Chao Cai

Intestinal colonization is a critical precursor to invasive Klebsiella pneumoniae infection, yet the host-derived metabolic cues that license this transition remain unclear. Here, we identify arginine as a consistently enriched amino acid across inflammation-, diet-, and antibiotic-induced gut perturbations. Arginine markedly enhances capsular polysaccharide production and virulence in both hypervirulent ST23-KL1 and carbapenem-resistant ST11-KL64 lineages under conditions reflective of the gut microenvironment. Mechanistically, arginine must be transported by the ArtP ATP-binding transporter to activate the regulator ArgR, which directly binds capsular polysaccharide operon promoters and indirectly upregulates rmpA , forming a conserved ArtP–ArgR–capsule signaling axis. In mouse models, elevated intestinal arginine increases gut colonization, accelerates mucosal invasion, and promotes systemic dissemination, whereas arginase-mediated arginine depletion or loss of ArtP/ArgR abrogates these effects. Together, our findings reveal intestinal arginine as a key host-derived signal that drives K. pneumoniae pathogenic progression and identify arginine metabolism as a tractable therapeutic target.

Liver cancer poses a significant global health challenge. Smoking and alcohol consumption are major risk factors for liver cancer. We analyzed data from the Global Burden of Disease (GBD) Study 2021. First, numbers and age-standardized rates of deaths and disability-adjusted life years (DALYs) were assessed globally and by sub-types in 2021. Furthermore, the temporal trend of the disease burden was explored by the linear regression model from 1990 to 2019. Based on the EAPC values, we conducted a hierarchical cluster analysis to categorize the 54 GBD regions into four groups. To explore potential associations between the EAPCs and socioeconomic factors, we employed the Spearman correlation analysis to evaluate the correlation between EAPCs and ASRs, as well as Human Development Index (HDI) scores. Finally, frontier analysis was used to visually demonstrate the potential for burden reduction in each country or region based on their development levels. All analyses were conducted using R software. From 1990 to 2021, the burden of liver cancer attributed to alcohol consumption increased significantly, whereas age-standardized rates (ASRs) remained relatively stable compared to those associated with smoking.In 2021, the number of deaths and disability-adjusted life years (DALYs) due to smoking-related liver cancer were 53,054 (95% uncertainty interval [UI]: 18,268–88,111) and 1,482,896 (95% UI: 505,000–2,478,906), respectively. The corresponding age-standardized rates (ASRs) were 0.61 per 100,000 population (95% UI: 0.21–1.01) for mortality and 16.9 per 100,000 (95% UI: 5.76–28.26) for DALYs. The estimated annual percentage changes (EAPCs) for these ASRs were − 0.84 (95% confidence interval [CI]: -0.96 to -0.73) for mortality and − 1.12 (95% CI: -1.24 to -1.01) for DALYs.Conversely, in 2021, deaths and DALYs attributable to alcohol-related liver cancer totaled 93,807 (95% UI: 77,476–113,542) and 2,385,090 (95% UI: 1,949,109–2,911,783), respectively. The corresponding ASRs were 1.08 per 100,000 (95% UI: 0.89–1.30) for mortality and 27.2 per 100,000 (95% UI: 22.25–33.1) for DALYs. The EAPCs were 0.26 (95% CI: 0.19–0.32) for mortality and 0.04 (95% CI: -0.03 to 0.10) for DALYs. Males, middle-aged, and older adults were high-risk populations, and middle socio-demographic index (SDI) regions were high-risk areas. The Western Pacific had the highest ASDR for smoking-related liver cancer, while East Asia recorded the highest ASDAR. For alcohol-related liver cancer, the Commonwealth High-Income region exhibited the highest ASDR, whereas Australasia had the highest ASDAR. Andean Latin America had the lowest ASRs for both smoking- and alcohol-related liver cancer. Notably, Mongolia had the highest ASRs for liver cancer attributed to both smoking and alcohol consumption, with values hundreds of times greater than those in the country with the lowest burden, Morocco. Although the ASRs of smoking-related liver cancer have continued to decline, the absolute number of cases remains high, and the burden of alcohol-related liver cancer continues to rise. Consequently, the overall disease burden associated with smoking and alcohol consumption remains significant, highlighting the urgent need for more effective risk factor control strategies. Furthermore, the establishment of accurate and efficient screening systems, as well as specialized cancer treatment centers, is imperative—particularly for high-risk populations, such as middle-aged and elderly men, and for high-risk regions classified as High and Middle SDI areas.

Background: Positive blood cultures for Klebsiella pneumoniae liver abscess (KPLA) are associated with an increased risk of extrahepatic organ infections and severe complications such as septicemia and septic shock, leading to higher mortality rates. This study aimed to investigate the clinical characteristics of patients with blood culture-positive KPLA and identify potential predictive indicators. Methods: We performed a retrospective analysis of clinical data from 263 KPLA patients diagnosed at our hospital between January 2019 and December 2023. The objective was to compare clinical characteristics between patients with positive and negative blood cultures and explore factors influencing blood culture positivity. Patients were divided into a blood culture-positive group (study group) and a blood culture-negative group (control group). We compared baseline characteristics, laboratory parameters, ultrasound findings, and complications. Logistic regression identified risk factors, and receiver operating characteristic (ROC) curves assessed the predictive value of inflammatory markers. Results: The study group exhibited higher ICU admission rates, longer hospital stays, and elevated qSOFA scores (≥ 2, 15.1 vs 2.6, P=0.003) along with a greater prevalence of diabetes and biliary diseases. Key laboratory values, including glucose, creatinine, procalcitonin (PCT), and C-reactive protein (CRP), were significantly higher, while albumin and platelet levels were lower (P < 0.05). Complications such as pleural effusion (35.1 vs 12.8, P< 0.001), ascites (15.1 vs 2.6, P=0.003), pulmonary infections (27.6 vs 7.7, P< 0.001), and extrahepatic abscesses (15.7 vs 5.1, P=0.018) were notably more common. Diabetes was identified as an independent risk factor for blood culture-positive KPLA. Among inflammatory markers, PCT showed the highest predictive value for blood culture positivity (AUC=0.683; cutoff=4.97 ng/mL; sensitivity=70.3%; specificity=62.8%). Conclusion: Patients with underlying diabetes mellitus are more prone to developing blood culture-positive KPLA. PCT demonstrates better predictive performance for blood culture-positive KPLA, and patients with PCT levels ≥ 4.97 ng/mL have a higher likelihood of positive blood culture results.

Objective: To analyze the clinical features of elderly patients with blood culture-positive bacterial liver abscess (BLA) and improve diagnostic and treatment strategies.Methods: Elderly BLA patients admitted to our hospital from December 2018 to December 2023 were included in the study. Diagnostic tests included routine blood analysis, biochemistry, C-reactive protein (CRP), procalcitonin (PCT), imaging, and cultures of blood or pus. Treatments involved anti-infective therapy, ultrasound-guided abscess drainage, and supportive care.Results: (1) Elderly patients with blood culture-positive BLA had higher rates of prolonged hospital stays (≥2 weeks), ICU admission, biliary system diseases, hepatitis B infection, maximum body temperature ≥ 39°C, and qSOFA scores ≥2 compared to controls (p < 0.05)0. (2) Laboratory findings showed higher levels of total bilirubin (≥34.2 μmol/L), ALT (≥50 U/L), serum creatinine (≥80 μmol/L), PCT (≥5 ng/mL), and lower platelet counts (≤100 × 10⁹/L) in the research group (p < 0.05). ESBL-positive cases and liver abscesses ≤5 cm were more common in the research group (p < 0.05). (3) Complications such as pleural effusion, ascites, pulmonary infections, and extrahepatic abscesses were significantly more frequent in the blood culture-positive group (p < 0.05). (4) Microbiological analysis indicated that Klebsiella pneumoniae was the leading pathogen (87.93%), followed by Escherichia coli. For ESBL-positive infections, E. coli was dominant (75.76%), especially in patients with biliary diseases (75.56%). (5) Logistic regression identified prolonged hospital stay, hepatitis B infection, biliary system diseases, temperature ≥ 39°C, PCT ≥5, and abscess size ≤5 cm as independent risk factors for blood culture-positive BLA. (6) The combined diagnostic indicator showed good predictive ability (AUC = 0.840, sensitivity 76.6%, specificity 72.2%).Conclusion: Elderly patients with biliary diseases, hepatitis B, high PCT levels (≥5 ng/mL), small abscesses (≤5 cm), and fever (≥39°C) are at higher risk for blood culture-positive BLA. Klebsiella pneumoniae remains the predominant pathogen (87.93%), highlighting the need for prompt empirical antibiotic therapy. The combined diagnostic model offers reliable predictive value for this condition. We developed a predictive model aimed at assisting clinicians in identifying high-risk patients prone to bloodstream infections secondary to BLA. This model provides valuable guidance for clinicians in formulating more rational and individualized treatment strategies.