Objective: Patients with diabetes mellitus, diabetic nephropathy (DN) and healthy donor were analyzed to test whether the early DN patients can be detected using both blood oxygenation level dependent (BOLD) and diffusion tensor imaging. Methods: This study was approved by the Ethics Committee of our hospital. MR images were acquired on a 3.0-Tesla MR system (Discovery MR750, General Electric, Milwaukee, WI). 30 diabetic patients were divided into NAU (normal to mildly increased albuminuria, N = 15) and MAU (moderately increased albuminuria, N = 15) group based on the absence or presence of microalbuminuria. 15 controls with sex- and age-matched were enrolled in the study. Prior to MRI scan, all participants were instructed to collect their fresh morning urine samples for quantitative measurement of urinary microalbumin and urinary creatinine. Then, the estimations of serum creatinine, serum uric acid, HbAlc and fasting plasma glucose as well as fundus examinations were performed in all subjects. Then, the values of albumin–creatinine ratio (ACR) and estimated glomerular filtration rate were also calculated. All subjects underwent renal diffusion tensor imaging (DTI) and BOLD acquisition after fasting for 4 h. Regions of interest were placed in renal medulla and cortex for evaluating apparent diffusion coefficient (ADC), fractional anisotropy (FA) and R2* values by two experienced radiologists. The consistency between the two observations was estimated using intragroup correlation coefficients. To test differences in ADC, FA and R2* values across the three groups, the data were analyzed using separate one-way ANOVAs. Post-hoc pair wise comparisons were then performed using t-test. To investigate the clinical relevance of imaging parameters in both regions across the three groups, the correlations of values of the ACR/estimated glomerular filtration rate and of the ADC/FA/R2* were calculated. Results: There was a high level of consistency of those ADC, FA and R2* values across the three groups on both renal cortex and medulla measured by the two doctors. The FA value of medulla in MAU group was lower than that in control (p < 0.01). The R2* value of medulla in the NAU group was higher than that in the control (p < 0.01), and the R2* value of medulla in the MAU group was lower than that in the control (p = 0.009) . Moreover, the current study revealed a decreasing trend in FA values of the renal medulla from the control group to NAU and MAU groups. Finally, a weak negatively correlation between medullary R2* and ACR was found in current study. Conclusion: Medullary R2* value might be a new more sensitive predictor of early DN. Meanwhile, BOLD imaging detected the medullary hypoxia at the simply diabetic stage, while DTI didn’t identify the medullary directional diffusion changes at this stage. Based on our assumption mentioned above, it’s presumable that BOLD imaging may be more sensitive for assessment of the early renal function changes than DTI. These imaging techniques are more accurate and practical than conventional tests. Advances in knowledge: Non-invasive MRI was used to detect renal function changes at early DN stage.

Purpose: Some chemotherapeutics have been shown to induce both the release of damageassociated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain. Methods: A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumorbearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses. Results: Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group. Conclusion: This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.

Mitochondria-targeted cancer therapy holds great promise for anticancer treatments. It is thus of great significance to explore effective strategies for targeted mitochondrial damage in cancer cells. Herein, a degradable carrier-free curcumin-based metal−phenolic network (MPN) theranostic agent, namely, the indocyanine green-loaded curcumin−Gd nanoparticle (ICG@cur-Gd NP), is reported for magnetic resonance (MR)/ fluorescence dual-modal imaging-guided chemo-/photodynamic combination cancer therapy. The ICG@cur-Gd NPs are fabricated by coordination-driven self-assembly of curcumin and Gd 3+ , followed by ICG loading. This theranostic agent intrinsically enables the MR and fluorescence imaging for real-time tumor visualization and precise guidance during anticancer treatments. Tumor-acidity-responsive degradation of ICG@cur-Gd NPs induces tumor-specific release of curcumin, ICG, and Gd 3+ with no long-term systemic toxicity. The results reveal that the curcumin component of ICG@cur-Gd NPs can induce efficient mitochondrial damage. The excellent anticancer efficacy of ICG@cur-Gd NPs with laser exposure is confirmed in vivo, highlighting its potential for clinical use. This study constitutes the first report of a curcumin-based MPN theranostic agent combined with the clinically approved and used MR imaging contrast agent Gd 3+ . This work provides a novel and efficient strategy to construct carrier-free theranostic agents for imaging-guided cancer theranostics.

Objective: The purpose of the present study was to evaluate the dynamics of endolymphatic hydrops (EH) and symptoms in a group of patients who underwent endolymphatic duct blockage (EDB) for treatment of intractable Meniere's Disease (MD), and to explore a metric for verifying the effectiveness of EDB procedure.Methods: A total of 22 patients with intractable MD patients who underwent EDB participated in the present study. EH was visualized using locally enhanced inner ear magnetic resonance imaging (MRI) prior to and following surgery. The vestibular hydrops ratio (VHR) in the second MRI examination was compared with the pre-surgery recordings.Results: Following EDB, 6 patients exhibited complete or partial reversal of EH, complete control of vertigo spells and reported improvement in hearing; 13 patients showed no changes in EH or hearing, but 5 of these patients exhibited complete control of vertigo attacks, and the other 8 patients exhibited improved control of vertigo attacks. The final 3 patients showed an increase in EH, but symptomatic worsening in 2 patients, and symptomatic improvement in 1 patient. There was a significant difference in the average VHR prior to and following EDB. Postoperative VHR was positively correlated with the frequency of vertigo spells in the latest 6 months of follow-up and improvement of postoperative average hearing threshold.Conclusion: The decreased EH accompanying the reduction in vertigo attacks and hearing preservation may provide a metric for verifying the effectiveness of EDB treatment in patients with MD.

The present study was to investigate the dynamics of endolymphatic hydrops (EH) and hearing function, and explore whether the hearing loss is caused by EH alone and whether the hearing function can be modulated by changes in the EH. The extent of EH visualized by gadolinium (Gd)-enhanced inner ear magnetic resonance imaging, hearing thresholds and the summating potential/action potential ratio (-SP/AP ratio) of electrocochleography (ECochG) were recorded prior to and following surgery in 22 patients with intractable Meniere’s disease (MD) who underwent endolymphatic duct blockage (EDB). The difference value of the hearing threshold and -SP/AP ratio was significantly positively correlated with the difference value of the endolymph to vestibule-volume ratio (EVVR) and grading of cochlear hydrops between prior to and following surgery. Among patients with a decreased EVVR, the average hearing threshold and -SP/AP ratio was significantly decreased following surgery, as compared to that prior to surgery. Six out of seven patients with a hearing improvement (≥10-dB decline) and 4/5 patients with a negative conversion of EcochG showed downgrading of their hydrops in the cochlea and/or vestibule. By contrast, among patients with an increased EVVR, the average hearing threshold and -SP/AP ratio tended to increase following EDB, as compared with that prior to surgery. One out of two patients with a hearing deterioration (≥10-dB elevation) showed upgrading of her hydrops in both cochlea and vestibule. The present results showed the downgrading of cochlear and/or vestibular hydrops accompanied by the downregulation of the hearing threshold and -SP/AP ratio of EcochG, as well as the upgrading of cochlear and/or vestibular hydrops that tended to upregulate the hearing threshold and -SP/AP ratio of EcochG; this suggested that hearing loss is likely to be caused by hydrops and that the impaired hearing function be modulated by changes in the hydrops.

Background: The aim of the present study was to investigate the pathological features of vestibular aqueduct (VA) related high jugular bulb (HJB) and explore the possible cause-consequence relation between HJB and endolymphatic hydrops (EH), and the potential specific radiological signs for screening causative HJB in Meniere's disease (MD). Methods: High-resolution computed tomography (HRCT) and three-dimensional reconstruction (3DRC) were used to detect the anatomical variables associated with VA and jugular bulb (JB) in hydropic and non-hydropic ears. The presence or absence of EH in the inner ear was determined by gadopentetate dimeglumine-enhanced magnetic resonance imaging. The presence of different types of HJB, the anatomical variables of the VA and JB and the three types of anatomical relationship between the VA and HJB were compared between the hydropic and non-hydropic ears using the χ 2 or Fisher's exact tests. P < 0.05 was considered to indicate a statistically significant difference. Results: JB was classified as: Type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (PSCC); type 3, between the inferior margin of the PSCC and the inferior margin of the internal auditory canal (IAC); type 4, above the inferior margin of the IAC. There were no significant differences in the presence of types 1, 2 and 3 JB between two groups. The presence of type 4 JB, average height of the JB and prevalence of the non-visualization of the VA in CT scans showed significant differences between two groups. The morphological pattern between the JB and VA revealing by 3DRC was classified as: Type I, the JB was not in contact with the VA; type II, the JB was in contact with the VA, but the latter was intact without obstruction; type III, the VA was obliterated by HJB encroachment. There were no significant differences in the presence of type I and II between two groups. Type III was identified in 5 hydropic ears but no non-hydropic ears, with a significant difference observed between the two groups.

Background: Colorectal cancer (CRC) is the third most common malignancy worldwide, and lymph node metastasis is considered to be a risk factor for local recurrence and a poor prognosis in colorectal cancer.However, there remains a lack of reliable and non-invasive biomarkers to identify the lymph node status of CRC patients preoperatively. The purpose of this study was to explore the ability of dual-energy computed tomography (DECT) to differentiate metastatic from non-metastatic lymph nodes in colorectal cancer.Methods: Seventy-one patients with primary colorectal cancer underwent contrast-enhanced dual-energy computed tomography imaging preoperatively. The colorectal specimen was scanned postoperatively, and lymph nodes were matched to the pathology report. The following dual-energy computed tomography quantitative parameters were analyzed: dual-energy curve slope value (λ HU ), standardized iodine concentration (n△HU), iodine water ratio (nIWR), electron density value (nρ eff ), and effective atom-number (nZ), based on metastatic and non-metastatic lymph node differentiation. Also, sensitivity and specificity analyses were performed using receiver operating characteristic curves.Results: In all patients, one hundred and fifty lymph nodes, including 66 non-metastatic and 84 metastatic lymph nodes, were matched using the radiological-pathological correlation. Metastatic nodes had significantly greater λ HU , n△HU, and nIWR values than non-metastatic nodes in both the arterial and venous phases (P<0.01). The area under curve (AUC), sensitivity, and specificity were 0.80, 80%, and 66% for λ HU ; 0.86, 70%, and 95% for n△HU; and 0.88, 71%, and 95% for nIWR in the arterial phase. There was no significant difference in electron density and effective Z values between metastatic and non-metastatic lymph nodes.Conclusions: DECT quantitative parameters may help differentiate between metastatic and normal lymph nodes in patients with CRC.

Objective: The aim of this study was to evaluate the feasibility and safety of transcanal underwater endoscopic bone resection (TUEBR) of the external auditory canal (EAC) for the management of cholesteatoma involving the antrum and mastoid. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Pediatric and adult patients with primary cholesteatoma extending to the antrum and mastoid who underwent transcanal endoscopic ear surgery (TEES) with TUEBR between March 2016 and June 2017. Intervention: A rigid 2.7 mm diameter, 18 cm length Hopkins-rod telescope with an endoscopic sheath was inserted in the EAC and continuously perfused with saline during the dissection. TUEBR was performed to expose extensive cholesteatoma by using a high speed drill with curved burrs and a protected shaft. Next, removal of visible disease, reconstruction of the resected EAC, ossiculoplasty, and tympanoplasty were accomplished with TEES. Results: There were no intra- or postoperative severe complications such as facial palsy and inner ear injury except one patient suffering from secondary labyrinthitis. There was a negative linear relationship (r = –0.909) between the procedure time and procedure number of TUEBR. There was a weak relationship (r = 0.224) between the procedure time of TUEBR and the degree of the extension of cholesteatoma into the antrum and mastoid. There were two cases with residual cholesteatoma at 12 and 22 months follow-up postoperatively. Conclusion: TUEBR is a safe and efficient technique for the resection of EAC bone and transcanal exposure of extensive cholesteatoma that would otherwise require mastoid dissection.