b median fluorescence on monocytes and neutrophils, mf) in response to 3.3 micromol/L adenosine diphosphate (ADP), 1.0 micromol/L platelet activating factor (PAF), 5.0 micromol/L adrenaline and 0.5 microg/mL collagen. We also evaluated the effect of its main component, water soluble extract of salvia miltiorrhiza (SME) on intracellular calcium mobilization in platelets triggered by 10 micromol/L ADP, 10 micromol/L PAF, 2 microg/mL collagen and 15 micromol/L thrombin receptor activating peptide (TRAP). Overall DS showed inhibition of platelet aggregation, platelet activation, platelet-leucocyte conjugate formation and leucocyte activation in response to all the agonists apart from adrenaline (all p < 0.01). DS showed inhibition of platelet aggregation and leucocyte activation equivalent to cangrelor 100 nmol/L and ASA 100 micromol/L. SME dose-dependently inhibited intracellular calcium mobilization in platelets following stimulation with all the platelet agonists with maximum effective at 0.36 mg/mL (all p < 0.01). When used at 0.18 mg/mL its inhibitory effect was equivalent to cangrelor and ASA. We conclude that DS is a potential inhibitor of both platelet and leucocyte activation.

OBJECTIVE: To analyze the effects of surgical treatment for gastrointestinal stromal tumors (GISTs) and influential factors of survival. METHODS: The clinical data and the tissue slices including immunohistochemical staining of 153 cases of GISTs from January 1990 to March 2006 were rechecked retrospectively. All patients were followed up carefully. More attention was paid to the surgical effects and the influential factors of survival. RESULTS: The overall survival rates at 1-, 2-, 3-, 4- and 5-year were 94.9%, 83.3%, 73.3%, 70.5% and 64.3%, respectively. The median survival time for patients with tumor resected completely was 66.0 months, and the 2- and 5-year survival rate were 89.4% and 70.9% respectively. The median survival time was 23.8 months for the patients with tumor resected partly, and only two of these patients survived over 2 years. Gender, tumor sites, preoperative metastasis, tumor size, pathological type, karyokinesis and recurrence and metastasis were related with survival rates for the patients with tumor resected completely on univariate analysis, but tumor size, pathology type, recurrence and metastasis were related with survival rates on Cox regression multivariate analysis (P < 0.05). CONCLUSIONS: Surgery should still be the main therapy for GISTs. Local complete resection is the principal treatment. The survival cannot be improved by extensive resection and lymph nodes clearance.