Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization.

BACKGROUND: The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative medicine. Stem cells can self-organise into microsized organ units, partially modelling tissue function and regeneration. Dental pulp organoids have been used to recapitulate the processes of tooth development and related diseases. However, the lack of vasculature limits the utility of dental pulp organoids. AIM: To improve survival and aid in recovery after stem cell transplantation, we demonstrated the three-dimensional (3D) self-assembly of adult stem cell-human dental pulp stem cells (hDPSCs) and endothelial cells (ECs) into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium (CM). METHODS: During culture, primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and CM. The hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp organoids. The biological characteristics of the organoids were analysed, and the regulatory pathways associated with angiogenesis were studied. RESULTS: The combination of these two agents resulted in prevascularized human dental pulp organoids (Vorganoids) that more closely resembled dental pulp tissue in terms of morphology and function. Single-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with angiogenesis. The biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of Vorganoids. CONCLUSION: In this innovative study, we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration, facilitating the development of clinical treatment strategies.

Intrinsic brain network abnormalities in codeine-containing cough syrup-dependent male individuals revealed in resting-state fMRI.

PURPOSE: To identify codeine-containing cough syrups (CCS)-related modulations of intrinsic connectivity network (ICN) and to investigate whether these changes of ICN can be related to duration of CCS use and to impulsivity behavior in CCS-dependent individuals. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) data in 41 CCS-dependent individuals and 34 healthy controls (HC) were scanned at 1.5T and analyzed using independent component analysis (ICA), in combination with a "dual-regression" technique to identify the group differences of three important resting-state networks, the default mode network (DMN), the executive control network (ECN), and the salience network (SN) between the CCS-dependent individuals and HC. RESULTS: Compared with the HC, CCS-dependent individuals had aberrant intrinsic connectivity within the DMN, ECN, and SN (P < 0.05, AlphaSim corrected). Furthermore, a longer duration of CCS use was associated with greater abnormalities in the intrinsic network functional connectivity (FC, P < 0.05, Bonferroni correction). Intrinsic network FC also correlated with higher impulsivity in CCS-dependent individuals (P < 0.05, AlphaSim corrected). CONCLUSION: Our findings revealed aberrant DMN, ECN, and SN connectivity patterns in CCS-dependent patients, which may provide new insight into how neuronal communication and information integration are disrupted among DMN, ECN, and SN key structures due to long duration of CCS use. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:177-186.

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. METHODS: We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. RESULTS: We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. CONCLUSIONS: These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. KEY POINTS: • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

Potential gray matter unpruned in adolescents and young adults dependent on dextromethorphan-containing cough syrups: evidence from cortical and subcortical study.

Adolescence is a unique period in neurodevelopment. Dextromethorphan (DXM)-containing cough syrups are new addictive drugs used by adolescents and young adults. The effects of chronic DXM abuse on neurodevelopment in adolescents and young adults are still unknown. The aim of this study was to investigate the differences in cortical thickness and subcortical gray matter volumes between DXM-dependent adolescents and young adults and healthy controls, and to explore relationships between alternations in cortical thickness/subcortical volume and DXM duration, initial age of DXM use, as well as impulsive behavior in DXM-dependent adolescents and young adults. Thirty-eight DXM-dependent adolescents and young adults and 18 healthy controls underwent magnetic resonance imaging scanning, and cortical thickness across the continuous cortical surface was compared between the groups. Subcortical volumes were compared on a structure-by-structure basis. DXM-dependent adolescents and young adults exhibited significantly increased cortical thickness in the bilateral precuneus (PreC), left dorsal lateral prefrontal cortex (DLPFC. L), left inferior parietal lobe (IPL. L), right precentral gyrus (PreCG. R), right lateral occipital cortex (LOC. R), right inferior temporal cortex (ITC. R), right lateral orbitofrontal cortex (lOFC. R) and right transverse temporal gyrus (TTG. R) (all p < 0.05, multiple comparison corrected) and increased subcortical volumes of the right thalamus and right pallidum. There was a significant correlation between initial age of DXM use and cortical thickness of the DLPFC. L and PreCG. R. A significant correlation was also found between cortical thickness of the DLPFC. L and impulsive behavior in patients. This was the first study to explore relationships between cortical thickness/subcortical volume and impulsive behavior in adolescents dependent on DXM. These structural changes might explain the neurobiological mechanism of impulsive behavior in adolescent DXM users.

Short-term UROD treatment on cerebral function in codeine-containing cough syrups dependent male individuals.

OBJECTIVE: To investigate alterations of resting brain function in codeine-containing cough syrups (CCS) dependent individuals before and after ultra-rapid opioid detoxification under general anaesthesia (UROD) combined with naltrexone treatment (NMT). METHODS: Fourteen CCS-dependent individuals were scanned using resting-state fMRI. After UROD and 2 weeks of NMT, CCS-dependent individuals were rescanned. Fourteen matched controls were studied at baseline and compared. The amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) were used to characterize resting-state cerebral function. RESULTS: After UROD and 2 weeks of NMT, CCS-dependent individuals had increased ALFF in the bilateral parahippocampal gyrus and right medial orbitofrontal cortex (mOFC), decreased ALFF in the left post-central gyrus (PoCG), left middle occipital cortex (MOC) and left dorsal lateral prefrontal cortex (DLPFC), and reduced FC between right mOFC and right DLPFC, and between left DLPFC and left inferior parietal lobe relative to pretreatment. Decreased ALFFs in the left PoCG and left MOC were associated with decreased withdrawal syndrome severity in CCS-dependent individuals. CONCLUSIONS: We offer the first report describing how regional and integral synchronous neural activity occurs after UROD and short-term NMT, accompanied by decreased withdrawal syndrome severity. These findings contribute to the understanding of complex systems involved in UROD-NMT effects. KEY POINTS: • CCS-dependent individuals had reduced ALFF and increased FC at baseline. • UROD treatment can change the regional and integral brain function of CCS-dependent individuals. • Attenuated ALFFs are correlated with the withdrawal syndrome after treatment.

Regional homogeneity changes in hemodialysis patients with end stage renal disease: in vivo resting-state functional MRI study.

OBJECTIVE: To prospectively investigate and detect early cerebral regional homogeneity (ReHo) changes in neurologically asymptomatic patients with end stage renal disease (ESRD) using in vivo resting-state functional MR imaging (Rs-fMRI). METHODS: We enrolled 20 patients (15 men, 5 women; meanage, 37.1 years; range, 19-49 years) with ESRD and 20 healthy controls (15 men, 5 women; mean age, 38.3 years; range, 28-49 years). The mean duration of hemodialysis for the patient group was 10.7±6.4 monthes. There was no significant sex or age difference between the ESRD and control groups. Rs-fMRI was performed using a gradient-echo echo-planar imaging sequence. ReHo was calculated using software (DPARSF). Voxel-based analysis of the ReHo maps between ESRD and control groups was performed with a two-samples t test. Statistical maps were set at P value less than 0.05 and were corrected for multiple comparisons. The Mini-Mental State Examination (MMSE) was administered to all participants at imaging. RESULTS: ReHo values were increased in the bilateral superior temporal gyrus and left medial frontal gyrus in the ERSD group compared with controls, but a significantly decreased ReHo value was found in the right middle temporal gyrus. There was no significant correlation between ReHo values and the duration of hemodialysis in the ESRD group. Both the patients and control subjects had normal MMSE scores (≥28). CONCLUSIONS: Our finding revealed that abnormal brain activity was distributed mainly in the memory and cognition related cotices in patients with ESRD. The abnormal spontaneous neuronal activity in those areas provide information on the neural mechanisms underlying cognitive impairment in patients with ESRD, and demonstrate that Rs-fMRI with ReHo analysis is a useful non-invasive imaging tool for the detection of early cerebral ReHo changes in hemodialysis patients with ESRD.

Reduced ventral medial prefrontal cortex (vmPFC) volume and impaired vmPFC-default mode network integration in codeine-containing cough syrups users.

OBJECTIVE: To characterize the association between clinical symptoms and anatomical and functional cerebral deficits in codeine-containing cough syrups (CCS) users using voxel-based morphometry and resting state functional connectivity analysis. METHODS: Participants were 30 CCS users and 30 matched controls. Both groups were scanned using a volumetric three-dimensional fast field echo sequence and a gradient-echo echo-planar imaging sequence. Impulsivity traits of both groups were evaluated with the Barratt Impulsiveness Scale 11 (BIS 11). Voxel-based morphometry was used to characterize gray matter (GM) deficits in CCS users. The clinical significance of regional volume reduction was investigated by evaluating its association with impulsivity in CCS users and with alterations in resting state functional connectivity when brain regions with GM volume reduction were used as seed areas. RESULTS: Significantly decreased GM volume was observed in CCS users in bilateral ventral medial prefrontal cortex (vmPFC) which was related to greater impulsivity in CCS users. Significantly decreased integration was found in CCS users between the vmPFC and the default mode network. Also, significantly enhanced functional connectivity was found between the vmPFC and the right insula, and the right dorsal lateral PFC. Negative correlation was observed between BIS total scores, scores for attentional impulsivity and vmPFC-inferior parietal lobe connectivity in CCS users. CONCLUSIONS: The findings revealed volume loss and aberrant functional organization in vmPFC among CCS users. In addition, the decreased vmPFC GM volume and attenuated functional connectivity of the vmPFC-inferior parietal lobe network were associated with clinical higher impulsivity trait in CCS users.

Abnormal regional homogeneity of resting-state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy.

BACKGROUND: Many studies have reported that cognitive deficits exist in cirrhotic patients without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these deficits are still not fully understood. AIM: To investigate regional activity abnormalities in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using resting-state functional MRI (Rs-fMRI), and to examine the relationship between regional activity abnormalities and impaired cognition. METHODS: A newly reported regional homogeneity (ReHo) approach was used to compare the local synchronization of Rs-fMRI signals in 32 patients with HBV-RC without OHE and 32 well-matched healthy controls. Cognition was measured in all patients using psychometric hepatic encephalopathy score (PHES) tests, and the relationship between ReHo variation and PHES was analysed. RESULTS: Relative to healthy controls, the cirrhosis group showed high ReHo in the prefrontal cortex, and widespread low ReHo in visual association areas (left lingual gyrus, middle temporal gyrus and right middle occipital gyrus), motor association areas (bilateral precentral gyrus and paracentral lobule) and the bilateral precuneus. Correlation analysis of the mean ReHo values in different brain areas and PHES in cirrhotic patients revealed a significantly positive correlation in the left lingual gyrus (r = 0.352; P = 0.048), right middle occipital gyrus (r = 0.453; P = 0.009) and bilateral precentral gyrus (left: r = 0.436, P = 0.013; right: r = 0.582, P < 0.001), paracentral lobule (r = 0.485; P = 0.005) and precuneus (r = 0.468; P = 0.007). CONCLUSIONS: Our results provide information on the pathophysiological mechanisms underlying cognitive alterations in cirrhotic patients and demonstrate the feasibility of using Rs-fMRI with ReHo analysis as a noninvasive modality with which to detect the progression of cognitive changes in cirrhotic patients.

The impulsivity behavior is correlated with prefrontal cortex gray matter volume reduction in heroin-dependent individuals.

PURPOSE: Chronic exposure to heroin induced cerebral structural abnormalities may underlie heroin-related behaviors. The aim of this study was to: (1) identify cerebral structural abnormalities in heroin-dependent individuals (HDIs) by an automated and unbiased morphometric technique. (2) Define the correlation between these cerebral structural abnormalities and the impulsivity characteristic in HDIs. METHODS: 24 HDIs and 24 control subjects were completed with (1) high resolution structural magnetic resonance imaging scanning and analysis of gray matter volume using voxel-based morphometry implemented in Statistical Parametric Mapping and (2) a Chinese translation Barratt Impulsiveness Scale-11 questionnaire survey. Differences in regional gray matter volume were tested using an analysis of covariance model, co-varying for global gray matter and age. Statistical maps were set at p<0.05, corrected for multiple comparisons. The abnormal brain regions were correlated with the duration of heroin use and impulsivity scores. RESULTS: After adjusting for effects of age and total gray matter volume, cortical gray matter volume in the bilateral medial prefrontal cortex, bilateral dorsal lateral prefrontal cortex, and right fusiform cortex were significantly reduced in HDIs. Moreover, the gray matter volume in prefrontal cortex that showed group differences was negatively correlated with the duration of heroin use and negatively correlated with the impulsivity characteristic in HDIs. CONCLUSION: These findings reveal the prefrontal cortex was impaired in HDIs, meanwhile, indicate the changes in gray matter volume are relating to the duration of heroin use and the impulsivity characteristic of the HDIs.

[Consciousness and abilities on health emergency and the roles of emergency response among public at the communities].

OBJECTIVE: To evaluate the consciousness of health emergency and the abilities on self- and mutual medical aids among the public at the community level, as well as the community responses on health-related emergencies and other factors. METHODS: Random equidistant sampling method was used to extract 617 households before choosing a family member sampled by Kish Grid method. All the members were investigated face to face on a questionnaire-"Health emergency and related ability regarding self and mutual medical aids of the residents". Data were entered into computer database by using software Epi Data 3.1 and were analyzed by SPSS 21.0. RESULTS: Among the 617 households under survey, 47.84% of the public had general awareness on health-related emergencies. Regarding the following items as:prevention and isolation strategies of infectious disease, on safely procedures of earthquake and fires, on prevention of food poisoning, on prevention and first aid of emerging infectious diseases etc., the rates of awareness were 65.04%, 62.92%, 43.62% and 18.79% respectively. Proportions of households which had the first aid supplies were:first aid medicine box as 56.08%; fire extinguisher as 43.60%; spare water and food as 39.40%; having facilities as ropes, whistles and smoke masks for escape were all less than 15%. Rates of awareness on the following items as: correct use of gas switch as 81.52%, knowing the location of the circuit with gear and the fire hydrant as 74.39% and 35.98% , respectively. The correct disposal rates of the residents on the following items were:electric shock and falls (89.63%), patients of infectious diseases (83.31%), gas poisoning (82.98%), suspected symptoms on infectious diseases(82.66%), explosion and burns (66.78%), scald (62.72%)and sprain (57.05%). Scores on the related abilities were as follows: emergency(7.65, out of 10 points), escape(3.55, out of 5 points), self- and mutual medical aids (10.71, out of 16 points). Proportions of having learned and applied of first aid techniques among residents on the following items were:artificial breathing, chest compressions and cardiopulmonary resuscitation were all less than 10%. Level of knowing the first aid techniques was correlated with age and culture of the residents (P < 0.05). CONCLUSION: Both consciousness on health emergency and the abilities on self- and mutual medical aids were low among the community public, suggesting that both the government and pubic should pay more attention to the role of the abilities on self- and mutual medical aids.

Primary haemangiopericytoma outside muscle cone in fossa orbitalis: a case report and review.

PURPOSE: Orbital haemangiopericytoma (HPC) is a rare tumor with great histological variability and unpredictable clinical and biological behavior. The precise cell type origin is uncertain. METHOD: A case report is provided. RESULTS: A 24-year-old male patient visited an ophthalmologist because of proptosis, strabismus, and movement limitation of the right eye one year ago. These symptoms worsened rapidly. Histopathology, MRI methods and microscopy coil were applied to study the features of HPC. The tumor was removed and the histological examination revealed that it was a primary HPC of the orbit. CONCLUSION: MRI determined the size, location, circumscription, morphological detail, growth pattern, and relationship between masses and surrounding tissues. The genesis location of this HPC was rare, and its internal morphological characters were different from cases reported in the literature. The new type of microscope showed more details of tumor MR image characters objectively.

Regional homogeneity changes in heroin-dependent individuals: resting-state functional MR imaging study.

PURPOSE: To identify heroin-related modulations of neural activity in the resting state in heroin-dependent individuals (HDIs) by using resting-state functional magnetic resonance (MR) imaging and a regional homogeneity method and to investigate whether these changes of neural activity can be related to duration of heroin use and to decision-making deficits in HDIs. MATERIALS AND METHODS: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from each participant. Thirty-one HDIs receiving methadone-maintained treatment and 24 control subjects participated. Resting-state functional MR imaging was performed by using a gradient-echo echo-planar imaging sequence. Regional homogeneity was calculated by using software. Voxel-based analysis of the regional homogeneity maps between control and HDI groups was performed with two-sample t tests by using software. Statistical maps were set at P less than .05 and were corrected for multiple comparisons. The Iowa gambling task (IGT) was used to assess participant decision making during uncertainty. Abnormal clusters revealed by group comparison were extracted and correlated with behavioral performance at the IGT and with duration of heroin use. RESULTS: Regional homogeneity was diminished in the bilateral medial orbitofrontal cortex (OFC), bilateral dorsal medial thalamus, bilateral cuneus, and lingual gyrus in HDIs compared with control subjects. There were negative correlations between mean regional homogeneity in the medial OFC, bilateral cuneus, and lingual gyrus and duration of heroin use. There was a positive correlation between mean regional homogeneity in the medial OFC and performance level at the IGT. CONCLUSION: The present study reveals resting-state abnormalities in HDIs that may lead to further improvement of the understanding of the neural substrates of cognitive impairment in HDIs.

Amplitude low-frequency oscillation abnormalities in the heroin users: a resting state fMRI study.

Functional neuroimaging studies have revealed abnormal functional organization of the heroin users' brain, including reward circuit, cognitive control circuit, memory circuit, motivation and salience evaluation circuits and so on. In the current study, we aimed to explore the functional changes in the regional brain of heroin users using the amplitude of low-frequency oscillations in the Blood Oxygenation Level Dependent (BOLD) signals. With fMRI data acquired during resting state from 24 chronic heroin users (all subjects were being treated with methadone) and 24 non-addicted controls, we investigated addiction related altered in the amplitude low-frequency fluctuate (ALFF) between the two groups. Compared with controls, we found that heroin addicts had decreased ALFF in the bilateral dorsal anterior cingulate cortex (dACC), bilateral medial orbit frontal cortex (mOFC), left dorsal lateral prefrontal cortex (dlPFC), left middle temporal gyrus, left inferior temporal gyrus, posterior cingulate cortex and left cuneus as well as increased ALFF in the bilateral angular gyrus, bilateral precuneus, bilateral supramarginal gyrus, left post cingulate cortex and left middle frontal gyrus. Moreover, we also found that the increased ALFF in the bilateral parietal lobe had a significantly positive correlation with the methadone does, thus we inferred that the reduced ALFF may due to heroin consumption, nevertheless, the increased ALFF in the bilateral parietal lobe may have resulted from the methadone treatment. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of heroin addicts.

[Correlation analysis between multi-slice CT perfusion imaging and microvessel density in ovarian tumors].

OBJECTIVE: To analyze the correlation between the perfusion data and microvessel density (MVD) in ovarian tumors, and investigate the hemodynamic features of the tumors in terms of anatomy and functional CT imaging. METHODS: Six patients with surgically confirmed benign ovarian tumors and 6 with malignant ovarian tumors underwent multi-slice CT perfusion imaging to acquire the perfusion parameters including perfusion, PEI, TTP, BV peak enhancement image(PEI), time to peak(TTP) and blood volume(BV). The tumors were stained and counted by Immunohistochemical staining of the microvessels in the tumor was performed to detect the MVD. RESULTS: s The time-density curves of the benign ovarian tumors increased slowly, reaching the peak at 40 s; the curves of the malignant tumors rose rapidly and continuously and reached the peak at 25 s. The differences in the perfusion data (PEI, TTP, BV) were statistically significant between the benign and malignant tumors (P<0.05). The MVD of the malignant tumors was significantly greater than that of the benign tumors (P<0.05). The mean BV of the malignant ovarian tumor was positively correlated to MVD (r=0.786, P<0.05). CONCLUSION: Multi-slice spiral CT perfusion imaging can provide accurate enhancement data of the ovarian tumors and helps in the diagnosis and differential diagnosis of the ovarian tumors by presenting the changes of the hemodynamic features in the tumors.

[Atypical magnetic resonance imaging vs pathological findings of leiomyoma in the female reproductive system].

OBJECTIVE: To investigate magnetic resonance imaging (MRI) findings of the atypical leiomyoma in the female reproductive system in comparison with the pathological features of the neoplasms. METHODS: A retrospective analysis of the MRI findings and the pathological features was conducted in 24 cases of atypical leiomyoma involving the female reproductive system. RESULTS: Atypical leiomyomas were displayed by MRI as solid tumor mass surrounded by cystic degeneration, pseudotumors, or solid mass with homogeneous signal intensity. Intrauterine lesions were found in 19 cases, involving the subserosal layer (n=11), intramural region (n=4), broad ligament (n=3), cervix (n=2), submucous layer (n=2), vagina (n=1), and the ovary (n=1). Except for two cases with submucous lesions shown as solid mass, all the cases had lesions appearing as solid cystic mass, whose solid part showed hypo or isointense signals on T1WI and moderate hyperintense signals on T2WI, with heterogeneous enhancement after contrast agent injection. Tumor cell and interstitial cell swelling, vascular hyalinosis, hyalinosis, myxoedema, cystic degeneration, and hemorrhage were found in the lesions. CONCLUSION: Leiomyoma can occur at almost any site in the female reproductive system, and atypical leiomyoma usually are shown as solid cystic mixed mass in the pelvic cavity. Evaluation of the relationship between the solid mass and cystic portion and observation for the presence of low signal on T2WI may help in the diagnosis of atypical leiomyoma.