Application of tumoroids derived from advanced colorectal cancer patients to predict individual response to chemotherapy.

Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.

lncRNA GAS5 inhibits malignant progression by regulating macroautophagy and forms a negative feedback regulatory loop with the miR­34a/mTOR/SIRT1 pathway in colorectal cancer.

Long non­coding RNA growth arrest specific 5 (GAS5) exerts inhibitory effects through the modulation of several target microRNAs (miRs) in cancer. However, its potential roles and underlying relationship during colorectal cancer (CRC) progression are unclear. Therefore, we explored the role of the negative feedback loop formed by the GAS5/miR­34a axis and mammalian target of rapamycin/sirtuin 1 (mTOR/SIRT1) pathway on macroautophagy and apoptosis in CRC. Expression of GAS5, miR­34a, SIRT1 and mTOR in CRC patients and cell lines was detected by quantitative reverse transcription polymerase chain reaction. Online bioinformatic analysis was used to predict the downstream miRs of GAS5. Luciferase assay and western blotting were performed to demonstrate miR­34a as a downstream target gene of GAS5 in CRC cells. The effects of the GAS5/miR­34a axis on apoptosis, macroautophagy, and the mTOR/SIRT1 pathway were assessed by flow cytometry, transmission electron microscopy and western blotting, respectively. Our results suggested that GAS5 was downregulated and acted as a molecular sponge of miR­34a during CRC progression. miR­34a participated in regulating GAS5­suppressed CRC cell macroautophagy and induced apoptosis through the mTOR/SIRT1 pathway. GAS5­mediated macroautophagy was maintained in an equilibrium state that might have a protective effect on CRC cell apoptosis. The mTOR signaling pathway suppressed GAS5 expression and formed a negative regulation feedback loop with miR­34a in CRC cells. Our results suggested that the GAS5/miR­34a/SIRT1/mTOR negative regulatory feedback loop mediated CRC cell macroautophagy, and maintained the cells in an autonomous equilibrium state, but not excessive activation state, which functions as a strong antiapoptotic phenotype during human CRC progression.

Catalpol­mediated microRNA­34a suppresses autophagy and malignancy by regulating SIRT1 in colorectal cancer.

Colorectal cancer (CRC) is one of the most common digestive tract tumors worldwide. Catalpol exerts inhibitory effects on the progression of several cancer types by regulating microRNAs (miRs). However, the precise role and carcinostatic mechanism of catalpol on CRC cells are poorly understood which limits the application of catalpol treatment. In the present study, miR­34a and sirtuin 1 (SIRT1) expression levels were detected in CRC tissues and CRC cell lines by RT­qPCR. Computational software analysis, luciferase assays and western blotting were used to demonstrate the downstream target of miR­34a in CRC cells. Effects of catalpol on cell viability, apoptosis, autophagic flux and the miR­34a/SIRT1 axis in the CRC cells were assessed by CCK­8 assay, flow cytometry, electron microscopy and western blotting, respectively. Whether the miR­34a/SIRT1 axis participated in catalpol­mediated autophagy and apoptosis was investigated. The effects of catalpol on the miR­34a/SIRT1 axis and malignant behavior were evaluated in a rat model of azoxymethane (AOM)­induced CRC. It was revealed that miR­34a expression levels were significantly decreased while SIRT1 was overexpressed in most of the CRC tissues and all the CRC cell lines. Clinically, a low level of miR­34a was correlated with poor clinicopathological characteristics in CRC patients. Catalpol reduced cell viability, suppressed autophagy, promoted apoptosis, and regulated the expression of SIRT1 by inducing miR­34a in vitro and in vivo. The autophagy­inhibiting effect of catalpol may be a mechanism to promote apoptosis of CRC cells. miR­34a mimic transfection resulted in autophagy­suppressive activity similar to that of catalpol, while the miR­34a inhibitor attenuated the antiautophagic effects of catalpol. In conclusion, miR­34a is involved in regulating catalpol­mediated autophagy and malignant behavior by directly inhibiting SIRT1 in CRC.

Evaluation and application of donors with primary central nervous system tumors.

BACKGROUND: This study aimed to explore the safety of donors with primary central nervous system tumors for kidney and liver transplantations. METHODOLOGY: Clinical data of 29 donors with primary CNS tumors in January 2007 to December 2017, as well as the follow-up data of 16 liver transplant recipients and 46 kidney transplant recipients, were analyzed. According to the risk factors, the high-risk group was classified as Group 1, the low-risk factors were classified as Group 2, and the unknown risk group was classified as Group 3. The incidence of donor-transmitted CNS tumors was calculated and compared. RESULTS: The duration from the diagnosis of 29 donors to donation was 5.67 ± 6.36 months. None of the liver and kidney transplant recipients who were followed up had tumor metastasis. Although the mean survival time of Group 1 was lower than that of Group 2 and Group 3, the Kaplan-Meier curve showed no significant difference in survival time. CONCLUSION: No obvious difference was observed between high-risk and low-risk and unknown risk CNS tumors in terms of the survival rate of transplants and tumor metastasis rate. High-risk CNS tumor donors can be used with the informed consent of recipients after a full evaluation.

Quantitative Evaluation of Compressed L4-5 and S1 Nerve Roots of Lumbar Disc Herniation Patients by Diffusion Tensor Imaging and Fiber Tractography.

OBJECTIVE: To delineate fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of compressed nerve roots in patients with lumbar disc herniation by diffusion tensor imaging and fiber bundle tracing and investigate the relationship between FA and ADC values and Swiss Spinal Stenosis Questionnaire and visual analog scale scores. METHODS: Twenty patients with lumbar disc herniation and 20 age- and sex-matched healthy volunteers were assessed using the Swiss Spinal Stenosis Questionnaire and visual analog scale. All subjects underwent conventional sagittal T1-weighted and T2-weighted magnetic resonance imaging, axial T2-weighted imaging, and diffusion tensor imaging and fiber tractography. RESULTS: In 20 patients with lumbar disc herniation, there were 31 nerve roots involved (9/31 L4, 15/31 L5, and 7/31 S1). Mean Swiss Spinal Stenosis Questionnaire scores of patients were 53.55% ± 11.91%, and mean visual analog scale scores were 5.96 ± 1.64. FA values of lumbar nerve roots were 0.332 ± 0.014 in healthy volunteers. FA values of compressed lumbar nerve roots were 0.251 ± 0.022, significantly lower than FA values of contralateral noncompressed nerve roots and lumbar nerve roots of healthy volunteers. ADC values of lumbar nerve roots were 1.763 ± 0.075 in healthy volunteers. ADC values of compressed lumbar nerve roots were 2.090 ± 0.078, significantly higher than ADC values of contralateral noncompressed nerve roots and lumbar nerve roots of healthy volunteers. CONCLUSIONS: Fiber tractography is capable of delineating microstructural changes of lumbosacral nerve roots, and radiculopathy in lumbar disc herniation is associated with significant changes in FA and ADC values.

Resting-State fMRI findings in patients with first-Episode idiopathic epilepsy before and after treatment.

OBJECTIVE: To detect resting-state functional MRI (rsfMRI) changes and their relationships with the clinical curative effect of anti-epileptic drugs (AEDs) for complex partial seizures (CPS) in epilepsy patients using the fractional amplitude of low frequency fluctuation (fALFF). METHODS: rfMRI data from 14 CPS patients enrolled between June 2015 and June 2016 in Department of Neurology, Affiliated Hospital of Inner Mongolia Medical University were retrospectively investigated and compared with findings from 14 healthy age-, gender-, handedness-, and education-matched subjects. The patients were treated with first-line antiepileptic drugs for 12 weeks before undergoing a second rfMRI scan. fALFF data were processed using REST and SPM8 software. Whole-brain data were compared between the 2 groups. RESULTS: The abnormal findings in CPS patients significantly decreased or disappeared after AED treatment. CONCLUSION: Measuring fALFF is useful for identifying brain functional changes in patients with first-episode epilepsy before and after treatment. Performing rfMRI is useful for evaluating treatment responses and may provide new insight into the pathophysiological mechanisms of epilepsy.

Application of high-field magnetic resonance imaging in Parkinson's disease.

The present study aimed to observe the structural changes of the extracorticospinal tract in Parkinson's disease (PD) using susceptibility-weighted imaging (SWI) and diffusion tensor imaging (DTI) magnetic resonance (MR) scans. The association of DTI parameters and brain-iron accumulation with PD was examined and imaging signs useful in the diagnosis of PD were explored. The study included 30 patients with PD and 30 age- and gender-matched healthy controls who underwent routine MR, SWI and DTI scans. The corrected phase (CP) values of the substantia nigra (SN), red nucleus (RN), globus pallidus (GP) and putamen (PUT) were measured, and fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained. Significant differences were found in the CP values between the PD and control groups in the SN, RN and PUT, but there were no differences in other regions of interest (ROIs). The FA values of the SN and PUT in the PD group were significantly decreased compared with those of the control group, but there was no significant difference in the FA values of the GP. Furthermore, there was no significant inter-group difference in the ADC values of any ROIs. In conclusion, SWI is a method useful for evaluating brain-iron deposition in PD. Increasing iron storage levels have previously been shown to be associated with PD pathogenesis but not with the degree of PD severity. FA values may be useful for diagnosing PD, and DTI may offer some insight into PD pathomechanisms and clinical diagnosis.

miR-34a mediates oxaliplatin resistance of colorectal cancer cells by inhibiting macroautophagy via transforming growth factor-ß/Smad4 pathway.

AIM: To investigate whether microRNA (miR)-34a mediates oxaliplatin (OXA) resistance of colorectal cancer (CRC) cells by inhibiting macroautophagy via the transforming growth factor (TGF)-ß/Smad4 pathway. METHODS: miR-34a expression levels were detected in CRC tissues and CRC cell lines by quantitative real-time polymerase chain reaction. Computational search, functional luciferase assay and western blotting were used to demonstrate the downstream target of miR-34a in CRC cells. Cell viability was measured with Cell Counting Kit-8. Apoptosis and macroautophagy of CRC cells were analyzed by flow cytometry and transmission electron microscopy, and expression of beclin I and LC3-II was detected by western blotting. RESULTS: Expression of miR-34a was significantly reduced while expression of TGF-ß and Smad4 was increased in CRC patients treated with OXA-based chemotherapy. OXA treatment also resulted in decreased miR-34a levels and increased TGF-ß and Smad4 levels in both parental cells and the OXA-resistant CRC cells. Activation of macroautophagy contributed to OXA resistance in CRC cells. Expression levels of Smad4 and miR-34a in CRC patients had a significant inverse correlation and overexpressing miR-34a inhibited macroautophagy activation by directly targeting Smad4 through the TGF-ß/Smad4 pathway. OXA-induced downregulation of miR-34a and increased drug resistance by activating macroautophagy in CRC cells. CONCLUSION: miR-34a mediates OXA resistance of CRC by inhibiting macroautophagy via the TGF-ß/Smad4 pathway.

Heat shock pretreatment improves stem cell repair following ischemia-reperfusion injury via autophagy.

AIM: To investigate whether heat shock pretreatment (HSP) improves mesenchymal stem cell (MSC) repair via autophagy following hepatic ischemia-reperfusion injury (HIRI). METHODS: Apoptosis of MSCs was induced by 250 mM hydrogen peroxide (H2O2) for 6 h. HSP was carried out using a 42 °C water bath for 1, 2 or 3 h. Apoptosis of MSCs was analyzed by flow cytometry, and Western blot was used to detect Bcl-2, Bax and cytochrome C expression. Autophagy of MSCs was analyzed by flow cytometry and transmission electron microscopy, and the expression of beclin I and LC3-II was detected by Western blot. MSCs were labeled in vivo with the fluorescent dye, CM-Dil, and subsequently transplanted into the portal veins of rats that had undergone HIRI. Liver levels of proliferating cell nuclear antigen (PCNA) were quantified by fluorescent microscopy. Serum aminotransferase activity and the extent of HIRI were also assessed at each time point. RESULTS: HSP for 2 h reduced apoptosis of MSCs induced by H2O2 as seen by a decrease in apoptotic rate, a decrease in Bax and cytochrome C expression and an increase in Bcl-2 expression (P < 0.001). In addition, HSP for 2 h induced autophagy of MSCs exposed to H2O2 as shown by an increase in acidic vesicular organelle-positive cells, beclin 1 and LC3-II expression, and autophagosome formation (P < 0.05). Treatment with 3-methyladenine attenuated HSP-induced autophagy and abolished the protective effects of HSP on the apoptosis of MSCs. Rapamycin failed to have additional effects on either autophagy or apoptosis compared with HSP alone. The phosphorylation of p38MAPK was significantly elevated and the phosphorylation of mTOR was downregulated in heat shock pretreated MSCs. Treatment with the p38MAPK inhibitor, SB203580, reduced HSP-induced autophagy in MSCs. In vivo studies showed that the transplantation of HSP-MSCs resulted in lower serum aminotransferase levels, lower Suzuki scores, improved histopathology and an increase in PCNA-positive cells (P < 0.05). CONCLUSION: HSP effectively induces autophagy following exposure to H2O2 via the p38MAPK/mTOR pathway, which leads to enhanced MSC survival and improved MSC repair following HIRI in rats.

Struma ovarii accompanied by mature cystic teratoma of the other ovary: A case report and literature review.

Struma ovarii, as a monodermal variant of ovarian teratoma, constitutes <3% of ovarian teratomas. It is difficult determine a diagnosis prior to surgery. The current study reports an unusual case of struma ovarii occurring in a 49 year-old female, which was accompanied by mature cystic teratoma involving the other ovary. The final pathological diagnosis was confirmed as struma ovarii based on the typical morphology of the thyroid follicles and the results of immunohistochemical staining. The bilateral tumors were resected and follow-up examinations were planned at four month intervals. At the time of writing, the patient was well and no tumor recurrence had been identified.

Alveolar soft part sarcoma: Clinicopathological analysis and imaging results.

Alveolar soft part sarcoma (ASPS) is a rare, malignant, soft-tissue tumor that accounts for ~1.2% of all soft-tissue sarcomas. Due to its low incidence, clinicians often overlook the diagnosis. However, it is difficult to form an accurate diagnosis prior to surgery due to the lack of experience in imaging diagnosis. The present study reviewed the pathological images, and the computed tomography and magnetic resonance imaging data of 6 ASPS cases in order to investigate the clinicopathological and imaging characteristics of the tumor. The present study indicated that the magnetic resonance imaging (MRI) appearances of ASPS are nonspecific, but malignancy may be determined to a certain degree, which may aid in diagnosis prior to surgery and provides information for treatment guidance.

Misdiagnosis of pancreatic papillary mucinous cystadenocarcinoma: A case report.

The morbidity of papillary cystadenocarcinoma of the pancreas is extremely low and the condition is rarely first found as spinal metastases, thus it is often misdiagnosed prior to surgery. The present study reports a case of papillary cystadenocarcinoma with thoracolumbar metastases in a 56-year-old male. The first symptom to occur was backache, however, computed tomography revealed no positive findings. The pain became exacerbated and the patient underwent lumbar and thoracic vertebrae magnetic resonance imaging, which identified abnormal signals. Imaging and pathological examinations were used for the final diagnosis. Due to multiple bone metastases, the patient the administration of induction chemotherapy was suggested, however, the patient refused. The patient succumbed to the disease in June 2013.

An ictal epilepsy case monitored by resting-state fMRI.

Most resting-state functional MRI studies of epilepsy are conducted in the interictal phase as the ictal phase is not suitable. We report and discuss a 13-year-old female epilepsy patient who had ictal examination. She was diagnosed with simple partial seizure epilepsy and on regular anti-epileptic drugs. There were no significant symptoms after careful treatment. We conclude that analysis of the amplitude of low frequency fluctuations may provide a useful tool in the functional MRI study of epilepsy.

Electronic band structures and optical properties of type-II superlattice photodetectors with interfacial effect.

The electronic band structures and optical properties of type-II superlattice (T2SL) photodetectors in the mid-infrared (IR) range are investigated. We formulate a rigorous band structure model using the 8-band k · p method to include the conduction and valence band mixing. After solving the 8 × 8 Hamiltonian and deriving explicitly the new momentum matrix elements in terms of envelope functions, optical transition rates are obtained through the Fermi's golden rule under various doping and injection conditions. Optical measurements on T2SL photodetectors are compared with our model and show good agreement. Our modeling results of quantum structures connect directly to the device-level design and simulation. The predicted doping effect is readily applicable to the optimization of photodetectors. We further include interfacial (IF) layers to study the significance of their effect. Optical properties of T2SLs are expected to have a large tunable range by controlling the thickness and material composition of the IF layers. Our model provides an efficient tool for the designs of novel photodetectors.

Research progress on resting state fMRI of epilepsy.

As a study method of resting state network (RSN), resting state functional MRI (rfMRI) can be applied to detect low frequency fluctuate (LFF) in various cerebral areas based on resting state blood oxygen level dependence (BOLD) signals; and it is easier and more consistent than task-related fMRI. The development, features and methods of rfMRI as well as the application in epilepsy were reviewed in this article.

Hemangioblastoma originating from the right cerebellopontine angle.

The morbidity of hemangioblastoma in the supratentorial region is very low, and is seldom found in the area of the cerebellopontine angle, so it is easily misdiagnosis before surgery. We report and discuss a case of hemangioblastoma originating at the right cerebellopontine angle in a 42-year-old female patient.