[Analysis of APTT Mixing Test Results in Factor â § Inhibitor-Positive Hemophilia Patients].

OBJECTIVE: To analyze the results of activated partial thromboplastin time (APTT) mixing test in coagulation factor Ⅷ inhibitor-positive hemophilia patients, so as to increase the value of APTT mixing test in the screen of factor Ⅷ inhibitor. METHODS: Eighty plasmas samples with different titers of coagulation factor Ⅷ inhibitors had been collected and diluted for routine immediate APTT mixing test and at 37 ℃ 2 hours incubation APTT mixing test. Fifteen samples were selected for immediate and normal temperature incubation for 15 min, 30min, 1 hour, 2 hours and 37 ℃ for 30 min, 1 hour, 2 hours APTT mixing test. RESULTS: The results of APTT mixing test were significantly correlated with the titers of coagulation factor Ⅷ inhibitors. The ROC curve result showed that the best diagnostic cut-off value for 2 hours incubation APTT mixing test at 37 ℃ to determine the presence or absence of coagulation factor Ⅷ inhibitors was 43.8 s (sensitivity and specificity was 85.90% and 100%, respectively), while the best diagnostic cut-off value for distinguishing high-titer and low-titer Ⅷ inhibitors was 52.4 s (sensitivity and specificity was 98.18% and 95.65%, respectively). The critical coagulation factor Ⅷ inhibitor titer that could not be corrected by immediate APTT was 5.14 BU/ml, while that could not be corrected by 37 ℃ 2 hours incubation APTT was 1.31 BU/ml. Paired samples t -test was performed on the APTT mixing test results at different times and temperatures, and the differences were statistically significant (P < 0.05). CONCLUSIONS: The APTT mixing test can be used as a screening index for coagulation factor Ⅷ inhibitors. APTT mixing test result shows a significant time-temperature dependence with lower titers of coagulation factor Ⅷ inhibitor. Patients with hemophilia who cannot be corrected by immediate APTT mixing test should be alert to the possibility of high titer of coagulation factor Ⅷ.

The therapeutic efficacy of guided therapy for PCI after acute myocardial infarction: A meta-analysis.

OBJECTIVE: To systematically evaluate the effects of lead therapies on percutaneous coronary intervention (PCI) after acute myocardial infarction (AMI). METHODS: A randomized controlled trial (RCT) in the CNKI, Wanfang, VIP, ProQuest, PubMed, Cochrane Library, Scopus, and Web of Science databases was searched until January 2023. Two researchers strictly screened and checked the included literature, extracted relevant data, and used the Cochrane Manual to assess the risk quality of the literature. Using RevMan 5.3 software, Meta-analysis of 4 main outcome measures [cardiac function-related indicators, 6-minute walking distance (6 MWT), quality of life (SF-36), Seattle angina pectoris scale (SAQ)], and 3 secondary outcome measures [adverse event incidence, death incidence, and readmission rate]. RESULTS: 22 studies were finally included with 1754 subjects, but the overall quality of the included studies was not high. The results of the meta-analysis showed that, in the cardiac function-related indicators compared to controls, improved left ventricular ejection fraction (LVEF) index (MD = 1.42, 95%CI [-0.94, 3.79], P < .00001); however, compared with the Baduanjin group, Tai Chi ball + Baduanjin group and control group, there was no significant difference (P > .05); compared with the control group, the guidance therapy group improved the left ventricular end-diastolic volume (LVEDV) index (MD = -4.67, 95%CI [-6.8, -2.71], P < .00001). In comparison, the lead group improved the 6 MWT (MD = 69.44, 95%CI [30.12, 108.76], P < .00001); the SF-36 score (MD = 10.05, 95%CI [8.68, 11.42], P < .00001])and the SAQ score (MD = 6.2, 95%CI [3.97, 8.44], P < .00001). Among the secondary outcome measures, the incidence of adverse events was statistically significant (RR = 0.17, 95%CI [0.1, 0.32], P < .00001); statistically significant (RR = 0.29, 95%CI (0.1, 0.87), P < .00001); readmission (RR = 0.39, 95%CI [0.17, 0.87, 0.89], P < .00001). CONCLUSION: Based on the current study, combining conventional therapy/ exercise or using simple lead therapy after PCI can improve the treatment effect and improve the quality of life.

Effect of repetition of rTMS at different frequencies on the efficacy of swallowing disorders after stroke: A systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the curative effect of repeated transcranial magnetic stimulation at different frequencies on swallowing disorders after stroke. METHODS: A search was conducted for randomized controlled trials of repeated transcranial magnetic stimulation for stroke patients in CNKI, Wanfang, VIP, ProQuest, PubMed, Cochrane Library, Scopus, and Web of Science databases until December 2022. The 2 researchers strictly screened and checked the included documents, extracted relevant data, assessed the risk quality of the literature using the Cochrane manual, and conducted a network meta-analysis of the data using State16.0. RESULTS: Eighteen studies included 680 participants. The results of the reticular meta-analysis showed that in the leakage-aspiration scale (PAS) indicators, 1 Hz, 3 Hz, 5 Hz, and 10 Hz were all better treatment effects compared with the control group, and there was a statistically significant difference (P < .05). In the standard swallowing function assessment (SSA) index, 3 Hz, 5 Hz, and 10 Hz compared with the control group were statistically significant (P < .05); there was no difference between 1 Hz and the control group (P > .05). The cumulative probability ranking results showed that the intervention effect of 3 Hz was the best in the PAS index, much greater than that of other frequencies, and the intervention effects of 10 Hz and 5 Hz were similar. For the SSA index, the intervention effect was optimal at 10 Hz, followed by 5 Hz. Note that the treatment effect of 1 Hz ranked last, even lower than that of the control group. The results of the 5 Hz treatment site grouping analysis showed that the affected side was > bilateral > healthy in PAS and > bilateral > healthy in SSA. CONCLUSION SUBSECTIONS: Based on the current study, the optimal frequency and site selection results of the 2 evaluation indicators are not uniform, but from the combination of the 2 evaluation indicators, the treatment effect of 10H is good, and the effect of bilateral stimulation for the selection of stimulation sites is good. The above conclusions need to be verified in high-quality studies.

A Novel and Rapid Smear Cytomorphology Detection Strategy Based on Upconversion Nanoparticles Immunolabeling Integrated with Wright's Staining for Accurate Diagnosis of Leukemia.

Background: Accurate, sensitive, and rapid identification of leukemia cells in blood and bone marrow is of paramount significance for clinical diagnosis. An integrative technique combining traditional cytomorphology with immunophenotyping was proposed to improve the diagnostic efficiency in leukemia. On account of high photostability, biocompatibility, and signal-to-background ratio, upconversion nanoparticles (UCNPs) as luminescent labels have drawn substantial research scrutiny in immunolabeling. Methods: To achieve simultaneous determination, NaYF4:Yb,Er UCNPs were coupled with CD38 antibodies to construct immunofluorescence probes that were developed to bind to diffuse large B cell lymphoma (DLBCL) cells, followed by Wright's staining that has been widely used in clinical work for morphological diagnosis. Further, the experimental conditions were optimized, such as medium, slice-making method, antibody dosage, incubation time, etc. Results: The cell morphology and immunolabeling could be observed simultaneously, and its simple operation rendered it a possibility for clinical diagnosis. The developed immunolabeling assay could achieve DLBCL cell counting with high reproducibility and stability, and the detection limit was as low as 1.54 cell/slice (>3 σ/s). Moreover, the proposed method also realized real blood and bone marrow sample analysis, and the results were consistent with the clinical diagnosis. Conclusion: Overall, this strategy can be carried out after simple laboratory training and has prospective biomedical applications in leukemia classification, diagnosis validation, and differential diagnostics.

Cobalt/Salox-Catalyzed Enantioselective Dehydrogenative C-H Alkoxylation and Amination.

The past decade has witnessed a rapid progress in asymmetric C-H activation. However, the enantioselective C-H alkoxylation and amination with alcohols and free amines remains elusive. Herein, we disclose the first enantioselective dehydrogenative C-H alkoxylation and amination enabled by a simple cobalt/salicyloxazoline (Salox) catalysis. The use of cheap and readily available cobalt(II) salts as catalysts and Saloxs as chiral ligands provides an efficient method to access P-stereogenic compounds in excellent enantioselectivities (up to >99 % ee). The practicality of this protocol is demonstrated by gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, which offering a flexible asymmetric alternative to access P-stereogenic mono- and diphosphine chiral ligands. Preliminary mechanistic studies on the enantioselective C-H alkoxylation reaction suggest that a cobalt(III/IV/II) catalytic cycle might be involved.

lncRNAs MALAT1 and LINC00657 upstream to miR-214-3p/BMP2 regulate osteogenic differentiation of human mesenchymal stem cells.

BACKGROUND: Osteogenic differentiation of human mesenchymal stem cells (hMSCs) holds significant clinical implications for patients with bone diseases. LncRNAs are an emerging group of epigenetic modulators involved in the osteogenesis of hMSCs. In this study, we explored lncRNA profiles that are upstream to the hsa-miR-214-3p/BMP2 axis in osteogenic differentiation of hMSCs. METHOD: HMSCs were induced toward osteogenesis for 14 days. Between day 1 and day 14, qRT-PCR was conducted to compare the expressions of BMP2, Runx2, hsa-miR-214-3p, and biochemical assays to compare alkaline phosphatase and Alizarin Red S activities. 145 lncRNAs, which were experimentally confirmed upstream to hsa-miR-214-3p were examined. Five significantly upregulated lncRNAs, MEG3, SNHG16, FAM83H-AS1, MALAT1 and LINC00657 were downregulated in differentiated hMSCs and their impact on osteogenic differentiation were examined. Hsa-miR-214-3p was silenced in lncRNAs-downregulated hMSCs to further examine the association between lncRNAs and hsa-miR-214-3p/BMP2 axis. RESULTS: From day 1 to day 14, hMSCs underwent significant osteogenic differentiation, and KCNQ1OT1, MEG3, SNHG16, FAM83H-AS1, MALAT1 and LINC00657 were significantly upregulated. Downregulations of MEG3, SNHG16, FAM83H-AS1, MALAT1 and LINC00657 all suppressed osteogenic differentiation. However, qRT-PCR and RIP assay demonstrated that only MALAT1 and LINC00657 acted through hsa-miR-214-3p/BMP2 to regulate osteogenic differentiation. Furthermore, silencing hsa-miR-214-3p only rescued osteogenic differentiation in MALAT1- or LINC00657- downregulated hMSCs. CONCLUSIONS: Our data strongly indicated that lncRNAs MALAT1 and LINC00657 acted through miR-214-3p/BMP2 axis to regulate osteogenic differentiation of hMSCs.

Highly Sensitive Lanthanide-Doped Nanoparticles-Based Point-of-Care Diagnosis of Human Cardiac Troponin I.

INTRODUCTION: Cardiac troponin I (cTnI) has been regarded as a gold standard for early diagnosis and prognosis monitoring of acute myocardial infarction (AMI) in clinical practice. Owing to its low concentration in blood, accurate determination of cTnI often requires high sensitivity. However, current established point-of-care (POC) assays are insufficient to meet clinically analytical requirements due to their low sensitivity. METHODS: To this end, we established a highly sensitive and reliable POC lateral flow strip based on lanthanide-doped nanoparticles (NPs) for cTnI determination in human blood samples. The capture of cTnI on the lateral flow strip was performed in a sandwich assay, where Eu3+-doped vanadate nanoparticles (GdVO4:30% Eu NPs) were used as luminescent probes to allow quantification. RESULTS: Our platform realized the analytical sensitivity enhancement with limit-of-detection (LOD) as low as 17 pg mL-1 for cTnI detection, which was lower than the commercial counterpart; meanwhile, it displayed high specificity, excellent reproducibility and outstanding accuracy for analyzing clinical serum samples. CONCLUSION: Overall, this strategy provided an ultrasensitive, cost-effective and user-friendly platform for on-site cTnI detection, demonstrating the prospect of lanthanide-doped NPs-based POC diagnosis of disease-related biomarkers.

Influence of hemoglobin level(Hb) on survival and prognosis of elderly hip fracture at admission / 中国骨伤

OBJECTIVE@#To analyze the relationship between hemoglobin(Hb) level on admission and survival prognosis of patients with hip fracture.@*METHODS@#From February 2016 to October 2018, 249 elderly patients with hip fracture were surgically treated including 62 males and 187 females;the age ranged from 60 to 91(73.67±10.52) years;the time from injury to operation was (6.79±2.27) d. The clinical and laboratory examination results were collected. The Hb level at admission and the mortality at 30, 90, 180 and 360 days after operation were observed. According to the Hb level at admission, the patients were divided into Hb<120 g/L and Hb≥120 g/L groups. The survival conditions of the two groups at 30, 90, 180 and 360 days after operation were compared and analyzed. Logistic regression was used to analyze the effect of Hb level on death 30, 90, 180 and 360 days after operation.@*RESULTS@#The mortality rates at 30, 90, 180 and 360 days after operation were 5.22%, 9.24%, 16.87% and 20.48% respectively. The level of Hb at admission was a risk factor for prognosis and death 30, 90, 180 and 360 days after operation(P<0.05). The OR(95% CI) were 2.431(1.475-4.006), 2.625(1.468-4.695), 2.276(1.320-3.925) and 2.082(1.221-3.551) respectively.@*CONCLUSION@#The level of Hb at admission can affect the survival and prognosis of elderly patients with hip fracture. We should further study how to manage the level of Hb before operation.

Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites' Identification, Network Pharmacology, and Experimental Validation.

Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut microbiota itself. Here, we report the identification of one anticancer gut bacterial strain AD16, which exhibited potent suppressive effects on a broad range of solid and blood malignancies. The secondary metabolites of the strain were isolated and characterized by a bioactivity-guided isolation strategy. Five new compounds, streptonaphthalenes A and B (1-2), pestaloficins F and G (3-4), and eudesmanetetraiol A (5), together with nine previously known compounds, were isolated from the effective fractions of AD16. Structures of the new compounds were established by 1D and 2D NMR and MS analysis, and the absolute configurations were determined by the CD method. The analysis of network pharmacology suggested that 3, 2, and 13 could be the key components for the anti-NSCLC activity of AD16. In addition to the PI3K-Akt signaling pathway, the proteoglycans in cancer pathway could be involved in the anti-NSCLC action of AD16.

The effect of dance-based mind-motor activities on the quality of life in the patients recovering from COVID-19: A protocol for systematic review and meta-analysis.

BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), with the improvement of diagnosis and treatment level in various countries, more and more patients have been discharged after systematic treatment. In order to effectively promote the overall recovery of patients' physical and mental function and quality of life (QOL), the focus of clinical work should be gradually shifted to rehabilitation treatment. Dance-based mind-motor activities were defined as coordinated upright mind-motor movements that emphasize dynamic balance, structured through music or an inner rhythm (e.g., breathing) and distinctive instructions or choreography, and that involve social interaction. It has positive effects on motor function, lung function, psychological mood and other aspects, so it can be used as a safe alternative therapy for patients recovering from COVID-19. At present, there are no relevant articles for systematic review. METHODS: From its inception until March 2021, we will conduct a comprehensive electronic search, including Cochrane Library, MEDLINE, PubMed, Springer, EMBASE, Chinese Science Citation Database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Wan-fang database. Two independent researchers will conduct article retrieval, screening, quality assessment, and data analysis through the Review Manager (V. 5.3.5). RESULTS: The results of this study will evaluate the effectiveness and safety of dance-based mind-motor activities for the improvement of QOL in COVID-19 patients during the recovery period. CONCLUSION: The conclusion of the study will provide an evidence to judge whether dance-based mind-motor activities is effective and safe for COVID-19 in recovery period. ETHICS AND DISSEMINATION: This protocol will not evaluate individual patient information or infringe patient rights and therefore does not require ethical approval. PROSPERO REGISTRATION NUMBER: CRD42021232995.

Novel Bacillus strains from the human gut exert anticancer effects on a broad range of malignancy types.

Cancer is one of the leading causes of death worldwide, but effective therapies remain the topic of many research activities. Many recent studies have thus focused on particular gut microbiota due to their important roles in treating cancers, but very few microbes of therapeutic value have been reported. In this study, we isolated four bacterial strains, BY38, BY40, BY43 and BY45, from the fecal specimens of healthy individuals and cancer patients. The treatment of cancer cells with the products of these cultured bacteria induced significant inhibitory effects on the proliferation of ovarian cancer cells and colorectal cancer cells in a dose-dependent manner. A phylogenetic analysis showed that the four anticancer strains belong to the genus Bacillus, and flow cytometry assays indicated that the inhibitory effects might be achieved through the induction of cell apoptosis. These results suggest that these bacteria could be novel and promising anticancer agents against cancers.

E. coli diversity: low in colorectal cancer.

BACKGROUND: Escherichia coli are mostly commensals but also contain pathogenic lineages. It is largely unclear whether the commensal E. coli as the potential origins of pathogenic lineages may consist of monophyletic or polyphyletic populations, elucidation of which is expected to lead to novel insights into the associations of E. coli diversity with human health and diseases. METHODS: Using genomic sequencing and pulsed field gel electrophoresis (PFGE) techniques, we analyzed E. coli from the intestinal microbiota of three groups of healthy individuals, including preschool children, university students, and seniors of a longevity village, as well as colorectal cancer (CRC) patients, to probe the commensal E. coli populations for their diversity. RESULTS: We delineated the 2280 fresh E. coli isolates from 185 subjects into distinct genome types (genotypes) by PFGE. The genomic diversity of the sampled E. coli populations was so high that a given subject may have multiple genotypes of E. coli, with the general diversity within a host going up from preschool children through university students to seniors. Compared to the healthy subjects, the CRC patients had the lowest diversity level among their E. coli isolates. Notably, E. coli isolates from CRC patients could suppress the growth of E. coli bacteria isolated from healthy controls under nutrient-limited culture conditions. CONCLUSIONS: The coexistence of multiple E. coli lineages in a host may help create and maintain a microbial environment that is beneficial to the host. As such, the low diversity of E. coli bacteria may be associated with unhealthy microenvironment in the intestine and hence facilitate the pathogenesis of diseases such as CRC.

LDL-C plays a causal role on T2DM: a Mendelian randomization analysis.

Diabetic dyslipidemia is a common condition in patients with Type 2 diabetes mellitus (T2DM). However, with the increasing application of statins which mainly decrease low-density lipoprotein cholesterol (LDL-C) levels, clinical trials and meta-analysis showed a clearly increase of the incidence of new-onset DMs, partly due to genetic factors. To determine whether a causal relationship exists between LDL-C and T2DM, we conducted a two-sample Mendelian Randomization (MR) analysis using genetic variations as instrumental variables (IVs). Initially, 29 SNPs significantly related to LDL-C (P≤ 5.0×10-8) were selected as based on results from the study of Henry et al, which processed loci data influencing lipids identified by the Global Lipids Genetics Consortium (GLGC) from 188,577 individuals of European ancestry. While 6 SNPs related to T2DM (P value < 5×10-2) were deleted, with the remaining 23 SNPs without LD eventually being deemed as IVs. The combined effect of all these 23 SNPs on T2DM, as generated with use of the penalized robust inverse-variance weighted (IVW) method (Beta value 0.24, 95%CI 0.087~0.393, P-value=0.002) demonstrated that elevated LDL-C levels significantly increased the risk of T2DM. The relationship between LDL-C and Type 1 diabetes mellitus (T1DM) with this analysis producing negative pooled results (Beta value -0.202, 95%CI -2.888~2.484, P-value=0.883).

gutMDisorder: a comprehensive database for dysbiosis of the gut microbiota in disorders and interventions.

gutMDisorder (http://bio-annotation.cn/gutMDisorder), a manually curated database, aims at providing a comprehensive resource of dysbiosis of the gut microbiota in disorders and interventions. Alterations in the composition of the gut microbial community play crucial roles in the development of chronic disorders. And the beneficial effects of drugs, foods and other intervention measures on disorders could be microbially mediated. The current version of gutMDisorder documents 2263 curated associations between 579 gut microbes and 123 disorders or 77 intervention measures in Human, and 930 curated associations between 273 gut microbes and 33 disorders or 151 intervention measures in Mouse. Each entry in the gutMDisorder contains detailed information on an association, including an intestinal microbe, a disorder name, intervention measures, experimental technology and platform, characteristic of samples, web sites for downloading the sequencing data, a brief description of the association, a literature reference, and so on. gutMDisorder provides a user-friendly interface to browse, retrieve each entry using gut microbes, disorders, and intervention measures. It also offers pages for downloading all the entries and submitting new experimentally validated associations.

The Assessment of Interleukin-18 on the Risk of Coronary Heart Disease.

BACKGROUND: Observational studies support the inflammation hypothesis in coronary heart disease (CHD). As a pleiotropic proinflammatory cytokine, Interleukin-18 (IL-18), has also been found to be associated with the risk of CHD. However, to our knowledge, the method of Mendelian Randomization has not been used to explore the causal effect of IL-18 on CHD. OBJECTIVE: To assess the causal effect of IL-18 on the risk of CHD. METHODS AND RESULTS: Genetic variant instruments for IL-18 were obtained from information of the CHS and InCHIANTI cohort, and consisted of the per-allele difference in mean IL-18 for 16 independent variants that reached genome-wide significance. The per-allele difference in log-odds of CHD for each of these variants was estimated from CARDIoGRAMplusC4D, a two-stage meta -analysis. Two-sample Mendelian Randomization (MR) was then performed. Various MR analyses were used, including weighted inverse-variance, MR-Egger regression, robust regression, and penalized regression. The OR of elevated IL-18 associated with CHD was only 0.005 (95%CI -0.105~0.095; P-value=0.927). Similar results were obtained with the use of MR-Egger regression, suggesting that directional pleiotropy was unlikely biasing these results (intercept -0.050, P-value=0.220). Moreover, results from the robust regression and penalized regression analyses also revealed essentially similar findings. CONCLUSION: Our findings indicate that, by itself, IL-18 is unlikely to represent even a modest causal factor for CHD risk.

A Mendelian Randomization Study on Infant Length and Type 2 Diabetes Mellitus Risk.

OBJECTIVE: Infant length (IL) is a positively associated phenotype of type 2 diabetes mellitus (T2DM), but the causal relationship of which is still unclear. Here, we applied a Mendelian randomization (MR) study to explore the causal relationship between IL and T2DM, which has the potential to provide guidance for assessing T2DM activity and T2DM- prevention in young at-risk populations. MATERIALS AND METHODS: To classify the study, a two-sample MR, using genetic instrumental variables (IVs) to explore the causal effect was applied to test the influence of IL on the risk of T2DM. In this study, MR was carried out on GWAS data using 8 independent IL SNPs as IVs. The pooled odds ratio (OR) of these SNPs was calculated by the inverse-variance weighted method for the assessment of the risk the shorter IL brings to T2DM. Sensitivity validation was conducted to identify the effect of individual SNPs. MR-Egger regression was used to detect pleiotropic bias of IVs. RESULTS: The pooled odds ratio from the IVW method was 1.03 (95% CI 0.89-1.18, P = 0.0785), low intercept was -0.477, P = 0.252, and small fluctuation of ORs ranged from -0.062 ((0.966 - 1.03) / 1.03) to 0.05 ((1.081 - 1.03) / 1.03) in leave-one-out validation. CONCLUSION: We validated that the shorter IL causes no additional risk to T2DM. The sensitivity analysis and the MR-Egger regression analysis also provided adequate evidence that the above result was not due to any heterogeneity or pleiotropic effect of IVs.

Dysbiosis of the Gut Microbiome in Lung Cancer.

Lung cancer (LC) is one of the most serious malignant tumors, which has the fastest growing morbidity and mortality worldwide. A role of the lung microbiota in LC pathogenesis has been analyzed, but a comparable role of the gut microbiota has not yet been investigated. In this study, the gut microbiota of 30 LC patients and 30 healthy controls were examined via next-generation sequencing of 16S rRNA and analyzed for diversity and biomarkers. We found that there was no decrease in significant microbial diversity (alpha diversity) in LC patients compared to controls (P observed = 0.1422), while the composition (beta diversity) differed significantly between patients and controls (phylum [stress = 0.153], class [stress = 0.16], order [stress = 0.146], family [stress = 0.153]). Controls had a higher abundance of the bacterial phylum Actinobacteria and genus Bifidobacterium, while patients with LC showed elevated levels of Enterococcus. These bacteria were found as possible biomarkers for LC. A decline of normal function of the gut microbiome in LC patients was also observed. These results provide the basic guidance for a systematic, multilayered assessment of the role of the gut microbiome in LC, which has a promising potential for early prevention and targeted intervention.

A Positive Causal Influence of IL-18 Levels on the Risk of T2DM: A Mendelian Randomization Study.

A large number of clinical studies have shown that interleukin-18 (IL-18) plasma levels are positively correlated with the pathogenesis and development of type 2 diabetes mellitus (T2DM), but it remains unclear whether IL-18 causes T2DM, primarily due to the influence of reverse causality and residual confounding factors. Genome-wide association studies have led to the discovery of numerous common variants associated with IL-18 and T2DM and opened unprecedented opportunities for investigating possible associations between genetic traits and diseases. In this study, we employed a two-sample Mendelian randomization (MR) method to analyze the causal relationships between IL-18 plasma levels and T2DM using IL18-related SNPs as genetic instrumental variables (IVs). We first selected eight SNPs that were significantly associated with IL-18 but independent of T2DM. We then used these SNPs as IVs to evaluate their effects on T2DM using the inverse-variance weighted (IVW) method. Finally, we conducted sensitivity analysis and MR-Egger regression analysis to evaluate the heterogeneity and pleiotropic effects of each variant. The results based on the IVW method demonstrate that high IL-18 plasma levels significantly increase the risk of T2DM, and no heterogeneity or pleiotropic effects appeared after the sensitivity and MR-Egger analyses.

Exposing the Causal Effect of Body Mass Index on the Risk of Type 2 Diabetes Mellitus: A Mendelian Randomization Study.

Introduction: High body mass index (BMI) is a positive associated phenotype of type 2 diabetes mellitus (T2DM). Abundant studies have observed this from a clinical perspective. Since the rapid increase in a large number of genetic variants from the genome-wide association studies (GWAS), common SNPs of BMI and T2DM were identified as the genetic basis for understanding their associations. Currently, their causality is beginning to blur. Materials and Methods: To classify it, a Mendelian randomisation (MR), using genetic instrumental variables (IVs) to explore the causality of intermediate phenotype and disease, was utilized here to test the effect of BMI on the risk of T2DM. In this article, MR was carried out on GWAS data using 52 independent BMI SNPs as IVs. The pooled odds ratio (OR) of these SNPs was calculated using inverse-variance weighted method for the assessment of 5 kg/m2 higher BMI on the risk of T2DM. The leave-one-out validation was conducted to identify the effect of individual SNPs. MR-Egger regression was utilized to detect potential pleiotropic bias of variants. Results: We obtained the high OR (1.470; 95% CI 1.170 to 1.847; P = 0.001), low intercept (0.004, P = 0.661), and small fluctuation of ORs {from -0.039 [(1.412 - 1.470) / 1.470)] to 0.075 [(1.568- 1.470) / 1.470)] in leave-one-out validation. Conclusion: We validate the causal effect of high BMI on the risk of T2DM. The low intercept shows no pleiotropic bias of IVs. The small alterations of ORs activated by removing individual SNPs showed no single SNP drives our estimate.