Volume computed tomography perfusion as a predictive marker for treatment response to concurrent chemoradiotherapy in cervical cancer: a prospective study.

BACKGROUND: Computed tomography perfusion (CTP) can provide information on blood perfusion as a reliable marker of tumor response to therapy. PURPOSE: To assess the role of volume CTP (vCTP) parameters in predicting treatment response to concurrent chemoradiotherapy (CCRT) for cervical cancer. MATERIAL AND METHODS: Thirty-three patients with cervical cancer underwent vCTP. Three CTP parameters of cervical cancer-including arterial flow (AF), blood volume (BV), and permeability surface (PS)-were measured in two different ways: the region of interest incorporating the "local hot" with the highest enhancement and "cold spot" with the lowest enhancement; and "whole-tumor" measurements. The patients were divided into non-residual and residual tumor groups according to the short-term response to treatment. The clinical and perfusion parameters were compared between the two groups. RESULTS: There was no significant difference in age, body mass index, FIGO stage, pathological grade, or pretreatment tumor size between the two groups (P > 0.05). The non-residual tumor group had higher pretreatment AF in high-perfusion and low-perfusion subregions than the residual tumor group (P <0.05), but the AF in whole-tumor regions was not different between the two groups (P > 0.05). There were no differences in BV and PS between the two groups (P > 0.05). The diagnostic potency of AF in the low-perfusion subregion was higher than that in the high-perfusion subregion. CONCLUSION: vCTP parameters are valuable for the prediction of short-term effects. The AF in the low-perfusion subregion was a more effective index for predicting treatment response to CCRT of cervical cancer.

Influence of menstrual status and pathological type on the apparent diffusion coefficient in cervical cancer: a primary study.

BACKGROUND: Apparent diffusion coefficient (ADC) value is an important quantitative parameter in the research of cervical cancer, affected by some factors. PURPOSE: To investigate the effect of pathological type and menstrual status on the ADC value of cervical cancer. MATERIAL AND METHODS: A total of 352 individuals with pathologically confirmed cervical cancer between January 2015 to December 2017 were retrospectively enrolled in this study, including 317 cases with squamous cell carcinomas (SCC) and 35 cases with adenocarcinomas (AC); 177 patients were non-menopausal and 175 were menopausal. All patients underwent a routine 3.0-T magnetic resonance imaging (MRI) scan and diffusion-weighted imaging (DWI) examination using b-values of 0, 800, and 1000 s/mm2. Three parameters including mean ADC (ADCmean), maximum ADC (ADCmax), and minimum ADC (ADCmin) of cervical cancer lesions were measured and retrospectively analyzed. Independent samples t-test was used to compare the difference of ADC values in different menstrual status and pathological types. RESULTS: In all menopausal and non-menopausal patients, the ADCmean and ADCmin values of SCC were lower than those of AC (P<0.05), the ADCmax of two pathological types showed no statistical difference (P > 0.05). In menopausal patients, the ADCmean, ADCmax, and ADCmin values of SCC were not statistically different compared with those of AC (P > 0.05). The ADCmean, ADCmax, and ADCmin values of different pathological types cervical cancers in non-menopausal patients were all higher than those in menopausal patients (P<0.05). CONCLUSION: The ADC values of the cervical cancers were different in different pathological types and were also affected by menstrual status.

Loss of Cochlear Ribbon Synapse Is a Critical Contributor to Chronic Salicylate Sodium Treatment-Induced Tinnitus without Change Hearing Threshold.

Tinnitus is a common auditory disease worldwide; it is estimated that more than 10% of all individuals experience this hearing disorder during their lifetime. Tinnitus is sometimes accompanied by hearing loss. However, hearing loss is not acquired in some other tinnitus generations. In this study, we injected adult rats with salicylate sodium (SS) (200 mg/kg/day for 10 days) and found no significant hearing threshold changes at 2, 4, 8, 12, 14, 16, 20, or 24 kHz (all p > 0.05). Tinnitus was confirmed in the treated rats via Behaviour Testing of Acoustic Startle Response (ASR) and Gap Prepulse Inhibition Test of Acoustic Startle Reflex (GPIAS). A immunostaining study showed that there is significant loss of anti-CtBP2 puncta (a marker of cochlear inner hair cell (HC) ribbon synapses) in treated animals in apical, middle, and basal turns (all p < 0.05). The ABR wave I amplitudes were significantly reduced at 4, 8, 12, 14, 16, and 20 kHz (all p < 0.05). No significant losses of outer HCs, inner HCs, or HC cilia were observed (all p > 0.05). Thus, our study suggests that loss of cochlear inner HC ribbon synapse after SS exposure is a contributor to the development of tinnitus without changing hearing threshold.

NADPH Oxidase 2-Mediated Insult in the Auditory Cortex of Zucker Diabetic Fatty Rats.

Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.

Morphological and Functional Evaluation of Ribbon Synapses at Specific Frequency Regions of the Mouse Cochlea.

Cochlear inner hair cells (IHCs) transmit acoustic signals to spiral ganglion neurons (SGNs) through ribbon synapses. Several experimental studies have indicated that hair cell synapses may be the initial targets in sensorineural hearing loss (SNHL). Such studies have proposed the concept of cochlear "synaptopathy", which refers to alterations in ribbon synapse number, structure, or function that result in abnormal synaptic transmission between IHCs and SGNs. While cochlear synaptopathy is irreversible, it does not affect the hearing threshold. In noise-induced experimental models, restricted damage to IHC synapses in select frequency regions is employed to identify the environmental factors that specifically cause synaptopathy, as well as the physiological consequences of disturbing this inner ear circuit. Here, we present a protocol for analyzing cochlear synaptic morphology and function at a specific frequency region in adult mice. In this protocol, cochlear localization of specific frequency regions is performed using place-frequency maps in conjunction with cochleogram data, following which the morphological characteristics of ribbon synapses are evaluated via synaptic immunostaining. The functional status of ribbon synapses is then determined based on the amplitudes of auditory brainstem response (ABR) wave I. The present report demonstrates that this approach can be used to deepen our understanding of the pathogenesis and mechanisms of synaptic dysfunction in the cochlea, which may aid in the development of novel therapeutic interventions.