Betaine and I-LG may have a predictive value for ATB: A causal study in a large European population.

PURPOSE: To analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population. METHODS: In this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis. RESULTS: A total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB. CONCLUSION: Betaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies.

The predictive value of TNF family for pulmonary tuberculosis: a pooled causal effect analysis of multiple datasets.

Objective: Despite extensive research on the relationship between pulmonary tuberculosis (PTB) and inflammatory factors, more robust causal evidence has yet to emerge. Therefore, this study aims to screen for inflammatory proteins that may contribute to the susceptibility to PTB in different populations and to explain the diversity of inflammatory and immune mechanisms of PTB in different ethnicity. Methods: The inverse variance weighted (IVW) model of a two-sample Mendelian Randomization (MR) study was employed to conduct causal analysis on data from a genome-wide association study (GWAS). This cohort consisting PTB GWAS datasets from two European and two East Asian populations, as well as 91 human inflammatory proteins collected from 14,824 participants. Colocalization analysis aimed to determine whether the input inflammatory protein and PTB shared the same causal single nucleotide polymorphisms (SNPs) variation within the fixed region, thereby enhancing the robustness of the MR Analysis. Meta-analyses were utilized to evaluate the combined causal effects among different datasets. Results: In this study, we observed a significant negative correlation between tumor necrosis factor-beta levels (The alternative we employ is Lymphotoxin-alpha, commonly referred to as LT) (P < 0.05) and tumor necrosis factor receptor superfamily member 9 levels (TNFRSF9) (P < 0.05). These two inflammatory proteins were crucial protective factors against PTB. Additionally, there was a significant positive correlation found between interleukin-20 receptor subunit alpha levels (IL20Ra) (P < 0.05), which may elevate the risk of PTB. Colocalization analysis revealed that there was no overlap in the causal variation between LT and PTB SNPs. A meta-analysis further confirmed the significant combined effect of LT, TNFRSF9, and IL20Ra in East Asian populations (P < 0.05). Conclusions: Levels of specific inflammatory proteins may play a crucial role in triggering an immune response to PTB. Altered levels of LT and TNFRSF9 have the potential to serve as predictive markers for PTB development, necessitating further clinical validation in real-world settings to ascertain the impact of these inflammatory proteins on PTB.

Development and Application of a Reference Manual for Diagnosis and Rational Use of Antimicrobial Agents for Outpatient Primary Care (Digestive System Part): A Delphi Study.

Purpose: To establish a concise and easy-to-understand reference manual for outpatient primary care providers, promoting correct diagnosis of digestive system diseases and rational antimicrobial use. Methods: The establishment of the manual encompassed two processes: the development of a draft manual and the validation of the manual. The development process was based on a literature review and expert discussion. The manual comprises portions for disease diagnosis and rationality of antimicrobial use. The validation process employed a two-round Delphi technique, collecting consensus through paper-based or mail-based communications. The response of the Delphi group was assessed by the level of authority and commitment of the panelists and the degree of agreement among them. Furthermore, the manual was preliminarily applied among primary care physicians. Results: A total of 29 panelists completed the Delphi working process. They were authoritative in their professional fields with authority coefficients of 0.813 and 0.818 for the two portions of the manual, respectively. The level of commitment of the panelists was measured by response rates, which were 100.00% and 96.67% for Round 1 and 2. After two rounds, a consensus was achieved with the consensus rates for the two portions of the manual being greater than 65% and 70%, respectively. Kendall W-tests had P-values < 0.001 in both rounds. This reference manual provides 200 diagnostic indicators for 29 common digestive diseases and recommendations for the rational use of antimicrobial agents for 13 categories of digestive diseases. The primary care physicians who used the reference manual reported high satisfaction and frequent usage. Conclusion: Based on a collective consensus of professionals, a reference manual has been established, to provide a concise and easy-to-understand guide specifically for physicians and pharmacists in outpatient primary care. It could facilitate rapid learning to improve the accuracy of diagnosis and treatment for digestive disorders.

[Study on degradation of protein of the edible birds' nest (Aerodramus) in vitro].

OBJECTIVE: To study the digestion of Bird's nest extract (BNE) in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). METHODS: BNE were prepared and digested at 37 degrees C in SGF/SIF. At intervals of 0, 1, 5, 10, 15, 30, 60 min,the samples were taken out. Protein contents were determined by the method of Bradford, and digestion of BNE in SGF/SIF was observed according to the results of polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: On SDS-PAGE,the crude BNE and the BNE in SGF/SIF gave different patterns, but all being rich in high molecular weight protein. After digestion in vitro, most of protein degraded to 40 kD below, but part of high molecular weight protein was stable, and a protein of 70 kD added. CONCLUSION: Most protein degraded to polypeptide, but there was anti-digest protein in the BNE, all being the high molecular weight protein. This suggested that the active component from BNE was probably exerted directly on human body.