An integrated strategy for in-depth profiling of N-acylethanolamines in biological samples by UHPLC-HRMS.

BACKGROUND: N-acylethanolamines (NAEs) are a class of naturally occurring bioactive lipids that play crucial roles in various physiological processes, particularly exhibiting neuroprotective and anti-inflammatory properties. However, the comprehensive profiling of endogenous NAEs in complex biological matrices is challenging due to their low abundance, structural similarity and the limited availability of commercial standards. Here, we propose an integrated strategy for comprehensive profiling of NAEs that combines chemical derivatization and a three-dimensional (3D) prediction model based on quantitative structure-retention time relationship (QSRR) using liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS). RESULTS: After acetyl chloride (ACC) derivatization, the detection sensitivity of NAEs was significantly improved. We developed a QSRR prediction model to construct an in-house database for 141 NAEs, encompassing information on RT, MS1 (m/z), and MS/MS spectra. Propargylamine-labeled fatty acids were synthesized as RT calibrants across various analytical conditions to enhance the robustness of the RT prediction model. NAEs in biological samples were then in-depth profiled using parallel reaction monitoring (PRM) acquisition. This integrated strategy identified and annotated a total of 50 NAEs across serum, hippocampus and cortex tissues from a 5xFAD mouse model of Alzheimer's disease (AD). Notably, the levels of polyunsaturated NAEs, particularly NAE 20:5 and NAE 22:6, were significantly decreased in 5xFAD mice compared to WT mice, as confirmed by accurate quantitation using ACC-d0/d3 derivatization. SIGNIFICANCE: Our integrated strategy exhibits great potential for the in-depth profiling of NAEs in complex biological samples, facilitating the elucidation of NAE functions in diverse physiological and pathological processes.

Resilient water quality management: Insights from Japan's environmental quality standards for conserving aquatic life framework.

Currently, chemicals and waste are recognized as key drivers of habitat degradation and biodiversity loss in aquatic ecosystems. To ensure vibrant habitats for aquatic species and maintain a sustainable aquatic food supply system, Japan promulgated its Environmental Quality Standards for the Conservation of Aquatic Life (EQS-CAL), based on its own aquatic life water quality criteria (ALWQC) derivation method and application mechanism. Here we overview Japan's EQS-CAL framework and highlight their best practices by examining the framework systems and related policies. Key experiences from Japan's EQS-CAL system include: (1) Classifying six types of aquatic organisms according to their adaptability to habitat status; (2) Using a risk-based chemical screening system for three groups of chemical pollutants; (3) Recommending a five-step method for determining ALWQC values based on the most sensitive life stage of the most sensitive species; (4) Applying site-specific implementation mechanisms through a series of Plan-Do-Check-Act loops. This paper offers scientific references for other jurisdictions, aiding in the development of more resilient ALWQC systems that can maintain healthy environments for aquatic life and potentially mitigate ongoing threats to human societies and global aquatic biodiversity.

Differential Pharmacodynamic Effects on Psoriatic Biomarkers by Guselkumab Versus Secukinumab Correlate with Long-Term Efficacy: An ECLIPSE Substudy.

IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at ClinicalTrials.gov (NCT03090100).

Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy.

Background: Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23-driven IL-17-producing T cell and other IL-23 receptor-positive IL-17-producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1. Design: Inflammatory cytokine serum levels were assessed (n = 118), and lesional and nonlesional skin biopsies were collected (n = 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA. Results: Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 (P < .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all P < .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway-associated and psoriasis-associated genes. Conclusion: These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. Trial registration:ClinicalTrials.govClinicalTrials.gov (NCT02207231).

Fatal hyperpyrexia caused by xylazine: a case report.

Xylazine is used in veterinary medicine as a sedative, analgesic, and muscle relaxant. However, in recent decades, it has frequently been detected in illicit drugs. Xylazine poisoning is characterized by depression of the central nervous and cardiovascular systems. Herein, we present a case of a 41-year-old man who not only had severe depression of the central nervous and cardiovascular systems, but also developed hyperpyrexia during the treatment of xylazine poisoning, which led to his death 3 days after poisoning. This case indicates that, in addition to its other effects, xylazine may also cause hyperthermia, which has not yet been reported in humans.

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis: The GUIDE Randomized Clinical Trial.

Importance: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies. Objective: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis. Design, Setting, and Participants: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively. Interventions: In GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks. Main Outcomes and Measures: Primary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI <3 at W68). Biomarker substudies assessed immunologic effects in skin and blood. Results: Overall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)-cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and ß defensin (BD)-2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified. Conclusions and Relevance: Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity. Trial Registration: ClinicalTrials.gov Identifier: NCT03818035.

Potential biomarkers for evaluating the BCG vaccination response based on humoral immunity.

Background: The current prophylactic tuberculosis vaccine Bacille Calmette-Guérin (BCG), was derived in the 1920s, but the humoral immune responses induced by BCG vaccination have not been fully elucidated to date. In this study, our aim was to reveal the profiles of antibody responses induced by BCG vaccination in adults and identify the potential biomarkers for evaluating the BCG vaccination response. Methods: Proteome microarrays were performed to reveal the serum profiles of antibody responses induced by BCG vaccination in adults. ELISA was used to validate the potential biomarkers in validation cohort (79 healthy controls and 58 BCG-vaccinated subjects). Then combined panel was established by logistic regression analysis based on OD values of potential biomarkers. Results: Multiple antigens elicited stronger serum IgG or IgM antibody responses in BCG vaccinated subjects than healthy subjects at 12 weeks post BCG vaccination; among the antigens, Rv0060, Rv2026c and Rv3379c were further verified using 137 serum samples and presented the moderate performance in assessment of the BCG vaccination response by receiver operating characteristic analysis. Furthermore, a combined panel exhibited an improved AUC of 0.923, and the sensitivity and specificity were 77.59 % and 91.14 %, respectively. In addition, the antibody response against Rv0060, Rv2026c and Rv3379c was related to the clinical background to a certain extent. Conclusions: The novel antigens identified in our study could offer better knowledge towards developing a more efficacious vaccine based on humoral immune responses, and they could be potential biomarkers in assessments of BCG vaccination responses.

Progress in Rice Breeding Based on Genomic Research.

The role of rice genomics in breeding progress is becoming increasingly important. Deeper research into the rice genome will contribute to the identification and utilization of outstanding functional genes, enriching the diversity and genetic basis of breeding materials and meeting the diverse demands for various improvements. Here, we review the significant contributions of rice genomics research to breeding progress over the last 25 years, discussing the profound impact of genomics on rice genome sequencing, functional gene exploration, and novel breeding methods, and we provide valuable insights for future research and breeding practices.

Effect of Regulation of Chemerin/Chemokine-like Receptor 1/Stimulator of Interferon Genes Pathway on Astrocyte Recruitment to Aß Plaques.

Recruitment and accumulation of reactive astrocytes around senile plaques are common pathological features of Alzheimer's disease (AD), with unclear mechanisms. Chemerin, an adipokine implicated in neuroinflammation, acts through its receptor, chemokine-like receptor 1 (CMKLR1), which also functions as a receptor for amyloid ß (Aß). The impact of the chemerin/CMKLR1 axis on astrocyte migration towards Aß plaques is unknown. Here we investigated the effect of CMKLR1 on astrocyte migration around Aß deposition in APP/PS1 mice with Cmklr1 knockout (APP/PS1-Cmklr1-/-). CMKLR1-expressed astrocytes were upregulated in the cortices and hippocampi of 9-month-old APP/PS1 mice. Chemerin mainly co-localized with neurons, and its expression was reduced in the brains of APP/PS1 mice, compared to WT mice. CMKLR1 deficiency decreased astrocyte colocalization with Aß plaques in APP/PS1-Cmklr1-/- mice, compared to APP/PS1 mice. Activation of the chemerin/CMKLR1 axis promoted the migration of primary cultured astrocytes and U251 cells, and reduced astrocyte clustering induced by Aß42. Mechanistic studies revealed that chemerin/CMKLR1 activation induced STING phosphorylation. Deletion of STING attenuated the promotion of the chemerin/CMKLR1 axis relative to astrocyte migration and abolished the inhibitory effect of chemerin on Aß42-induced astrocyte clustering. These findings suggest the involvement of the chemerin/CMKLR1/STING pathway in the regulation of astrocyte migration and recruitment to Aß plaques/Aß42.

Differential cytokine expression in gastric tissues highlights helicobacter pylori's role in gastritis.

Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1ß, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1ß, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.

Risk of heart disease and stroke among individuals with prehypertension or blood pressure progression: a national population-based cohort study.

OBJECTIVE: The purpose of our study was to analyze the association of blood pressure and blood pressure progression with heart disease and stroke among Chinese population. METHOD: We included a total of 10 122 adults aged 45 years and above free of heart disease or stroke at baseline from the China Health and Retirement Longitudinal Study cohort. We used Cox proportional hazards models to analyze the relationship between cardiovascular risk and prehypertension in subjects with or without progression to hypertension. RESULT: During a mean follow-up of 6.5 years, 1972 subjects were either diagnosed with heart disease or had a stroke (composite outcome). Compared with individuals with normotension at baseline, the fully adjusted hazard ratio (HR) [95% confidence interval (CI)] was 1.25 (1.10-1.42) and 1.52 (1.34-1.74) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. The subjects who progressed to hypertension had higher risk of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. The subjects who progressed from prehypertension to hypertension had 1.72 times higher risk [HR (95% CI): 1.72 (1.37-2.16)] of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. CONCLUSION: The cardiovascular risk of subjects with prehypertension is higher than that of subjects with normal blood pressure. After a diagnosis of hypertension, subjects who progressed from normal blood pressure to hypertension had an increased risk of heart disease and stroke.

The Application of Preoperative Computed Tomography Angiography and Color Ultrasound Assisted Lower Limb Perforator Flap Design in the Repair of Lower Limb Soft Tissue Defects.

Objective: The goal of this study was to explore the application effect of preoperative computed tomography (CT) angiography and color ultrasound-assisted design of lower limb perforator flaps in the repair of lower limb soft tissue defects. Repair of soft tissue defects in the lower limbs is a challenging surgical task, and accurate preoperative location of vascular structures and detailed design of the surgical plan are crucial to the success of the surgery. This study aims to improve the accuracy and effectiveness of lower limb perforator flap repair surgery by introducing CT angiography and color ultrasound technology. Methods: Sixty-four patients who underwent lower limb soft tissue defect repair with perforator flaps were enrolled at our hospital from February 2020 to February 2023. According to their admission time, they were divided into two groups: 32 patients admitted before June 31, 2022, were included in the control group, and preoperative color Doppler ultrasound was used to assist in designing the lower limb perforator flap; 32 patients admitted after June 31, 2022, were included in the study group, and preoperative CT angiography and color Doppler ultrasound were used to assist in designing the lower limb perforator flap. Specifically, we conducted detailed records and analyzes of patients' age distribution, gender ratio, and relevant medical history. This demographic information will help reveal whether there are differences in the effectiveness of preoperative CT angiography and color ultrasound-assisted lower extremity perforator flap design among different patient groups. By considering these key factors, we can more accurately assess the actual utility of new technologies in different patient groups and provide more specific guidance for clinical practice.The therapeutic effects of the two groups of patients were recorded. The differences between the preoperative CT angiography measurements and intraoperative actual measurements of the study group were compared. Clinical indicators, sensory function in the graft area, flap survival rate, flap complication rate, and donor area complication rate were compared between the two groups. The satisfaction of patients in the two groups with the recovery of the surgical area was also compared. Results: The treatment success rate of the study group was higher than that of the control group (P < .05). There was no significant difference in the preoperative CT angiography measurements (shallow branch localization, shallow branch starting diameter, shallow branch length, deep branch starting diameter) and intraoperative actual measurements of the study group (P > .05). The operation time and intraoperative blood loss of the study group were shorter than those of the control group (P < .05), and there was no significant difference in flap harvesting area and length of hospital stay between the two groups (P > .05). There was a difference in sensory function in the graft area between the two groups, with a higher proportion of S4 grade in the study group and better recovery compared to the control group (P < .05). There was no significant difference in satisfaction evaluation between the two groups (P > .05). Conclusion: Preoperative CT angiography and color ultrasound-assisted design of lower limb perforator flaps have shown significant clinical advantages in repairing lower limb soft tissue defects, improving treatment effects and surgical efficiency. In clinical practice, this technology is expected to reduce surgical complexity, shorten surgical time, reduce the risk of intraoperative bleeding, and achieve effective defect repair while maintaining or improving the patient's sensory function.However, there are some limitations to the study, such as the relatively small sample size and single-center nature. Future research can optimize the operation process of this technology, expand the scope of research, and explore its application in the repair of soft tissue defects caused by specific causes. This technology may provide more precise and effective options for personalized treatment, especially for patients who need to preserve more sensory function.

Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS.

As the aging population increases, the focus on elderly patients with acute respiratory distress syndrome (ARDS) is also increasing. In this article, we found progranulin (PGRN) differential expression in ARDS patients and healthy controls, even in young and old ARDS patients. Its expression strongly correlates with several cytokines in both young and elderly ARDS patients. PGRN has comparable therapeutic effects in young and elderly mice with lipopolysaccharide-induced acute lung injury, manifesting as lung injury, apoptosis, inflammation, and regulatory T cells (Tregs) differentiation. Considering that Tregs differentiation relies on metabolic reprogramming, we discovered that Tregs differentiation was mediated by mitochondrial function, especially in the aged population. Furthermore, we demonstrated that PGRN alleviated the mitochondrial damage during Tregs differentiation through the AMPK/PGC-1α pathway in T cells. Collectively, PGRN may regulate mitochondria function to promote Tregs differentiation through the AMPK/PGC-1α pathway to improve ARDS.

Effects of pelvic floor myofascial manipulation intervention on primiparas and neonates during the second stage of vaginal delivery.

A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes.

NRTPredictor: identifying rice root cell state in single-cell RNA-seq via ensemble learning.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) measurements of gene expression show great promise for studying the cellular heterogeneity of rice roots. How precisely annotating cell identity is a major unresolved problem in plant scRNA-seq analysis due to the inherent high dimensionality and sparsity. RESULTS: To address this challenge, we present NRTPredictor, an ensemble-learning system, to predict rice root cell stage and mine biomarkers through complete model interpretability. The performance of NRTPredictor was evaluated using a test dataset, with 98.01% accuracy and 95.45% recall. With the power of interpretability provided by NRTPredictor, our model recognizes 110 marker genes partially involved in phenylpropanoid biosynthesis. Expression patterns of rice root could be mapped by the above-mentioned candidate genes, showing the superiority of NRTPredictor. Integrated analysis of scRNA and bulk RNA-seq data revealed aberrant expression of Epidermis cell subpopulations in flooding, Pi, and salt stresses. CONCLUSION: Taken together, our results demonstrate that NRTPredictor is a useful tool for automated prediction of rice root cell stage and provides a valuable resource for deciphering the rice root cellular heterogeneity and the molecular mechanisms of flooding, Pi, and salt stresses. Based on the proposed model, a free webserver has been established, which is available at https://www.cgris.net/nrtp .

Creating a near-perfect circularly polarized terahertz beam through the nonreciprocity of a magnetoplasma.

Compared to other parts of the electromagnetic spectrum, the terahertz frequency range lacks efficient polarization manipulation techniques, which is impeding the proliferation of terahertz technology. In this work, we demonstrate a tunable and broadband linear-to-circular polarization converter based on an InSb plate containing a free-carrier magnetoplasma. In a wide spectral region (∼ 0.45 THz), the magnetoplasma selectively absorbs one circularly polarized mode due to electron cyclotron resonance and also reflects it at the edges of the absorption band. Both effects are nonreciprocal and contribute to form a near-zero transmission band with a high isolation of -36 dB, resulting in the output of a near-perfect circularly polarized terahertz wave for an incident linearly polarized beam. The near-zero transmission band is tunable with magnetic field to cover a wide frequency range from 0.3 to 4.8 THz.

Guselkumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa: A phase 2 randomized study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin-23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis. OBJECTIVE: To evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo-controlled, double-blind, proof-of-concept study was conducted. METHODS: Patients ≥18 years of age with moderate-to-severe HS for ≥1 year were randomized to (1) guselkumab 200 mg by subcutaneous (SC) injection every 4 weeks (q4w) through Week 36 (guselkumab SC); (2) guselkumab 1200 mg intravenously (IV) q4w for 12 weeks, then switched to guselkumab 200 mg SC q4w from Weeks 12 through 36 (guselkumab IV); or (3) placebo for 12 weeks, with re-randomization to guselkumab 200 mg SC q4w at Weeks 16 through 36 (placebo → guselkumab 200 mg) or guselkumab 100 mg SC at Weeks 16, 20, 28 and 36 and placebo at Weeks 24 and 32 (placebo → guselkumab 100 mg). End points included HS clinical response (HiSCR) and patient-reported outcomes. RESULTS: Although guselkumab SC or guselkumab IV resulted in numerically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%, respectively), statistical significance was not achieved. Numerically greater improvements in patient-reported outcomes were also observed for guselkumab SC and guselkumab IV versus placebo at Week 16. Through Week 40, no clear differences to suggest a dose response were observed for HiSCR and patient-reported outcomes. CONCLUSIONS: Despite modest improvements, the primary end point was not met and the overall findings do not support the efficacy of guselkumab in the treatment of HS. CLINICALTRIALS: gov: NCT03628924.

Genomic characteristics of Mycobacterium tuberculosis isolates of cutaneous tuberculosis.

Objectives: Cutaneous tuberculosis with various manifestations can be divided into several clinical types according to the host's immune status and infective route. However, the etiological factors of this disease remain unclear. The objective of this study is to investigate the pathogens associated with the occurrence and different types of cutaneous tuberculosis. Methods: 58 Mycobacterium tuberculosis strains isolated from cutaneous tuberculosis over the last 20 years were sequenced and analyzed for genomic characteristics including lineage distribution, drug-resistance mutations, and mutations potentially associated with different sites of infection. Results: The M. tuberculosis strains from four major types of cutaneous tuberculosis and pulmonary tuberculosis shared similar genotypes and genomic composition. The strains isolated from cutaneous tuberculosis had a lower rate of drug resistance. Phylogenic analysis showed cutaneous tuberculosis and pulmonary tuberculosis isolates scattered on the three. Several SNPs in metabolism related genes exhibited a strong correlation with different infection sites. Conclusions: The different infection sites of TB may barely be affected by large genomic changes in M. tuberculosis isolates, but the significant difference in SNPs of drug resistance gene and metabolism-related genes still deserves more attention.

[Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years].

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, ß-amyloid(Aß), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.