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AimsThis study aimed to investigate the association between the gut microbiota and the risk of stroke.MethodsFaecal samples from 60 participants in South China, including 45 individuals with risk factors for stroke and 15 healthy controls, were collected and subjected to 16S rRNA sequencing. A bioinformatics analysis was performed to characterise the gut microbial diversity and taxonomic compositions at different risk levels (low, moderate, and high) of stroke. Functional prediction and correlation analyses between the microbiota and laboratory markers were performed to explore the potential mechanisms.ResultsA significant difference in beta diversity was observed between the participants from the stroke risk and healthy control groups. Linear discriminant effect size analysis revealed a large number of vascular beneficial bacteria enriched in the participants from the healthy control and low-risk groups, but a few vascular harmful bacteria were more abundant in the participants from the high-risk group than in those from the other groups. In addition, Anaerostipes, Clostridium_XlVb, and Flavonifractor, all of which belonged to the Firmicutes phylum, were enriched in the participants from the low-risk group, and their relative abundances gradually decreased as the stroke risk increased. Spearman’s analysis revealed that these outstanding microbiota correlated with the levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, white blood cells, neutrophils, and carotid intima-media thickness.ConclusionThe preliminary evidence suggests that gut microbiota is associated with stroke risk. It potentially ameliorates atherosclerosis by targeting lipid metabolism and inflammation. This provides novel insights into the early screening of stroke risk and primary prevention.

Background: Cerebral resuscitation is one of the main therapeutic aims in the treatment of cardiac arrest (CA) patients who experience a return of spontaneous circulation (ROSC). However, the therapeutic effects of current treatments are not ideal. The purpose of this study was to evaluate the efficacy of neurological function of acupuncture combined with conventional cardiopulmonary cerebral resuscitationthe (CPCR) for patients after ROSC. Methods: Seven electronic databases and other related websites were searched to identify studies on acupuncture combined with conventional CPCR for patients after ROSC. R software was used to conduct a meta-analysis, and the outcomes that could not be pooled were analyzed using a descriptive analysis. Results: Seven RCTs involving 411 participants who had experienced ROSC were eligible for inclusion. The main acupoints were Neiguan (PC6), Shuigou (DU26), Baihui (DU20), Yongquan (KI1), and Sanyinjiao (SP6). Compared to conventional CPCR, acupuncture combined with conventional CPCR led to significantly higher Glasgow Coma Scale (GCS) scores on day 3 (mean difference (MD)=0.89, 95% CI: 0.43, 1.35, I2 = 0%), day 5 (MD = 1.21, 95% CI: 0.27, 2.15; I2 = 0%), and day 7 (MD = 1.92, 95% CI: 1.35, 2.50; I2 = 0%). Conclusion: Acupuncture-assisted conventional CPCR may have a potential role in improving neurological function in CA patients after ROSC, but the certainty of evidence is very low and more high-quality studies are required. Protocol registration: This review was registered at the International Prospective Registry of Systematic Reviews (PROSPERO): CRD42021262262.

Background: Alcohol use disorder (AUD) is characterized by chronic excessive alcohol consumption, often alternating with periods of abstinence known as alcohol withdrawal syndrome (AWS). Diazepam is the preferred benzodiazepine for treatment of alcohol withdrawal syndrome under most circumstances, but the specific mechanism underlying the treatment needs further research.Methods: We constructed an animal model of two-bottle choices and chronic intermittent ethanol exposure. LC-MS/MS proteomic analysis based on the label-free and intensity-based quantification approach was used to detect the protein profile of the whole brain. Weighted gene correlated network analysis was applied for scale-free network topology analysis. We established a protein–protein interaction network based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software and identified hub proteins by CytoHubba and MCODE plugins of Cytoscape. The online tool Targetscan identified miRNA–mRNA pair interactions.Results: Seven hub proteins (Dlg3, Dlg4, Shank3, Grin2b, Camk2b, Camk2a and Syngap1) were implicated in alcohol withdrawal syndrome or diazepam treatment. In enrichment analysis, glutamatergic synapses were considered the most important pathway related to alcohol use disorder. Decreased glutamatergic synapses were observed in the late stage of withdrawal, as a protective mechanism that attenuated withdrawal-induced excitotoxicity. Diazepam treatment during withdrawal increased glutamatergic synapses, alleviating withdrawal-induced synapse inhibition.Conclusion: Glutamatergic synapses are considered the most important pathway related to alcohol use disorder that may be a potential molecular target for new interventional strategies.

Introduction: Venlafaxine (VEN) is a widely used dual selective serotonin/noradrenaline reuptake inhibitor indicated for depression and anxiety. It undergoes first-pass metabolism to its active metabolite, O-desmethyl venlafaxine (ODV). The aim of the present study was to develop a joint population pharmacokinetic (PPK) model to characterize their pharmacokinetic characters simultaneously.Methods: Plasma concentrations with demographic and clinical data were derived from a bioequivalence study in 24 healthy subjects and a naturalistic TDM setting containing 127 psychiatric patients. A parent-metabolite PPK modeling was performed with NONMEM software using a non-linear mixed effect modeling approach. Goodness of fit plots and normalized prediction distribution error method were used for model validation.Results and conclusion: Concentrations of VEN and ODV were well described with a one-compartment model incorporating first-pass metabolism. The first-pass metabolism was modeled as a first-order conversion. The morbid state and concomitant amisulpride were identified as two significant covariates affecting the clearance of VEN and ODV, which may account for some of the variations in exposure. This model may contribute to the precision medication in clinical practice and may inspire other drugs with pre-system metabolism.

Background: This study aims to summarize the available evidence and guideline/consensus recommendations for acupuncture and moxibustion in the treatment, prevention and rehabilitation of patients with coronavirus disease 2019 (COVID-19). Methods: A scoping review was performed. Eight electronic databases and other related websites were searched. All studies related to acupuncture and moxibustion for COVID-19 were considered. Descriptive analysis was applied to analyze the all included studies and guideline recommendations. Results: We ultimately included 131 eligible studies. The main topics of the included studies were the treatment (82.4%) and prevention (38.9%) of COVID-19. The most included studies were literature reviews (65, 49.6%), protocols of systematic reviews (20, 15.3%), and guidelines and consensuses (18, 13.7%). The 18 (13.7%) COVID-19 guidelines and consensuses included 47 recommendations on acupuncture and moxibustion, which focused on the treatment (21/47, 44.7%), rehabilitation (17/47, 36.2%) and prevention (6, 12.8%) of COVID-19 patients. Zusanli (ST36), Feishu (BL13), Guanyuan (RN4) were recommended mostly for the treatment, rehabilitation and prevention respectively. Conclusions: Acupuncture and moxibustion are effective in the treatment of COVID-19 patients to some extent. However, more high-quality of clinical trials still needed to determine the feasibility of acupuncture and moxibustion in COVID-19 patients to better guide clinical practice. Study registration: Open Science Framework Registries (Registration DOI: 10.17605/OSF.IO/Z35WN; https://osf.io/z35wn).

Abstract Objectives To analyze the effectiveness and quality of stroke clinical practice guidelines (CPGs) published in recent years in order to guide future guideline developers to develop better guidelines. Participants No patient involved Method PubMed, China Biology Medicine (CBM), Wanfang, CNKI, and CPG-relevant websites were searched from January 2015 to December 2019 by two researchers independently. The RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was used to assess the reporting quality in terms of domains and items. Then, a subgroup analysis of the results was performed. Primary and secondary outcome measures RIGHT checklist reporting rate Results A total of 66 CPGs were included. Twice as many CPGs were published internationally as were published in China. More than half were updated. Most CPGs are published in journals, developed by societies or associations, and were evidence-based grading. The average reporting rate for all included CPGs was 47.6%. Basic information got the highest (71.7% ± 19.7%) reporting rate, while review and quality assurance got the lowest (22.0% ± 24.6%). Then, a cluster analysis between countries, publishing channels, and institutions was performed. There were no statistically significant differences in the reporting quality on the CPGs between publishing countries (China vs. international), publishing channels (journals vs. websites), and institutions (associations vs. non-associations). Conclusions Current stroke CPGs reports are of low quality. We recommend that guideline developers improve the quality of reporting of key information and improve the management of conflicts of interest. We recommend that guideline developers consider the RIGHT checklist as an important tool for guideline development. Trial registration https://doi.org/10.17605/OSF.IO/PBWUX .

Abstract The pharmacokinetic variability of lamotrigine (LTG) plays a significant role in its dosing requirements. Our goal here was to use noninvasive clinical parameters to predict the dose-adjusted concentrations (C/D ratio) of LTG based on machine learning (ML) algorithms. A total of 1141 therapeutic drug-monitoring measurements were used, 80% of which were randomly selected as the "derivation cohort" to develop the prediction algorithm, and the remaining 20% constituted the "validation cohort" to test the finally selected model. Fifteen ML models were optimized and evaluated by tenfold cross-validation on the "derivation cohort,” and were filtered by the mean absolute error (MAE). On the whole, the nonlinear models outperformed the linear models. The extra-trees’ regression algorithm delivered good performance, and was chosen to establish the predictive model. The important features were then analyzed and parameters of the model adjusted to develop the best prediction model, which accurately described the C/D ratio of LTG, especially in the intermediate-to-high range (≥ 22.1 μg mL−1 g−1 day), as illustrated by a minimal bias (mean relative error (%) = + 3%), good precision (MAE = 8.7 μg mL−1 g−1 day), and a high percentage of predictions within ± 20% of the empirical values (60.47%). This is the first study, to the best of our knowledge, to use ML algorithms to predict the C/D ratio of LTG. The results here can help clinicians adjust doses of LTG administered to patients to minimize adverse reactions.

Abstract Objective To assess the registration quality of traditional Chinese medicine (TCM) clinical trials for COVID-19, H1N1, and SARS. Method We searched for clinical trial registrations of TCM in the WHO International Clinical Trials Registry Platform (ICTRP) and Chinese Clinical Trial Registry (ChiCTR) on April 30, 2020. The registration quality assessment is based on the WHO Trial Registration Data Set (Version 1.3.1) and extra items for TCM information, including TCM background, theoretical origin, specific diagnosis criteria, description of intervention, and outcomes. Results A total of 136 records were examined, including 129 severe acute respiratory syndrome coronavirus 2 (COVID-19) and 7 H1N1 influenza (H1N1) patients. The deficiencies in the registration of TCM clinical trials (CTs) mainly focus on a low percentage reporting detailed information about interventions (46.6%), primary outcome(s) (37.7%), and key secondary outcome(s) (18.4%) and a lack of summary result (0%). For the TCM items, none of the clinical trial registrations reported the TCM background and rationale; only 6.6% provided the TCM diagnosis criteria or a description of the TCM intervention; and 27.9% provided TCM outcome(s). Conclusion Overall, although the number of registrations of TCM CTs increased, the registration quality was low. The registration quality of TCM CTs should be improved by more detailed reporting of interventions and outcomes, TCM-specific information, and sharing of the result data.

IntroductionAbnormal neurotransmission of glutamate and γ-aminobutyric acid (GABA) is a key characteristic of alcohol-related disorders. To track research output, we conducted a bibliometric analysis to explore the current status and trends in this field over the past decades.MethodsStudies related to neurotransmitters and alcohol use disorder published in English from 2005–2021 were retrieved from the Web of Science Core Collection and Scopus databases. The R–bibliometrix package was used for a descriptive analysis of the publications. Citespace, WOSviewer, and R–bibliometrix were used to construct networks of countries/institutions/authors based on co-authorship, co-citation analysis of cited references and co-occurrence as well as burst detection of keywords.ResultsA total of 4,250 unique articles and reviews were included in the final analysis. The annual growth rate of publications was 5.4%. The USA was the most productive country in this field, contributing nearly half of the total documents. The top ten most productive institutions were all located in the USA. The most frequent worldwide collaboration was between the USA and Italy. The most productive and influential institution was the University of California. The author contributing the most productions to this field was Marisa Roberto from the Scripps Research Institute. The top co-cited reference was a review titled “Neurocircuitry of addiction.” The top journal in terms of the number of records and citations was Alcoholism: Clinical and Experimental Research. Comprehensive analyses have been conducted over past decades based on co-cited reference analysis, including modulators, transporters, receptor subtypes, and animal models. In recent years, the research frontiers have been shifting to the identification of risk factors/biomarkers, drug development for alcohol use disorder, and mechanisms related to alcoholic and non-alcoholic fatty liver.ConclusionOur bibliometric analysis shows that glutamate and GABA continue to be of interest in alcohol use disorder. The focus has evolved from mechanisms and medications related to glutamate and GABA in alcohol use disorder, to novel drug development, risk factor/biomarker identification targeting neurotransmitters, and the mechanisms of related diseases.

Objective: To establish a population pharmacokinetic model in Chinese psychiatric patients to characterize escitalopram pharmacokinetic profile to identify factors influencing drug exposure, and through simulation to compare the results with the established therapeutic reference range.Methods: Demographic information, dosing regimen, CYP2C19 genotype, concomitant medications, and liver and kidney function indicators were retrospectively collected for inpatients taking escitalopram with therapeutic drug monitoring from 2018 to 2021. Nonlinear mixed-effects modeling was used to model the pharmacokinetic characteristics of escitalopram. Goodness-of-fit plots, bootstrapping, and normalized prediction distribution errors were used to evaluate the model. Simulation for different dosing regimens was based on the final estimations.Results: The study comprised 106 patients and 337 measurements of serum sample. A structural model with one compartment with first-order absorption and elimination described the data adequately. The population-estimated apparent volume of distribution and apparent clearance were 815 and 16.3 L/h, respectively. Age and CYP2C19 phenotype had a significant effect on the apparent clearance (CL/F). CL/F of escitalopram decreased with increased age, and CL/F of poor metabolizer patients was significantly lower than in extensive and immediate metabolizer patients. The final model-based simulation showed that the daily dose of adolescents with poor metabolizer might be as high as 15 mg or 20 mg and referring to the therapeutic range for adults may result in overdose and a high risk of adverse effects in older patients.Conclusion: A population pharmacokinetics model of escitalopram was successfully created for the Chinese population. Depending on the age of the patients, CYP2C19 genotype and serum drug concentrations throughout treatment are required for adequate individualization of dosing regimens. When developing a regimen for older patients, especially those who are poor metabolizers, vigilance is required.

Background and PurposeRecently, there are a number of clinical studies on traditional Chinese medicine (TCM) for post-stroke sleep disorders (PSSDs). This study aimed to map the current clinical studies and identify gaps to inform future study agendas.MethodsPubMed, Embase, Cochrane Library, and Chinese databases, including SinoMed, CNKI, and Wanfang, were searched for clinical studies on PSSDs treated with TCM from their inception to September 2021. Evidence sources, number of studies, types of PSSDs, intervention categories, effectiveness, and quality assessment were graphically displayed.ResultsThe evidence map involved 810 clinical studies, of which the earliest report was dated back to 1993, and an advanced growth of the whole evidence was observed in 2012. Randomized controlled trials (RCTs) were the most common type of study design (78.15%), and post-stroke insomnia was the most common type of sleep disorders (65.80%). The benefits of Chinese herbal medicine (CHM) and acupuncture therapies for post-stroke insomnia have been widely reported in RCTs (81.60% and 75.38%, respectively). However, the benefits of CHM interventions were assessed using a global approach rather than being based on a specific formula, and the highest level of evidence supporting the effectiveness of acupuncture therapies was of low methodological quality. In addition, evidence from primary studies was insufficient in the areas of TCM for post-stroke sleep-related breathing disorders (SBDs) and Chinese mind-body exercises for post-stroke insomnia.ConclusionsPSSDs treated with TCM have been widely assessed in clinical studies. For better evidence translation, clinical trials on specific CHM interventions and high-quality systematic reviews on acupuncture for post-stroke insomnia should be conducted. For a better solution to clinical questions, TCM on SBDs after stroke and the benefits of Chinese mind-body exercises for post-stroke insomnia should be explored in future clinical studies.

Background and PurposeOverweight/obesity is a modified risk factor for stroke. This systematic review and meta-analysis aimed to assess the impact of different obesity phenotypes on stroke risk in adults.MethodsThe PubMed, Embase, and Cochrane Library databases were searched from their inception to 7 March 2021 to identify the prospective cohort studies investigating stroke risk among different metabolic overweight/obesity phenotypes. The methodological quality of the included studies was evaluated using the Newcastle–Ottawa Scale. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model.ResultsA total of eleven prospective cohorts (n = 5,609,945 participants) were included in the systematic review, nine of which were included in the meta-analysis. All metabolically unhealthy phenotypes had a higher risk of stroke than the metabolically healthy normal-weight phenotypes, including metabolically unhealthy normal weight (HR = 1.63, 95% CI: 1.41–1.89, I2 = 89.74%, n = 7 cohort studies, 1,042,542 participants), metabolically unhealthy overweight (HR = 1.94, 95% CI: 1.58–2.40, I2 = 91.17%, n = 4 cohort studies, 676,166 participants), and metabolically unhealthy obese (HR = 1.99, 95% CI: 1.66–2.40, I2 = 93.49%, n = 6 cohort studies, 1,035,420 participants) phenotypes. However, no risk of stroke was observed in the populations with metabolically healthy overweight (MHOW) (HR = 1.07, 95% CI: 1.00–1.14, I2 = 69.50%, n = 5 studies, 4,171,943 participants) and metabolically healthy obese (MHO) (HR = 1.07, 95% CI: 0.99–1.16, I2 = 54.82%, n = 8 studies, 5,333,485 participants) phenotypes. The subgroup analyses for the MHO studies suggested that the risk of stroke increased only when the MHO participants were mainly females, from North America, and when the World Health Organization standard was applied to define obesity. In the subgroup analysis of the risk of stroke in MHOW, a longer follow-up duration was also associated with a higher risk of stroke.ConclusionThe risk of stroke increase for all metabolically unhealthy phenotypes irrespective of the body mass index (BMI). The associated risk of stroke with metabolic health but high BMI shows substantial heterogeneity, which requires future research considering the impact of sex and transition of the metabolic status on the risk of stroke.Systematic Review RegistrationThe study protocol was prospectively registered in PROSPERO (No. CRD42021251021).

Background: Acute infectious diseases constitute the most prevalent public health emergency (PHE) in China. Chinese herbal medicine (CHM) has long been used in the treatment of acute infections, but the overall evidence of its benefit and harm has not been comprehensively and systematically evaluated.Methods: We searched CBM, CNKI, Wanfang, PubMed, Cochrane Library, embase and preprint platforms to retrieve systematic reviews (SRs) on CHM for acute infectious. Participants with COVID-19, SARS, H1N1, tuberculosis, bacillary dysentery, mumps, herpangina, hand-foot-and-mouth disease (HFMD), and other acute infectious diseases were included. Interventional group consisting of patients treated with CHM combined with Western medicine or CHM alone. The AMSTAR 2 tool was used to assess the methodological quality of the retrieved studies. Information on interventions, control measures and outcomes of the included studies was extracted, and meta-analyses were qualitatively synthesized.Results: A total of 51 SRs and meta-analyses were eligible for this overview, including 19 for COVID-19, 11 for hand-foot-and-mouth disease, 8 for severe acute respiratory syndrome (SARS), 4 for tuberculosis, 3 for mumps, 2 for bacillary dysentery, 2 for H1N1 influenza and 2 for herpangina. Six systematic reviews were of high quality, all of which were on the use of CHM for COVID-19; 24 were of moderate quality; 10 were of low quality; and 11 were of very low quality. CHM appeared to have potential benefits in improving clinical symptoms and signs for most infections with an acceptable safety profile, and the clinical evidence of the benefits of CHM for acute respiratory infections such as COVID-19, SARS and H1N1 seems more sufficient than that for other acute infections.Conclusion: Overall, CHM, both decoction and Chinese patent medicine, used alone or in combination with conventional medicine may offer potential benefits to relieving symptoms of people with acute respiratory infections. Full reporting of disease typing, staging, and severity, and intervention details is further required for a better evidence translation to the responses for PHE. Future CHM research should focus mainly on the specific aspects of respiratory infections such as its single use for mild infections, and the adjunct administration for sever infections, and individual CHM prescriptions for well-selected outcomes should be prioritized.

An amendment to this paper has been published and can be accessed via the original article.

Background: Emerging evidence implicates the dysregulated kynurenine pathway (KP), an immune-inflammatory pathway, in the pathophysiology of mood disorders (MD), including depression and bipolar disorder characterized by a low-grade chronic pro-inflammatory state. The metabolites of the KP, an important part of the microbiota-gut-brain axis, serve as immune system modulators linking the gut microbiota (GM) with the host central nervous system.Aim: This bibliometric analysis aimed to provide a first glimpse into the KP in MD, with a focus on GM research in this field, to guide future research and promote the development of this field.Methods: Publications relating to the KP in MD between the years 2000 and 2020 were retrieved from the Scopus and Web of Science Core Collection (WoSCC), and analyzed in CiteSpace (5.7 R5W), biblioshiny (using R-Studio), and VOSviewer (1.6.16).Results: In total, 1,064 and 948 documents were extracted from the Scopus and WoSCC databases, respectively. The publications have shown rapid growth since 2006, partly owing to the largest research hotspot appearing since then, “quinolinic acid.” All the top five most relevant journals were in the neuropsychiatry field, such as Brain Behavior and Immunity. The United States and Innsbruck Medical University were the most influential country and institute, respectively. Journal co-citation analysis showed a strong tendency toward co-citation of research in the psychiatry field. Reference co-citation analysis revealed that the top four most important research focuses were “kynurenine pathway,” “psychoneuroimmunology,” “indoleamine 2,3-dioxygenase,” and “proinflammatory cytokines,” and the most recent focus was “gut-brain axis,” thus indicating the role of the KP in bridging the GM and the host immune system, and together reflecting the field’s research foundations. Overlap analysis between the thematic map of keywords and the keyword burst analysis revealed that the topics “Alzheimer’s disease,” “prefrontal cortex,” and “acid,” were research frontiers.Conclusion: This comprehensive bibliometric study provides an updated perspective on research associated with the KP in MD, with a focus on the current status of GM research in this field. This perspective may benefit researchers in choosing suitable journals and collaborators, and aid in the further understanding of the field’s hotspots and frontiers, thus facilitating future research.

Background: There is a crucial link between the gut microbiota and the host central nervous system, and the communication between them occurs via a bidirectional pathway termed the “microbiota-gut-brain axis.” The gut microbiome in the modern environment has markedly changed in response to environmental factors. These changes may affect a broad range of host psychiatric disorders, such as depression, by interacting with the host through metabolic, immune, neural, and endocrine pathways. Nevertheless, the general aspects of the links between the gut microbiota and depression have not been systematically investigated through bibliometric analysis.Aim: This study aimed to analyze the current status and developing trends in gut microbiota research in the depression field through bibliometric and visual analysis.Methods: A total of 1,962 publications published between 1999 and 2019 were retrieved from the Web of Science Core Collection. CiteSpace (5.6 R5) was used to perform collaboration network analysis, co-citation analysis, co-occurrence analysis, and citation burst detection.Results: The number of publications has been rapidly growing since 2010. The collaboration network analysis revealed that the USA, University College Cork, and John F. Cryan were the most influential country, institute, and scholar, respectively. The most productive and co-cited journals were Brain Behavior and Immunity and Proceedings of the National Academy of Sciences of the United States of America, respectively. The co-citation analysis of references revealed that the most recent research focus was in the largest theme cluster, “cytokines,” thus reflecting the important research foundation in this field. The co-occurrence analysis of keywords revealed that “fecal microbiota” and “microbiome” have become the top two research hotspots since 2013. The citation burst detection for keywords identified several keywords, including “Parkinson's disease,” “microbiota-gut-brain axis,” “microbiome,” “dysbiosis,” “bipolar disorder,” “impact,” “C reactive protein,” and “immune system,” as new research frontiers, which have currently ongoing bursts.Conclusions: These results provide an instructive perspective on the current research and future directions in the study of the links between the gut microbiota and depression, which may help researchers choose suitable cooperators or journals, and promote their research illustrating the underlying molecular mechanisms of depression, including its etiology, prevention, and treatment.

L-Asparagine (ASN) is the catalyze substrate of L-asparaginase (ASNase), which is an important drug for acute lymphoblastic leukemia (ALL) patients. The ASN level is found to be closely associated with the effectiveness of ASNase treatment. In this study, a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method was developed for the determination of ASN in the human serum using a stable isotope-labeled internal standard (ASN-D3). Serum samples were prepared by a one-step precipitation procedure using methanol and separated by an Agilent HILIC Plus column with the mobile phase of methanol-water (95 : 5, v/v, containing 5 mM ammonium formate and 0.1% formic acid), at a constant flow rate of 0.3 mL/min. Mass spectrometric analysis was conducted using multiple-reaction monitoring in the positive electrospray ionization mode. Serum ASN concentrations were determined over a linear calibration curve range of 2–200 μM, with acceptable accuracies and precisions. The validated HILIC-MS/MS method was successfully applied to the quantification of ASN levels in the serum from patients with ALL. Collectively, the research may shed new light on an alternative rapid, simple, and convenient quantitative method for determination of serum ASN in ALL patients treated with ASNase.

BACKGROUND AND OBJECTIVE:In Parkinson's disease (PD), wearing off and side effects of long-term medication and complications pose challenges for neurologists. Although Tai Chi is beneficial for many illnesses, its efficacy for PD remains uncertain. The purpose of this review was to evaluate the efficacy and safety of Tai Chi for PD. METHODS:Randomized controlled trials (RCTs) of Tai Chi for PD were electronically searched by the end of December 2013 and identified by two independent reviewers. The tool from the Cochrane Handbook 5.1 was used to assess the risk of bias. A standard meta-analysis was performed using RevMan 5.2 software. RESULTS:Ten trials with PD of mild-to-moderate severity were included in the review, and nine trials (n = 409) were included in the meta-analysis. The risk of bias was generally high in the blinding of participants and personnel. Improvements in the Unified Parkinson's Disease Rating Scale Part III (mean difference (MD) -4.34, 95% confidence interval (CI) -6.67--2.01), Berg Balance Scale (MD: 4.25, 95% CI: 2.83-5.66), functional reach test (MD: 3.89, 95% CI: 1.73-6.04), Timed Up and Go test (MD: -0.75, 95% CI: -1.30--0.21), stride length (standardized MD: 0.56, 95% CI: 0.03-1.09), health-related quality of life (standardized MD: -1.10, 95% CI: -1.81--0.39) and reduction of falls were greater after interventions with Tai Chi plus medication. Satisfaction and safety were high. Intervention with Tai Chi alone was more effective for only a few balance and mobility outcomes. CONCLUSIONS:Tai Chi performed with medication resulted in promising gains in mobility and balance, and it was safe and popular among PD patients at an early stage of the disease. This provides a new evidence for PD management. More RCTs with larger sample size that carefully address blinding and prudently select outcomes are needed. PROSPERO registration number CRD42013004989.

Objectives: To analyze the factors affecting the concentrations of the active moiety of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in psychiatric outpatients taking immediate-release formulations. Methods: This is a retrospective study on the therapeutic drug monitoring (TDM) data regarding RIS and 9-OH-RIS in adult psychiatric outpatients. TDM data with simultaneous RIS and 9-OH-RIS monitoring from March 2018 to February 2020 and relevant medical records (including dosage, dosage form, sex, age, diagnosis, combined medication, and comorbid disease) from 399 adult psychiatric outpatients (223 males and 176 females) were included in this study. Results: The daily dose of RIS was 5.56 ± 2.05 mg, the concentration of total active moiety was 42.35 ± 25.46 ng/mL, and the dose-adjusted plasma concentration (C/D) of active moiety was 7.83 ± 3.87 (ng/ml)/(mg/day). Dose, sex, and age were identified as important factors influencing concentrations of RIS and 9-OH-RIS in adult psychiatric outpatients. Conclusions: Individualized medication adjustments should be made according to the specific conditions of psychiatric outpatients. The findings strongly support the use of TDM to guide dosing decisions in psychiatric outpatients taking RIS. [ABSTRACT FROM AUTHOR]

Abstract Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.

Mitochondria, as the core metabolic organelles, play a crucial role in aerobic respiration/biosynthesis in fungi. Numerous studies have demonstrated a close relationship between mitochondria and Candida albicans virulence and drug resistance. Here, we report an octapeptide-aminopeptidase located in the mitochondrial matrix named Oct1p. Its homolog in the model fungus Saccharomyces cerevisiae is one of the key proteins in maintaining mitochondrial respiration and protein stability. In this study, we utilized evolutionary tree analysis, gene knockout experiments, mitochondrial function detection, and other methods to demonstrate the impact of Oct1p on the mitochondrial function of C. albicans. Furthermore, through transcriptome analysis, real-time quantitative PCR, and morphological observation, we discovered that the absence of Oct1p results in functional abnormalities in C. albicans, affecting hyphal growth, cell adhesion, and biofilm formation. Finally, the in vivo results of the infection of Galleria mellonella larvae and vulvovaginal candidiasis in mice indicate that the loss of Oct1p led to the decreased virulence of C. albicans. In conclusion, this study provides a solid theoretical foundation for treating Candida diseases, developing new targeted drugs, and serves as a valuable reference for investigating the connection between mitochondria and virulence in other pathogenic fungi.

IntroductionPseudomonas aeruginosa is a major nosocomial pathogen that frequently causes ventilator-associated pneumonia in specific populations. Sodium houttuyfonate (SH) has shown mild antibacterial activity against P. aeruginosa in vitro, but the mechanism of potent antimicrobial activity of SH against P. aeruginosa infection in vivo remains unclear.MethodsHere, using the mouse pneumonia model induced by P. aeruginosa nasal drip to explore the therapeutic effects of SH.ResultsWe found that SH exhibits dose-dependent therapeutic effects of reducing P. aeruginosa burden and systemic inflammation in pneumonia mice. SH ameliorates inflammatory gene expression and production of inflammatory proteins, such as interleukin-6 (IL-6), nuclear factor kappa-B (NF-κB) and toll-like receptor 4 (TLR4), associated with the TLR4/NF-κB pathway in mice with P. aeruginosa pneumonia. Furthermore, we analyzed the intestinal flora of mice and found that compared with the model group, the abundance and diversity of beneficial bacterial flora of SH treatment groups increased significantly, suggesting that SH can improve the intestinal flora disorder caused by inflammation. In addition, SH improves alpha and beta diversity index and reduces species abundance differences of intestinal flora in pneumonia mice.DiscussionTaken together, our presented results indicate that SH may effectively alleviate the acute pulmonary infection induced by P. aeruginosa by reducing the disturbance of regulating immunity and intestinal flora in mice.

The influence of the defocusing distance on melt pool morphology, defect, microstructure and mechanical properties of the laser powder bed fusion (L-PBF) of high strength Al–Cu–Mg–Mn alloy was studied. It is found that because of the different laser energy distribution, the defocusing distance has significant effects on melt pool morphology, defects, microstructure and mechanical properties of the L-PBF parts using same process parameters and laser spot size. When defocusing distance in the range of −3.0 to 0 mm, specimens with cracks, fine grains and keyhole or transition melt mode are obtained. When defocusing distance is positive or −3.0 mm, specimens with no cracks, columnar grains and conduction mode are obtained. The best mechanical properties are obtained when defocusing distance is 1.0 mm in this experiment. This paper provides a novel method for tailoring the microstructure and mechanical properties of L-PBF parts.

Background Dermatological disease significantly affects patient's health-related quality of life (HrQoL). Skindex is one of the most frequently used dermatology-specific HrQoL measures. Currently no Chinese version of Skindex is available. The aim of this study was to translate and culturally adapt Skindex-29 and Skindex-16 into Chinese, and to evaluate their reliability and validity. Methods Translation and cultural adaption were performed following guidelines for cross-cultural adaption of health-related quality of life measures. Subsequently, a cross-sectional study was conducted in which patients with dermatological disease (n = 225) were enrolled. The Chinese version of Skindex-29 and Skindex-16 and Dermatology Life Quality Index (DLQI) were completed. Reliability was evaluated with internal consistency using Cronbach's alpha. Validity was evaluated using known-groups validity, convergent validity and factor structure validity. Results There were both seven items of Skindex-29 and Skindex-16 requiring a second forward- and backward- translation to achieve the final satisfactory Chinese version. The internal consistency reliability was high (range of Cronbach's alpha for the scales of Skindex-29 0.85-0.97, Skindex-16 0.86-0.96). Known-group validity was demonstrated by higher scores from patients with inflammatory dermatosis than from patients with isolated skin lesions (P < 0.05). Evidence of factor structure validity of the Skindex-29 and Skindex-16 was demonstrated by both exploratory factor analysis that accounted for 68.66% and 77.78% of the total variance, respectively, and confirmatory factor analysis with acceptable fitness into the expected three-factor structure. Conclusion This study has developed semantically equivalent translations of Skindex-29 and Skindex-16 into Chinese. The evaluation of the instruments' psychometric properties shows they have substantial evidence of reliability and validity for use as HrQoL instruments in Chinese patients with dermatological disease. [ABSTRACT FROM AUTHOR]