Expression and functional implications of YME1L in nasopharyngeal carcinoma.

Mitochondria play a crucial role in the progression of nasopharyngeal carcinoma (NPC). YME1L, a member of the AAA ATPase family, is a key regulator of mitochondrial function and has been implicated in various cellular processes and diseases. This study investigates the expression and functional significance of YME1L in NPC. YME1L exhibits significant upregulation in NPC tissues from patients and across various primary human NPC cells, while its expression remains relatively low in adjacent normal tissues and primary nasal epithelial cells. Employing genetic silencing through the shRNA strategy or knockout (KO) via the CRISPR-sgRNA method, we demonstrated that YME1L depletion disrupted mitochondrial function, leading to mitochondrial depolarization, reactive oxygen species (ROS) generation, lipid peroxidation, and ATP reduction within primary NPC cells. Additionally, YME1L silencing or KO substantially impeded cell viability, proliferation, cell cycle progression, and migratory capabilities, concomitant with an augmentation of Caspase-apoptosis activation in primary NPC cells. Conversely, ectopic YME1L expression conferred pro-tumorigenic attributes, enhancing ATP production and bolstering NPC cell proliferation and migration. Moreover, our findings illuminate the pivotal role of YME1L in Akt-mTOR activation within NPC cells, with Akt-S6K phosphorylation exhibiting a significant decline upon YME1L depletion but enhancement upon YME1L overexpression. In YME1L-silenced primary NPC cells, the introduction of a constitutively-active Akt1 mutant (caAkt1, at S473D) restored Akt-S6K phosphorylation, effectively ameliorating the inhibitory effects imposed by YME1L shRNA. In vivo studies revealed that intratumoral administration of YME1L-shRNA-expressing adeno-associated virus (AAV) curtailed subcutaneous NPC xenograft growth in nude mice. Furthermore, YME1L downregulation, concurrent with mitochondrial dysfunction and ATP reduction, oxidative injury, Akt-mTOR inactivation, and apoptosis induction were evident within YME1L-silenced NPC xenograft tissues. Collectively, these findings shed light on the notable pro-tumorigenic role by overexpressed YME1L in NPC, with a plausible mechanism involving the promotion of Akt-mTOR activation.

A clinical predictive model for pre-transplantation Klebsiella pneumoniae colonization and relevance for clinical outcomes in patients receiving allogeneic hematopoietic stem cell transplantation.

The purpose of this study is to establish a clinical prediction model to discriminate patients at high risk of Klebsiella pneumoniae (KP) colonization before allogeneic hematopoietic stem cell transplantation (allo-HSCT) and evaluate the impact of KP colonization on clinical outcomes after allo-HSCT. We retrospectively collected data from 2,157 consecutive patients receiving allo-HSCT between January 2018 and March 2022. KP colonization was defined as a positive test for KP from a pharyngeal or anal swab before allo-HSCT. Logistic regression was used to build a clinical prediction model. Cox regression analyses were performed to explore the effect of KP colonization on clinical outcomes. Among all the inpatients, 166 patients had KP colonization and 581 with no positive pathogenic finding before transplantation. Seven candidate predictors were entered into the final prediction model. The prediction model had an area under the curve of 0.775 (95% CI 0.723-0.828) in the derivation cohort and 0.846 (95% CI: 0.790-0.902) in the validation cohort. Statistically significantly different incidence rates were observed among patient groups with clinically predicted low, medium, and high risk for KP infection (P < 0.001). The presence of KP colonization delayed platelet engraftment (P < 0.001) and patients with KP colonization were more likely to develop KP bloodstream infections within 100 days after allo-HSCT (P < 0.0001). Patients with KP colonization had higher non-relapse mortality (P = 0.032), worse progression-free survival (P = 0.0027), and worse overall survival within 100 days after allo-HSCT (P = 0.013). Our findings suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted.IMPORTANCESeveral studies have identified that Klebsiella pneumoniae (KP) is among the most common and deadly pathogens for patients in hospital intensive care units and those receiving transplantation. However, there are currently no studies that evaluate the impact of KP colonization to patients undergoing allogeneic hematopoietic stem cell transplantation. Our results confirm that pre-existing KP colonization is relatively common in a hematology transplant ward setting and negatively affects post-transplantation prognosis. Our clinical prediction model for KP colonization can support early intervention in patients at high risk to avoid subsequent bloodstream infections and improve survival outcomes. Altogether, our data suggest that increased awareness of risks associated with pre-transplantation bacterial colonization is warranted. Future studies are needed to confirm these findings and to test early intervention strategies for patients at risk of complications from KP infection.

The protein kinase A signaling pathway mediates the effect of electroacupuncture on excessive contraction of the bladder detrusor in a rat model of neurogenic bladder.

BACKGROUND: Neurogenic bladder (NB) is a form of neurological bladder dysfunction characterized by excessive contraction of the bladder detrusor. Protein kinase A (PKA) signaling is involved in the contraction of the detrusor muscle. AIMS: To investigate whether PKA signaling mediates the effect of electroacupuncture (EA) on the excessive contraction of the bladder detrusor in NB. METHODS: Sixty rats were randomly divided into control, sham, NB, NB + EA, and NB + EA + H89 (a PKA receptor antagonist) groups. The modified Hassan Shaker spinal cord transection method was used to generate a NB model. After EA intervention for one week, urodynamic tests were used to evaluate bladder function, hematoxylin and eosin staining was conducted to assess morphological changes, enzyme-linked immunosorbent assay (ELISA) was performed to measure the concentration of PKA, and Western blotting was conducted to measure the protein levels of phosphorylated myosin light chain kinase (p-MLCK)/p-MLC. RESULTS: The results showed that NB resulted in morphological disruption, impairment of urodynamics, and decreases in the concentration of PKA and the protein levels of p-MLCK/p-MLC. EA reversed the changes induced by NB dysfunction. However, the improvement in urodynamics and the increases in the concentration of PKA and the protein levels of p-MLCK/p-MLC were inhibited by H89. CONCLUSION: Our findings indicate that the PKA signaling pathway mediates the beneficial effect of EA on excessive contraction of the bladder detrusor in a rat model of NB.

Overexpressed Gαi1 exerts pro-tumorigenic activity in nasopharyngeal carcinoma.

The current study tested the expression and potential functions of Gαi1 in nasopharyngeal carcinoma (NPC). The Cancer Genome Atlas (TCGA) database results demonstrate that Gαi1 transcripts' number in NPC tissues is significantly higher than that in the normal nasal epithelial tissues. Its overexpression correlates with poor survival in certain NPC patients. Moreover, Gαi1 is significantly upregulated in NPC tissues of local primary patients and in different primary human NPC cells. Whereas its expression is relatively low in cancer-surrounding normal tissues and in primary nasal epithelial cells. Genetic silencing (via shRNA strategy) or knockout (via CRISPR-sgRNA method) of Gαi1 substantially suppressed viability, proliferation, cell cycle progression, and migration in primary NPC cells, causing significant caspase-apoptosis activation. Contrarily, ectopic Gαi1 expression exerted pro-tumorigenic activity and strengthened cell proliferation and migration in primary NPC cells. Gαi1 is important for Akt-mTOR activation in NPC cells. Akt-S6K phosphorylation was downregulated after Gαi1 shRNA or KO in primary NPC cells, but strengthened following Gαi1 overexpression. In Gαi1-silenced primary NPC cells, a S473D constitutively-active mutant Akt1 (caAkt1) restored Akt-S6K phosphorylation and ameliorated Gαi1 shRNA-induced proliferation inhibition, migration reduction and apoptosis. Bioinformatics analyses proposed zinc finger protein 384 (ZNF384) as a potential transcription factor of Gαi1. In primary NPC cells, ZNF384 shRNA or knockout (via CRISPR-sgRNA method) decreased Gαi1 mRNA and protein expression, whereas ZNF384 overexpression upregulated it. Importantly, there was an increased binding between ZNF384 protein and the Gαi1 promoter in human NPC tissues and different NPC cells. In vivo studies showed that intratumoral injection of Gαi1-shRNA-expressing adeno-associated virus (AAV) impeded subcutaneous NPC xenograft growth in nude mice. Gαi1 downregulation, Akt-mTOR inactivation, and apoptosis induction were detected in Gαi1-silenced NPC xenograft tissues. Gαi1 KO also effectively inhibited the growth of NPC xenografts in nude mice. Together, overexpressed Gαi1 exerts pro-tumorigenic activity in NPC possibly by promoting Akt-mTOR activation.

Risk Factors for Carbapenem-Resistant Enterobacteriaceae Colonization and the Effect on Clinical Outcomes and Prognosis in Allogeneic Hematopoietic Stem Cell Transplanted Patients.

Purpose: The current study assesses which are the main risk factors, clinical outcome and prognosis following the colonization of CRE in patients that underwent allo-HSCT. Patients and Methods: A total of 343 patients subjected to allo-HSCT in the period comprised between June 2021 and June 2022 were enrolled in this retrospective study. The CRE colonization was diagnosed by clinical history and routine microbial culture of perirectal swab. In this regard, a clinical prediction model was designed based on independent risk factors underlying the pre-transplantation CRE colonization using a backward stepwise logistic regression, followed by the evaluation of its discrimination and calibration efficacies, along with clinical usefulness. Furthermore, univariate and multivariate Cox regression analyses were then conducted to assess the risk factors for post-transplantation clinical outcomes. Results: Out of 343 patients enrolled in this study, 135 (39.3%) reported CRE colonization. The independent risk factor variables for CRE colonization were incorporated into the nomogram to build a prediction model, which showed an area under the curve of 0.767 (95% CI: 0.716-0.818), and well-fitted calibration curves (χ2 = 1.737, P = 0.9788). The patients with CRE colonization reported a significantly lower platelet engraftment rate with a higher risk of post-transplantation BSI when compared with the non-CRE colonization group (P = 0.02 and P < 0.001; respectively). The non-relapse mortality (NRM) value was higher in the CRE patients (P < 0.05), consistently with a survival probability that was thus significantly lower for the same timeframe (P < 0.05). Conclusion: A reliable clinical prediction model for pre-transplantation CRE colonization was developed that demonstrated that the CRE colonization negatively affects platelet engraftment and survival outcomes following allo-HSCT.

Frequency detection, frequency discrimination, and spectro-temporal pattern perception in older and younger typically hearing adults.

Elderly adults often experience difficulties in speech understanding, possibly due to age-related deficits in frequency perception. It is unclear whether age-related deficits in frequency perception differ between the apical or basal regions of the cochlea. It is also unclear how aging might differently affect frequency discrimination or detection of a change in frequency within a stimulus. In the present study, pure-tone frequency thresholds were measured in 19 older (61-74 years) and 20 younger (22-28 years) typically hearing adults. Participants were asked to discriminate between reference and probe frequencies or to detect changes in frequency within a probe stimulus. Broadband spectro-temporal pattern perception was also measured using the spectro-temporal modulated ripple test (SMRT). Frequency thresholds were significantly poorer in the basal than in the apical region of the cochlea; the deficit in the basal region was 2 times larger for the older than for the younger group. Frequency thresholds were significantly poorer in the older group, especially in the basal region where frequency detection thresholds were 3.9 times poorer for the older than for the younger group. SMRT thresholds were 1.5 times better for the younger than for the older group. Significant age effects were observed for SMRT thresholds and for frequency thresholds only in the basal region. SMRT thresholds were significantly correlated with frequency thresholds only in the older group. The poorer frequency and spectro-temporal pattern perception may contribute to age-related deficits in speech perception, even when audiometric thresholds are nearly normal.

Acoustic analysis of tone production in Mandarin-speaking bimodal cochlear implant users.

The benefit of using a hearing aid with a cochlear implant (bimodal hearing) has been demonstrated for tone perception under certain conditions. The present study evaluated bimodal effects for tone production by comparing performance between a bimodal and a unimodal implant group. Results showed that acoustic differentiation of tones produced by the bimodal group was better than the unimodal implant group, and performance was dependent on the subject's acoustic thresholds but not related to implant experience or age at implantation. The findings support the use of amplified acoustic hearing in conjunction with the implant for better development of pitch production.

Effect of Ipsilateral, Contralateral or Bilateral Repetitive Transcranial Magnetic Stimulation in Patients with Lateralized Tinnitus: A Placebo-Controlled Randomized Study.

The relative benefit of ipsilateral, contralateral, and bilateral repetitive transcranial magnetic stimulation (rTMS) for tinnitus treatment remains unclear, especially for patients with lateralized tinnitus. In this study, we compared outcomes after 10 sessions of 1-Hz rTMS at 110% of resting motor threshold over a two-week period. In total, 104 right-handed patients with lateralized subjective tinnitus were randomly divided into four groups according to rTMS treatment: Left (n = 29), Right (n = 23), Bilateral (n = 30), and Sham stimulation (n = 22). Outcomes included estimates of tinnitus severity, psychological state, and psychoacoustic measures. Patients with left- or right-sided tinnitus were similarly distributed across treatment groups. There were no significant changes in outcome measures for the Right or Sham treatment groups. For the Left and Bilateral groups, tinnitus severity was significantly lower after treatment (p < 0.05). The reduction in tinnitus severity was largest for ipsilateral treatment in the Left group. The overall response rate was 56.1% for the Left group, 46.7% for the Bilateral group, 8.3% for the Right group, and 8.3% for the Sham group. For the Left and Bilateral groups, the response rate was larger for patients with left- than right-sided tinnitus. Changes in tinnitus severity were best predicted by changes in anxiety, depression, and the loudness of the tinnitus. The results suggests that rTMS on the left temporoparietal cortex is more effective for patients with left-sided than with right-sided tinnitus.

The P300 Auditory Event-Related Potential May Predict Segregation of Competing Speech by Bimodal Cochlear Implant Listeners.

Compared to normal-hearing (NH) listeners, cochlear implant (CI) listeners have greater difficulty segregating competing speech. Neurophysiological studies have largely investigated the neural foundations for CI listeners' speech recognition in quiet, mainly using the P300 component of event-related potentials (ERPs). P300 is closely related to cognitive processes involving auditory discrimination, selective attention, and working memory. Different from speech perception in quiet, little is known about the neurophysiological foundations for segregation of competing speech by CI listeners. In this study, ERPs were measured for a 1 vs. 2 kHz contrast in 11 Mandarin-speaking bimodal CI listeners and 11 NH listeners. Speech reception thresholds (SRTs) for a male target talker were measured in steady noise or with a male or female masker. Results showed that P300 amplitudes were significantly larger and latencies were significantly shorter for the NH than for the CI group. Similarly, SRTs were significantly better for the NH than for the CI group. Across all participants, P300 amplitude was significantly correlated with SRTs in steady noise (r = -0.65, p = 0.001) and with the competing male (r = -0.62, p = 0.002) and female maskers (r = -0.60, p = 0.003). Within the CI group, there was a significant correlation between P300 amplitude and SRTs with the male masker (r = -0.78, p = 0.005), which produced the most informational masking. The results suggest that P300 amplitude may be a clinically useful neural correlate of central auditory processing capabilities (e.g., susceptibility to informational masking) in bimodal CI patients.

The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.

It is urgent to identify and validate biomarkers for early diagnosis and efficient treatment of nasopharyngeal carcinoma (NPC). Recent studies have proposed p38 gamma (p38γ) as a cyclin-dependent kinase (CDK)-like kinase that phosphorylates retinoblastoma (Rb) to promote cyclins expression and tumorigenesis. Here the Gene Expression Profiling Interactive Analysis (GEPIA) database and results from the local NPC tissues demonstrate that p38γ is significantly upregulated in NPC tissues, correlating with poor overall survival. Furthermore, p38γ mRNA and protein expression is elevated in established NPC cell lines (CNE-1 HONE-1 and CNE-2) and primary human NPC cells, but low expression detected in human nasal epithelial cells. In established and primary NPC cells, p38γ depletion, using the shRNA strategy or the CRISPR/Cas9 gene-editing method, largely inhibited cell growth, proliferation and migration, and induced significant apoptosis activation. Contrarily, ectopic p38γ overexpression exerted opposite activity and promoted NPC cell proliferation and migration. Retinoblastoma (Rb) phosphorylation and cyclin E1/A expression were decreased in NPC cells with p38γ silencing or knockout, but increased after p38γ overexpression. Moreover, mitochondrial subcellular p38γ localization was detected in NPC cells. Significantly, p38γ depletion disrupted mitochondrial functions, causing mitochondrial depolarization, reactive oxygen species production, oxidative injury and ATP depletion in NPC cells. In vivo, intratumoral injection of adeno-associated virus-packed p38γ shRNA potently inhibited primary human NPC xenograft growth in nude mice. In p38γ shRNA virus-injected NPC xenograft tissues, p38γ expression, Rb phosphorylation, cyclin E1/A expression and ATP levels were dramatically decreased. Taken together, we conclude that p38γ overexpression is required for NPC cell growth, acting as a promising therapeutic target of NPC.

[Effect of electroacupuncture on urodynamics of neurogenic bladder and PACAP/cAMP/PKA signaling pathway in detrusor tissue of rats after suprasacral spinal cord injury].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on urodynamics of neurogenic bladder and pituitary adenylate cyclase activating peptide(PACAP)/cyclic adenosine monophosphate (cAMP)/protein kinase A(PKA) signaling pathway in detrusor tissue of rats after suprasacral spinal cord injury (SCI), so as to explore its possible mechanism in improving detrusor hyperreflexia bladder function after shock stage of suprasacral SCI. METHODS: Female SD rats were randomly divided into control, sham operation, model and EA groups, with 12 rats in each group. T10 spinal cord transection (SCT) was performed by surgery. Rats in the EA group were given EA (10 Hz/50 Hz, 20 min) at "Ciliao" (BL32), "Zhongji" (CV3) and "Sanyinjiao" (SP6) once daily for 7 days. After the intervention, urodynamics testing was detected in each group. HE staining was used to observe the morphological changes of bladder detrusor. The protein and mRNA expression of PACAP38 in detrusor was detected by immunohistochemistry, Western blot and real-time quantitive PCR, respectively. The contents of cAMP and PKA were determined by ELISA. RESULTS: Compared with the control and sham operation groups, the maximum bladder capacity and bladder com-pliance, and the protein and mRNA expression of PACAP38, and the contents of cAMP and PKA of the model group were significantly decreased (P<0.01, P<0.05), while the base pressure and leakage point pressure of bladder were significantly increased (P<0.01). After EA intervention, the above indexes were all reversed in the EA group relevant to those of the model group (P<0.01, P<0.05). CONCLUSION: EA at BL32, CV3 and SP6 can improve the bladder function in rats with bladder detrusor hyperreflexia after SCI, which may be related to its effect in activating the PACAP/cAMP/PKA signaling pathway in detrusor tissue.

Segregation of competing speech in adults and children with normal hearing and in children with cochlear implants.

Children with normal hearing (CNH) have greater difficulty segregating competing speech than do adults with normal hearing (ANH). Children with cochlear implants (CCI) have greater difficulty segregating competing speech than do CNH. In the present study, speech reception thresholds (SRTs) in competing speech were measured in Chinese Mandarin-speaking ANH, CNH, and CCIs. Target sentences were produced by a male Mandarin-speaking talker. Maskers were time-forward or -reversed sentences produced by a native Mandarin-speaking male (different from the target) or female or a non-native English-speaking male. The SRTs were lowest (best) for the ANH group, followed by the CNH and CCI groups. The masking release (MR) was comparable between the ANH and CNH group, but much poorer in the CCI group. The temporal properties differed between the native and non-native maskers and between forward and reversed speech. The temporal properties of the maskers were significantly associated with the SRTs for the CCI and CNH groups but not for the ANH group. Whereas the temporal properties of the maskers were significantly associated with the MR for all three groups, the association was stronger for the CCI and CNH groups than for the ANH group.

Effects of Monaural Asymmetry and Target-Masker Similarity on Binaural Advantage in Children and Adults With Normal Hearing.

Purpose For colocated targets and maskers, binaural listening typically offers a small but significant advantage over monaural listening. This study investigated how monaural asymmetry and target-masker similarity may limit binaural advantage in adults and children. Method Ten Mandarin-speaking Chinese adults (aged 22-27 years) and 12 children (aged 7-14 years) with normal hearing participated in the study. Monaural and binaural speech recognition thresholds (SRTs) were adaptively measured for colocated competing speech. The target-masker sex was the same or different. Performance was measured using headphones for three listening conditions: left ear, right ear, and both ears. Binaural advantage was calculated relative to the poorer or better ear. Results Mean SRTs were significantly lower for adults than children. When the target-masker sex was the same, SRTs were significantly lower with the better ear than with the poorer ear or both ears (p < .05). When the target-masker sex was different, SRTs were significantly lower with the better ear or both ears than with the poorer ear (p < .05). Children and adults similarly benefitted from target-masker sex differences. Substantial monaural asymmetry was observed, but the effects of asymmetry on binaural advantage were similar between adults and children. Monaural asymmetry was significantly correlated with binaural advantage relative to the poorer ear (p = .004), but not to the better ear (p = .056). Conclusions Binaural listening may offer little advantage (or even a disadvantage) over monaural listening with the better ear, especially when competing talkers have similar vocal characteristics. Monaural asymmetry appears to limit binaural advantage in listeners with normal hearing, similar to observations in listeners with hearing impairment. While language development may limit perception of competing speech, it does not appear to limit the effects of monaural asymmetry or target-masker sex on binaural advantage.

Bilaterally Combined Electric and Acoustic Hearing in Mandarin-Speaking Listeners: The Population With Poor Residual Hearing.

The hearing loss criterion for cochlear implant candidacy in mainland China is extremely stringent (bilateral severe to profound hearing loss), resulting in few patients with substantial residual hearing in the nonimplanted ear. The main objective of the current study was to examine the benefit of bimodal hearing in typical Mandarin-speaking implant users who have poorer residual hearing in the nonimplanted ear relative to those used in the English-speaking studies. Seventeen Mandarin-speaking bimodal users with pure-tone averages of ∼80 dB HL participated in the study. Sentence recognition in quiet and in noise as well as tone and word recognition in quiet were measured in monaural and bilateral conditions. There was no significant bimodal effect for word and sentence recognition in quiet. Small bimodal effects were observed for sentence recognition in noise (6%) and tone recognition (4%). The magnitude of both effects was correlated with unaided thresholds at frequencies near voice fundamental frequencies (F0s). A weak correlation between the bimodal effect for word recognition and unaided thresholds at frequencies higher than F0s was identified. These results were consistent with previous findings that showed more robust bimodal benefits for speech recognition tasks that require higher spectral resolution than speech recognition in quiet. The significant but small F0-related bimodal benefit was also consistent with the limited acoustic hearing in the nonimplanted ear of the current subject sample, who are representative of the bimodal users in mainland China. These results advocate for a more relaxed implant candidacy criterion to be used in mainland China.

Changes in Histopathology, Enzyme Activities, and the Expression of Relevant Genes in Zebrafish (Danio rerio) Following Long-Term Exposure to Environmental Levels of Thallium.

Thallium is a rare-earth element, but widely distributed in water environments, posing a potential risk to our health. This study was designed to investigate the chronic effects of thallium based on physiological responses, gene expression, and changes in the activity of relevant enzymes in adult zebra fish exposed to thallium at low doses. The endpoints assessed include mRNA expression of metallothionein (MT)2 and heat shock protein HSP70; enzymatic activities of superoxide dismutase (SOD) and Na+/K+-ATPase; and the histopathology of gill, gonad, and liver tissues. The results showed significant increases in HSP70 mRNA expression following exposure to 100 ng/L thallium and in MT2 expression following exposure to 500 ng/L thallium. Significantly higher activities were observed for SOD in liver and Na+/K+-ATPase activity in gill in zebra fish exposed to thallium (20 and 100 ng/L, respectively) in comparison to control fish. Gill, liver, and gonad tissues displayed different degrees of damage. The overall results imply that thallium may cause toxicity to zebra fish at environmentally relevant aqueous concentrations.

Atypical imaging observations of branchial cleft cysts.

The aim of the present study was to assess the atypical imaging manifestations of branchial cleft cysts (BCCs) confirmed by pathology. Computerized tomography (CT) or magnetic resonance imaging (MRI) of 17 BCC cases were reviewed. The imaging features, including laterality, location, border, attenuation and internal architecture, were evaluated. All 17 cases were second BCCs, including 5 cases of Bailey type I classification cysts and 12 cases of type II classification cysts. The atypical imaging features included signal and morphological abnormalities. The abnormal signal intensities were caused by intracapsular bleeding (n=2) or solidification of cystic fluid (n=2). Intracystic hemorrhaging revealed homogeneous hyperintensity on T1-weighted image (T1WI) and T2-weighted image (T2WI). Solidification of cystic fluid revealed slightly homogeneous hyperintensity compared with muscle on T1WI and homogeneous hypointensity on T2WI without enhancement. The aberrant morphology mainly presented as thickening of the cystic wall (n=13). Thickened walls of BCCs with ill- (n=5) or well- (n=8) defined borders were observed in 13 patients. In 3 patients, significant enhancement was identified following intravenous gadolinium administration (n=4). When with atypical CT or MRI features are presented, the typical location of BCCs can help in the diagnosis, as it is located at the lateral portion of the neck adjacent to the anterior border of the mandibular angle or sternocleidomastoid muscle. The atypical observations, including variable signals, imply that the cystic content has changed. Thickened walls indicate inflammation or cancerous tendency and patients with ill-defined margins, vascular involvement or lymphadenopathy atelectasis indicate malignant conversion.

[Adenovirus-mediated interleukin-24 enhanced the antitumor effect of radiotherapy on nasopharyngeal carcinoma in vitro and in vivo].

OBJECTIVE: To investigate the inhibitory effect of adenovirus-mediated interleukin-24 (AdVIL-24) in conjunction with ionizing radiation on the growth of CNE-2Z human NPC cells in vitro and in vivo and underlying mechanisms. METHODS: The CNE-2Z cells were transfected with AdVIL-24 alone or combined with radiotherapy. The transfection efficacy of AdVIL-24 in CNE-2Z cells was determined by RT-PCR and Western blot. Cell growth was assessed by MTT assay, apoptosis was detected by flow cytometry through double staining of cells with propidium iodide (PI) and the expressions of P21, P27, cyclin E, CDK2, Bax, Bcl-2 and caspase-3 were detected with semi-quantitative RT-PCR and western blot, respectively. Anti-tumor effect of AdVIL-24 was observed using CNE-2Z human nasopharyngeal carcinoma transplanted tumor in athymic nude mouse model. The volume and weight of the xenografted tumors were measured and the expressions of P21, P27, cyclin E, CDK2, Bax, Bcl-2, caspase-3, CD34 and VEGF and the microvessel density in xenografted tumors were determined by immunohistochemistry analysis. RESULTS: AdVIL-24 plus radiotherapy induced cell growth inhibition (P < 0.05, Q3d, 4d = 0.916, 1.050) , cell cycle G1 phase arrest(50.37%, P < 0.05, Q = 1.042) and apoptosis (48.82%, P < 0.05, Q = 1.042) , substantial up regulations of P21, P27, the ratio of Bax/Bcl-2 and cleaved caspase-3 and down regulations of cyclin E and CDK2 (P < 0.05, QP21 = 0.959, QP27 = 0.956, Qcyclin E = 1.078, QCDK2 = 1.046, QBax/Bcl-2 = 0.995) in vitro. In the xenografted tumors, AdVIL-24 plus radiotherapy induced cell growth inhibition (P < 0.05, Qvolume14 = 1.053, Qweight = 1.004) , apoptosis (P < 0.05, Q = 0.974) , substantial upregulation of P21, P27, the ratio of Bax/Bcl-2 and cleaved caspase-3 and downregulation of cyclin E and CDK2 (P < 0.05; QP21 = 0.920, QP27 = 0.937, QcyclinE = 1.060, QCDK2 = 1.019, QBax/Bcl-2 = 0.982, Qcleaved-Caspase-3 = 0.927) , decreased the tumor vessel CD34 expression and microvessel density. AdVIL-24 potentially blocked the radiation-induced enhancement of VEGF. CONCLUSION: AdVIL-24 gene therapy combined with radiotherapy may be a novel and effective treatment strategy for human NPC.