Gut microbiota and risk of coronary heart disease: a two-sample Mendelian randomization study.

Background: The relationship between gut microbiota composition and coronary heart disease (CHD) has been recently reported in several observational studies. However, the causal effect of gut microbiota on coronary heart disease is uncharted. Objective: This study attempted to investigate the effect of gut microbiota on coronary heart disease by Mendelian randomization (MR) analysis. Methods: Through the two-sample MR method, single-nucleotide polymorphisms relevant to gut microbiota were selected as instrument variables to evaluate the causal association between gut microbiota and the risk of CHD. Results: According to the selection criteria of the inverse variance-weighted average method, Class Actinobacteria, Class Lentisphaeria, Family Clostridiales vadinBB60group, Genus Clostridium innocuum group, Genus Bifidobacterium, Genus Butyricicoccus, Genus Oxalobacter, Genus Turicibacter, and Order Victivallales, presented a suggestive association with coronary heart disease. Conclusion: This two-sample Mendelian randomization study found that gut microbiota was causally associated with coronary heart disease. Further randomized controlled trials are needed to clarify the protective effect of probiotics on coronary heart disease and their specific protective mechanisms.

Association of Anxiety and Depressive Symptoms with Thyroid Hormone Concentrations in Patients with Primary Bone Tumors.

BACKGROUND: Timely identification and intervention of psychological disorders bear significant import in ameliorating the ensuing therapeutic trajectories in primary bone tumor patients. Moreover, perturbations in thyroxine and thyroid-stimulating hormone (TSH) levels have been linked to manifestations of depressive and anxiety-related symptoms. However, the precise interplay governing the nexus of anxiety, depression, and the levels of thyroxine and TSH within the context of primary bone tumor patients remains presently unexplored. OBJECTIVE: The objective of this study is to investigate the potential correlation between the hypothalamus- pituitary-thyroxine (HPT) axis and the depressive as well as anxious states observed in patients afflicted with bone tumors. METHODS: Patients with primary bone tumors were required to accept the assessments of anxiety and depressive symptoms as well as thyroid axis hormone concentrations. The depressive and anxiety symptoms were assessed using the Hamilton Depression Rating Scale (HAMD) and the Hamilton Anxiety Scale (HAMA) score. During each follow-up, peripheral venous blood samples were collected for subsequent analysis using radioimmunoassay methods to measure serum- free T3, free T4, and TSH levels, with the calculated free T3 to free T4 ratio indicating peripheral free T4 to free T3 conversion. Tests for trend were conducted to assess thyroid axis hormone concentrations, HAMA scores, and HAMD scores, while the correlation between HAMA or HAMD scores and thyroid axis hormone concentrations was examined through univariate regression analyses. RESULTS: The study included 30 primary bone tumor patients. Initial high HAMA and HAMD scores decreased over a year after surgery (P < 0.05), reflecting diminishing anxiety and depression. TSH levels reduced postoperatively, contrasting with increased free-T3 and free-T4 levels (p < 0.01). Multivariate analysis affirmed that positive correlations were noted between TSH and anxiety/depression scores, while free-T3 correlated negatively, adjusted for demographic factors (p < 0.05). No significant associations emerged between HAMA/HAMD scores and free-T4 or free-T3 to free-T4 ratio (p > 0.05). CONCLUSION: The early identification of the low T3 syndrome could prove instrumental in both intervening and preventing adverse emotional states associated with primary bone tumors.

Genomic selection to improve husk tightness based on genomic molecular markers in maize.

Introduction: The husk tightness (HTI) in maize plays a crucial role in regulating the water content of ears during the maturity stage, thereby influencing the quality of mechanical grain harvesting in China. Genomic selection (GS), which employs molecular markers, offers a promising approach for identifying and selecting inbred lines with the desired HTI trait in maize breeding. However, the effectiveness of GS is contingent upon various factors, including the genetic architecture of breeding populations, sequencing platforms, and statistical models. Methods: An association panel of maize inbred lines was grown across three sites over two years, divided into four subgroups. GS analysis for HTI prediction was performed using marker data from three sequencing platforms and six marker densities with six statistical methods. Results: The findings indicate that a loosely attached husk can aid in the dissipation of water from kernels in temperate maize germplasms across most environments but not nessarily for tropical-origin maize. Considering the balance between GS prediction accuracy and breeding cost, the optimal prediction strategy is the rrBLUP model, the 50K sequencing platform, a 30% proportion of the test population, and a marker density of r2=0.1. Additionally, selecting a specific SS subgroup for sampling the testing set significantly enhances the predictive capacity for husk tightness. Discussion: The determination of the optimal GS prediction strategy for HTI provides an economically feasible reference for the practice of molecular breeding. It also serves as a reference method for GS breeding of other agronomic traits.

Correlations between schizophrenia and lichen planus: a two-sample bidirectional Mendelian randomization study.

Background: Several existing studies have shown a correlation between schizophrenia and lichen planus (LP). However, the causality of this relationship remains uncertain. Thus, this study aimed to examine the causal association between schizophrenia and LP. Methods: A two-sample Mendelian randomization (MR) study was carried out to investigate whether schizophrenia is causally related to LP and vice versa, and genetic variants in this study were taken from previous genome-wide association studies. We used the inverse variance weighted (IVW) method as the main analysis. Furthermore, several sensitivity analyses were performed to assess heterogeneity, horizontal pleiotropy, and stability. Results: Our results show that schizophrenia has a protective effect on LP (OR = 0.881, 95%CI = 0.795-0.975, p = 0.015). Conversely, we observed no significant relationship between LP and schizophrenia in reverse MR analysis (OR = 0.934, 95%CI = 0.851-1.026, p = 0.156). Conclusion: Our two-sample Mendelian randomization study supports a significant causal relationship between LP and schizophrenia and finds that schizophrenia can reduce the incidence of LP. This is in contrast to previous findings and provides new insights into the relationship between LP and schizophrenia, but the exact mechanism needs further investigation.

Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study.

Purpose: Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method. Methods: Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP. Results: According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP. Conclusion: The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.

Changes in T lymphocyte subsets in peripheral blood of patients with middle-advanced cervical cancer before and after nimotuzumab combined with concurrent chemoradiotherapy.

The current study sought to investigate the effect of nimotuzumab combined with concurrent chemoradiotherapy (CCRT + Nim) on T lymphocyte subsets in middle-advanced CC. Firstly, patients with middle-advanced CC were administered CCRT or CCRT + Nim. Next, levels of T lymphocytes in peripheral blood of CC patients pre- or post-treatment and healthy females were determined by flow cytometry. The short-term efficacy was evaluated, and overall survival (OS) and progression-free survival (PFS) of patients were recorded. In addition, the correlation of T lymphocyte subsets post-treatment with OS/PFS was assessed with Pearson analysis. CC patients exhibited decreased total T cells/T helper cells/CD4+/CD8+ ratio and increased T suppressor cells/Tregs in peripheral blood. Meanwhile, CCRT and CCRT + Nim improved T lymphocyte subset imbalance, with CCRT + Nim exhibiting better efficacy. CCRT + Nim exhibited better short-term efficacy and higher PFS than CCRT, with no evident difference in OS. The levels of total T cells/T helper cells/T suppressor cells/Tregs were not significantly-correlated with OS/PFS, and the CD4+/CD8+ ratio was correlated with PFS but not OS. Collectively, CCRT + nimotuzumab ameliorate the imbalance of T lymphocyte subsets in peripheral blood of middle-advanced CC patients, and the CD4+/CD8+ ratio after therapy is correlated with PFS.IMPACT STATEMENTWhat is already known on this subject? The utilisation of Nimotuzumab targeting epidermal growth factor receptor (EGFR) combined with concurrent chemoradiotherapy (CCRT) as an efficient treatment for middle-advanced cervical cancer (CC) has garnered the attention of numerous researchers over the years. T cells represent a major immune cell type in the tumour microenvironment and serve as the basis for maintaining cellular immune functions.What do the results of this study add? Our findings revealed that nimotuzumab combined with CCRT improves the abnormality of T lymphocyte subsets in peripheral blood of patients with middle-advanced CC, such that the CD4+/CD8+ ratio after treatment was significantly correlated with progression-free survival (PFS).What are the implications of these findings for clinical practice and/or further research? CCRT of CC may have a short-term negative impact on the peripheral T-cell immune micro-environment, and the combination of nimotuzumab, cisplatin-based chemotherapy, and radiotherapy enhances the frequency of Tregs in peripheral blood. Our findings illustrated that nimotuzumab combined with CCRT can improve the imbalance of T lymphocyte subsets in peripheral blood of patients with middle-advanced CC. A better understanding of the mechanisms of these therapies will optimise the selection of patients most likely to benefit from treatment, serving as a reference for further research on the relationship between EGFR-specific T cells and clinical benefit in patients treated with nimotuzumab in combination with CCRT.

Efficacy and safety of compound Kushen injection combined with chemotherapy on postoperative Patients with breast cancer: A meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis aimed to assess efficacy and safety of combination of Kushen and chemotherapy or chemotherapy alone among postoperative patients with breast cancer receiving. METHODS: A systematic literature search was conducted for relevant randomized controlled trials from 2000 to July 2017. Primary outcomes were clinical response rate (CRR) and performance status improvement by Karnofsky performance scale score (KPSS); secondary outcomes were adverse drug reactions (ADRs) rate and tumor marker decrease rate. Quality assessment and data analysis were performed with Review Manager 5.3. RESULTS: A total of 16 studies with 1315 participants were included in the analysis. Compared with chemotherapy alone, compound Kushen injection (CKI or KI) combined with chemotherapy did not significant increase CRR. However, performance status improvement rate was significantly higher among patients given Kushen injection combined with chemotherapy (relative risk 1.25, 95% confidence interval 1.09-1.42, P = .001). In the analysis of ADRs, combination of Kushen and chemotherapy was indicated to significantly reduce the rate liver dysfunction, kidney dysfunction, nausea and vomiting, diarrhea, hair loss, platelet decrease, and oral mucositis. CONCLUSION: Using CKI on the basis of chemotherapy might improve performance status and reduce ADRs among postoperative patients with breast cancer.

Low density lipoprotein modified silica nanoparticles loaded with docetaxel and thalidomide for effective chemotherapy of liver cancer.

In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs. In vivo imaging and anti-cancer assays also confirmed the preferable tumor-homing and synergetic anti-cancer effects of LDL/SLN/DTX/TDD.

Effect of matrine against breast cancer by downregulating the vascular endothelial growth factor via the Wnt/ß-catenin pathway.

The aim of the present study was to investigate the effect of matrine on breast cancer and its underlying mechanism. Matrine is a major component of Sophora flavescens, exhibited antitumor activity in a number of neoplasms, including breast cancer. The present study revealed that matrine inhibited cell viability and induced apoptosis in 4T1 and MCF-7 cells in a dose- and time-dependent manner in vitro. In addition, matrine suppressed the 4T1-tumor growth, induced apoptosis, inhibited the expression of vascular endothelial growth factor and downregulated the Wnt/ß-catenin signaling pathway in vivo. All these findings indicated that matrine may be a novel effective candidate for the treatment of breast cancer.

Low density lipoprotein modified silica nanoparticles loaded with docetaxel and thalidomide for effective chemotherapy of liver cancer

In the present study, we successfully developed a docetaxel (DTX) and thalidomide (TDD) co-delivery system based on low density lipoprotein (LDL) modified silica nanoparticles (LDL/SLN/DTX/TDD). By employing the tumor homing property of LDL and the drug-loading capability of silica nanoparticles, the prepared LDL/SLN/DTX/TDD was expected to locate and specifically deliver the loaded drugs (DTX and TDD) to achieve effective chemotherapy of liver cancer. In vitro analysis revealed that nano-sized LDL/SLN/DTX/TDD with decent drug loading capabilities was able to increase the delivery efficiency by targeting the low density lipoprotein receptors, which were overexpressed on HepG2 human hepatocellular liver carcinoma cell line, which exerted better cytotoxicity than unmodified silica nanoparticles and free drugs. In vivo imaging and anti-cancer assays also confirmed the preferable tumor-homing and synergetic anti-cancer effects of LDL/SLN/DTX/TDD.

Atomic Force Microscopy Study of the Anti-inflammatory Effects of Triptolide on Rheumatoid Arthritis Fibroblast-like Synoviocytes.

High-resolution atomic force microscopy (AFM) was used for the in situ evaluation of the anti-inflammatory effects of triptolide on rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) to understand the anti-RA effects of triptolide, based on the morphological and biophysical changes observed in RA-FLS. RA-FLS have been reported to play a primary role in inflammatory bone destruction during the development of RA and thus are regarded as an important target for RA treatment. Triptolide pretreatment significantly inhibited tumor necrosis factor-α-induced expression of the interleukin (IL)-1ß, IL-6, and IL-8 genes in MH7A cells. Using AFM, we showed that triptolide-induced morphological damage in MH7A cells by inducing significant ultrastructure changes in the membrane, which were closely related to triptolide-induced apoptosis in MH7A cells. Using force measurements determined with AFM, triptolide was shown to increase the stiffness of MH7A cells. These findings not only revealed the strong anti-inflammatory effects of triptolide on RA-FLS, highlighting triptolide as a potential anti-RA agent, but also revealed the possible use of AFM for studying anti-inflammatory responses in RA-FLS, which we expect to be developed into a potential tool for anti-RA drug studies in RA-FLS.

Biofeedback relaxation for pain associated with continuous passive motion in Taiwanese patients after total knee arthroplasty.

Effective pain management is crucial for patient recovery after total knee arthroplasty (TKA). Biofeedback therapy, which encourages relaxation and helps alleviate various conditions associated with stress, may help to decrease postoperative pain in patients undergoing TKA. A quasi- experimental design was used to investigate the efficacy of a biofeedback relaxation intervention in reducing pain associated with postoperative continuous passive motion (CPM) therapy. Sixty-six patients admitted to a general hospital in Taiwan for TKA were recruited and randomly assigned to the intervention or control group. The intervention group received biofeedback training twice daily for 5 days, concurrent with CPM therapy, whereas the control group did not receive the biofeedback intervention. Pain was measured using a numeric rating scale before and after each CPM therapy session on postoperative days 1 through 5. The CPM-elicited pain score was calculated by subtracting the pre-CPM pain score from the post-CPM pain score. Results of repeated-measures analysis of variance showed intervention group reported significantly less pain caused by CPM than did the control group (f = 29.70, p < 0.001). The study results provide preliminary support for biofeedback relaxation, a non-invasive and non-pharmacological intervention, as a complementary treatment option for pain management in this population.

Volatile compound in cut and un-cut flowers of tetraploid Freesia hybrida.

The flower volatile compounds (FVCs) of two tetraploid Freesia hybrida (pink-yellow and yellow) cultivars and their cut flowers were analysed by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry. Twelve FVCs were identified in the pink-yellow cultivar, with linalool as the major compound; 30 FVCs were identified in the yellow cultivar, with linalool and terpineol as the two major compounds. The FVCs (>1%) of the two cut flower cultivars were very similar to that of the un-cut flowers, and no significant difference was observed.

cDNA cloning and characterization of UDP-glucose: anthocyanidin 3-O-glucosyltransferase in Freesia hybrida.

The enzyme that catalyzes the formation of the first stable anthocyanin in the biosynthesis of natural compounds is UDP-glucose: anthocyanidin 3-O-glucosyltransferase (UF3GT). A cDNA clone (Fh3GT1) encoding UF3GT was isolated from Freesia hybrida. Phylogenetic tree analysis indicated that Fh3GT1 was a novel member of glycosyltransferase, which was classified into monocot subgroups. Semi-quantitative RT-PCR analysis detected transcripts of Fh3GT1 in different organs of F. hybrida and in petals of Freesia cultivars of different colors, and the expression level reached the maximum at the fully opened stage of petals. Characterization of the enzymatic assays indicated that Fh3GT1 had a role in anthocyanin glycoside biosyntheses in vitro. To elucidate the function of Fh3GT1, RNA interference vector (pART-Fh3GT1i) was constructed, and introduced into Petunia grandiflora by Agrobacterium-mediated transformation. Integration of the Fh3GT1 in petunia genome was confirmed by PCR and Southern blotting. SqRT-PCR revealed that the endogenous Ph3GT1 mRNA expression levels decreased in transgenic lines compared with the wild-type. The content of total anthocyanin pigments also decreased with the reduction of mRNA transcript levels, and the transgenic petunia plants had significant changes on their flower colors. In summary, this work identified a UF3GT gene from Freesia hybrida and demonstrated a method to modify plant flower color by redirecting the anthocyanin biosynthesis.