bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of rhythmic visual stimulation on left–right attentional asymmetry
Authors: Li Rong , Xu Minpeng , You Jia , Zhou Xiaoyu , Meng Jiayuan , Xiao Xiaolin , Jung Tzyy-Ping , Ming Dong
Published: May 2023

The rhythmic visual stimulation (RVS)-induced oscillatory brain responses, namely steady-state visual evoked potentials (SSVEPs), have been widely used as a biomarker in studies of neural processing based on the assumption that they would not affect cognition. However, recent studies have suggested that the generation of SSVEPs might be attributed to neural entrainment and thus could impact brain functions. But their neural and behavioral effects are yet to be explored. No study has reported the SSVEP influence on functional cerebral asymmetry (FCA). We propose a novel lateralized visual discrimination paradigm to test the SSVEP effects on visuospatial selective attention by FCA analyses. Thirty-eight participants covertly shifted their attention to a target triangle appearing in either the lower-left or -right visual field (LVF or RVF), and judged its orientation. Meanwhile, participants were exposed to a series of task-independent RVSs at different frequencies, including 0 (no RVS), 10, 15, and 40-Hz. As a result, it showed that target discrimination accuracy and reaction time (RT) varied significantly across RVS frequency. Furthermore, attentional asymmetries differed for the 40-Hz condition relative to the 10-Hz condition as indexed by enhanced RT bias to the right visual field, and larger Pd EEG component for attentional suppression. Our results demonstrated that RVSs had frequency-specific effects on left–right attentional asymmetries in both behavior and neural activities. These findings provided new insights into the functional role of SSVEP on FCAs.
Delayed cortical development in mice with a neural specific deletion of β1 integrin
Authors: Rashid Mamunur , Olson Eric C.
Published: May 2023

The adhesion systems employed by migrating cortical neurons are not well understood. Genetic deletion studies of focal adhesion kinase (FAK) and paxillin in mice suggested that these classical focal adhesion molecules control the morphology and speed of cortical neuron migration, but whether β1 integrins also regulate migration morphology and speed is not known. We hypothesized that a β1 integrin adhesion complex is required for proper neuronal migration and for proper cortical development. To test this, we have specifically deleted β1 integrin from postmitotic migrating and differentiating neurons by crossing conditional β1 integrin floxed mice into the NEX-Cre transgenic line. Similar to our prior findings with conditional paxillin deficiency, we found that both homozygous and heterozygous deletion of β1 integrin causes transient mispositioning of cortical neurons in the developing cortex when analyzed pre- and perinatally. Paxillin and β1 integrin colocalize in the migrating neurons and deletion of paxillin in the migrating neuron causes an overall reduction of the β1 integrin immunofluorescence signal and reduction in the number of activated β1 integrin puncta in the migrating neurons. These findings suggest that these molecules may form a functional complex in migrating neurons. Similarly, there was an overall reduced number of paxillin+ puncta in the β1 integrin deficient neurons, despite the normal distribution of FAK and Cx26, a connexin required for cortical migration. The double knockout of paxillin and β1 integrin produces a cortical malpositioning phenotype similar to the paxillin or β1 integrin single knockouts, as would be expected if paxillin and β1 integrin function on a common pathway. Importantly, an isolation-induced pup vocalization test showed that β1 integrin mutants produced a significantly smaller number of calls compared to their littermate controls when analyzed at postnatal day 4 (P4) and revealed a several days trend in reduced vocalization development compared to controls. The current study establishes a role for β1 integrin in cortical development and suggests that β1 integrin deficiency leads to migration and neurodevelopmental delays.
Persistent olfactory dysfunction associated with poor sleep quality and anxiety in patients with long COVID
Authors: Paranhos Alna Carolina Mendes , Dias Apio Ricardo Nazareth , Bastos Thalita da Rocha , Rodrigues Arthur Nascimento , Santana Karem Harumy Yamamoto , Dias Lorena Henriete Araujo , dos Santos Lidiane Palheta Miranda , Cerasi Antônio José , Mendes Michely Caroline Nascimento , de Oliveira Cleiziane Lima , Domingues Mariângela Moreno , Koury Gisele Vieira Hennemann , Vasconcelos Pedro Fernando da Costa , Souza Givago Silva , Quaresma Juarez Antônio Simões , Falcão Luiz Fábio Magno
Published: May 2023

Introduction

Poor sleep quality have been widely reported in patients with long COVID. Determining the characteristics, type, severity, and relationship of long COVID with other neurological symptoms is essential for the prognosis and management of poor sleep quality.

Methods

This cross-sectional study was conducted at a public university in the eastern Amazon region of Brazil between November 2020 and October 2022. The study involved 288 patients with long COVID with self-report neurological symptoms. One hundred thirty-one patients were evaluated by using standardised protocols: Pittsburgh sleep quality index (PSQI), Beck Anxiety Inventory, Chemosensory Clinical Research Center (CCRC), and Montreal Cognitive Assessment (MoCA). This study aimed to describe the sociodemographic and clinical characteristics of patients with long COVID with poor sleep quality and their relationship with other neurological symptoms (anxiety, cognitive impairment, and olfactory disorder).

Results

Patients with poor sleep quality were mainly women (76.3%), 44.04 ± 12.73 years old, with >12 years of education (93.1%), and had monthly incomes of up to US $240.00 (54.2%). Anxiety and olfactory disorder were more common in patients with poor sleep quality.

Discussion

Multivariate analysis shows that the prevalence of poor sleep quality was higher in patients with anxiety, and olfactory disorder is associated with poor sleep quality. In this cohort of patients with long COVID, the prevalence of poor sleep quality was highest in the group tested by PSQI and were associated with other neurological symptoms, such as anxiety and olfactory dysfunction. A previous study indicates a significant association between poor sleep quality and psychological disorders over time. Recent studies involving neuroimaging found functional and structural changes in Long COVID patients with persistent olfactory disfunction. Poor sleep quality are integral part of complex changes related to Long COVID and should be part of patient’s clinical management.
Altered resting-state brain activity in functional dyspepsia patients: a coordinate-based meta-analysis
Authors: Mao Yangke , Zhang Pan , Sun Ruirui , Zhang Xinyue , He Yuqi , Li Siyang , Yin Tao , Zeng Fang
Published: May 2023

Background

Neuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.

Methods

Eight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.

Results

A total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.

Conclusion

The current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.
Is Drp1 a link between mitochondrial dysfunction and inflammation in Alzheimer’s disease?
Authors: Sbai Oualid , Bazzani Veronica , Tapaswi Shreya , McHale Joshua , Vascotto Carlo , Perrone Lorena
Published: May 2023

Recent advances highlight that inflammation is critical to Alzheimer Disease (AD) pathogenesis. Indeed, several diseases characterized by inflammation are considered risk factors for AD, such as type 2 diabetes, obesity, hypertension, and traumatic brain injury. Moreover, allelic variations in genes involved in the inflammatory cascade are risk factors for AD. AD is also characterized by mitochondrial dysfunction, which affects the energy homeostasis of the brain. The role of mitochondrial dysfunction has been characterized mostly in neuronal cells. However, recent data are demonstrating that mitochondrial dysfunction occurs also in inflammatory cells, promoting inflammation and the secretion of pro-inflammatory cytokines, which in turn induce neurodegeneration. In this review, we summarize the recent finding supporting the hypothesis of the inflammatory-amyloid cascade in AD. Moreover, we describe the recent data that demonstrate the link between altered mitochondrial dysfunction and the inflammatory cascade. We focus in summarizing the role of Drp1, which is involved in mitochondrial fission, showing that altered Drp1 activation affects the mitochondrial homeostasis and leads to the activation of the NLRP3 inflammasome, promoting the inflammatory cascade, which in turn aggravates Amyloid beta (Ab) deposition and tau-induced neurodegeneration, showing the relevance of this pro-inflammatory pathway as an early event in AD.
ICA69 regulates activity-dependent synaptic strengthening and learning and memory
Authors: Chiu Shu-Ling , Chen Chih-Ming , Huganir Richard L.
Published: May 2023

Long-term potentiation (LTP) is one of the major cellular mechanisms for learning and memory. Activity-dependent increases in surface AMPA receptors (AMPARs) are important for enhanced synaptic efficacy during LTP. Here, we report a novel function of a secretory trafficking protein, ICA69, in AMPAR trafficking, synaptic plasticity, and animal cognition. ICA69 is first identified as a diabetes-associated protein well characterized for its function in the biogenesis of secretory vesicles and trafficking of insulin from ER, Golgi to post-Golgi in pancreatic beta cells. In the brain, ICA69 is found in the AMPAR protein complex through its interaction with PICK1, which binds directly to GluA2 or GluA3 AMPAR subunits. Here, we showed that ICA69 regulates PICK1's distribution in neurons and stability in the mouse hippocampus, which in turn can impact AMPAR function in the brain. Biochemical analysis of postsynaptic density (PSD) proteins from hippocampi of mice lacking ICA69 (Ica1 knockout) and their wild-type littermates revealed comparable AMPAR protein levels. Electrophysiological recording and morphological analysis of CA1 pyramidal neurons from Ica1 knockout also showed normal AMPAR-mediated currents and dendrite architecture, indicating that ICA69 does not regulate synaptic AMPAR function and neuron morphology at the basal state. However, genetic deletion of ICA69 in mice selectively impairs NMDA receptor (NMDAR)-dependent LTP but not LTD at Schaffer collateral to CA1 synapses, which correlates with behavioral deficits in tests of spatial and associative learning and memory. Together, we identified a critical and selective role of ICA69 in LTP, linking ICA69-mediated synaptic strengthening to hippocampus-dependent learning and memory.
Progressive mitochondrial dysfunction in cerebellar synaptosomes of cystatin B-deficient mice
Authors: Gorski Katarin , Jackson Christopher B. , Nyman Tuula A. , Rezov Veronika , Battersby Brendan J. , Lehesjoki Anna-Elina
Published: May 2023

The involvement of mitochondrial dysfunction in cystatin B (CSTB) deficiency has been suggested, but its role in the onset of neurodegeneration, myoclonus, and ataxia in the CSTB-deficient mouse model (Cstb−/−) is yet unknown. CSTB is an inhibitor of lysosomal and nuclear cysteine cathepsins. In humans, partial loss-of-function mutations cause the progressive myoclonus epilepsy neurodegenerative disorder, EPM1. Here we applied proteome analysis and respirometry on cerebellar synaptosomes from early symptomatic (Cstb−/−) mice to identify the molecular mechanisms involved in the onset of CSTB-deficiency associated neural pathogenesis. Proteome analysis showed that CSTB deficiency is associated with differential expression of mitochondrial and synaptic proteins, and respirometry revealed a progressive impairment in mitochondrial function coinciding with the onset of myoclonus and neurodegeneration in (Cstb−/−) mice. This mitochondrial dysfunction was not associated with alterations in mitochondrial DNA copy number or membrane ultrastructure. Collectively, our results show that CSTB deficiency generates a defect in synaptic mitochondrial bioenergetics that coincides with the onset and progression of the clinical phenotypes, and thus is likely a contributor to the pathogenesis of EPM1.
Building better brains: the pleiotropic function of neurotrophic factors in postnatal cerebellar development
Authors: Boxy Pia , Nykjær Anders , Kisiswa Lilian
Published: May 2023

The cerebellum is a multifunctional brain region that controls diverse motor and non-motor behaviors. As a result, impairments in the cerebellar architecture and circuitry lead to a vast array of neuropsychiatric and neurodevelopmental disorders. Neurotrophins and neurotrophic growth factors play essential roles in the development as well as maintenance of the central and peripheral nervous system which is crucial for normal brain function. Their timely expression throughout embryonic and postnatal stages is important for promoting growth and survival of both neurons and glial cells. During postnatal development, the cerebellum undergoes changes in its cellular organization, which is regulated by a variety of molecular factors, including neurotrophic factors. Studies have shown that these factors and their receptors promote proper formation of the cerebellar cytoarchitecture as well as maintenance of the cerebellar circuits. In this review, we will summarize what is known on the neurotrophic factors’ role in cerebellar postnatal development and how their dysregulation assists in developing various neurological disorders. Understanding the expression patterns and signaling mechanisms of these factors and their receptors is crucial for elucidating their function within the cerebellum and for developing therapeutic strategies for cerebellar-related disorders.
The efficacy of branched-chain amino acid granules to restore phagocytic activity in cirrhosis patients, a randomized controlled trial
Authors: Chamroonkul Naichaya , Rujeerapaiboon Natthapat , Sripongpun Pimsiri , Kaewdech Apichat , Piratvisuth Teerha
Published: May 2023

Background

Infection is a detrimental complication among cirrhotic patients, leading to major morbidity and mortality. Reduction in phagocytic activation, as part of immunoparesis, is a distinctive key component of cirrhosis-associated immune dysfunction (CAID) and predicts the development of infection. However, there are limited data on immunotherapeutic approaches to restore phagocytosis.

Aims

We aimed to determine the effect of branched-chain amino acid (BCAA) granules on phagocytic activity in patients with CAID.

Methods

In this double-blind randomized controlled trial, Participants were randomly assigned (1:1 ratio stratified by Child-Pugh status) to receive either BCAA granules or placebo. In the 3rd and 6th months, phagocytic activity was assessed by flow cytometry. The primary endpoint was the restoration of innate immunity at the 6th month, defined as ≥75% phagocytic activity; the secondary endpoints were the accretion of phagocytic activity and hospitalization due to infection.

Results

A total of 37 patients were included. There were no differences among the patients in the baseline characteristics and phagocytic activity. At the 6th month, a higher proportion of patients with phagocytic restoration was observed in the BCAA granule group compared to the placebo group (68 vs. 5.6%, p < 0.001). The mean phagocytic activity was 75.4 and 63.4% in the BCAA granule and placebo groups, respectively (p < 0.001). Progressive accretion of phagocytic activity was observed during the 3rd and 6th months. There was no difference in hospitalization due to infection (3 vs. 2 events, p = 0.487).

Conclusion

Our results suggest that BCAA granules significantly restore phagocytic activity across various stages of cirrhosis. A longer follow-up period is required to demonstrate infection prevention.

Clinical Trial Registration: www.clinicaltrials.in.th, TCTR20190830005.
Dietary inflammatory potential is associated with sarcopenia in patients with hypertension: national health and nutrition examination study
Authors: Tu Jiabin , Shi Shanshan , Liu Yuchen , Xiu Jiaming , Zhang Yanbin , Wu Bo , Liao Ying , Chen Kaihong , Li Ganyang , Chen Llling
Published: May 2023

Background

Study has shown that sarcopenia increases the risk of poor outcomes in patients with hypertension. Inflammation is one of the important reasons for the occurrence and development of sarcopenia. Regulating systemic inflammation may be a potential intervention for sarcopenia in hypertensive patients. Diet is one of the important measures to improve systemic inflammation. The dietary inflammatory index (DII) is a tool designed to assess the inflammatory potential of the diet, the association between DII and sarcopenia in hypertensive patients is unclear.

Objective

To explore the relationship between the DII and sarcopenia in patients with hypertension.

Method

Data from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 and 2011–2018. A total of 7,829 participants were evaluated. Participants were divided into four groups based on the quartile of the DII: Q1 group (n = 1,958), Q2 group (n = 1,956), Q3 group (n = 1,958) and Q4 group (n = 1,957). The relationship between the DII and sarcopenia was assessed by logistic regression analysis based on the NHANES recommended weights.

Result

The DII was significantly associated with sarcopenia in patients with hypertension. After full adjustment, patients with higher DII (OR: 1.22, 95% CI: 1.13–1.32, p < 0.001) have a higher risk of sarcopenia. Compared with Q1 group, the group with higher DII levels had a higher risk of sarcopenia (Q2: OR: 1.23, 95%CI: 0.89–1.72, p = 0.209; Q3: OR: 1.68, 95%CI: 1.20–2.35, p = 0.003; Q4: OR: 2.43, 95%CI: 1.74–3.39, p < 0.001).

Conclusion

High DII is associated with an increased risk of sarcopenia in hypertensive patients. The higher the level of DII, the higher the risk of sarcopenia in hypertensive patients.
Identification of a chemoresistance-related prognostic gene signature by comprehensive analysis and experimental validation in pancreatic cancer
Authors: Chen Junliang , Liu Zhihao , Wu Zhiyuan , Li Wenjun , Tan Xiaodong
Published: May 2023

Background

Chemoresistance is a major hurdle to improving the prognosis of pancreatic cancer (PC). This study aimed to identify key genes regulating chemoresistance and develop a chemoresistance-related gene signature for prognosis prediction.

Methods

A total of 30 PC cell lines were subtyped according to gemcitabine sensitivity data from the Cancer Therapeutics Response Portal (CTRP v2). Differentially expressed genes (DEGs) between gemcitabine-resistant and gemcitabine-sensitive cells were subsequently identified. These upregulated DEGs associated with prognostic values were incorporated to build a LASSO Cox risk model for The Cancer Genome Atlas (TCGA) cohort. Four datasets (GSE28735, GSE62452, GSE85916, and GSE102238) from the Gene Expression Omnibus (GEO) were used as an external validation cohort. Then, a nomogram was developed based on independent prognostic factors. The responses to multiple anti-PC chemotherapeutics were estimated by the “oncoPredict” method. Tumor mutation burden (TMB) was calculated using the “TCGAbiolinks” package. Analysis of the tumor microenvironment (TME) was performed using the “IOBR” package, while the TIDE and “easier” algorithms were employed to estimate immunotherapy efficacy. Finally, RT-qPCR, Western blot and CCK-8 assays were conducted to validate the expression and functions of ALDH3B1 and NCEH1.

Results

A five-gene signature and a predictive nomogram were developed from six prognostic DEGs, including EGFR, MSLN, ERAP2, ALDH3B1, and NCEH1. Bulk and single-cell RNA sequencing analyses indicated that all five genes were highly expressed in tumor samples. This gene signature was not only an independent prognostic factor but also a biomarker forecasting chemoresistance, TMB, and immune cells. In vitro experiments suggested that ALDH3B1 and NCEH1 were involved in PC progression and gemcitabine chemoresistance.

Conclusion

This chemoresistance-related gene signature links prognosis with chemoresistance, TMB, and immune features. ALDH3B1 and NCEH1 are two promising targets for treating PC.
Identification of the hub genes associated with prostate cancer tumorigenesis
Authors: Zhu Honghui , Lin Qi , Gao Xiaomin , Huang Xixi
Published: May 2023

Introduction

Prostate cancer (PCa) is one of the most common malignant tumors of the male urogenital system; however, the underlying mechanisms remain largely unclear. This study integrated two cohort profile datasets to elucidate the potential hub genes and mechanisms in PCa.

Methods and Results

Gene expression profiles GSE55945 and GSE6919 were filtered from the Gene Expression Omnibus (GEO) database to obtain 134 differentially expressed genes (DEGs) (14 upregulated and 120 downregulated) in PCa. Gene Ontology and pathway enrichment were performed using the Database for Annotation, Visualization, and Integrated Discovery, showing that these DEGs were mainly involved in biological functions such as cell adhesion, extracellular matrix, migration, focal adhesion, and vascular smooth muscle contraction. The STRING database and Cytoscape tools were used to analyze protein-protein interactions and identify 15 hub candidate genes. Violin plot, boxplot, and prognostic curve analyses were performed using Gene Expression Profiling Interactive Analysis, which identified seven hub genes, including upregulated expressed SPP1 and downregulated expressed MYLK, MYL9, MYH11, CALD1, ACTA2, and CNN1 in PCa compared with normal tissue. Correlation analysis was performed using the OmicStudio tools, which showed that these hub genes were moderately to strongly correlated with each other. Finally, quantitative reverse transcription PCR and western blotting were performed to validate the hub genes, showing that the abnormal expression of the seven hub genes in PCa was consistent with the analysis results of the GEO database.

Discussion

Taken together, MYLK, MYL9, MYH11, CALD1, ACTA2, SPP1, and CNN1 are hub genes significantly associated with PCa occurrence. These genes are abnormally expressed, leading to the formation, proliferation, invasion, and migration of PCa cells and promoting tumor neovascularization. These genes may serve as potential biomarkers and therapeutic targets in patients with PCa.
Primary blastic plasmacytoid dendritic cell neoplasm: a US population-based study
Authors: Huang Lifang , Wang Fan
Published: May 2023

Background

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and poorly understood hematopoietic malignancy. This study aimed to investigate the clinical characteristics and prognostic factors in patients with primary BPDCN.

Methods

Patients diagnosed with primary BPDCN from 2001 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Survival outcome was analysed with Kaplan-Meier method. Prognostic factors were evaluated based on the univariate and multivariate accelerated failure time (AFT) regression analysis.

Results

A total of 340 primary BPDCN patients were included in this study. The average age was 53.7 ± 19.4 years, with 71.5% being male. The mostly affected sites were lymph nodes (31.8%). Most patients (82.1%) received chemotherapy, while 14.7% received radiation therapy. For all the patients, the 1-year, 3-year, 5-year, and 10-year overall survival (OS) were 68.7%, 49.8%, 43.9%, and 39.2%, respectively, and the corresponding disease-specific survival (DSS) were 73.6%, 56.0%, 50.2%, and 48.1%, respectively. Univariate AFT analysis showed that older age, marital status of divorced, widowed and separated at diagnosis, primary BPDCN only, treatment delay for 3-6 months and without radiation therapy were significantly associated with poor prognosis of primary BPDCN patients. But multivariate AFT analysis indicated that older age was independently associated with worse survival, while second primary malignancies (SPMs) and radiation therapy were independently associated with extended survival.

Conclusions

Primary BPDCN is a rare disease with poor prognosis. Advanced age was linked independently to poorer survival, while SPMs and radiation therapy were linked independently to prolonged survival.
Comprehensive analysis of untargeted metabolomics and lipidomics in girls with central precocious puberty
Authors: Zhao Hong-Ying , Zhang Ya-Rong , Zhang Ran , Li Yu-Ting , Guo Rong-Lian , Shi Wen-Sheng
Published: May 2023

Objective

Central precocious puberty (CPP) is a rare condition that causes early sexual development in children. Although the cure is effective, the etiology of central precocious puberty is unclear.

Methods

In total, 10 girls with central precocious puberty and same number of age-matched female controls were enrolled. Plasma samples were collected from each participant and subjected to untargeted metabolomics and lipidomics. Student's t-tests were employed to compare the mean of each metabolite and lipid. Furthermore, orthogonal partial least-squares discriminant analysis was conducted and the variable importance in the projection was calculated to identify differentially expressed metabolites or lipids. Subsequent bioinformatics was conducted to investigate the potential function of differentially expressed metabolites and lipids.

Results

Fifty-nine differentially expressed metabolites were identified based on the criteria used (variable importance in the projection >1 and a P value < 0.05). Kyoto Encyclopedia Genes and Genome (KEGG) enrichment analysis showed that differentially expressed metabolites were enriched in four pathways: beta-alanine metabolism, histidine metabolism, bile secretion, and steroid hormone biosynthesis. As for the lipidomics, 41 differentially expressed lipids were observed and chain length analysis and lipid saturation analysis yielded similar results. Significant differences between the two groups were only observed in (O-acyl) ω-hydroxy fatty acids (OAHFA).

Conclusion

The present study showed that antibiotic overuse, increased meat consumption, and obesity may have potential roles in the development of central precocious puberty in girls. Several metabolites have diagnostic value but further research is required.
Median effective volume of 0.2% ropivacaine for ultrasound-guided supraclavicular brachial plexus block in children aged 1–6 years: a prospective dose-finding study
Authors: Liu Ling , Yang Fei , Gao Wen , Li Shangyingying , Tian Yaqiong , Yang Li , Tu Shengfen
Published: May 2023

Objective

To determine the median effective volume (EV50) of 0.2% ropivacaine for ultrasound-guided supraclavicular brachial plexus block (SC-BPB) in children aged 1–6 years.

Methods

Children aged from 1 to 6 years with an American Society of Anaesthesiologists (ASA) physical status I–II who were scheduled for unilateral upper extremity surgery at the Children's Hospital of Chongqing Medical University were recruited. All patients underwent surgery under general anaesthesia combined with brachial plexus block. SC-BPB was guided by ultrasound after anaesthesia induction, and 0.2% ropivacaine was given after localization. In the study, we used Dixon's up-and-down approach with an initial dose of 0.50 ml/kg. Considering the effect of the previous block, a successful or failed block could produce a 0.05 ml/kg decrement or increment in volume, correspondingly. The experiment was stopped when there were 7 inflection points. Using isotonic regression and bootstrapping algorithms, the EV50, the 95% effective volume (EV95) and the 95% confidence interval (CI) were calculated. The patients’ general information, postoperative pain scores, and adverse events were also recorded.

Results

Twenty-seven patients were involved in this study. The EV50 of 0.2% ropivacaine was 0.150 ml/kg (95% CI, 0.131–0.169 ml/kg) and the EV95 (secondary metric) was 0.195 ml/kg (95% CI, 0.188–0.197 ml/kg). No adverse events occurred during the research study.

Conclusions

For ultrasound-guided SC-BPB in children aged 1–6 years undergoing unilateral upper extremity surgery, the EV50 of 0.2% ropivacaine was 0.150 ml/kg (95% CI, 0.131–0.169 ml/kg).
Single botanical drugs in the Ayurvedic Pharmacopoeia of India—A quantitative ethnobotanical analysis
Authors: Yao Ruyu , Heinrich Michael , Zhang Bengang , Wei Xueping , Qi Yaodong , Gao Weiwei
Published: May 2023

Developing evidence-based uses of herbal medicines and natural product-based drug discovery are two core aims of ethnopharmacology. This requires an understanding of the medicinal plants and the traditional medical knowledge associated with them which is a basis for cross-cultural comparison. The botanical drugs of traditional medical systems are still not understood well, even for well-known and widely respected traditions like Ayurveda. In this study, a quantitative ethnobotanical analysis was performed on the single botanical drugs included in the Ayurvedic Pharmacopoeia of India (API), presenting an overview on the medicinal plants of Ayurveda from perspectives of plant systematics and medical ethnobotany. Part-I of API includes 621 single botanical drugs, which are sourced from 393 species (323 genera in 115 families). Of these, 96 species yield two or more drugs, together accounting for 238 drugs. Taking the traditional concepts, biomedical uses and the pragmatic disease classification into account, therapeutic uses of these botanical drugs are sorted into 20 categories, which meet primary health demands. The therapeutic uses of the drugs sourced from the same species may differ considerably, but 30 of the 238 drugs are used in highly similar way. The comparative phylogenetic analysis identifies 172 species with high potential for specific therapeutic uses. This medical ethnobotanical assessment for the first time provides a comprehensive understanding on the single botanical drugs in API from the perspective of medical botany using an “etic” (scientist-oriented) approach. This study also highlights the importance of quantitative ethnobotanic methods in understanding traditional medical knowledge.
Whole-genome sequencing of Alcaligenes sp. strain MMA: insight into the antibiotic and heavy metal resistant genes
Authors: Sodhi Kushneet Kaur , Singh Chandra Kant , Kumar Mohit , Singh Dileep Kumar
Published: May 2023

Introduction: A wide range of pollutants, including the likes of xenobiotics, heavy metals, and antibiotics, are characteristic of marine ecosystems. The ability of the bacteria to flourish under high metal stress favors the selection of antibiotic resistance in aquatic environments. Increased use and misuse of antibiotics in medicine, agriculture, and veterinary have posed a grave concern over antimicrobial resistance. The exposure to these heavy metals and antibiotics in the bacteria drives the evolution of antibiotic and heavy metal resistance genes. In the earlier study by the author Alcaligenes sp. MMA was involved in the removal of heavy metals and antibiotics. Alcaligenes display diverse bioremediation capabilities but remain unexplored at the level of the genome.

Methods: To shed light on its genome, the Alcaligenes sp. strain MMA, was sequenced using Illumina Nova Seq sequencer, which resulted in a draft genome of 3.9 Mb. The genome annotation was done using Rapid annotation using subsystem technology (RAST). Given the spread of antimicrobial resistance and the generation of multi-drug resistant pathogens (MDR), the strain MMA was checked for potential antibiotic and heavy metal resistance genes Further, we checked for the presence of biosynthetic gene clusters in the draft genome.

Results:Alcaligenes sp. strain MMA, was sequenced using Illumina Nova Seq sequencer, which resulted in a draft genome of 3.9 Mb. The RAST analysis revealed the presence of 3685 protein-coding genes, involved in the removal of antibiotics and heavy metals. Multiple metal-resistant genes and genes conferring resistance to tetracycline, beta-lactams, and fluoroquinolones were present in the draft genome. Many types of BGCs were predicted, such as siderophore. The secondary metabolites of fungi and bacteria are a rich source of novel bioactive compounds which have the potential to in new drug candidates.

Discussion: The results of this study provide information on the strain MMA genome and are valuable for the researcher in further exploitation of the strain MMA for bioremediation. Moreover, whole-genome sequencing has become a useful tool to monitor the spread of antibiotic resistance, a global threat to healthcare.
Interaction and potential mechanisms between atorvastatin and voriconazole, agents used to treat dyslipidemia and fungal infections
Authors: Xun Tianrong , Rong Yan , Lv Bin , Tian Jinfei , Zhang Qing , Yang Xixiao
Published: May 2023

Purpose: Voriconazole (VOR) is combined with atorvastatin (ATO) to treat fungal infections in patients with dyslipidemia in clinical practice. However, the pharmacokinetic interactions and potential mechanisms between them are unknown. Therefore, this study aimed to investigate the pharmacokinetic interactions and potential mechanisms between ATO and VOR.

Patients and methods: We collected plasma samples from three patients using ATO and VOR. Rats were administered either VOR or normal saline for 6 days, followed by a single dose of 2 mg/kg ATO, and then plasma samples were collected at different time points. The incubation models of human liver microsomes or HepG2 cells were constructed in vitro. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system was developed to determine the concentration of ATO, 2-hydroxy-ATO, 4-hydroxy-ATO, and VOR.

Results: In patients, VOR significantly reduced the metabolism of ATO and slowed the formation of 2-hydroxy- and 4-hydroxy-ATO. In rats pretreated with orally administered VOR for 6 days or normal saline given a single dose of 2 mg/kg ATO administered orally on Day 6, the t1/2 of ATO was significantly prolonged from 3.61 to 6.43 h, and the area under the concentration-time curve (AUC0–24h) values of ATO increased from 53.86 to 176.84 h μg.L−1. However, the pharmacokinetic parameters of VOR (20 mg/kg) with or without pretreatment with ATO (2 mg/kg) only slightly changed. In vitro studies indicated that VOR inhibited the metabolism of ATO and testosterone, and the IC50 values were 45.94 and 49.81 μM. However, no significant change in transporter behaviors of ATO was observed when VOR or transporter inhibitors were co-administered.

Conclusion: Our study demonstrated that VOR has significant interactions with ATO, probably due to VOR’s inhibition of the CYP3A4-mediated metabolism of ATO. Based on the clinical cases and potential interactions, the basic data obtained in our study are expected to help adjust the dose of ATO and promote the design of rational dosage regimens for pharmacotherapy for fungal infections in patients with dyslipidemia.
An insight into novel therapeutic potentials of taxifolin
Authors: Liu Yang , Shi Xiaolu , Tian Ye , Zhai Shaobo , Liu Yuyan , Xiong Zhengrong , Chu Shunli
Published: May 2023

Taxifolin is a flavonoid compound, originally isolated from the bark of Douglas fir trees, which is often found in foods such as onions and olive oil, and is also used in commercial preparations, and has attracted the interest of nutritionists and medicinal chemists due to its broad range of health-promoting effects. It is a powerful antioxidant with excellent antioxidant, anti-inflammatory, anti-microbial and other pharmacological activities. This review focuses on the breakthroughs in taxifolin for the treatment of diseases from 2019 to 2022 according to various systems of the human body, such as the nervous system, immune system, and digestive system, and on the basis of this review, we summarize the problems of current research and try to suggest solutions and future research directions.
Gallbladder cancer: current and future treatment options
Authors: Zhou Yanzhao , Yuan Kun , Yang Yi , Ji Zemin , Zhou Dezheng , Ouyang Jingzhong , Wang Zhengzheng , Wang Fuqiang , Liu Chang , Li Qingjun , Zhang Qi , Li Qiang , Shan Xiao , Zhou Jinxue
Published: May 2023

Surgery remains the preferred treatment option for early-stage gallbladder cancer (GBC). According to the anatomical position of the primary tumor, accurate preoperative stage and strict control of surgical indications, appropriate surgical strategies are selected to achieve the optimal surgical effect. However, most patients have already been at the locally advanced stage or the tumor has metastasized at the initial diagnosis. The postoperative recurrence rate and 5-year survival rate remain unsatisfactory even after radical resection for gallbladder cancer. Hence, there is an urgent need for more treatment options, such as neoadjuvant therapy, postoperative adjuvant therapy and first-line and second-line treatments of local progression and metastasis, in the whole-course treatment management of gallbladder cancer patients. In recent years, the application of molecular targeted drugs and immunotherapy has brought greater hope and broader prospects for the treatment of gallbladder cancer, but their effects in improving the prognosis of patients still lack sufficient evidence-based medicine evidence, so many problems should be addressed by further research. Based on the latest progress in gallbladder cancer research, this review systematically analyzes the treatment trends of gallbladder cancer.
The effect of ginsenosides on liver injury in preclinical studies: a systematic review and meta-analysis
Authors: Bian Xing-Bo , Yu Peng-Cheng , Yang Xiao-Hang , Han Liu , Wang Qi-Yao , Zhang Li , Zhang Lian-Xue , Sun Xin
Published: May 2023

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported.

Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis.

Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity.

Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.
Review on the protective mechanism of astragaloside IV against cardiovascular diseases
Authors: Yang Chunkun , Pan Qingquan , Ji Kui , Tian Zhuang , Zhou Hongyuan , Li Shuanghong , Luo Chuanchao , Li Jun
Published: May 2023

Cardiovascular disease is a global health problem. Astragaloside IV (AS-IV) is a saponin compound extracted from the roots of the Chinese herb Astragalus. Over the past few decades, AS-IV has been shown to possess various pharmacological properties. It can protect the myocardium through antioxidative stress, anti-inflammatory effects, regulation of calcium homeostasis, improvement of myocardial energy metabolism, anti-apoptosis, anti-cardiomyocyte hypertrophy, anti-myocardial fibrosis, regulation of myocardial autophagy, and improvement of myocardial microcirculation. AS-IV exerts protective effects on blood vessels. For example, it can protect vascular endothelial cells through antioxidative stress and anti-inflammatory pathways, relax blood vessels, stabilize atherosclerotic plaques, and inhibit the proliferation and migration of vascular smooth muscle cells. Thus, the bioavailability of AS-IV is low. Toxicology indicates that AS-IV is safe, but should be used cautiously in pregnant women. In this paper, we review the mechanisms of AS-IV prevention and treatment of cardiovascular diseases in recent years to provide a reference for future research and drug development.
RETRACTED: FEM analysis of the impact of surface undulations on the natural convective flow of viscous fluid in a permeable trapezoidal enclosure
Authors: Bilal Sardar , Khan Noor Zeb , Eldin Sayed M.
Published: May 2023

Examination of the transport mechanism in a permeable trapezoidal enclosure with an undulation effect is commenced. A formulation describing naturally convective flow in a permeable domain is conceded by employing Boussinesq and Darcy approximations. Uniform temperature is provided at the circular cylinder and base wall of the enclosure, whereas non-parallel side extremities are kept cold. No heat flux condition is applied at a wavy surface (upper) to maintain the potential difference in temperature for generation of convection. A finite element scheme is opted to resolve the governing system for accounted physical problems. The grid sensitivity test is also executed to assure the credibility of the code and results. A wide range of physical parameters is selected to comprehend their impact on streamlines and isotherm patterns. Results are revealed comparatively for zero undulation (upper solid straight wall) and with undulations (wavy wall). Heat flux and kinetic energy are also enumerated as key quantities against concerning parameters. It is depicted that the average Nusselt number and kinetic energy are more in the absence of undulations than when it is present. Additionally, it is manifested that the placement of a heated cylinder helps transfer heat in the domain and the production of thermal convective potential.
A THz fiber polarization splitter based on anti-resonant hollow-core fiber with the asymmetric dual-suspended cores
Authors: Lu Yipeng , Han Zhongrui , Tian Fengjun , Zeng Zhibin , Chen Youzhi , Xiu Zhiguo , Liu Sichen , liu Chao , Yang Xinghua , Zhang Jianzhong
Published: May 2023

In this paper a novel THz fiber polarization splitter based on anti-resonant hollow-core fiber with asymmetric dual-suspended cores has been proposed. For the proposed polarization splitter, the ultra-low confinement loss and great polarization splitting performance in the THz band can be achieved, which benefits from the good combination of anti-resonance mechanism with refractive index guidance mechanism. In order to confine the THz wave well in the central large air hole, 8 sets of anti-resonance rings are introduced into the cladding of the fiber. Moreover, the asymmetric dual-suspended cores are used to control the polarization state of the guiding light for enhancing the polarization splitting effect, which exists in the central large air hole of anti-resonant hollow-core fiber. One of the dual cores is designed with a symmetrical structure to reduce the birefringence effect. The other core is designed with an asymmetric structure to increase that in the THz band. The numerical simulations results show that the THz polarization splitter with a length of 0.37 cm is realized in the operating band around 1 THz by optimizing the geometric structure of the dual-suspended-core fiber, and the confinement losses of both x and y polarization modes are lower than 6 × 10−3 dB/cm. Furthermore, the working bandwidth at the center frequency of 1 THz can reach ∼0.06 THz, and the extinction ratio is better than 20 dB. The proposed THz polarization splitter has the characteristics of special short length, low loss and broad bandwidth. In conclusion, it has some potential applications of polarization devices in the field of optical fiber sensing and optical fiber communications.
An improved YOLOv5 for object detection in visible and thermal infrared images based on contrastive learning
Authors: Tu Xiaoguang , Yuan Zihao , Liu Bokai , Liu Jianhua , Hu Yan , Hua Houqiang , Wei Lin
Published: May 2023

An improved algorithm has been proposed to address the challenges encountered in object detection using visible and thermal infrared images. These challenges include the diversity of object detection perspectives, deformation of the object, occlusion, illumination, and detection of small objects. The proposed algorithm introduces the concept of contrastive learning into the YOLOv5 object detection network. To extract image features for contrastive loss calculation, object and background image regions are randomly cropped from image samples. The contrastive loss is then integrated into the YOLOv5 network, and the combined loss function of both object detection and contrastive learning is used to optimize the network parameters. By utilizing the strategy of contrastive learning, the distinction between the background and the object in the feature space is improved, leading to enhanced object detection performance of the YOLOv5 network. The proposed algorithm has shown pleasing detection results in both visible and thermal infrared images.