Divergent electroencephalogram resting-state functional network alterations in subgroups of autism spectrum disorder: a symptom-based clustering analysis.

Autism spectrum disorder (ASD) is characterized by etiological and phenotypic heterogeneity. Despite efforts to categorize ASD into subtypes, research on specific functional connectivity changes within ASD subgroups based on clinical presentations is limited. This study proposed a symptom-based clustering approach to identify subgroups of ASD based on multiple clinical rating scales and investigate their distinct Electroencephalogram (EEG) functional connectivity patterns. Eyes-opened resting-state EEG data were collected from 72 children with ASD and 63 typically developing (TD) children. A data-driven clustering approach based on Social Responsiveness Scales-Second Edition and Vinland-3 scores was used to identify subgroups. EEG functional connectivity and topological characteristics in four frequency bands were assessed. Two subgroups were identified: mild ASD (mASD, n = 37) and severe ASD (sASD, n = 35). Compared to TD, mASD showed increased functional connectivity in the beta band, while sASD exhibited decreased connectivity in the alpha band. Significant between-group differences in global and regional topological abnormalities were found in both alpha and beta bands. The proposed symptom-based clustering approach revealed the divergent functional connectivity patterns in the ASD subgroups that was not observed in typical ASD studies. Our study thus provides a new perspective to address the heterogeneity in ASD research.

Global evolving patterns and cross-country inequalities of inflammatory bowel disease burden from 1990 to 2019: a worldwide report.

AIMS: Inflammatory bowel disease (IBD) is a global disease. We aim to summarize the latest epidemiological patterns of IBD at the national, regional and global levels to give well-deserved attention and outline facilitating measures to reduce the disease burden. METHODS: We collected the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of IBD in 204 countries and territories from 1990 to 2019 using data from the Global Burden of Disease Study 2019. We further calculated the estimated annual percentage change (EAPC) to qualify the temporal trends of IBD burden by sex, age and region over the past 30 years. RESULTS: Globally, a total of 404.55 thousand incident cases, 4898.56 thousand prevalent cases, 41.00 thousand deaths and 1622.50 thousand DALYs of IBD were estimated in 2019. The age-standardized DALYs decreased from 27.2 in 1990 to 20.15 per 100,000 people in 2019, with an EAPC of -1.04. The high socio-demographic index regions presented pronounced age-standardized rates (ASRs) consistently over the last 30 years. The high-income North America had the highest ASRs in 2019, followed by Western Europe and Australasia. No gender difference was observed after being stratified by sex. CONCLUSIONS: The accumulated IBD patients are expected to increase in the future due to the increased rate of IBD in developing countries, and social aging in developed countries. Understanding the changes in epidemiological patterns helps to provide evidence to mitigate the rising burden of IBD.

Safety Assessment of Microcatheter-Protected Rotational Atherectomy with the Double Guiding Catheter Technique for Severely Calcified Left Main Bifurcation.

Background: Rotational atherectomy (RA) is a tool for calcium modification, but there is a risk of losing the side branch in left main coronary artery (LM) bifurcation lesions, resulting in disastrous consequences. Microcatheter-protected RA with the double guiding catheter (GC) technique for severely calcified LM bifurcations has been described previously, but its safety warrants further investigation. Methods: Various sizes of coronary calcification vascular simulators were utilized to model calcified LM bifurcation lesions for RA in in vitro. The damage to the side branch protective microcatheters and guidewires was accessed after microcatheter-protected RA with the double GC technique. In clinical practice, microcatheter-protected RA with the double GC technique was carried out in two patients. Results: In vitro, none of the protective microcatheters or guidewires were completely fractured, although the majority of them were damaged to varying degrees. In clinical practice, we successfully carried out two cases of percutaneous coronary intervention for severely calcified LM bifurcation with microcatheter-protected RA using the double GC technique. Conclusion: RA of severely calcified LM bifurcation lesions may be successfully performed using microcatheter-protected RA with the double GC technique, potentially reducing the risk of side branch occlusion. Since majority of protective microcatheters or guidewires were damaged, there was still some risk, and it is recommended to use this technique only in highly selected patient population of severely calcified true (Medina 1, 1, 1) LM bifurcations.

Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.

Modified superior oblique intrasheath tenectomy in A-pattern with superior oblique overaction.

BACKGROUND: To evaluate the effect of modified superior oblique intrasheath tenectomy (MSOIT) on superior oblique overaction (SOOA) with A-pattern. METHODS: We retrospectively reviewed the data of 66 patients (130 eyes) with SOOA and A-pattern underwent MSOIT at the nasal border of the superior rectus under an operating microscope between January 1, 2004 and December 31, 2018. The superior oblique (SO) tendon fibres were resected, and the sheath was preserved in all patients. The preoperative and postoperative SOOA, objective torsion, ocular motility, and A-pattern deviation findings were compared. The correlation between the preoperative A-pattern deviation and the corrected deviation was analysed. The average follow-up period was 33.45 ± 29.88 (range: 12-122) months. RESULTS: The mean SOOA deviation improved from 2.95 ± 0.54 to 0.34 ± 0.55 (P < 0.001), while the A-pattern deviation difference between upgaze and downgaze improved from 23.15 ± 7.59 prism diopters (PD) to 3.50 ± 2.90 PD (P < 0.001). The average objective fundus intorsion value improved from + 2.96 ± 0.58 to + 0.38 ± 0.60 (P < 0.001). The magnitude of correction in A-pattern was significantly correlated with the preoperative severity of A-pattern (r = 0.812, P < 0.001). CONCLUSIONS: MSOIT at the nasal border of the superior rectus (SR) under an operating microscope is safe and yields beneficial outcomes in patients with SOOA and A-pattern.

The inhibitory effect of microRNA-1827 on anoikis resistance in lung adenocarcinoma A549 cells via targeting caveolin-1.

Anoikis resistance is a critical process for cancer cell metastasis in non-small cell lung cancer (NSCLC), and microRNA-1827 (miR-1827) is closely correlated with NSCLC metastasis. In this study, we aimed to evaluate the role of miR-1827 in regulating the anoikis resistance of NSCLC. The results showed that miR-1827 level was decreased in tumor tissues and cells and was correlated with tumor grade and lymph node (LN) metastasis. Overexpression of miR-1827 inhibited anchorage-independent growth and anoikis resistance in A549 cells. Bioinformatics and functional analysis identified that caveolin-1 (CAV-1) is directly targeted by miR-1827. Restoration of CAV-1 significantly attenuated miR-1827's effect on anoikis resistance in A549 cells. Our data identified a novel signaling axis of miR-1827/CAV-1 in regulating anoikis resistance, which might serve as a potential therapeutic target for metastatic NSCLC.

Associations between pre-S deletion mutation of hepatitis B virus and risk of hepatocellular carcinoma in the Asian population: a meta-analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver cancer, leading to many cancer-related deaths worldwide. Several studies have shown an association between pre-S deletion mutation of hepatitis B virus (HBV) and HCC risk, but the results remain conflicting. We aimed to verify HBV pre-S deletion mutations in relation to the risk of HCC. MATERIAL AND METHODS: We searched the commonly used electronic databases for relevant studies of this association among the Asian population until September 30th, 2014. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to calculate the association. RESULTS: A total of 17 case-control studies were screened out, including 2837 HBV-infected patients, of whom 1246 had HCC. The results showed that the frequency of pre-S deletion of HBV in patients with HCC was higher than that in patients without HCC (35.7% vs. 11.5%), indicating the prevalence of this mutation in patients with HCC. Statistically significant correlations were observed for pre-S deletion mutation and risk of HCC in a random-effects model (OR=3.90, 95% CI=2.80-5.44, P<0.00001). This association was also found in Chinese populations (OR=4.84, 95% CI=2.86-8.20, P<0.00001). CONCLUSIONS: Our data indicate that HBV pre-S deletion mutations might be associated with HCC risk. Their oncogenic role may be important in studying the potential mechanism of HBV hepatocarcinogenesis.

MicroRNA­1224 inhibits cell proliferation by downregulating CBX3 expression in chordoma.

MicroRNAs (miRNAs/miRs) have abnormal expression in numerous tumors and are closely related to tumor development and resistance to radiotherapy and chemotherapy. However, there are few studies assessing the role and mechanism of miRNA in chordoma. The sequencing data of three pairs of chordoma and notochord tissues from the GSE56183 dataset were analyzed in the present study. Cell proliferation was assessed in vitro using Cell Counting Kit-8. Bioinformatics analysis and the dual luciferase reporter assay were used to evaluate the regulatory relationship between miR-1224 and chromobox 3 (CBX3) in chordoma. The results demonstrated that miR-1224 had a significantly lower expression level in chordoma tissues and cell lines. Overexpression of miR-1224 inhibited proliferation in the chordoma cells, while the knockdown of miR-1224 promoted proliferation of the chordoma cells. Bioinformatics analysis and the dual luciferase reporter assay confirmed that CBX3 was a direct target gene of miR-1224 and that miR-1224 induced the proliferation of chordoma cells through the inhibition of CBX3. In summary, miR-1224 reduced the proliferation of chordoma cells through inhibition of CBX3, which provides a theoretical basis for selecting a novel therapeutic target for chordoma.

Intestinal flora and pregnancy complications: Current insights and future prospects.

Numerous studies have demonstrated the pivotal roles of intestinal microbiota in many physiopathological processes through complex interactions with the host. As a unique period in a woman's lifespan, pregnancy is characterized by changes in hormones, immunity, and metabolism. The gut microbiota also changes during this period and plays a crucial role in maintaining a healthy pregnancy. Consequently, anomalies in the composition and function of the gut microbiota, namely, gut microbiota dysbiosis, can predispose individuals to various pregnancy complications, posing substantial risks to both maternal and neonatal health. However, there are still many controversies in this field, such as "sterile womb" versus "in utero colonization." Therefore, a thorough understanding of the roles and mechanisms of gut microbiota in pregnancy and its complications is essential to safeguard the health of both mother and child. This review provides a comprehensive overview of the changes in gut microbiota during pregnancy, its abnormalities in common pregnancy complications, and potential etiological implications. It also explores the potential of gut microbiota in diagnosing and treating pregnancy complications and examines the possibility of gut-derived bacteria residing in the uterus/placenta. Our aim is to expand knowledge in maternal and infant health from the gut microbiota perspective, aiding in developing new preventive and therapeutic strategies for pregnancy complications based on intestinal microecology.

Prognostic value of pre-treatment FDG PET/CT SUVmax for metastatic lesions in de novo metastatic nasopharyngeal carcinoma following chemotherapy and locoregional radiotherapy.

BACKGROUND: To explore the prognostic role of FDG PET/CT maximal standard uptake values of metastatic lesions (SUVmax-M) in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) following palliative chemotherapy and locoregional radiotherapy (LRRT). METHODS: We retrospectively collected the information of 86 eligible patients between Jan 2012 and Oct 2020. All the parameters involving SUVmax and serum lactate dehydrogenase (LDH) at diagnosis were evaluated and cutoff values were determined by the maximum log-rank statistic method. The multivariate analysis was performed using Cox proportional hazards regression to identify the independent prognostic factors associated with overall survival (OS). All estimated survival rates were conducted with Kaplan-Meier method. RESULTS: Median survival and progression time in the cohort were 38.2 and 13.9 months, respectively. The univariable analysis showed that male, number of metastatic sites ≥ 4, presence of liver, serum LDH ≥ 229, SUVmax-M ≥ 10, SUVmax-M-sum ≥ 10, and SUVmax-M-mean ≥ 8.8 were significant prognostic factors. Five variables were identified after LASSO regression and entered into the multivariate analysis. Furthermore, liver involvement (P = 0.039), elevated LDH (≥ 229) (P = 0.05) and higher SUVmax-M (≥ 10) (P = 0.004) were significantly associated with worse OS. CONCLUSION: The high SUVmax of metastatic lesions (≥ 10), liver involvement, and elevated serum LDH (≥ 229) at diagnosis could independently predict poor survival for de novo mNPC patients treated with palliative chemotherapy following LRRT.

A Comprehensive Review of Interventional Clinical Trials in Patients with Bone Metastases.

Bone metastasis is one of the most important factors associated with poor prognosis for patients with prostate, breast, thyroid, and lung cancer. In the past two decades, 651 clinical trials, including 554 interventional trials, were being registered in ClinicalTrials.gov and pharma.id.informa.com to combat bone metastases from different perspectives. In this review, we comprehensively analyzed, regrouped, and discussed all the interventional trials on bone metastases. Clinical trials were re-grouped into bone-targeting agents, radiotherapy, small molecule targeted therapy, combination therapy, and others, based on the different mechanisms of action including modifying the bone microenvironment and preventing the growth of cancer cells. We also discussed the potential strategies that might improve overall survival and progression-free survival of patients with bone metastases in the future.

Transition mechanisms of translational motions of bubbles in an ultrasonic field.

The translation behaviors of oscillating bubbles are closely related to the polymerizations and dispersions between them, which are crucial for the ultrasonic cavitation effect. In this study, six types of translational motion of bubbles with a wide range of sizes (2-100 µm) in the R01-R02 plane are investigated. Our results demonstrate that in addition (to the 2nd order harmonic), the 1/2 order subharmonic can change the bubble pairs from the three states of the attraction, stable after attraction, and repulsion to that of the repulsion, coalescence, and attraction, respectively. Furthermore, within the range of the main resonance radius and the 1/2 order subharmonic resonance radius, the chaotic bubble pairs with alternating attractive and repulsive forces appear in the region between the coalescence pairs and stable pairs after attraction. Finally, the corresponding physical mechanisms of the chaotic translational motions are also revealed.

Integrative proteomic and metabonomic profiling elucidates amino acid and lipid metabolism disorder in CA-MRSA-infected breast abscesses.

Objective: Bacterial culture and drug sensitivity testing have been the gold standard for confirming community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in breast abscess with a long history. However, these tests may delay treatment and increase the risk of nosocomial infections. To handle and improve this critical situation, this study aimed to explore biomarkers that could facilitate the rapid diagnosis of CA-MRSA infection. Methods: This study for the first time applied label-free quantitative proteomics and non-targeted metabonomics to identify potential differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs) in breast abscess infected with CA-MRSA compared to methicillin-susceptible S. aureus (MSSA). The two omics data were integrated and analyzed using bioinformatics, and the results were validated using Parallel Reaction Monitoring (PRM). Receiver operating characteristic (ROC) curves were generated to evaluate the predictive efficiency of the identified biomarkers for diagnosing CA-MRSA infection. Results: After using the above-mentioned strategies, 109 DEPs were identified, out of which 86 were upregulated and 23 were downregulated. Additionally, a total of 61 and 26 DEMs were initially screened in the positive and negative ion modes, respectively. A conjoint analysis indicated that the amino acid metabolism, glycosphingolipid biosynthesis, and glycerophospholipid metabolism pathways were co-enriched by the upstream DEPs and downstream DEMs, which may be involved in structuring the related network of CA-MRSA infection. Furthermore, three significant DEMs, namely, indole-3-acetic acid, L-(-)-methionine, and D-sedoheptulose 7-phosphate, displayed good discriminative abilities in early identification of CA-MRSA infection in ROC analysis. Conclusion: As there is limited high-quality evidence and multiple omics research in this field, the explored candidate biomarkers and pathways may provide new insights into the early diagnosis and drug resistance mechanisms of CA-MRSA infection in Chinese women.

[Study on the structure and function of inferior oblique connective tissue in different mammals].

OBJECTIVE: The purpose of this research lied in studying the structure and function of connective tissue of inferior oblique (IO) in rhesus, rabbit and rat. METHODS: It was an experimental study. Two adult monkeys (rhesus), five adult rabbits and five adult Wistar rats were involved in this study. The gross anatomy of an orbit in each animal was observed. Meanwhile, the fellow orbit was processed with paraffin imbedding and coronal serial section. Masson trichrome stain was used to distinguish muscle and collagen, and Weigert stain was performed for identification of elastin. RESULTS: The connective tissue around IO muscle in rhesus, rabbits and rats all connected with inferior rectus (IR) and lateral rectus (LR), but the arrangements among them were not entirely similar. Only the connective tissue around IO in rhesus consisted of dense collagen, scattered elastic fiber, and connected closely with IR, LR Pulley. The connective tissue circling IO in rabbit and rat were crumbly, and was not connected closely with the connective tissue around IR. CONCLUSION: IR and LR Pulley has some mechanics link with IO in rhesus, and can play roles in covergence in rhesus.

[Study on the structure and function of superior oblique connective tissue in different mammals].

OBJECTIVE: The purpose of this research lied in studying the structure and function of connective tissue of superior oblique (SO) in rhesus and rabbit. METHODS: It was an experimental study. Two adult monkeys (rhesus) and five adult rabbits were involved in this study. The gross anatomy of an orbit in each animal was observed. Meanwhile, the fellow orbit was processed with paraffin imbedding and coronal serial section. Masson trichrome stain was used to distinguish muscle and collagen, and Weigert stain was performed for identification of elastin. RESULTS: Connective tissue around SO in both mammals thickened anteriorly, reflected in the trochlea along with the SO tendon, and became contiguous with the nasal aspect of the SR connective tissue ring, while the tendon passed inferior to the SR pulley to insert on the sclera. CONCLUSION: The contraction of SO OL can cause SR shift nasally. This may explain the mechanism of vestibulo-ocular reflex (VOR) partly.

Comparative effectiveness of different treatment modalities for active, moderate-to-severe Graves' orbitopathy: a systematic review and network meta-analysis.

To compare the effects of different treatment modalities on active, moderate-to-severe Graves' orbitopathy (GO). We searched PubMed and Embase for randomized controlled trials published up to 30 Nov 2020, of different modalities for the treatment of active, moderate-to-severe GO. We performed Bayesian network meta-analyses. This study is registered with PROSPERO (CRD42020166287). Fifteen RCTs were identified. Network meta-analysis showed that in comparison with placebo, teprotumumab, mycophenolate plus intravenous glucocorticoids (IVGCs), mycophenolate, rituximab, azathioprine, IVGCs, orbital radiotherapy, oral glucocorticoids (OGCs) were effective treatments (ordered from most effective to least effective). Teprotumumab was more efficacious in reducing proptosis than IVGCs. No significant difference in changes in diplopia grade was recorded between teprotumumab, rituximab, orbital radiotherapy and IVGCs. Low (4.5-5 g), middle (6 g) and high (7-8 g) cumulative doses of IVGCs were shown to be more effective than OGC in improving the overall response rate, but the very low-group (<3 g) seemed to have a lower risk of adverse events. We found that teprotumumab offered the highest level of efficacy in terms of the overall response rate and was more efficacious in reducing proptosis than IVGCs. With regard to different dosages of IVGCs, the cumulative dose of 4.5-5 g of IVGCs seems to be the most appropriate schedule in terms of efficacy and safety outcomes. Due to the limited number of patients treated with teprotumumab and the lack of comparison with other effective therapeutics, teprotumumab might not become the standard first-line therapy for active, moderate-to-severe GO.

Surgical correction of severe congenital ptosis using a modified frontalis muscle advancement technique: A single-arm trial.

PURPOSE: To describe our experience with a modified frontal muscle advancement flap to treat patients with severe congenital ptosis. METHODS: Analysis of the clinical charts of 154 patients who underwent a modified frontal muscle advancement flap. The FM was exposed by a crease incision. The FM flap was created by deep dissection between the orbicularis muscle and orbital septum from the skin crease incision to the supraorbital margin and subcutaneous dissection from the inferior margin of the eyebrow to 0.5 cm above the eyebrow. No vertical incision was made on the FM flap to ensure an intact flap wide enough to cover the entire upper tarsal plate. Contour, symmetry of height, marginal reflex distance (MRD1), and complications were assessed. Mean follow-up was 10 months. RESULTS: The mean patient age was 7.6 ± 5.6 (range, 2-18) years. The mean MRD1 was 3.2 ± 1.3 mm after the operation. All bilateral cases achieved symmetry and optimal lid contour; 17 unilateral cases were under corrected, with a success rate of 89.0%. Complications such as entropion, exposure keratitis, FM paralysis, frontal hypoesthesia, severe haematoma, and entropion were not observed in our series. CONCLUSION: A modified frontal muscle advancement flap produced a high success rate with a clear field of vision, mild trauma, and few complications. This technique is relatively simple and should be considered for correcting severe congenital ptosis.Date of registration: 29-03-2020Trial registration number: ChiCTR2000031364Registration site: http://www.chictr.org/.

[Study on arsenic speciation changes in crude and processed traditional Chinese medicines by HPLC-ICP-MS].

A HPLC-ICP-MS method for simultaneous determination of As(III), As(V), MMA and DMA in traditional Chinese medicines (TCMs) was established, and the contents of As(III), As(V), MMA and DMA in a TCM with high total arsenic content (Cordyceps) and 5 crude and processed TCMs (Radix Astragali, Radix et Rhizoma Rhei, Radix Scutellariae, Radix Polygoni Multiflori and Radix Rehmanniae) were determined and analyzed. The method validation indicated that the correlative coefficients (r) for all speciations were bigger than 0.9984; the limits of quantitation (LOQ) were from 0.8 to 1.0 microg x L(-1); the reproducibility and stability were satisfactory with all RSDs less than 10%; the spiked recoveries ranged from 82.40% to 119.5%. The results of samples analysis showed that the inorganic arsenic (As(III) and As(V)) was the dominating speciation in the tested TCMs; MMA and DMA were not found in all plant resourced TCMs, but MMA was found in Cordyceps; all the tested TCMs indicated a content increasing of inorganic arsenic after processing.

Comprehensive Hospitals Nurses' Cognition on Palliative Care in Shandong Province, China: A Cross-Sectional Study.

BACKGROUND: Palliative care is an essential part of medical practice, however, it has developed slowly in China. We aimed to analyze the current situations of the cognition on palliative care among the nurses in Shandong Province, China. METHODS: This was a cross sectional study. Investigation of 1050 nurses came from 5 third-class hospitals and 5 second-class hospitals in Shandong Province, China from Jul to Oct in 2018. The questionnaire included 4 parts: general information of the subject, the questionnaire of palliative nursing knowledge, attitude, and the behavior. Data were collected by the APP. Overall, after eliminating the invalid questionnaires, 1026 questionnaires were included in the final analyses. The software Stata 14.2 was used for all statistical analyses. RESULTS: The score of knowledge and attitude was low, the practice was higher. Multivariate analysis results: the significant independent variables of univariate analysis were included in the multivariate non-conditional logistic regression model for analysis. Some departments had statistical significance in knowledge multivariate Logistic regression analysis. The multivariate logistic regression analysis of practice was significant for physical health and religious beliefs. The statistical variables of the total score of cognition were gender, age of care, health status and religious beliefs. CONCLUSION: Nursing knowledge is lacking and attitude remains to be improved as soon as possible. It is vital to improve the cognition of palliative care of nurses in Shandong general hospitals by developing relevant rules and regulations, strengthening the supervision of relevant ant departments, and enhancing training for nurses.