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Background Generalized anxiety disorder (GAD) is common among perimenopausal women. Acupuncture may be an effective treatment for GAD, but evidence is limited. The pathogenesis of GAD is not yet clear, but it is related to the hypothalamic-pituitary-adrenal axis and its excretion, cortisol (CORT), and adrenocorticotropic hormone (ACTH). The object of this study is to evaluate the efficacy of manual acupuncture (MA) versus placebo acupuncture (PA) for perimenopausal women with GAD. Methods This study is a single-center, randomized, single-blind clinical trial that will be conducted in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. A total of 112 eligible GAD patients will be randomly assigned (1:1) to receive MA (n=56) or PA (n=56) three times per week for 4 weeks. The primary outcome measure will be the HAMA score. The secondary outcome measures will be the GAD-7 and PSQI scores and the levels of CORT and ACTH. The evaluation will be executed at baseline, 2 weeks, the end of the treatment, and a follow-up 3-month period. All main analyses will be carried out based on the intention-to-treat (ITT) principle. Discussion This study intends to compare the efficacy between MA and PA in the treatment of perimenopausal women with GAD and to further study the mechanisms underlying the effect. Trial registration Chinese Clinical Trial Registry ChiCTR2100046604. Registered on 22 May 2021.

The efficiency of drug delivery and bioavailability to tumor cells are crucial for effective cancer chemotherapy. Herein, a doxorubicin (DOX) encapsulated lysolipid-based thermosensitive liposome decorated with cRGD peptide (RTSL) is conjugated on the surface of an IR780-loaded microbubble (IMB) to synthesize RTSL-IMBs. Sequentially taking advantage of acoustic-assisted early extravasation and thermo-triggered interstitium ultrafast drug release, RTSL-IMBs combine with ultrasound (US) and laser irradiation can advance drug delivery and bioavailability. In vitro experiments demonstrate that RTSL-IMBs associated with a two-step protocol (subsequently US irradiation for 1 min and laser irradiation for 5 min) can dramatically enhance the cellular uptake and bioavailability of DOX. In vivo fluorescence imaging studies reveal that the combination of RTSL-IMBs and US shows a 2.8-fold intratumoral drug accumulation increase at 0.5 h post-injection, while it will take 48 h to reach the same level of intratumoral drug accumulation for the RTSL-IMB group alone. Interestingly, the following localized application of a laser can further increase drug accumulation and slow tumor clearance. Histological analysis demonstrates that the combinational RTSL-IMBs, US and laser significantly improve the drug penetration distance and delivery efficiency in the tumor core. In this study, the acoustic/thermo-responsive hybrid system shows potential for advancing DOX chemotherapy in breast cancer cell MCF-7 xenograft nude mice.

Photodynamic therapy (PDT) and radiotherapy (RT) are oxygen-dependent treatment strategies for solid tumors in clinics. However, the hypoxic tumor microenvironment induced by uncontrolled cancer cell proliferation significantly reduces the therapeutic efficacy of these strategies. Here, we rationally constructed indocyanine green (ICG)-loaded ultrasmall gold nanoclusters (Au NCs-ICG) as theranostic nanozymes for modulating tumor hypoxia and augmenting cancer PDT and RT, respectively. The constructed Au NC-ICG nanozymes with an ultrasmall particle size (∼1 nm) exhibited favorable renal clearance performance, high substrate affinity (Km≈ 2 mM) and good catalase-like activity (Vmax≈ 4.55 × 10-3 mM s-1). In 4T1 tumor-bearing mouse models, high tumor accumulation of Au NC-ICG nanozymes was clearly visualized by near-infrared fluorescence, photoacoustic and computed tomography imaging, showing the potential for the monitoring and guidance of PDT and RT. In addition, the Au NCs-ICG nanozymes effectively decomposed intratumoral H2O2 into O2 for overcoming hypoxia and subsequently enhancing PDT and RT, respectively. Moreover, the inherent X-ray absorption capacity of Au NCs-ICG greatly deposited radiation energy within the tumor region and further improved cancer RT. The integration of multimodal imaging, tumor hypoxia regulation, and effective therapy into ultrasmall Au NCs-ICG nanozymes shows great potential for cancer theranostic applications.

Radiotherapy (RT) is one of the most widely used cancer treatments in the clinical setting, while hypoxia-associated resistance often occurs. Herein, a PEGylated TaOx-based oxygen-carrying nanoplatform was constructed for triple sensitizing tumor radiotherapy. The high-Z element based hollow mesoporous TaOx nanospheres were prepared following the in situ growth of ultrasmall CuS nanocrystals and then packaged with O2-saturated perfluoropentane (PFP). NIR laser-triggered mild hyperthermia would lead to the increase of intratumoral blood flow, together with the release of O2, the radiotherapeutic efficiency would be enhanced. Alternatively, radiant energy would be deposited inside the tumor by the Ta element, therefore triple sensitization of radiotherapy could be achieved. The in vivo studies showed that the as-prepared nanospheres could achieve almost total inhibition of tumor growth without obvious side effects, which provides new possibilities for multisensitizing tumor radiotherapy.

Resting-state functional MRI (rsfMRI) is a useful technique for investigating the functional organization of human gray-matter in neuroscience and neuropsychiatry. Nevertheless, most studies have demonstrated the functional connectivity and/or task-related functional activity in the gray-matter. White-matter functional networks have been investigated in healthy subjects. Schizophrenia has been hypothesized to be a brain disorder involving insufficient or ineffective communication associated with white-matter abnormalities. However, previous studies have mainly examined the structural architecture of white-matter using MRI or diffusion tensor imaging and failed to uncover any dysfunctional connectivity within the white-matter on rsfMRI. The current study used rsfMRI to evaluate white-matter functional connectivity in a large cohort of ninety-seven schizophrenia patients and 126 healthy controls. Ten large-scale white-matter networks were identified by a cluster analysis of voxel-based white-matter functional connectivity and classified into superficial, middle and deep layers of networks. Evaluation of the spontaneous oscillation of white-matter networks and the functional connectivity between them showed that patients with schizophrenia had decreased amplitudes of low-frequency oscillation and increased functional connectivity in the superficial perception-motor networks. Additionally, we examined the interactions between white-matter and gray-matter networks. The superficial perception-motor white-matter network had decreased functional connectivity with the cortical perception-motor gray-matter networks. In contrast, the middle and deep white-matter networks had increased functional connectivity with the superficial perception-motor white-matter network and the cortical perception-motor gray-matter network. Thus, we presumed that the disrupted association between the gray-matter and white-matter networks in the perception-motor system may be compensated for through the middle-deep white-matter networks, which may be the foundation of the extensively disrupted connections in schizophrenia.

Previous studies suggest that schizophrenia-related visual perceptual abnormalities are primarily attributed to deficits of the dorsal rather than ventral visual pathway. In this study, we comparatively explored changes in dorsal and ventral networks in schizophrenia patients in both static and dynamic functional connectivity (FC). Resting-state MR scans were acquired for forty schizophrenia patients and twenty-four healthy controls matched for age and gender. The dorsal and ventral visual networks were defined based on the resultant coordinates from activation likelihood estimation analyses. Static and dynamic network properties were calculated based on the full-range and segmented blood oxygen level dependent time series, respectively. The results indicated that the ventral and dorsal visual networks exhibited abnormalities in static FC and dynamic FC, respectively, in the schizophrenia group. Static FC assessments in the ventral visual network showed a significantly decreased clustering coefficient and shortened characteristic path length in patients with schizophrenia. Dynamic FC assessments in the dorsal visual network showed significantly higher mean temporal variability (p = 0.026) and higher regional FC variability of the right fusiform gyrus (p 0.001) in patients with schizophrenia, and the latter was correlated with the total and negative scores of the Positive and Negative Syndrome Scale. In summary, this study reveals differential patterns of connectivity abnormalities of the ventral and dorsal visual networks in patients with schizophrenia. These preliminary evidences may help us better interpret the mechanisms underlying visual perceptual impairments in patients with schizophrenia and their relationship with psychosis.

ObjectiveTo provide an accurate assessment of the prevalence of breast fibroadenoma in a large population and to confirm the diagnostic accuracy of ultrasound for fibroadenoma.DesignThis was a cross-sectional survey.SettingThis research was conducted at Nanfang Hospital, Guangzhou, Guangdong, China.ParticipantsA total of 11 898 women aged 18–40 years who underwent breast screening between 1 January 2019 and 31 December 2019 were included in the fibroadenoma prevalence study. From 1 June 2019 to 31 December 2019, 342 breast lesions with pathology reports and preoperative ultrasound images were collected for diagnostic fibroadenoma testing (vs histological diagnostic testing).Primary outcome measuresPearson’s χ2 test was performed to compare the prevalence of different lesions between age groups, and descriptive statistics were used to report the clinical characteristics of fibroadenoma. For ultrasound diagnosis, fibroadenoma was defined as a well-circumscribed lesion with round or oval shape, consisting of a homogeneously hypoechoic or isoechoic solid mass, located parallel to the chest wall with a smooth margin and no posterior shadowing. Diagnostic test results for breast fibroadenoma were stratified by diagnostic type (histological vs ultrasound).ResultsOf the women aged 18–40 years, 27.6% (3285/11 898) had an ultrasound diagnosis offibroadenoma. Of these, the prevalence of fibroadenoma was stable across age groups (p=0.14) and did not differ between the left and right sides of the breast. Almost two-thirds of women presented with a single fibroadenoma, and most fibroadenomas did not exceed 1 cm in size. The sensitivity and specificity for fibroadenoma were 97.0% (95% CI for sensitivity: 93.7% to 98.8%) and 91.4% (95% CI for specificity: 85.4% to 95.5%) for ultrasonography, respectively.ConclusionsThe prevalence of fibroadenoma in South China is as high as 27.6%, and ultrasound could be used as a tool to diagnose fibroadenoma.

Purpose To date, digital subtraction angiography (DSA) has been considered as the gold imaging modality for assessing graft patency after extracranial–intracranial bypass. The utility of a noninvasive and quantitative method of assessing graft flow postoperatively was evaluated by using quantitative ultrasonography. Method All STA-MCA bypass surgery performed over a 5-year period at a single institution were reviewed. Measured by duplex ultrasonography, pre-operative (day1) and post-operative (day1, day7, 3month and 6 month) graft blood flow rates were recorded and analyzed. Results were correlated to Matsushima grade determined by DSA performed within 24 h when ultrasonography was conducted to confirm the graft function. Results 100 patients with 131 operated hemispheres were included in this study. The mean flow rates in the STA graft on pre-operative day1, post-operative day 1 and 7, at 3- and 6-month postoperatively were 24.1, 106.7, 112.6, 97.4 and 79.7 ml/min respectively. The mean post-operative flow in the STA graft graded as A/B/C were significantly different (168.0 ± 34.8 ml/min, 91.0 ± 15.5, 42.1 ± 17.2 ml/min, respectively, p = 0.000). 124.5 ml/min and 65.5 ml/min are good cut-off value for predicting post-operative graft Matsushima grade. The analysis also showed excellent agreement between ultrasonography and DSA for assessing bypass function (κ = 0.78). Conclusions The patency of the STA grafts can be assessed noninvasively by quantitative ultrasonography, which results are comparable to those of conventional DSA. This, therefore, suggest that quantitative ultrasonography may be an alternative method to standard DSA for serial follow up of STA grafts.

Purpose Our purpose was to report a case of adult pancreatoblastoma, and review the literature in order to assist clinicians in the management of the disease. Materials and methods The demographic, clinical, and imaging findings of 41 patients with pathologically proven pancreatoblastoma from 1986 to 2017 identified in PubMed were reviewed. The key words used for searching PubMed were: “pancreatoblastoma”, “pancreatic tumor”, and “adult pancreatoblastoma.” We also reported the details of a case of adult pancreatoblastoma treated at our institution. Results We identified 41 cases of adult pancreatoblastomas, and the mean age at diagnosis was 41.4 ± 17.4 years. Pancreatoblastomas occurred in the pancreatic head in 48.4% of patients, and in 39.0% of cases the tumor was >8 cm in diameter at diagnosis. Patient age and tumor size were similar between males and females (P = 0.59; P = 0.32, respectively). Metastases was present in 17 of the 41 adult patients (41.5%). No significant difference in age, sex, tumor size, and tumor location was found between patients with and without metastases (P = 0.57, 0.58, 0.64, 0.39, respectively). Conclusion Preoperative diagnosis of adult pancreatoblastoma is difficult because of the heterogeneous, variable cellular differentiation and atypical clinical and imaging features. A pancreatoblastoma should be considered when tumors in the pancreas are solid and cystic.

Impairment of face perception in schizophrenia is a core aspect of social cognitive dysfunction. This impairment is particularly marked in threatening face processing. Identifying reliable neural correlates of the impairment of threatening face processing is crucial for targeting more effective treatments. However, neuroimaging studies have not yet obtained robust conclusions. Through comprehensive literature search, twenty-one whole brain datasets were included in this meta-analysis. Using seed-based d-Mapping, in this voxel-based meta-analysis, we aimed to: 1) establish the most consistent brain dysfunctions related to threating face processing in schizophrenia; 2) address task-type heterogeneity in this impairment; 3) explore the effect of potential demographic or clinical moderator variables on this impairment. Main meta-analysis indicated that patients with chronic schizophrenia demonstrated attenuated activations in limbic emotional system along with compensatory over-activation in medial prefrontal cortex (MPFC) during threatening faces processing. Sub-task analyses revealed under-activations in right amygdala and left fusiform gyrus in both implicit and explicit tasks. The remaining clusters were found to be differently involved in different types of tasks. Moreover, meta-regression analyses showed brain abnormalities in schizophrenia were partly modulated by age, gender, medication and severity of symptoms. Our results highlighted breakdowns in limbic-MPFC circuit in schizophrenia, suggesting general inability to coordinate and contextualize salient threat stimuli. These findings provide potential targets for neurotherapeutic and pharmacological interventions for schizophrenia.

Background Schizophrenia (SCH) and depression (DEP) are prevalent psychiatric disorders and share common and distinguished elements in their pathophysiology. A triple network model composed of the default mode network (DMN), salience network (SN) and central executive network (CEN) may represent a major abnormality across several psychiatric disorders including SCH and DEP. However, common and distinct dysfunctional patterns between SCH and DEP across three core networks remain unclear. Method Resting-state functional magnetic resonance imaging (fMRI) was obtained in 20 patients with SCH, 20 patients with DEP and 20 healthy controls (HC). Both functional connectivity (FC) and Granger causal connectivity across DMN, SN and CEN were evaluated to uncover common and distinct dysfunctional patterns between SCH and DEP. Results Two patient groups showed identical abnormal causal connectivity between key nodes of DMN and SN, as well as opposing aberrant FC of DMN-CEN and SN-CEN. Compared with HC, the FC between CEN and DMN was increased in SCH while decreased in DEP. Conversely, DEP showed enhanced FC between CEN and SN, whereas SCH showed decreased FC. Limitations The sample size was relatively small, and all participants were taking medication. Conclusions Our results identified common patterns including dysconnectivity between DMN and SN, which may contribute to shared cognitive and affective impairment in DEP and SCH. Moreover, opposing dysconnectivity patterns of DMN-CEN may be associated with different self-referential processing abnormalities. These opposing dysconnectivity patterns may indicate an unbalanced recruitment between SN and CEN. Therefore, this study provides dysconnectivity patterns to advance the understanding of the triple network model with regard to psychiatric disorders.

Schizophrenia is thought as a self-disorder with dysfunctional brain connectivity. This self-disorder is often attributed to high-order cognitive impairment. Yet due to the frequent report of sensorial and perceptual deficits, it has been hypothesized that self-disorder in schizophrenia is dysfunctional communication between sensory and cognitive processes. To further verify this assumption, the present study comprehensively examined dynamic reconfigurations of resting-state functional connectivity (rsFC) in schizophrenia at voxel level, region level, and network levels (102 patients vs. 124 controls). We found patients who show consistently increased rsFC variability in sensory and perceptual system, including visual network, sensorimotor network, attention network, and thalamus at all the three levels. However, decreased variability in high-order networks, such as default mode network and frontal–parietal network were only consistently observed at region and network levels. Taken together, these findings highlighted the rudimentary role of elevated instability of information communication in sensory and perceptual system and attenuated whole-brain integration of high-order network in schizophrenia, which provided novel neural evidence to support the hypothesis of disrupted perceptual and cognitive function in schizophrenia. The foci of effects also highlighted that targeting perceptual deficits can be regarded as the key to enhance our understanding of pathophysiology in schizophrenia and promote new treatment intervention.

The presence of blood‐brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles (PS‐80‐PTX‐NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P‐glycoprotein expression and ApoE‐dependent PS‐80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour‐bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma.

Objectives—The purpose of this study was to investigate the perfusion heterogeneity of malignant and benign breast tumors and assay their vascular architecture changes and molecular expression, thereby evaluating the relevance between imaging and histologic characteristics of angiogenesis. Methods—Real-time grayscale contrast-enhanced sonography was performed in 310 women with 317 breast tumors. The enhancement patterns and perfusion parameters for malignant and benign tumors were analyzed by contrast-enhanced sonography with microvascular imaging and quantitative time-intensity curve analysis. Structural characteristics were observed by light and electron microscopy. The microvessel density, vascular endothelial growth factor (VEGF) expression, and human kinase insert domain-containing receptor (KDR) expression for all tumors were assessed by immunohistochemical staining of CD31, KDR, and VEGF. Results—Surgical pathologic analysis showed 163 malignant and 154 benign tumors. Significant morphologic differences, including perfusion defects, vessel distortion, vessel dilatation, and heterogeneous enhancement, were observed between the malignant and benign groups (P < .05). The mean perfusion parameters (peak intensity, ascending slope, area under the curve, and wash-out time) were greater in the malignant tumors (P < .05). There were significant differences in the peak intensity, ascending slope, area under the curve, and wash-out time between peripheral and central regions of the malignant tumors (P < .05) but none in the benign tumors. Vessels had various morphologic and distributional characteristics in the peripheral and central regions of the malignant tumors. The microvessel density and VEGF and KDR expression were significantly higher in the malignant group (P < .05), especially in the peripheral regions. Conclusions—Perfusion heterogeneity was closely associated with the tumor micro vascular architecture and molecular expression. Perfusion features, especially regional morphologic and hemodynamic features, can provide valuable information for differentiating malignant from benign breast tumors. Key Words—angiogenesis; breast tumors; microvascular architecture; regional perfusion heterogeneity

Jing Yuan,1,* Ge Wen,2,* Yingjia Li,3 Changxing Liu1 1Department of Medical Information, General Hospital of Jinan Military Command, Jinan, People’s Republic of China; 2Imaging Center, Nanfang Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 3Ultrasound Diagnosis Department, Nanfang Hospital of Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workBackground: Both Alzheimer’s disease (AD) and cerebrovascular atherosclerosis (CA) contributed to dementia in an aged population. Whether they share the same mechanism is unknown.Aim: Our goal was to explore the occurrence rates of CA in AD patients.Method: Here we examined the degree of CA in different groups of AD patients with contrast angiography. Ninety-three AD patients were recruited to the present study. Contrast computed tomography scanning and contrast angiography were performed for CA analyses.Result: We found that the cerebrovascular plaques were common in AD patients, which was partly correlated with the severity of AD (as determined by cognitive decline).Conclusion: We concluded that vascular dementia may partly correlate with AD pathology.Keywords: Alzheimer’s disease, cerebrovascular atherosclerosis, aging, patients

Background Depression and schizophrenia are two of the most serious psychiatric disorders. They share similar symptoms but the pathology-specific commonalities and differences remain unknown. This study was conducted to acquire a full picture of the functional alterations in schizophrenia and depression patients. Methods The resting-state fMRI data from 20 patients with schizophrenia, 20 patients with depression and 20 healthy control subjects were collected. A data-driven approach that included local functional connectivity density (FCD) analysis combined with multivariate pattern analysis (MVPA) was used to compare the three groups. Results Based on the results of the MVPA, the local FCD value in the orbitofrontal cortex (OFC) can differentiate depression patients from schizophrenia patients. The patients with depression had a higher local FCD value in the medial and anterior parts of the OFC than the subjects in the other two groups, which suggested altered abstract and reward reinforces processing in depression patients. Subsequent functional connectivity analysis indicated that the connection in the prefrontal cortex was significantly lower in people with schizophrenia compared to people with depression and healthy controls. Limitation The systematically different medications for schizophrenia and depression may have different effects on functional connectivity. Conclusions These results suggested that the resting-state functional connectivity pattern in the prefrontal cortex may be a transdiagnostic difference between depression and schizophrenia patients.

To study angiogenesis and the expression of nm23-H(1) tumor metastatic suppressor gene in primary breast carcinoma and their relationship with axillary lymph node metastasis.Intratumoral vascularization in 80 cases of breast cancer was observed preoperatively by power doppler imaging (PDI) and analysed with computer-assisted quantative assessment, and the expression of microvessel density (MVD) and nm23 protein was determined by immunohistochemical technique.Blood flow signals and blood vessels postitive area within masses were more in axillary node positive (LN+) group than in axillary node negative (LN-) group (t = 7.07, P0.01), MVD expression were higher in the LN+ group than in the LN- group (t = 6.34, P0.01). Meanwhile the expression of nm23-H(1) protein was lower in the LN+ group than in the LN- group, and significant correlation was found between angiogenesis and the expression of nm23-H(1) protein.Angiogenesis and the expression of nm23-H(1) protein may play an important role in the lymphatic metastasis process of breast cancer. Furthermore, angiogenesis may correlates with the expression of nm23-H(1) protein in that progress.