Diffusion Kurtosis Imaging in Diagnosing Parkinson's Disease: A Preliminary Comparison Study Between Kurtosis Metric and Radiomic Features.

RATIONALE AND OBJECTIVES: Parkinson's disease (PD) shows small structural changes in nigrostriatal pathways, which can be sensitively captured through diffusion kurtosis imaging (DKI). However, the value of DKI and its radiomic features in the classification performance of PD still need confirmation. This study aimed to compare the diagnostic efficiency of DKI-derived kurtosis metric and its radiomic features with different machine learning models for PD classification. MATERIALS AND METHODS: 75 people with PD and 80 healthy individuals had their brains scanned using DKI. These images were pre-processed and the standard atlas were non-linearly registered to them. With the labels in atlas, different brain regions in nigrostriatal pathways, including the caudate nucleus, putamen, pallidum, thalamus, and substantia nigra, were chosen as the region of interests (ROIs) to warped to the native space to measure the mean kurtosis (MK). Additionally, new radiomic features were developed for comparison. To handle the large amount of data, a statistical method called Z-score normalization and another method called LASSO regression were used to simplify the information. From this, a few most important features were chosen, and a combined score called Radscore was calculated using LASSO regression. For the comprehensive analyses, three different conventional machine learning models were then created: logistic regression (LR), support vector machine (SVM), and random forest (RF). To ensure the models were accurate, a process called 10-fold cross-validation was used, where the data were split into 10 parts for training and testing. RESULTS: Using MK alone, the models achieved good results in correctly identifying PD in the validation set, with LR at 0.90, RF at 0.93, and SVM at 0.90. When the radiomic features were added, the models performed even better, with LR at 0.92, RF at 0.95, and SVM at 0.91. Additionally, a nomogram combining all the information was created to predict the likelihood of someone having PD, which had an AUC of 0.91. CONCLUSION: These findings suggest that the combination of DKI measurements and radiomic features can effectively diagnose PD by providing more detailed information about the brain's condition and the processes involved in the disease.

Variations of soil metal content, soil enzyme activity and soil bacterial community in Rhododendron delavayi natural shrub forest at different elevations.

BACKGROUND: Rhododendron delavayi is a natural shrub that is distributed at different elevations in the karst region of Bijie, China, and that has an important role in preventing land degradation in this region. In this study, we determined the soil mineral element contents and soil enzyme activities. The composition of the soil bacterial community of R. delavayi at three elevations (1448 m, 1643 m, and 1821 m) was analyzed by high-throughput sequencing, and the interrelationships among the soil bacterial communities, mineral elements, and enzyme activities were determined. RESULTS: The Shannon index of the soil bacterial community increased and then decreased with increasing elevation and was highest at 1643 m. Elevations increased the number of total nodes and edges of the soil bacterial community network, and more positive correlations at 1821 m suggested stronger intraspecific cooperation. Acidobacteria, Actinobacteria and Proteobacteria were the dominant phyla at all three elevations. The Mantel test and correlation analysis showed that Fe and soil urease significantly affected bacterial communities at 1448 m; interestingly, Chloroflexi was positively related to soil urease at 1448 m, and Actinobacteria was positively correlated with Ni and Zn at 1821 m. Fe and soil urease significantly influenced the bacterial communities at lower elevations, and high elevation (1821 m) enhanced the positive interactions of the soil bacteria, which might be a strategy for R. delavayi to adapt to high elevation environments. CONCLUSION: Elevation significantly influenced the composition of soil bacterial communities by affecting the content of soil mineral elements and soil enzyme activity.

lncRNA SOX21-AS1 promotes activation of BV2 cells via epigenetically silencing of SOCS3 and aggravates Parkinson's disease.

BACKGROUND: LncRNAs perform a crucial impact on microglia's activation in Parkinson's disease (PD). Here, our purpose is to probe the function and involved mechanism of lncRNA SOX21-AS1 on microglial activation in PD. METHODS: Mice were treated with MPTP, and BV2 cells were treated with LPS/ATP to build PD animal and cell models. Genes' expression was measured using RT-qPCR, immunoblotting, and IHC. ELISA was applied for testing inflammatory factors' levels. Cell viability and apoptosis were tested using kits. RIP and RNA pull-down assay were utilized for monitoring the bond of SOX21-AS1 to EZH2, and ChIP was applied for affirming the bond between EZH2 and SOCS3's promoter. RESULTS: The expression of SOX21-AS1 and SOCS3 was abnormal in PD cell and animal models. Inhibition of SOX21-AS1 repressed LPS/ATP-induced activation in BV2 cells and nerve damage caused by activated BV2 cells, alleviating the pathological features of PD mice. Further studies found that SOX21-AS1 epigenetically inhibited SOCS3 by recruiting EZH2 to SOCS3 promoter. SOX21-AS1 overexpression partially offset the repressive impact of SOCS3 enhancement on BV2 cell activation and the protective effect on nerve cells. CONCLUSION: SOX21-AS1 enhances LPS/ATP-induced activation of BV2 cells and nerve damage caused by activated BV2 cells though recruiting EZH2 to SOCS3's promoter, thereby alleviating PD progression. Our research supplies new potential target for curing PD.

Temperature-Activated Near-Infrared-II Fluorescence and SERS Dynamic-Reversible Probes for Long-Term Assessment of Osteoarthritis In Vivo.

The abnormal fluctuation of temperature in vivo usually reflects the progression of inflammatory diseases. Noninvasive, real-time, and accurate monitoring and imaging of temperature variation in vivo is advantageous for guiding the early diagnosis and treatment of disease, but it remains difficult to achieve. Herein, we developed a temperature-activated near-infrared-II fluorescence (NIR-II FL) and surface-enhanced Raman scattering (SERS) nanoprobe for long-term monitoring of temperature changes in rat arthritis and timely assessment of the status of osteoarthritis. The thermosensitive polymer bearing NIR-II FL dye was grafted onto the surface of nanoporous core-satellite gold nanostructures to form the nanoprobe, wherein the nanoprobe contains NIR-II FL and Raman reference signals that are independent of temperature change. The ratiometric FL1150/FL1550 and S1528/S2226 values of the nanoprobe exhibited a reversible conversion with temperature changes. The nanoprobe accurately distinguishes the temperature variations in the inflamed joint versus the normal joint in vivo by ratiometric FL and SERS imaging, allowing for an accurate diagnosis of inflammation. Meanwhile, it can continuously monitor fluctuations in temperature over an extended period during the onset and treatment of inflammation. The tested temperature change trend could be used as an indicator for early diagnosis of inflammation and real-time evaluation of therapeutic effects.

Abdominal multi-organ segmentation in Multi-sequence MRIs based on visual attention guided network and knowledge distillation.

PURPOSE: The segmentation of abdominal organs in magnetic resonance imaging (MRI) plays a pivotal role in various therapeutic applications. Nevertheless, the application of deep-learning methods to abdominal organ segmentation encounters numerous challenges, especially in addressing blurred boundaries and regions characterized by low-contrast. METHODS: In this study, a multi-scale visual attention-guided network (VAG-Net) was proposed for abdominal multi-organ segmentation based on unpaired multi-sequence MRI. A new visual attention-guided (VAG) mechanism was designed to enhance the extraction of contextual information, particularly at the edge of organs. Furthermore, a new loss function inspired by knowledge distillation was introduced to minimize the semantic disparity between different MRI sequences. RESULTS: The proposed method was evaluated on the CHAOS 2019 Challenge dataset and compared with six state-of-the-art methods. The results demonstrated that our model outperformed these methods, achieving DSC values of 91.83 ± 0.24% and 94.09 ± 0.66% for abdominal multi-organ segmentation in T1-DUAL and T2-SPIR modality, respectively. CONCLUSION: The experimental results show that our proposed method has superior performance in abdominal multi-organ segmentation, especially in the case of small organs such as the kidneys.

Causal Links Between Systemic Disorders and Keratoconus in European Population.

PURPOSE: To establish the presence of a causal linkage between prevalent systemic diseases and keratoconus (KC). DESIGN: Mendelian randomization (MR) analysis. METHODS: After an exhaustive screening process, genetic variants linked to various systemic diseases were identified as instrumental variables at the genome-wide significance level. Subsequently, MR analyses were conducted to elucidate their potential causal connection with KC (N = 26,742). The encompassed systemic ailments comprise diabetes, hay fever/allergic rhinitis/eczema, obstructive sleep apnea, thyroid dysfunction, aortic aneurysm, major depressive disorder, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), and mitral valve prolapse. Our study adheres to the principles of Strengthening the Reporting of Observational Studies in Epidemiology Using MR guidelines. RESULTS: Using inverse variance weighting as the primary MR analysis method, our findings revealed that hay fever/allergic rhinitis/eczema (odds ratio, 10.144; 95% CI, 2.441-42.149; P = .001) and ulcerative colitis (odds ratio, 1.147; 95% CI, 1.054-1.248; P = .002) were associated with an increased risk of KC within the largest population under scrutiny. Conversely, the prolonged hyperglycemic state did not exhibit a potentially protective effect in delaying the pathogenesis of KC, and no correlation was observed between the two (odds ratio, 0.320; 95% CI, 0.029-3.549; P = .353). Also, obstructive sleep apnea, thyroid function, aortic aneurysm, major depressive disorder, Crohn's disease, and mitral valve prolapse did not exhibit a causal association with KC (P > .05 for all comparisons). CONCLUSIONS: This study indicates an increased risk of KC related to hay fever/allergic rhinitis/eczema and ulcerative colitis, with diabetes not providing a protective effect. These findings may potentially contribute some insights to inform clinical interventions.

Facile preparation of high-efficiency peroxidase mimics: modulation of the catalytic microenvironment of LDH nanozymes through defect engineering induced by amino acid intercalation.

Nanozymes have gained much attention as a replacement for natural enzymes duo to their unique advantages. Two-dimensional layered double hydroxide (LDH) nanomaterials with high physicochemical plasticity are emerging as the main forces for the construction of nanozymes. Unfortunately, high-performance LDH nanozymes are still scarce. Recently, defects in nanomaterials have been verified to play a significant role in modulating the catalytic microenvironment, thereby improving catalytic performances of nanozymes. Therefore, the marriage between defect engineering and LDH nanozymes is expected to spark new possibilities. In this work, twenty kinds of natural amino acids were separately inserted into the interlayer of CoFe-LDH to obtain defect-rich CoFe-LDH nanozymes. The peroxidase (POD)-like activity and catalytic mechanism of the as-prepared LDH nanozymes were systematically studied. The results showed that the intercalation of amino acids can effectively enhance the POD-like activity of LDH nanozymes owing to the increasing oxygen/metal vacancies. And l-cysteine intercalated LDH exhibited the highest catalytic activity ascribed to its thiol group. As a proof of concept, LDH nanozymes with superb POD-like activity were used in biosensing and antibacterial applications. This work suggests that modulating the catalytic microenvironment through defect engineering is an effective way to obtain high-efficiency POD mimics.

Multi-omics Mendelian randomization integrating GWAS, eQTL, and mQTL data identified genes associated with breast cancer.

Breast cancer (BC) remains a major disease posing a threat to women's health, but the underlying biological interpretation remains largely unknown. Here, we aimed to identify genes associated with breast cancer and analyze their pathophysiological mechanisms based on multi-omics Mendelian randomization (MR). Summary-data-based MR (SMR) was performed to estimate the causal effects of blood and breast mammary tissue expression quantitative trait loci (eQTLs) on BC. External validation analysis was used to validate the identified genes. Integration analyses BC GWAS summaries with eQTLs and DNA methylation QTLs (mQTLs) from the blood were conducted using SMR to prioritize putative blood genes and their regulatory elements associated with BC risk. Finally, two prior genes (ATG10 and RCCD1) from blood tissue reached significant levels in both BCAC (ATG10: ORBRCR = 0.91, PBRCR = 1.29 × 10-11; RCCD1: ORBRCR = 0.90, PBRCR = 3.72 × 10-15) and FinnGen cohorts (ATG10: ORFinnGen = 0.89, PFinnGen = 8.55 × 10-5; RCCD1: ORFinnGen = 0.89, PFinnGen = 2.38 × 10-8). Additionally, those two genes from breast tissues also replicated in both BCAC (ATG10: ORBRCR = 0.95, PBRCR = 1.02 × 10-9; RCCD1: ORBRCR = 0.87, PBRCR = 4.70 × 10-10) and FinnGen cohorts (ATG10: ORFinnGen = 0.93, PFinnGen = 2.38 × 10-4; RCCD1: ORFinnGen = 0.85, PFinnGen = 3.81 × 10-6). Sensitive analysis and external validation analysis validated those two identified genes. Multi-omics MR analysis showed that the SNP signals associated with ATG10 and RCCD1 were significant across the data from BC Genome-wide association study (GWAS), eQTL, and mQTL studies. In conclusion, we identified two priority genes that are potentially associated with BC. These findings improve our limited understanding of the mechanism of BC and shed light on the development of therapeutic agents for treating BC.

Recent advances in the application of Mendelian randomization to chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. METHODS: Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. RESULTS: Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. CONCLUSION: This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.

Engineering Logic DNA Nanoprobes on Live Cell Membranes for Simultaneously Monitoring Extracellular pH and Precise Drug Delivery.

It remains a challenge to use a single probe to simultaneously detect extracellular pH fluctuations and specifically recognize cancer cells for precise drug delivery. Here, we engineered a tetrahedral framework nucleic acid-based logic nanoprobe (isgc8-tFNA) on live cell membranes for simultaneously monitoring extracellular pH and targeted drug delivery. Isgc8-tFNA was anchored stably on the cell surface through three cholesterol molecules inserting into the bilayer of the cell membrane. Once responding to the acidic tumor microenvironment, isgc8-tFNA formed an i-motif structure, leading to turn-on FRET signals for monitoring changes of extracellular pH. The nanoprobe exhibited a narrow pH-response window and excellent reversibility. Moreover, the nanoprobe could execute logic identification on the cell surface for precise drug delivery. Only if both in the acidic microenvironment and aptamer-targeting marker are present on the cell surface, the sgc8-ASO-chimera strand, carrying an antisense oligonucleotide drug, was released from the nanoprobe and entered into targeted cancer cells for gene silence. Additionally, the in situ drug release facilitated the uptake of drugs mediated by the interaction between sgc8 aptamer and membrane proteins, resulting in enhanced inhibition of cancer cell migration and proliferation. This logic nanoprobe will provide inspiration for designing smart devices for diagnosis of pH-related diseases and targeted drug delivery.

Parkinson's disease patients with absence of normal dipping status were more vulnerable to cognitive impairment from the early stages.

INTRODUCTION: The objective of this study was to determine the characteristics of cognitive function in Parkinson's disease (PD) patients with different dipping statuses. METHODS: Consecutive PD patients were recruited for this study. All participants underwent 24-h ambulatory blood pressure monitor (ABPM). Corresponding scales were employed to evaluate both motor and non-motor symptoms. The subjects were categorized into reverse, reduced, normal, and extreme dipping groups based on dipping patterns. Additionally, they were divided into early and non-early stage groups according to the disease duration being more than 5 years. RESULTS: The proportions of the four dipping groups in the early and non-early stage groups exhibited no significant differences. The Montreal Cognitive Assessment (MoCA) scores in the reverse group were significantly lower than those in the normal dipping group (16.2 ± 5.8 vs 21.1 ± 6.1,P = 0.003). The attention as well as delayed recall scores in the reverse dipping group were significant lower than those in the normal dipping group (P = 0.042; P < 0.001). The multivariate linear regression analysis revealed that absence of normal dipping was an independent risk factor (OR = -2.252; P = 0.027) for MoCA scores for PD patients. CONCLUSIONS: PD patients with absence of normal dipping status were more vulnerable to cognitive impairment from the early stages of the disease. The 24-h ABPM is recommended for early detection of abnormal dipping status and identification of individuals at risk for cognitive decline.

A Self-Consistent Framework for Tailored Single-Atom Catalysts in Electrocatalytic Nitrogen Reduction.

The catalytic activity of single-atom catalysts (SACs) is crucially affected by the actual ligand configurations under the reaction condition; thus, carefully considering the reaction condition is crucial for the theoretical design of SACs. With single metal atoms supported by g-C3N4 as a model system, a self-consistent screening framework is proposed for the theoretical design of SACs with respect to the nitrogen reduction reaction (NRR). Pourbaix diagrams are constructed on the basis of various co-adsorption configurations of N2, H, and OH. Possible stable configurations containing N2 under the expected reaction condition are considered to obtain the limiting potential of NRR, and the stability of the configuration at the calculated UL is rechecked. With this framework, AC stacking of double-layer g-C3N4-supported Nb and AA stacking and AB stacking of double-layer g-C3N4-supported W are predicted to exhibit superior NRR activity with UL values of -0.36, -0.45, and -0.52 V, respectively. This procedure can be widely applied to the screening of SACs for electrocatalytic reactions.

Metagenomic next-generation sequencing for diagnosis of infectious encephalitis and meningitis: a retrospective study of 90 patients.

BACKGROUND: Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. METHODS: Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. RESULTS: Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. CONCLUSION: mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results.

Proteome-wide Mendelian randomization highlights AIF1 and HLA-DQA2 as targets for primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a kind of cholestatic liver disease without effective therapies and its pathogenesis is largely unknown. METHODS: We performed the proteome-wide Mendelian randomization (MR) design to estimate the causal associations of protein levels with PSC risk. Therein, genetic associations with 4,907 plasma protein levels were extracted from a proteome-wide genome-wide association study (GWAS) with 35,559 individuals and those with PSC were obtained from the International PSC Study Group (2,871 cases and 12,019 controls) and the FinnGen study (1,491 cases and 301,383 controls). The colocalization analysis was performed to detect causal variants shared by proteins and PSC. The identified proteins were further enriched in pathways and diseases. A phenome-wide association screening was performed and potential drugs were assessed as well. RESULTS: The results indicated that genetically predicted plasma levels of 14 proteins were positively associated with an increased risk of PSC and 8 proteins were inversely associated with PSC risk in both PSC GWAS data sets, and they all survived in sensitivity analyses. The colocalization indicated that AIF1 (allograft inflammatory factor 1) and HLA-DQA2 (major histocompatibility complex, class II, DQ alpha 2) were shared proteins with PSC, and they should be direct targets for PSC. The phenome-wide screening suggested that variants located at AIF1 or HLA-DQA2 region were closely associated with several autoimmune diseases, such as rheumatoid arthritis, implicating the shared pathogenesis among them. CONCLUSIONS: Our study highly pinpointed two candidate targets (AIF1 and HLA-DQA2) for PSC.

Novel insights into causal effects of serum lipids and lipid-modifying targets on cholelithiasis.

OBJECTIVE: Different serum lipids and lipid-modifying targets should affect the risk of cholelithiasis differently, however, whether such effects are causal is still controversial and we aimed to answer this question. DESIGN: We prospectively estimated the associations of four serum lipids with cholelithiasis in UK Biobank using the Cox proportional hazard model, including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Furthermore, we estimated the causal associations of the genetically predicted serum lipids with cholelithiasis in Europeans using the Mendelian randomisation (MR) design. Finally, both drug-target MR and colocalisation analyses were performed to estimate the lipid-modifying targets' effects on cholelithiasis, including HMGCR, NPC1L1, PCSK9, APOB, LDLR, ACLY, ANGPTL3, MTTP, PPARA, PPARD and PPARG. RESULTS: We found that serum levels of LDL-C and HDL-C were inversely associated with cholelithiasis risk and such associations were linear. However, the serum level of TC was non-linearly associated with cholelithiasis risk where lower TC was associated with higher risk of cholelithiasis, and the serum TG should be in an inverted 'U-shaped' relationship with it. The MR analyses supported that lower TC and higher TG levels were two independent causal risk factors. The drug-target MR analysis suggested that HMGCR inhibition should reduce the risk of cholelithiasis, which was corroborated by colocalisation analysis. CONCLUSION: Lower serum TC can causally increase the risk of cholelithiasis. The cholelithiasis risk would increase with the elevation of serum TG but would decrease when exceeding 2.57 mmol/L. The use of HMGCR inhibitors should prevent its risk.

Causal relationship between female reproductive factors, sex hormones and uterine leiomyoma: a Mendelian randomization study.

RESEARCH QUESTION: Are the observed associations between female reproductive factors and sex hormones with the risk of uterine leiomyoma truly causal associations? DESIGN: The putative causal relationships between female reproductive factors and sex hormones with uterine leiomyoma were investigated using two-sample Mendelian randomization. Statistics on exposure-associated genetic variants were obtained from genome-wide association studies (GWAS). The uterine leiomyoma GWAS from the FinnGen and FibroGENE consortia were used as outcome data for discovery and replication analyses, respectively. Results were pooled by meta-analysis. Sensitivity analyses ensured robustness of the Mendelian randomization analysis. RESULTS: When FinnGen GWAS were used as outcome data, a causal relationship was found between age at menarche (OR 0.84, P < 0.0001), age at menopause (OR 1.08, P < 0.0001), number of live births (OR 0.25, P < 0.001) and total testosterone levels (OR 0.90, P < 0.001) with the risk of uterine leiomyoma. When FibroGENE GWAS were used as outcome data, Mendelian randomization results for age at menopause, the number of live births and total testosterone levels were replicated. In the meta-analysis, a later age at menopause (OR 1.08, P < 0.0001) was associated with an increased risk of uterine leiomyoma. A higher number of live births (OR 0.25, P < 0.0001) and higher total testosterone levels (OR 0.90, P < 0.0001) were associated with a decreased risk of uterine leiomyoma. CONCLUSIONS: A causal relationship between later age at menopause, lower number of live births and lower total testosterone levels with increased risk of uterine leiomyoma was found.

Common gastrointestinal diseases and chronic obstructive pulmonary disease risk: a bidirectional Mendelian randomization analysis.

Background: Observational studies suggest an association between gastrointestinal diseases and chronic obstructive pulmonary disease (COPD), but the causal relationship remains unclear. Methods: We conducted bidirectional Mendelian randomization (MR) analysis using summary data from genome-wide association study (GWAS) to explore the causal relationship between common gastrointestinal diseases and COPD. Gastrointestinal diseases included gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), irritable bowel syndrome (IBS), Crohn's disease (CD), ulcerative colitis (UC), functional dyspepsia (FD), non-infectious gastroenteritis (NGE), and constipation (CP). Significant MR analysis results were replicated in the COPD validation cohort. Results: Bidirectional MR analysis supported a bidirectional causal relationship between GERD and COPD, and COPD was also found to increase the risk of IBS and CP. Our study also provided evidence for a bidirectional causal relationship between PUD and COPD, although the strength of evidence may be insufficient. Furthermore, we provided evidence that there is no causal association between CD, UC, FD, NGE, and COPD. Conclusion: This study offers some evidence to clarify the causal relationship between common gastrointestinal diseases and COPD. Further research is needed to understand the underlying mechanisms of these associations.

Multidisciplinary team collaboration impact on NGF, BDNF, serum IGF-1, and life quality in patients with hemiplegia after stroke.

This study aimed to study the impact of multidisciplinary team collaboration on NGF, BDNF, serum IGF-1, and life quality in patients with hemiplegia after stroke. For this purpose, 200 post-stroke hemiplegic patients admitted from March 2022 to February 2023 were selected and randomly divided into a control group (100) and an observation group (100). The control group was given routine nursing care, while the observation group was given a multidisciplinary team collaboration model. The neurotroph in [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)] and nutritional status [hemoglobin (HGB), serum albumin (ALB), transferrin (TRF)] of patients were compared before and after the intervention on the second day of admission and on the 30th day of intervention. The FUGL Meyer (FM) motor function assessment scale, NIHSS National Institutes of Health Stroke Scale, and the Specialized Quality of Life Scale (SS-QIL) for stroke patients were used to assess limb motor function, balance function, degree of neurological impairment, and life quality. Results showed that before intervention, there was no statistically significant difference in the levels of NGF, BDNF, IGF-1, HGB, ALB, TRF, limb motor function, balance function, neurological deficits, and quality of life scores between the two (P>0.05); After intervention, the levels of NGF, BDNF, IGF-1, HGB, ALB, and TRF in the observation group were significantly higher (P<0.05); The FM and SS-QOL of patients in the observation group were significantly higher (P<0.05); The NIHSS score of patients in the observation group was significantly lower (P<0.05). In conclusion, multidisciplinary team cooperation can significantly improve the level of neurotrophin, reduce the degree of nerve defect, and promote the recovery of limb function, balance function and life quality for stroke patients with hemiplegia.

Associations of 10 dietary habits with breast cancer: a Mendelian randomization study.

Introduction: Epidemiological studies have revealed a link between dietary habits and the breast cancer risk. The causality of the association between food consumption and breast cancer requires further investigation. Methods: Using Mendelian randomization, we assessed the causal effects of 10 dietary habits on the risks of breast cancer and its subtypes (estrogen receptor [ER] + and ER- breast cancer). We obtained dietary pattern data in 2018 (number of single-nucleotide polymorphisms [SNPs] = 9,851,867) and breast cancer data in 2017 (number of SNPs = 10,680,257) from IEU OpenGWAS. Rigorous sensitivity analyses were conducted to ensure that the study results were credible and robust. Results: We identified that genetic predisposition to higher dried fruit intake was linked to a reduced risk of overall breast cancer (inverse variance-weighted [IVW] odds ratio [OR] = 0.55; 95% confidence interval [CI]: 0.43-0.70; p = 1.75 × 10-6), ER+ breast cancer (IVW OR = 0.62; 95% CI: 0.47-0.82; p = 8.96 × 10-4) and ER- breast cancer (IVW OR = 0.48; 95% CI: 0.34-0.68; p = 3.18 × 10-5), whereas genetic predisposition to more oily fish intake was linked to a lower risk of ER+ breast cancer (IVW OR = 0.73; 95% CI: 0.53-0.99; p = 0.04). Discussion: Our findings suggest that a genetic predisposition for dried fruit and oily fish consumption may be protective against breast cancer; however, further investigation is required.