Chinese Medical Journal最新文献

Background: Gut microbiota are important for uric acid (UA) metabolism in hyperuricemia (HUA); however, the underlying mechanisms of how the gut microbiota regulate intestinal UA metabolism remain unclear. This study aimed to explore the function of the intestine in HUA and to further reveal the possible mechanism.

Methods: We conducted gut microbiota depletion to validate the role of gut microbiota in UA metabolism. A mouse model of HUA was established, and the gut microbiota and microbiome-derived metabolites were analyzed via 16S RNA gene sequencing and metabolomics analysis. The mechanism of the gut microbiota in HUA was elucidated by in vivo and in vitro experiments.

Results: Antibiotic treatment elevated serum UA, disturbed purine metabolism, and decreased the relative abundance of Lactobacillus. HUA mice had a lower relative abundance of Lactobacillus johnsonii (L. johnsonii ) and decreased gut butyrate concentration. Supplementation of L. johnsonii significantly reduces serum UA in hyperuricemia mice by preventing UA synthesis and promoting the excretion of gut purine metabolites. In addition, L. johnsonii enhanced intestinal UA excretion by heightening the urate transporter ABCG2 (adenosine triphosphate-binding cassette transporter, subfamily G, member 2) expression, and increasing the levels of butyrate, which upregulated ABCG2 expression via the Wnt5a/b/β-catenin signaling pathway.

Conclusion: Our results suggest that gut microbiota and microbiota-derived metabolites directly regulate gut UA metabolism, highlighting potential applications in the treatment of diet-induced HUA by targeting gut microbiota and its metabolites.

Abstract: Gastrointestinal tumors are among the most prevalent and deadly cancers worldwide and have been increasingly associated with the gut microbiota. Particularly, colorectal cancer (CRC) has become a focal point for unraveling the complex interplay between microbial dynamics and gastrointestinal tumor development, as extensive studies have shown that gut microbiota dysbiosis is closely associated with CRC, affecting energy harvest, metabolism, and mucosal and systemic immune responses. Clostridioides difficile ( C. difficile ) is the major causative agent of gut microbiota dysbiosis, with toxins A and B being its main pathogenic factors. These toxins reportedly trigger a complex cascade of host cellular responses, leading to diarrhea, inflammation, and tissue necrosis. However, recent experimental evidence suggests that chronic infection with C. difficile is a previously unrecognized contributor to colonic tumorigenesis. In this concise review, we summarize the hypothetical models and provide a comprehensive overview of the mechanisms linking the microbiota to colorectal carcinogenesis, focusing on the reasonable extrapolation of the interaction between C. difficile and CRC. Understanding the significance of C. difficile as a potential pro-carcinogenic bacterium and its potential role as a biomarker in CRC is crucial for advancing our knowledge in preventing tumorigenesis, recurrence, and gastrointestinal tumor metastasis.

Background: Data on antiviral treatment for infants with chronic hepatitis B (CHB) are limited. This study is aimed to investigate whether and how antiviral treatment can achieve a functional cure in infants with CHB.

Methods: This real-world study enrolled 21 infants (9 boys and 12 girls) with active hepatitis B e antigen (HBeAg)-positive CHB from the Fifth Medical Center of Chinese PLA General Hospital, who were perinatally infected with hepatitis B virus (HBV) by mother-to-child transmission. The median baseline age was 9 months. Twenty-one cases initially received Lamivudine (LAM) monotherapy, and interferon-α (IFN-α) treatment was added when they were more than 12 months old. The virological responses, functional cure, and treatment safety were analyzed for 36 months (treatment plus follow-up visit duration).

Results: All 21 infants with CHB (baseline median HBV DNA was 7.75 log10 IU/mL) had full viral suppression on antiviral treatment, and the median time taken for undetectable HBV DNA was 6 months (range: 1-19 months). Correspondingly, the median time taken for HBeAg seroconversion was 7 months (range: 3-18 months) for 20 infants, and one case did not obtain HBeAg seroconversion; 19 of the 21 infants achieved a functional cure through a median time of 9 months (range: 4-27 months) since baseline. Two infants did not achieve a functional cure at the 36-month endpoint, but they achieved undetectable HBV DNA, and one of them had HBeAg seroconversion. Flu-like symptoms associated with IFN-α treatment were the common side effects; however, no serious adverse events were observed.

Conclusion: Our findings indicate that under 1-year-old infants with active CHB can achieve a significantly high probability of a functional cure when they receive a definite duration of antiviral treatment using LAM add-on IFN-α therapy.

Background: Family history (FH) of cancer is an established risk factor for early onset of cancer. However, reliable estimates on the difference in onset age between familial and sporadic cancers remain scarce in the Chinese population.

Methods: This multicenter, hospital-based, cross-sectional study included 23 hospitals across 12 provinces in China. Patients diagnosed with cancers of the lung, stomach, esophagus, or colorectum between January 1, 2016 and December 31, 2017 were identified. Detailed information on sociodemographic characteristics, lifestyle factors, stage at diagnosis, and onset age was collected. We analyzed the association between FH and onset age across different cancer types using quantile regressions.

Results: Among 41,072 eligible patients, 3054 (7.44%) reported a first-degree FH of cancer, and they were diagnosed at younger ages than those without FH (median difference: -1.19, 95% confidence interval [CI]: -1.59 to -0.79). Stratified by cancer type, the most pronounced difference was observed in colorectal cancer (median difference: -2.25, 95% CI: -3.31 to -1.19). Failure to account for lead time bias resulted in an overestimation of the FH effect, ranging from 3.4% to 15.4% across cancer types. Quantile regression analysis revealed that the impact of FH on age at diagnosis was more pronounced at the upper tail of the age distribution for all cancers combined and for each cancer type individually.

Conclusions: Our findings suggest that FH of cancer is associated with the early onset of lung, stomach, esophageal, and colorectal cancers in China. Cancer screening at earlier ages is needed for individuals with an FH.