Search

As a developmental disorder, autism spectrum disorder (ASD) has drawn much attention due to its severe impacts on one's language capacity. Broca's area, an important brain region of the language network, is largely involved in language-related functions. Using the Autism Brain Image Data Exchange (ABIDE) dataset, a mega-analysis was performed involving a total of 1454 participants (including 618 individuals with ASD and 836 healthy controls (HCs). To detect the neural pathophysiological mechanism of ASD from the perspective of language, we conducted a functional connectivity (FC) analysis with Broca's area as the seed in multiple frequency bands (conventional: 0.01-0.08 Hz; slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz). We found that compared with HC, ASD patients demonstrated increased FC in the left thalamus, left precuneus, left anterior cingulate and paracingulate gyri, and left medial orbital of the superior frontal gyrus in the conventional frequency band (0.01-0.08 Hz). The results of the slow-5 frequency band (0.01-0.027 Hz) presented increased FC values of the left precuneus, left medial orbital of the superior frontal gyrus, right medial orbital of the superior frontal gyrus and right thalamus. No significant cluster was detected in the slow-4 frequency band (0.027-0.073 Hz). In conclusion, the abnormal functional connectivity in patients with ASD has frequency-specific properties. Furthermore, the slow-5 frequency band (0.01-0.027 Hz) mainly contributed to the findings of the conventional frequency band (0.01-0.08 Hz). The current study might shed new light on the neural pathophysiological mechanism of language impairments in people with ASD.

Autism spectrum disorder (ASD) is associated with altered brain connectivity. Previous studies have focused on the static functional connectivity pattern from amygdala subregions in ASD while ignoring its dynamics. Considering that dynamic functional connectivity (dFC) can provide different perspectives, the present study aims to investigate the dFC pattern of the amygdala subregions in ASD patients.Data of 618 ASD patients and 836 typical controls (TCs) of 30 sites were obtained from the Autism Brain Imaging Data Exchange (ABIDE) database. The sliding window approach was applied to conduct seed-based dFC analysis. The seed regions were bilateral basolateral (BLA) and centromedial-superficial amygdala (CSA). A two-sample t-test was done at each site. Image-based meta-analysis (IBMA) based on the results from all sites was performed. Correlation analysis was conducted between the dFC values and the clinical scores.The ASD patients showed lower dFC between the left BLA and the bilateral inferior temporal (ITG)/left superior frontal gyrus, between the right BLA and right ITG/right thalamus/left superior temporal gyrus, and between the right CSA and middle temporal gyrus. The ASD patients showed higher dFC between the left BLA and temporal lobe/right supramarginal gyrus, between the right BLA and left calcarine gyrus, and between the left CSA and left calcarine gyrus. Correlation analysis revealed that the symptom severity was positively correlated with the dFC between the bilateral BLA and ITG in ASD.Abnormal dFC of the specific amygdala subregions may provide new insights into the pathological mechanisms of ASD.

Purpose. Several functional magnetic resonance imaging (fMRI) studies have investigated the resting-state functional connectivity (rs-FC) changes in the primary motor cortex (M1) in patients with acute basal ganglia ischemic stroke (BGIS). However, the frequency-specific FC changes of M1 in acute BGIS patients are still unclear. Our study was aimed at exploring the altered FC of M1 in three frequency bands and the potential features as biomarkers for the identification by using a support vector machine (SVM). Methods. We included 28 acute BGIS patients and 42 healthy controls (HCs). Seed-based FC of two regions of interest (ROI, bilateral M1s) were calculated in conventional, slow-5, and slow-4 frequency bands. The abnormal voxel-wise FC values were defined as the features for SVM in different frequency bands. Results. In the ipsilesional M1, the acute BGIS patients exhibited decreased FC with the right lingual gyrus in the conventional and slow-4 frequency band. Besides, the acute BGIS patients showed increased FC with the right medial superior frontal gyrus (SFGmed) in the conventional and slow-5 frequency band and decreased FC with the left lingual gyrus in the slow-5 frequency band. In the contralesional M1, the BGIS patients showed lower FC with the right SFGmed in the conventional frequency band. The higher FC values with the right lingual gyrus and left SFGmed were detected in the slow-4 frequency band. In the slow-5 frequency band, the BGIS patients showed decreased FC with the left calcarine sulcus. SVM results showed that the combined features (slow-4+slow-5) had the highest accuracy in classification prediction of acute BGIS patients, with an area under curve (AUC) of 0.86. Conclusion. Acute BGIS patients had frequency-specific alterations in FC; SVM is a promising method for exploring these frequency-dependent FC alterations. The abnormal brain regions might be potential targets for future researchers in the rehabilitation and treatment of stroke patients.

Objective. The purpose of this study was to investigate the characteristics of different frequency bands in the spontaneous brain activity among patients with acute basal ganglia ischemic stroke (BGIS). Methods. In the present study, thirty-four patients with acute BGIS and forty-four healthy controls were examined by resting-state functional magnetic resonance imaging (rs-fMRI) from May 2019 to December 2020. Two amplitude methods including amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) calculated in three frequency bands (conventional frequency band: 0.01-0.08 Hz; slow-5 frequency band: 0.01-0.027 Hz; and slow-4 frequency band: 0.027-0.073 Hz) were conducted to evaluate the spontaneous brain activity in patients with acute BGIS and healthy controls (HCs). Gaussian Random Field Theory (GRF, voxel p < 0.01 and cluster p < 0.05 ) correction was applied. The correlation analyses were performed between clinical scores and altered metrics values. Results. Compared to HCs, patients with acute BGIS showed decreased ALFF in the right supramarginal gyrus (SMG) in the conventional and slow-4 bands, increased fALFF in the right middle frontal gyrus (MFG) in the conventional and slow-4 bands, and increased fALFF in the bilateral caudate in the slow-5 frequency band. The fALFF value of the right caudate in the slow-5 frequency band was negatively correlated with the clinical scores. Conclusion. In conclusion, this study showed the alterations in ALFF and fALFF in three frequency bands between patients with acute BGIS and HCs. The results reflected that the abnormal LFO amplitude might be related with different frequency bands and promoted our understanding of pathophysiological mechanism in acute BGIS.

Vaccinations can prevent COVID-19 and control its spread quickly and efficiently. This study aimed to investigate knowledge and willingness of geriatric care facility staff to receive a COVID-19 vaccine, and to provide a basis for the government to promote the COVID-19 vaccine and guide people to get vaccinated.A cross-sectional study.Data on characteristics of the participants, knowledge about the COVID-19 vaccine, and willingness to get vaccinated for COVID-19 were collected through an online survey from May 19 to June 18, 2021. Statistical analyses were conducted with ANOVA, chi-square, logistic regression.The survey illustrated that the highest score of COVID-19 vaccine knowledge was 50, the lowest 20, and the average 44.22. It also demonstrated that 91.3% of the participants had a good knowledge of COVID-19 vaccine, and that 97.3% participants were willing to receive the COVID-19 vaccine. The results showed that geriatric care facility staff had varied level of the COVID-19 vaccine knowledge depending upon their age, educational background, and other factors, and correspondingly, their willingness to receive COVID-19 vaccine was affected by their knowledge level of COVID-19 vaccine.In general, the participants, the staff of geriatric care facilities in Anhui Province, had good mastery of the COVID-19 vaccine, and they were willing to get vaccinated. However, there still existed a few participants with poor knowledge, who were unwilling to get vaccinated against COVID-19. Government can guide people to accept vaccination by enhancing publicity about the effects and adverse reactions of COVID-19 vaccines.

Stroke is a brain system disease with a high fatality rate and disability rate. About 80% of strokes are ischemic strokes. Cerebral ischemia-reperfusion injury (CIRI) caused by ischemic stroke seriously affects the prognosis of stroke patients. The purpose of this study is to investigate the effect of sufentanil (SUF) on CIRI model rats. We used middle cerebral artery occlusion (MCAO) to make the CIRI model in rats and monitored region cerebral blood flow (rCBF) to ensure that blood flow was blocked and recanalized. We used ELISA and RT-PCR to detect the expression of inflammatory factors in rat serum and brain tissue. In addition, we detected the expression of metalloproteinase (MMP) 2, MMP9 and collagen IV in brain tissues and performed Evans blue (EB) assay to determine the permeability of the blood-brain barrier (BBB). Finally, we clarified the apoptosis of brain tissue through the TUNEL staining and the detection of caspase3, Bcl2 and Bax. Various concentrations of SUF, especially 5, 10 and 25 μg/kg of SUF, all alleviated the infarct size, neurological function and brain edema of MCAO rats. SUF pretreatment also effectively reduced the expression of inflammatory cytokines in MCAO rats, including interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α. In addition, SUF also inhibited MMP2 and MMP9 and promoted the expression of collagen IV, indicating that SUF attenuated the destruction of the BBB. SUF also inhibited caspase3 and Bax rats and promoted Bcl2 in MCAO rats, thus inhibiting cell apoptosis. SUF pretreatment effectively improved the neurological function and cerebral infarction of MCAO rats, inhibited excessive inflammation in rats, protected the BBB, and inhibited cell apoptosis in brain tissue.

The reactive oxygen species (ROS)-responsive intelligent drug delivery system has developed rapidly in recent years. However, because of the low concentration of ROS in most types of tumor cells, it is not possible to rapidly and effectively stimulate the drug delivery system to release the active drug. Here, we introduced "sequential induced activation processes" for efficient tumor therapy by designing a new ROS-responsive drug release platform. β-Lapachone, a positively charged nitrogen mustard (NM) prodrug, and two diblock molecules (mPEG-AcMH and PAsp-AcMH) are self-assembled to form prodrug primary micelles, which are further aggregated into nanoparticles that facilitate drug codelivery. When administered by intravenous injection, the nanoparticles reach the tumor site and enter the tumor cells by endocytosis. The β-lapachone released in the tumor cells induces a large amount of H2O2, and the ROS-responsive NM prodrug is activated to form activated NM, quinone methide, and boric acid under the induction of H2O2. The activated NM leads to tumor cell apoptosis.

The aim of the study is to characterize the clinical ocular phenotype with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) and to confirm whether the kinesin family member 21A (KIF21A) mutation was the pathogenic gene in this Chinese family. Three affected individuals and 2 asymptomatic kinsfolk from a Chinese family underwent comprehensive ophthalmic examinations, orbital computerized tomography (CT), and postoperative histological examinations were performed in the proband. All the recruited members were screened for 3 exons (8, 20, and 21) of KIF21A mutations using the polymerase chain reaction (PCR) amplification and direct sequencing of corresponding PCR products. All patients shared the clinical characteristics including bilateral ophthalmoplegia, blepharoptosis, hypertropic, and exotropic position with inability to raise either eye above the midline and a chin-up head position. Direct DNA sequence analysis from the affected members revealed a missense mutation in KIF21A (c.2860C>T, p.R954W). The unaffected members did not harbor the p.R954W mutation. The candidate mutation was not present in multiple web-accessible and in-house exome databases. The p.Arg954Trp mutation of KIF21A was the causative mutation in this Chinese pedigree with CFEOM1.

Retinitis pigmentosa (RP) is a genetically highly heterogeneous retinal disease and one of the leading causes of blindness in the world. Next-generation sequencing technology has enormous potential for determining the genetic etiology of RP. We sought to identify the underlying genetic defect in a 35-year-old male from an autosomal-dominant RP family with 14 affected individuals. By capturing next-generation sequencing (CNGS) of 144 genes associated with retinal diseases, we identified eight novel DNA variants; however, none of them cosegregated for all the members of the family. Further analysis of the CNGS data led to identification of a recurrent missense mutation (c.403C > T, p.R135W) in the rhodopsin (RHO) gene, which cosegregated with all affected individuals in the family and was not observed in any of the unaffected family members. The p.R135W mutation has a reference single nucleotide polymorphism (SNP) ID (rs104893775) and it appears to be responsible for the disease in this large family. This study highlights the importance of examining NGS data with reference SNP IDs. Thus, our study is important for data analysis of NGS-based clinical genetic diagnoses.

Hyaluronan (HA) and its derivatives have been extensively researched for many biomedical applications. To precisely tailor the property of HA by derivatizing it to a pre-determined extent is challenging, yet critical. In this paper, we used 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) to derivatize HA via a triazine-based coupling reaction. Using a fractional factorial (FF) design, we observed that water content in the solvent, and molar ratios of CDMT and NaHCO3 to the carboxylate were the significant factors controlling the derivatization. We investigated how the effect of each factor changes as reaction conditions change. Moreover, by altering the amount of CDMT and NaHCO3, we developed a cubic regression model for precise control of the extent of derivatization using a response surface methodology (RSM) with a D-optimal design. No spurious peaks were detected by (1)H NMR spectrum and only 10% decrease of molecular weight of the derivatized HA was determined by GPC. The HA with 6% modification was relatively biocompatible up to 15 mg/mL.

Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

PURPOSE The purpose of this study was to report on Tsukamurella as a mimic of atypical mycobacterial infection. METHODS We report a patient who had received repeated corneal grafts with culture-proven Tsukamurella keratitis. RESULTS A slow-progressing corneal abscess that initially developed adjacent to a corneal stitch responded poorly to empiric antibiotic treatment. A preliminary culture report revealed fast-growing mycobacterial species. Treatment adjustments successfully controlled the disease. A final diagnosis of Tsukamurella was subsequently made on the basis of cultures. CONCLUSIONS Tsukamurella exhibits laboratory similarities to mycobacteria and should be considered in the differential of atypical infection of the ocular surface.