Staufen1 Represses the FOXA1-Regulated Transcriptome by Destabilizing FOXA1 mRNA in Colorectal Cancer Cells.

Transcription factors play key roles in development and disease by controlling gene expression. Forkhead box A1 (FOXA1), is a pioneer transcription factor essential for mouse development and functions as an oncogene in prostate and breast cancer. In colorectal cancer (CRC), FOXA1 is significantly downregulated and high FOXA1 expression is associated with better prognosis, suggesting potential tumor suppressive functions. We therefore investigated the regulation of FOXA1 expression in CRC, focusing on well-differentiated CRC cells, where FOXA1 is robustly expressed. Genome-wide RNA stability assays identified FOXA1 as an unstable mRNA in CRC cells. We validated FOXA1 mRNA instability in multiple CRC cell lines and in patient-derived CRC organoids, and found that the FOXA1 3'UTR confers instability to the FOXA1 transcript. RNA pulldowns and mass spectrometry identified Staufen1 (STAU1) as a potential regulator of FOXA1 mRNA. Indeed, STAU1 knockdown resulted in increased FOXA1 mRNA and protein expression due to increased FOXA1 mRNA stability. Consistent with these data, RNA-seq following STAU1 knockdown in CRC cells revealed that FOXA1 targets were upregulated upon STAU1 knockdown. Collectively, this study uncovers a molecular mechanism by which FOXA1 is regulated in CRC cells and provides insights into our understanding of the complex mechanisms of gene regulation in cancer.

Based on Serum Pharmacochemistry and Virtual Screening Technique Analysis Used to Explore the Potential Active Ingredients and Possible Anti- Coronary Heart Disease Mechanisms of Salvia miltiorrhiza Bunge.

AIMS AND OBJECTIVE: This study aimed to identify the bioactive compounds and explore the multi-target mechanisms of Salvia miltiorrhiza Bunge (SMB) against coronary heart disease (CHD) using an integrated serum pharmacochemistry and network pharmacology approach. MATERIALS AND METHODS: The chemical constituents of SMB were characterized by UPLC-MS. The absorbed ingredients and metabolites after oral SMB administration were identified in rat serum. Therapeutic targets of SMB against CHD were predicted by intersecting the targets of absorbed compounds from databases and CHD-associated genes. Protein-protein interaction network, pathway analysis, molecular docking, and molecular dynamic simulation were performed. RESULTS: A total of 61 SMB-derived compounds were identified in rat serum. Network analysis revealed 111 candidate targets highly related to CHD pathways. Further topological analysis identified 10 hub targets and 20 key active compounds, constructing an informative compoundtarget- pathway network. PTGS2 and TNF were predicted as primary targets of SMB against CHD based on molecular dynamic simulation. CONCLUSION: This integrated approach identified bioactive compounds and multi-target mechanisms of SMB against CHD. The results provide scientific evidence supporting SMB's clinical efficacy and reveal potential anti-CHD targets.

Comparing verum and sham acupoint catgut embedding for adults with obesity: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Previous clinical trials have reported that acupoint catgut embedding (ACE) is a useful modality for weight loss. However, no study has specifically investigated the effectiveness and safety of comparing verum and sham ACE in adults with obesity. Thus, this study aimed to evaluate the effectiveness and safety of comparing verum and sham ACE in obese adults. METHODS: A comprehensive literature search was conducted in the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and China Biomedical Literature Service System from inception to April 1, 2022. Randomized clinical trials that focused on evaluating the effectiveness of comparing verum and sham ACE in adults with obesity were included. The primary outcomes included reduction in body weight, body mass index, hip circumference, and waist circumference. The secondary outcomes consisted of a decrease in body fat percentage and the occurrence rate of adverse events. The methodological quality of the included randomized clinical trials was evaluated using the Cochrane Risk-of-bias tool. Statistical analysis was performed using RevMan 5.4 software. RESULTS: Six trials involving 679 adults with obesity were included in this study and entered in the data analysis of systematic review and meta-analysis. Results of the meta-analysis revealed significant reduction in body weight (mean difference [MD] = -1.68, 95% confidence intervals (CI) [-2.34, -1.01], I2 = 51%, P < .001), body mass index (MD = -0.51, 95% CI [-0.81, -0.21], I2 = 74%, P < .001), hip circumference (MD = -1.11, 95% CI [-1.67, -0.55], I2 = 0%, P < .001), waist circumference (MD = -2.42, 95% CI [-3.38, -1.45], I2 = 68%, P < .001), and decrease in body fat percentage (MD = -0.83, 95% CI [-1.30, -0.36], I2 = 16%, P < .001) in comparing verum and sham ACE. However, no significant difference was identified in AEs (odds ratio = 1.53, 95% CI [0.80, 2.95], I2 = 0%, P = .20) between the 2 groups. CONCLUSION: ACE is effective in the treatment of obesity in adults with safety profile. Further studies with higher quality and larger sample size are warranted to confirm the current findings.

Neuronal intranuclear inclusion disease with cortical involvement in left hemisphere: a case report.

BACKGROUND: Neuronal intranuclear inclusion disease (NIID) is a rare highly heterogeneous disease. In this paper, we present a case of NIID featured in cortical involvement in left hemisphere of brain and the imaging changes in the process of the disease. CASE PRESENTATION: A 57-year-old female was hospitalized due to recurrent attacks of headache with cognitive impairment and tremor for 2 years. The symptoms of headache episodes were reversible. The characteristic radiologic change was high intensity signal involving the grey matter-white matter junction on the brain diffusion-weighted imaging (DWI), which existed in the frontal lobe and then extended backwards. Atypical features on fluid-attenuated inversion recovery (FLAIR) sequences showing small patchy high signals in the cerebellar vermis. High signals and edema were detected on FLAIR images along the cortex of the left occipito-parieto-temporal lobes, expanding and gradually shrinking in the follow-up visit. Besides, cerebral atrophy and bilateral symmetrical leukoencephalopathy were also detected. Skin biopsy and genetic testing confirmed the diagnosis of NIID. CONCLUSION: Except for typical radiological change strongly suggesting NIID, it is also necessary to notice the insidious symptoms of NIID combining with some atypical imaging features to make an early diagnosis. Skin biopsies or genetic testing should be carried out early in patients with highly suspected NIID.

Magnetic resonance imaging on brain structure and function changes in diabetic peripheral neuropathy.

With the significant increase in the global prevalence of diabetes mellitus (DM), the occurrence of diabetic peripheral neuropathy (DPN) has become increasingly common complication associated with DM. It is particularly in the peripheral nerves of the hands, legs, and feet. DPN can lead to various adverse consequences that greatly affect the quality of life for individuals with DM. Despite the profound impact of DPN, the specific mechanisms underlying its development and progression are still not well understood. Advancements in magnetic resonance imaging (MRI) technology have provided valuable tools for investigating the central mechanisms involved in DPN. Structural and functional MRI techniques have emerged as important methods for studying the brain structures and functions associated with DPN. Voxel-based morphometry allows researchers to assess changes in the volume and density of different brain regions, providing insights into potential structural alterations related to DPN. Functional MRI investigates brain activity patterns, helping elucidate the neural networks engaged during sensory processing and pain perception in DPN patients. Lastly, magnetic resonance spectroscopy provides information about the neurochemical composition of specific brain regions, shedding light on potential metabolic changes associated with DPN. By synthesizing available literature employing these MRI techniques, this study aims to enhance our understanding of the neural mechanisms underlying DPN and contribute to the improvement of clinical diagnosis.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and the Risk of Leukoaraiosis in a South Chinese Han Population: A Case-Control Study.

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case-control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185-8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187-9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results.

Functional brain activity in patients with amnestic mild cognitive impairment: an rs-fMRI study.

Background: Amnestic mild cognitive impairment (aMCI) is an early stage of Alzheimer's disease (AD). Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) are employed to explore spontaneous brain function in patients with aMCI. This study applied ALFF and ReHo indicators to analyze the neural mechanism of aMCI by resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Twenty-six patients with aMCI were included and assigned to the aMCI group. The other 26 healthy subjects were included as a healthy control (HC) group. Rs-fMRI was performed for all participants in both groups. Between-group comparisons of demographic data and neuropsychological scores were analyzed using SPSS 25.0. Functional imaging data were analyzed using DPARSF and SPM12 software based on MATLAB 2017a. Gender, age, and years of education were used as covariates to obtain ALFF and ReHo indices. Results: Compared with HC group, ALFF decreased in the left fusiform gyrus, left superior temporal gyrus, and increased in the left cerebellum 8, left inferior temporal gyrus, left superior frontal gyrus (BA11), and right inferior temporal gyrus (BA20) in the aMCI group (p < 0.05, FWE correction). In addition, ReHo decreased in the right middle temporal gyrus and right anterior cuneiform lobe, while it increased in the left middle temporal gyrus, left inferior temporal gyrus, cerebellar vermis, right parahippocampal gyrus, left caudate nucleus, right thalamus, and left superior frontal gyrus (BA6) (p < 0.05, FWE correction). In the aMCI group, the ALFF of the left superior frontal gyrus was negatively correlated with Montreal Cognitive Assessment (MoCA) score (r = -0.437, p = 0.026), and the ALFF of the left superior temporal gyrus was positively correlated with the MoCA score (r = 0.550, p = 0.004). The ReHo of the right hippocampus was negatively correlated with the Mini-Mental State Examination (MMSE) score (r = -0.434, p = 0.027), and the ReHo of the right middle temporal gyrus was positively correlated with MMSE score (r = 0.392, p = 0.048). Conclusion: Functional changes in multiple brain regions rather than in a single brain region have been observed in patients with aMCI. The abnormal activity of multiple specific brain regions may be a manifestation of impaired central function in patients with aMCI.

Multimodal magnetic resonance imaging on brain network in amnestic mild cognitive impairment: A mini-review.

Amnestic mild cognitive impairment (aMCI) is a stage between normal aging and Alzheimer disease (AD) where individuals experience a noticeable decline in memory that is greater than what is expected with normal aging, but dose not meet the clinical criteria for AD. This stage is considered a transitional phase that puts individuals at a high risk for developing AD. It is crucial to intervene during this stage to reduce the changes of AD development. Recently, advanced multimodal magnetic resonance imaging techniques have been used to study the brain structure and functional networks in individuals with aMCI. Through the use of structural magnetic resonance imaging, diffusion tensor imaging, and functional magnetic resonance imaging, abnormalities in certain brain regions have been observed in individuals with aMCI. Specifically, the default mode network, salience network, and executive control network have been found to show abnormalities in both structure and function. This review aims to provide a comprehensive understanding of the brain structure and functional networks associated with aMCI. By analyzing the existing literature on multimodal magnetic resonance imaging and aMCI, this study seeks to uncover potential biomarkers and gain insight into the underlying pathogenesis of aMCI. This knowledge can then guide the development of future treatments and interventions to delay or prevent the progression of aMCI to AD.

Bibliometric analysis of acupuncture for headache from 1974 to 2022: A scoping literature review based on international database.

This study aimed to investigate the research hotspots and global trends of acupuncture in the treatment of headaches from 1974 to 2022. The Web of Science core collection database and literature related to acupuncture for headache treatment were retrieved. The CiteSpace (version 5.1.R8) and VOSviewer (version 1.6.19) software perform collaborative network analysis on the information of countries, academic institutions, authors, and co-occurrence network analysis on keywords, co-cited journals, and references. A total of 841 studies were included. Overall, the number of publications has increased over the past 5 decades. We identified and analyzed the countries, institutions, authors, and journals that were most active in the domain of acupuncture treatment for headaches. The most productive countries were the United States and China. Chengdu University of Traditional Chinese Medicine was the most productive institution and Linde Klaus was the most productive author. Cephalalgia was the most productive and co-cited journal, whereas Lancet had the highest impact factor. The research hotspots mainly focus on headache, migraine, tension headache, electroacupuncture, and acupuncture. Research trends have mainly focused on acupuncture therapy and its curative effects, migraine without aura, paroxysmal migraine, and the mechanism of acupuncture treatment. The main research hotspots and frontier trends were the therapeutic effect and mechanism of acupuncture for headaches. The mechanism of acupuncture in the treatment of headache mainly focused on the neural mechanism by multimodal MRI.

Comparison on greenhouse gas footprint of three types of oriented strand board manufacturing process in China.

The greenhouse gas (GHG) footprints of oriented strand boards (OSB) have been gaining growing concern. China is one of the largest manufacturers and traders of OSB in the world. However, little data are available concerning the GHG footprint of Chinese OSB production. The purpose of this study is to quantify and compare the GHG footprints of three types of OSB produced in China. Cradle-to-gate GHG footprints assessment models were built for OSB according to PAS 2050 guidelines. The results showed that the cradle-to-gate GHG footprints of OSB/2, OSB/3, and OSB/4 were 142.7 kg CO2 e/m3, 173.2 kg CO2 e/m3, and 374.2 kg CO2 e/m3, respectively. Raw material acquisition was the largest contributor to GHG footprint for three types of OSB (52.6~57.6%), followed by the production process of OSB (25.6~27.3%) and transportation (15.3~20.1%). The consumption of wood, MDI, electricity, and the transportation of wood were main emission hotspots in Chinese OSB production. Ultimately, four feasible GHG emission reduction measures were put forward from the perspective of reducing the usage of wood and MDI adhesive, decreasing the electricity consumption, and shortening the transport distance of wood.

Magnetic resonance imaging of white matter in Alzheimer's disease: a global bibliometric analysis from 1990 to 2022.

Background: Alzheimer's disease (AD) is a common, progressive, irreversible, and fatal neurodegenerative disorder with rapidly increasing worldwide incidence. Although much research on magnetic resonance imaging (MRI) of the white matter (WM) in AD has been published, no bibliometric analysis study has investigated this issue. Thus, this study aimed to provide an overview of the current status, hotspots, and trends in MRI of WM in AD. Methods: We searched for records related to MRI studies of WM in AD from 1990 to 2022 in the Web of Science Core Collection (WOSCC) database. CiteSpace (version 5.1.R8) and VOSviewer (version 1.6.19) software were used for bibliometric analyses. Results: A total of 2,199 articles were obtained from this study. From 1990 to 2022, the number of published articles showed exponential growth of y = 4.1374e0.1294x, with an average of 17.9 articles per year. The top country and institutions were the United States and the University of California Davis, accounting for 44.52 and 5.32% of the total studies, respectively. The most productive journal was Neurology, and the most co-cited journal was Lancet Neurology. Decarli C was the most productive author. The current research frontier trend focuses on the association between small vessel disease and AD, the clinical application and exploration of diffusion MRI, and related markers. Conclusion: This study provides an in-depth overview of publications on MRI of WM in AD, identifying the current research status, hotspots, and frontier trends in the field.

Real-world treatment and outcome patterns of patients with mantle cell lymphoma in China: A large, multicenter retrospective analysis.

BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non-Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient-specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. METHODS: A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan-Meier method coupled with the log-rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. RESULTS: The median age of the cohort was 60.0 years with a male-to-female ratio of 3.36:1. Five-year progression-free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High-intermediate/high-risk group according to MIPI-c, without high-dose cytarabine, lack of Auto-SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high-intermediate/high risk group according to MIPI-c, without high-dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. CONCLUSIONS: First-line high dose cytarabine exposure, auto-SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

Structural and functional activities of brain in patients with vascular cognitive impairment: A case-controlled magnetic resonance imaging study.

This study aimed to identify abnormal brain regions and imaging indices of vascular cognitive impairment (VCI) and explore specific imaging diagnostic markers of VCI. In this study, 24 patients with VCI were allocated to the VCI group and 25 healthy subjects were assigned to the healthy control (HC) group. Demographic data and neuropsychological test scores were compared using SPSS 25.0. The structural and functional imaging data were post-processed and statistically analyzed using CAT12, DPARSF and SPM12 software, based on the MATLAB platform. The structural and functional indices of gray matter volume (GMV) and regional homogeneity (ReHo) were obtained, and inter-group data were analyzed using an independent-sample t test. Sex, age, years of education, and total brain volume were used as covariates. Compared to the HC group, the GMV of VCI in the VCI group decreased significantly in the rectus muscles of the bilateral gyrus, left superior temporal gyrus, left supplementary motor area (SMA), right insula, right superior temporal gyrus, right anterior cuneiform lobe, and right anterior central gyrus (PRECG) (P < .05, FWE correction), without GMV enlargement in the brain area. ReHo decreased in the right inferior temporal gyrus (ITG), right parahippocampal gyrus, and left temporal pole (middle temporal gyrus, right lingual gyrus, left posterior central gyrus, and right middle temporal gyrus), the areas of increased ReHo were the left caudate nucleus, left rectus gyrus, right anterior cingulate gyrus and lateral cingulate gyrus (P < .05, FWE correction). Correlation analysis showed that the GMV of the left superior temporal gyrus was positively correlated with the Montreal Cognitive Assessment (MoCA) score (P < .05), and the GMV of the right insula was positively correlated with the MESE and long delayed memory scores (P < .05). There was a significant positive correlation between the ReHo and short-term delayed memory scores in the middle temporal gyrus of the left temporal pole (P < .05). The volume of GMV and ReHo decreased in VCI patients, suggesting that impairment of brain structure and function in specific regions is the central mechanism of cognitive impairment in these patients. Meanwhile, the functional indices of some brain regions were increased, which may be a compensatory mechanism for the cognitive impairment associated with VCI.

The functional change of the P2X7R containing the Ala348 to Thr polymorphism is associated with the pathogenesis of gout.

Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1ß signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1ß pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala348 to Thr mutants increased P2X7-dependent ethidium+ bromide uptake, upregulated IL-1ß and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease.

Matrin3 regulates mitotic spindle dynamics by controlling alternative splicing of CDC14B.

Matrin3 is an RNA-binding protein that regulates diverse RNA-related processes, including mRNA splicing. Although Matrin3 has been intensively studied in neurodegenerative diseases, its function in cancer remains unclear. Here, we report Matrin3-mediated regulation of mitotic spindle dynamics in colorectal cancer (CRC) cells. We comprehensively identified RNAs bound and regulated by Matrin3 in CRC cells and focused on CDC14B, one of the top Matrin3 targets. Matrin3 knockdown results in increased inclusion of an exon containing a premature termination codon in the CDC14B transcript and simultaneous down-regulation of the standard CDC14B transcript. Knockdown of CDC14B phenocopies the defects in mitotic spindle dynamics upon Matrin3 knockdown, and the elongated and misoriented mitotic spindle observed upon Matrin3 knockdown are rescued upon overexpression of CDC14B, suggesting that CDC14B is a key downstream effector of Matrin3. Collectively, these data reveal a role for the Matrin3/CDC14B axis in control of mitotic spindle dynamics.

Correlation between methylenetetrahydrofolate reductase gene-specific methylation and recurrent spontaneous abortion.

OBJECTIVE: To investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) gene-specific methylation and recurrent spontaneous abortion (RSA). METHODS: A total of 50 RSA patients who visited our hospital were recruited in the study group; 50 multiparous women who underwent physical examinations during the same period were enrolled in the control group. The levels of homocysteine, folic acid, and vitamin B12 and their MTHFR gene polymorphism and specific methylation were measured in both groups. The Logistic regression equation was used to analyze the correlation between MTHFR gene-specific methylation and RSA. RESULTS: The methylated allele MM was not found in the control group, and the frequency in the study group was 1.19%. The frequency of the MU genotype in the study group 32.93% was higher than that in the control group 12.45%. The frequency of methylated alleles of CC and CT genotypes carrying MTHFR C677T polymorphism in the study group was higher than that in the control group (P < 0.05). There was no significant difference in the TT genotype between the two groups (P > 0.05). Multivariate Logistic regression analysis exhibited that patients with methylated alleles of CC genotype had a risk of RSA increased by 1.167 times, and the risk increased by 2.500 times in patients with methylated alleles of CT genotype (P < 0.05). 83.33% of RSA patients carrying methylated alleles affected hyperhomocysteinemia. In patients with elevated homocysteine levels, the risk of RSA caused by methylated allele was significantly increased by 7.321 times. CONCLUSION: MTHFR gene-specific methylation can significantly increase the risk of RSA.

Nebulizer versus metered dose inhaler with space chamber (MDI spacer) for acute asthma and chronic obstructive pulmonary disease exacerbation: attitudes of patients and healthcare providers in the COVID-19 era.

OBJECTIVE: Short-acting bronchodilators for asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly delivered by nebulizers although administration using metered dose inhaler with space chamber (MDI spacer) has been shown to be equally efficacious. There are few studies examining patients' and healthcare providers' attitudes on the two administration methods in adults. This study explores patients' and healthcare providers' attitudes on the use of nebulizer versus MDI spacer for acute asthma and COPD exacerbations in adults. METHODS: Patients admitted for asthma or COPD exacerbations, doctors, and nurses in a university-affiliated hospital were surveyed from 1 April 2021 to 30 September 2021 regarding their views on the effectiveness, ease of use, preparation and administration, side effects, and infection risk of the two administration methods. RESULTS: Ninety-nine patients, 103 doctors, and 650 nurses completed the survey. 60.6% of patients perceived nebulizer to be more effective. Patients who found nebulizer more comfortable were more likely to prefer nebulizer (OR 43.97, p = 0.01), while those who associated it with a greater infection risk were less likely to prefer nebulizer (OR 0.15, p = 0.03). 49.5% of doctors and 49.1% of nurses perceived nebulizer to be more effective, compared to 10.7% and 34.5%, respectively, for MDI spacer. Effectiveness and patient comfort influenced doctors' and nurses' preference for nebulizer while ease of preparation and administration influenced nurses' preference only. CONCLUSIONS: Patients and healthcare providers perceived nebulizer to be more effective. Factors unique to each group influenced their preference for nebulizer.

Single-cell analysis identifies phospholysine phosphohistidine inorganic pyrophosphate phosphatase as a target in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic gastrointestinal disorder characterized by inflammation and ulceration, representing a significant predisposition to colorectal cancer. Recent advances in single-cell RNA sequencing (scRNA-seq) technology offer a promising avenue for dissecting the complex cellular inter-actions and molecular signatures driving UC pathology. AIM: To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology. METHODS: In this research, we integrated and analyzed the scRNA-seq data from UC patients. Moreover, we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples. RESULTS: In this study, we identified the sustained upregulation of inflammatory response pathways during UC progression, characterized the features of damaged endo-thelial cells in colitis. Furthermore, we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has a negative correlation with signal transducer and activator of transcription 3. Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC. This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation. CONCLUSION: The findings suggest that LHPP may serve as a potential therapeutic target for UC, emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.

Efficacy and Safety Assessment of Rivaroxaban for the Treatment of Cerebral Venous Sinus Thrombosis in a Chinese Population.

We aimed to investigate the efficacy and safety of rivaroxaban for acute and long-term management of cerebral venous sinus thrombosis (CVST). This study reviewed CVST-diagnosed patients admitted to the First Affiliated Hospital of Guangxi Medical University from January 2015 to December 2020. The primary outcome was a composite of recurrent thrombosis or major bleeding events. The secondary efficacy outcomes included a disease recovery time (DRT) presenting the time from admission to the endpoint as recovery (the modified Rankin scale [mRS] score [0-1]) within 30 and 90 days, and length of hospital stay (LHS). Patients treated with rivaroxaban (38) and warfarin (45) were enrolled in the final analysis. The primary outcome had no significant difference (5.3% vs 11.1%, P = .576) between the 2 groups. The secondary efficacy outcome regarding the median 30-d DRT was 17 days (95% confidence interval [CI], 14.6-19.4) in the rivaroxaban group, compared with 26.0 days (95% CI, 16.8-35.2) in the warfarin group (hazard ratio, 1.806; 95% CI, 1.051-3.103; log-rank P = .026). Two groups have a significant difference in LHS (P = .041). Patients with cerebral edema, intracerebral hemorrhage, and mild/moderate disability (admission mRS score [2-3]) treated with rivaroxaban recovered faster than those with warfarin (log-rank P < .05). Patients with cerebral edema, intracerebral hemorrhage, and mild/moderate disability treated with rivaroxaban had a shorter recovery time than those treated with warfarin within 1 month from admission, indicating that rivaroxaban a promising convenient therapy for CVST, helping them speedily restore social functions.

[Protective effects of estrogen modified hBMSC on HG-induced injury of vascular endothelial cells].

Objective: To investigate the protective effects and potential mechanisms of estrogen modified human bone marrow mesenchymal stem cells (hBMSC) on high glucose (HG)-induced injury of vascular endothelial cells. Methods: hBMSCs were cultured under 30 mmol/l glucose to establish a high glucose model (HG), and then were divided into four groups as following: HG group (HG control, without any treatment), HG+E2 group (cells were treated with 20 µmol/L estrogen), HG+E2+ Triciribine group (cells were pretreated with 5 µmol/L protein kinase B (PKB/Akt) inhibitor for 45 min, and then modified by 20 µmol/L estrogen), and NG group (cells were cultured under normal conditions). After 12 h treatment, the cell viability of hBMSC was detected by CCK8 assay, and the contents of NO, VEGF and IL8 in the supernatant of cultured medium in each group were detected by nitrate reductase and ELISA assay (n=6). After 48 h, the expression levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) were detected by Western blot (n=3). In addition, the cell supernatant of each group was further extracted as conditioned medium to culture HUVECs, and the cells were subsequently divided into HG-CM group (HUVECs were treated with HG group's conditioned medium), HG+E2-CM group (HUVECs were treated with HG+E2 group's conditioned medium), HG+E2+Triciribine-CM group (HUVECs were treated with HG+E2+ Triciribine group's conditioned medium) and HG-H group (HUVEC were cultured under HG condition, which were treated with final concentration 30 mmol/l glucose). The cell viability of HUVECs in each group was detected by CCK8 assay after 12 h cultured (n=6). After 24 h treatment, the apoptosis rate of HUVECs in each group was detected by flow cytometry (n=3). Furthermore, the migration rate of HUVECs in each group was observed by wound healing assay after 48 h cultured (n=3). Results: Compared with NG group, the cell viability and eNOS protein phosphorylation level of hBMSC in HG group and the contents of NO, VEGF and IL-8 in the supernatant of cultured medium were decreased (P<0.05). Compared with HG group, the cell viability and eNOS protein phosphorylation level in HG+E2 group and the contents of NO, VEGF and IL-8 in cultured medium supernatant were increased significantly (P<0.05), whereas pre-treatment of hBMSC cells with a Akt inhibitor Triciribine, the above indexes showed reverse changes (P<0.05). Furthermore, compared with HG-CM group, the cell viability and migration ability (P<0.05) of HUVECs in HG+E2-CM group were increased significantly (P<0.05), and the proportion of apoptosis was decreased (P<0.05). While compared with HG+E2-CM group, the cell viability and migration ability of HUVECs in HG+E2+Triciribine-CM group were decreased (P<0.05), and the proportion of apoptosis was increased (P<0.05). Conclusion: Estrogen may promote the secretion of NO, VEGF and IL-8 by activating the Akt/eNOS signaling pathway of hBMSC cells, increase the cell viability and migration ability of HUVECs and inhibit the occurrence of apoptosis, play a protective role against the injury of HUVECs induced by HG condition.