From creep to flow: Granular materials under cyclic shear.

When unperturbed, granular materials form stable structures that resemble the ones of other amorphous solids like metallic or colloidal glasses. Whether or not granular materials under shear have an elastic response is not known, and also the influence of particle surface roughness on the yielding transition has so far remained elusive. Here we use X-ray tomography to determine the three-dimensional microscopic dynamics of two granular systems that have different roughness and that are driven by cyclic shear. Both systems, and for all shear amplitudes Γ considered, show a cross-over from creep to diffusive dynamics, indicating that rough granular materials have no elastic response and always yield, in stark contrast to simple glasses. For the system with small roughness, we observe a clear dynamic change at Γ ≈ 0.1, accompanied by a pronounced slowing down and dynamical heterogeneity. For the large roughness system, the dynamics evolves instead continuously as a function of Γ. We rationalize this roughness dependence using the potential energy landscape of the systems: The roughness induces to this landscape a micro-corrugation with a new length scale, whose ratio over the particle size is the relevant parameter. Our results reveal the unexpected richness in relaxation mechanisms for real granular materials.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (ß=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). CONCLUSIONS: Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

Candida albicans accelerates atherosclerosis by activating intestinal hypoxia-inducible factor2α signaling.

The gut microbiota is closely linked to atherosclerosis. However, the role of intestinal fungi, essential members of the complex microbial community, in atherosclerosis is poorly understood. Herein, we show that gut fungi dysbiosis is implicated in patients with dyslipidemia, characterized by higher levels of Candida albicans (C. albicans), which are positively correlated with plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels. Furthermore, C. albicans colonization aggravates atherosclerosis progression in a mouse model of the disease. Through gain- and loss-of-function studies, we show that an intestinal hypoxia-inducible factor 2α (HIF-2α)-ceramide pathway mediates the effect of C. albicans. Mechanistically, formyl-methionine, a metabolite of C. albicans, activates intestinal HIF-2α signaling, which drives increased ceramide synthesis to accelerate atherosclerosis. Administration of the HIF-2α selective antagonist PT2385 alleviates atherosclerosis in mice by reducing ceramide levels. Our findings identify a role for intestinal fungi in atherosclerosis progression and highlight the intestinal HIF-2α-ceramide pathway as a target for atherosclerosis treatment.

Influence of plasma collection tubes on N-glycome in human blood samples.

Background and aims: Quantitative analysis of plasma N-glycome is a promising method for identifying disease biomarkers. This study aimed to investigate the impact of using blood collection tubes with different anticoagulants on plasma N-glycome. Materials and methods: We used a robust mass spectrometry method to profile plasma N-glycomes in two cohorts of healthy volunteers (cohort 1, n = 16; cohort 2, n = 53). The influence of three commonly used blood collection tubes on fully characterized N-glycomic profiles were explored. Results: Principal component analysis revealed distinct clustering of blood samples based on the collection tubes. Pairwise comparisons demonstrated significant differences between EDTA and heparin plasma in 55 out of 82 quantified N-glycan traits, and between EDTA and citrate plasma in 62 out of 82 traits. These differences encompassed various N-glycan features, including glycan type, sialylation, galactosylation, fucosylation, and bisection. Trends in N-glycan variations in citrate and heparin plasma were largely consistent compared to EDTA plasma. In correlation analysis (EDTA vs. heparin; EDTA vs. citrate), Pearson's correlation coefficients were consistently higher than 0.7 for the majority of N-glycan traits. Conclusion: Sample matrix variations impact plasma N-glycome measurements. Caution is crucial when comparing samples from different plasma collection tubes in glycomics projects.

Toxicity profiles of immune checkpoint inhibitors for recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive. METHODS: Clinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment-related adverse events (trAEs), grade three or more trAEs, treatment-related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted. RESULTS: Twenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment-related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%-65.02%), 13.82% (95% CI, 11.23%-16.62%), 0.39% (95% CI, 0.15%-0.71%), 3.99% (95% CI, 2.36%-5.95%), respectively. Programmed cell death protein 1 (PD-1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05-1.49 and 1.36, 95% CI, 1.15-1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08-1.84 and 1.79, 95% CI, 1.39-2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06-7.70 and 10.14, 95% CI, 5.49-18.70, respectively) compared with programmed death-ligand 1 (PD-L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD-1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03-1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different. CONCLUSIONS: Our study suggests that the incidences of grade three or more trAEs, treatment-related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD-L1 inhibitors monotherapy may be safer compared with PD-1 inhibitors monotherapy and ICIs combination therapy.

Transcriptome and open chromatin analysis reveals the process of myocardial cell development and key pathogenic target proteins in Long QT syndrome type 7.

OBJECTIVE: Long QT syndrome type 7 (Andersen-Tawil syndrome, ATS), which is caused by KCNJ2 gene mutation, often leads to ventricular arrhythmia, periodic paralysis and skeletal malformations. The development, differentiation and electrophysiological maturation of cardiomyocytes (CMs) changes promote the pathophysiology of Long QT syndrome type 7(LQT7). We aimed to specifically reproduce the ATS disease phenotype and study the pathogenic mechanism. METHODS AND RESULTS: We established a cardiac cell model derived from human induced pluripotent stem cells (hiPSCs) to the phenotypes and electrophysiological function, and the establishment of a human myocardial cell model that specifically reproduces the symptoms of ATS provides a reliable platform for exploring the mechanism of this disease or potential drugs. The spontaneous pulsation rate of myocardial cells in the mutation group was significantly lower than that in the repair CRISPR group, the action potential duration was prolonged, and the Kir2.1 current of the inward rectifier potassium ion channel was decreased, which is consistent with the clinical symptoms of ATS patients. Only ZNF528, a chromatin-accessible TF related to pathogenicity, was continuously regulated beginning from the cardiac mesodermal precursor cell stage (day 4), and continued to be expressed at low levels, which was identified by WGCNA method and verified with ATAC-seq data in the mutation group. Subsequently, it indicated that seven pathways were downregulated (all p < 0.05) by used single sample Gene Set Enrichment Analysis to evaluate the overall regulation of potassium-related pathways enriched in the transcriptome and proteome of late mature CMs. Among them, the three pathways (GO: 0008076, GO: 1990573 and GO: 0030007) containing the mutated gene KCNJ2 is involved that are related to the whole process by which a potassium ion enters the cell via the inward rectifier potassium channel to exert its effect were inhibited. The other four pathways are related to regulation of the potassium transmembrane pathway and sodium:potassium exchange ATPase (p < 0.05). ZNF528 small interfering (si)-RNA was applied to hiPSC-derived cardiomyocytes for CRISPR group to explore changes in potassium ion currents and growth and development related target protein levels that affect disease phenotype. Three consistently downregulated proteins (KCNJ2, CTTN and ATP1B1) associated with pathogenicity were verificated through correlation and intersection analysis. CONCLUSION: This study uncovers TFs and target proteins related to electrophysiology and developmental pathogenicity in ATS myocardial cells, obtaining novel targets for potential therapeutic candidate development that does not rely on gene editing.

Rare Disease Day: Amplifying voices, advocating hope.

Every year on February 28, the global community comes together to observe Rare Disease Day, a day dedicated to raising awareness and understanding for the millions of individuals who live with rare disorders. While individual rare diseases may seem uncommon, their collective impact is significant, affecting the lives of countless families and communities worldwide. This day serves as a crucial platform to amplify the voices of those affected, advocate for increased research and support, and inspire hope for a future where rare diseases can be prevented, diagnosed earlier, and effectively treated.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

BACKGROUND: It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. METHODS AND RESULTS: In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. CONCLUSIONS: Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

Identification and validation of the association of Janus kinase 2 mutations with the response to immune checkpoint inhibitor therapy.

BACKGROUND: Janus kinase 2 (JAK2) mutation plays an important role in T cell immunity. However, the effect of JAK2 mutation on immunotherapy is largely uncharacterized. METHODS: In this study, we analyzed the effect of JAK2 mutation on the efficacy and outcomes of immune checkpoint inhibitor (ICI) therapy in the discovery cohort (n = 662) and the verification cohort (n = 1423). Furthermore, we explored the association of JAK2 mutation with the tumor immune microenvironment in a multiomics cohort. RESULTS: In the discovery cohort (n = 662), JAK2 mutant-type patients had a better objective response rate (58.8% vs. 26.7%, P = 0.010), durable clinical benefit (64.7% vs. 38.9%, P = 0.043), progression-free survival (hazard ratio [HR] = 0.431, P = 0.015), and overall survival (HR = 0.378, P = 0.025), relative to JAK2 wild-type patients. Moreover, we further verified the prognostic significance of JAK2 mutation in an independent ICI treatment cohort with a larger sample size (n = 1423). In addition, we discovered that the JAK2 mutation was remarkably related to increased immunogenicity, such as a higher TMB, higher expression of costimulatory molecules and stimulation of antigen processing mechanisms. In addition, JAK2 mutation was positively correlated with activated anticancer immunity, such as infiltration of various immune cells and higher expression of chemokines. CONCLUSION: Our study demonstrates that JAK2 mutation is a novel marker that can be used to effectively predict prognosis and response to ICI therapy.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

AIMS: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. METHODS AND RESULTS: This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%). CONCLUSIONS: Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies.

Assessing validity of the EQ-5D-5L proxy in children and adolescents with Duchenne muscular dystrophy or spinal muscular atrophy.

OBJECTIVE: To assess the psychometric properties of the EuroQol-5-Dimension five-level instrument (EQ-5D-5L) proxy in caregivers of children and adolescents with Duchenne muscular dystrophy (DMD) or spinal muscular atrophy (SMA). METHOD: Data were collected using the EQ-5D-5L proxy for individuals with DMD or SMA, as reported by their caregivers. Ceiling and floor effects, reliability (Cronbach's alpha), convergent and divergent validity (Spearman's correlation coefficient and Bland-Altman plot) and known-group validity (analysis of variance) was used to assess the instrument's psychometric properties. RESULTS: Totally, 855 caregivers completed the questionnaire. Significant floor effects were observed for most dimensions of the EQ-5D-5L in both SMA and DMD samples. The EQ-5D-5L was strongly correlated with the hypothesized subscales of the SF-12, which confirmed satisfactory convergent and divergent validity. The EQ-5D-5L can significantly differentiate between impaired functional groups for individuals, demonstrating satisfactory discriminative ability. The agreement between the EQ-5D-5L utility and EQ-VAS scores was poor. CONCLUSIONS: Based on the measurement properties assessed in this study, the EQ-5D-5L proxy is a valid and reliable tool for measuring the health-related quality of life of individuals with DMD or SMA rated by caregivers. Further studies should examine the content validity of the EQ-5D as well as the performance of its young version in these two patient groups.

Exhaustive matching of 3D/2D coronary artery structure based on imperfect segmentations.

PURPOSE: The 3D/2D coronary artery registration technique has been developed for the guidance of the percutaneous coronary intervention. It introduces the absent 3D structural information by fusing the pre-operative computed tomography angiography (CTA) volume with the intra-operative X-ray coronary angiography (XCA) image. To conduct the registration, an accurate matching of the coronary artery structures extracted from the two imaging modalities is an essential step. METHODS: In this study, we propose an exhaustive matching algorithm to solve this problem. First, by recognizing the fake bifurcations in the XCA image caused by projection and concatenating the fractured centerline fragments, the original XCA topological structure is restored. Then, the vessel segments in the two imaging modalities are removed orderly, which generates all the potential structures to simulate the imperfect segmentation results. Finally, the CTA and XCA structures are compared pairwise, and the matching result is obtained by searching for the structure pair with the minimum similarity score. RESULTS: The experiments were conducted based on a clinical dataset collected from 46 patients and comprising of 240 CTA/XCA data pairs. And the results show that the proposed method is very effective, which achieves an accuracy of 0.960 for recognizing the fake bifurcations in the XCA image and an accuracy of 0.896 for matching the CTA/XCA vascular structures. CONCLUSION: The proposed exhaustive structure matching algorithm is simple and straightforward without any impractical assumption or time-consuming computations. With this method, the influence of the imperfect segmentations is eliminated and the accurate matching could be achieved efficiently. This lays a good foundation for the subsequent 3D/2D coronary artery registration task.

Drug Repositioning for Amyloid Transthyretin Amyloidosis by Interactome Network Corrected by Graph Neural Networks and Transcriptome Analysis.

Amyloid transthyretin (ATTR) amyloidosis caused by transthyretin misfolded into amyloid deposits in nerve and heart is a progressive rare disease. The unknown pathogenesis and the lack of therapy make the 5-year survival prognosis extremely poor. Currently available ATTR drugs can only relieve symptoms and slow down progression, but no drug has demonstrated curable effect for this disease. The growing volume of pharmacological data and large-scale genome and transcriptome data bring new opportunities to find potential new ATTR drugs through computational drug repositioning. We collected the ATTR-related in the disease pathogenesis and differentially expressed (DE) genes from five public databases and Gene Expression Omnibus expression profiles, respectively, then screened drug candidates by a corrected protein-protein network analysis of the ATTR-related genes as well as the drug targets from DrugBank database, and then filtered the drug candidates on the basis of gene expression data perturbed by compounds. We collected 139 and 56 ATTR-related genes from five public databases and transcriptome data, respectively, and performed functional enrichment analysis. We screened out 355 drug candidates based on the proximity to ATTR-related genes in the corrected interactome network, refined by graph neural networks. An Inverted Gene Set Enrichment analysis was further applied to estimate the effect of perturbations on ATTR-related and DE genes. High probability drug candidates were discussed. Drug repositioning using systematic computational processes on an interactome network with transcriptome data were performed to screen out several potential new drug candidates for ATTR.

Economic Burden of Huntington's Disease in China: Results from a National-Wide Cross-Sectional Study.

BACKGROUND: Huntington's disease (HD) poses a significant socio-economic burden globally. Existing research on HD's economic burden predominantly comes from Western settings, leaving a gap in data from Asian countries. This study aimed to assess the economic burden of HD in China and identify cost-driving factors. METHODS: This study used data from a 2019 nationwide cross-sectional survey of individuals affected by rare diseases in China. Data included socio-demographic characteristics, income, disease stage, health and social insurance coverage status, treatment-seeking behaviour, and costs. Logistic regression and linear regression were used to explore potential contributors to treatment-seeking behaviour and associated costs. RESULTS: Of the 269 individuals with HD included in this study, 80.6% were actively seeking treatment. The average annual direct medical cost, direct non-medical cost, and indirect cost were 3,265.65, 805.82, and 801.97 Euros, respectively. Compared to participants with early-stage HD, those with middle- or advanced-stage HD reported higher direct medical costs (coefficient 1,612.70, 95% confidence interval [CI]: [141.92, 3,083.48] and 2,398.58, 95% CI: [791.16, 4,006.00], respectively). However, the disease stage was not significantly associated with direct non-medical costs or indirect costs. CONCLUSIONS: This study provides crucial insights into the economic burden of HD in China. It emphasises a need for targeted policies that better cater to the financial needs of HD patients.

Real-time carotid plaque recognition from dynamic ultrasound videos based on artificial neural network.

PURPOSE: Carotid ultrasound allows noninvasive assessment of vascular anatomy and function with real-time display. Based on the transfer learning method, a series of research results have been obtained on the optimal image recognition and analysis of static images. However, for carotid plaque recognition, there are high requirements for self-developed algorithms in real-time ultrasound detection. This study aims to establish an automatic recognition system, Be Easy to Use (BETU), for the real-time and synchronous diagnosis of carotid plaque from ultrasound videos based on an artificial neural network. MATERIALS AND METHODS: 445 participants (mean age, 54.6±7.8 years; 227 men) were evaluated. Radiologists labeled a total of 3259 segmented ultrasound images from 445 videos with the diagnosis of carotid plaque, 2725 images were collected as a training dataset, and 554 images as a testing dataset. The automatic plaque recognition system BETU was established based on an artificial neural network, and remote application on a 5G environment was performed to test its diagnostic performance. RESULTS: The diagnostic accuracy of BETU (98.5%) was consistent with the radiologist's (Kappa = 0.967, P < 0.001). Remote diagnostic feedback based on BETU-processed ultrasound videos could be obtained in 150ms across a distance of 1023 km between the ultrasound/BETU station and the consultation workstation. CONCLUSION: Based on the good performance of BETU in real-time plaque recognition from ultrasound videos, 5G plus Artificial intelligence (AI)-assisted ultrasound real-time carotid plaque screening was achieved, and the diagnosis was made.

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity.

Bullous pemphigoid (BP) is a severe autoimmune blistering disease affecting patients' quality of life. Gut microbiota (GM) dysbiosis have been investigated to be associated with multiple autoimmune diseases. However, the relationship between GM and BP onset and remission remains to be established by a systematic study. We conducted a study that enrolled 24 patients with BP onset (BP group), 24 patients under remission stage (BP-R group) and 24 healthy controls (HC group). We applied 16S rRNA sequencing on faecal samples and revealed a separation of the microbiota structure. At the family level, Lachnospiraceae, Prevotellaceae and Veillonellaceae were more abundant in the HC and BP-R groups, while Bacteroidaceae, Ruminococcaceae and Enterobacteriaceae were more abundant in the BP group. Bugbase analysis revealed the potentially pathogenic bacteria had an increasing trend in the BP group compared with the HC group and this variation vanished in the BP-R group. At the amplicon sequence variants (ASV) level, Bacteroides ovatus (ASV40) and Veillonella dispar (ASV140) significantly decreased, while Prevotella copri (ASV54) increased in the BP group compared to the HC and BP-R groups. The HC group and BP-R group shared similar abundance. Furthermore, by correlation analysis, we investigated key ASVs correlated with clinical parameters and found some discriminate biomarkers between the BP and BP-R groups. Our study established a dynamic GM profile in BP patients under different disease activity, providing a new direction to understand the role of GM in BP pathogenesis and therapeutic effects.

Immunotherapy as a later-line option for HER2-altered advanced non-small-cell lung cancer: taxane might be a favorable partner.

Aim: To assess the effectiveness of different types of taxanes, including nab-paclitaxel, paclitaxel and docetaxel, and further compare the effectiveness of taxane-based chemotherapy, taxane-based chemotherapy plus angiogenesis inhibitors or taxane-based chemotherapy plus immune checkpoint inhibitors in HER2-altered non-small-cell lung cancer in the second- or third-line setting. Materials & methods: A total of 52 patients were included in the study. Progression-free survival was compared between subgroups. Results: A clinically meaningful improvement in progression-free survival was observed among patients in the nab-paclitaxel group compared with the docetaxel group. Taxane-based chemotherapy plus immune checkpoint inhibitors achieved longer progression-free survival than taxane-based chemotherapy. There was no difference between taxane-based chemotherapy plus immune checkpoint inhibitors and taxane-based chemotherapy plus angiogenesis inhibitors. Conclusion: Nab-paclitaxel appears to be a reasonable alternative to docetaxel. Chemotherapy plus immune checkpoint inhibitors might yield more survival benefits than chemotherapy alone.