Lanqing Ma

Chemoresistance is a main cause of colorectal cancer (CRC) treatment failure. We identified that Bacteroides fragilis is enriched in patients with CRC resistant to chemotherapy in two independent cohorts, and its abundance is associated with poor survival. Consistently, administration of B. fragilis to CRC xenografts and Apc Min/+ - and AOM/DSS-induced CRC mice all significantly attenuated the antitumor efficacy of 5-FU and OXA. Mechanistically, B. fragilis colonized colon tumors and mediated its effect via its surface protein SusD/RagB binding to the Notch1 receptor in CRC cells, leading to activation of the Notch1 signaling pathway and the induction of epithelial-to-mesenchymal transition (EMT)/stemness to suppress chemotherapy-induced apoptosis. Either deletion of SusD/RagB or blockade of Notch1 signaling abrogated B. fragilis -mediated chemoresistance. Finally, B. fragilis -targeting phage VA7 selectively suppressed B. fragilis and restored chemosensitivity in preclinical CRC mouse models. Our findings have offered insights into the potential of precise gut microbiota manipulation for the clinical management of CRC. • B. fragilis is enriched in non-responders of patients with CRC to chemotherapy • B. fragilis compromises 5-FU/OXA efficacy in CRC cells and in mouse models • B. fragilis surface SusD/RagB binds to host receptor Notch1, inducing chemoresistance • Phage VA7 eliminates B. fragilis and restores chemosensitivity of CRC in mice Ding et al. identify Bacteroides fragilis as a bacterial pathogen that promotes colorectal cancer (CRC) chemoresistance by activating host Notch1 signaling through its surface protein SusD/RagB. Targeting B. fragilis with a phage therapy restores chemotherapy sensitivity in CRC mouse models.

Background: Hepatitis B is an important public health challenge facing China. Understanding the long-term epidemiological trends and evolving spatial distribution patterns is critical for optimizing prevention strategies and achieving the World Health Organization's 2030 hepatitis elimination targets. Objective: This study aimed to explore the epidemic trends and spatial distribution characteristics of hepatitis B in China from 2004 to 2020. Methods: This study used data on hepatitis B incidence from 2004 to 2020 from the China Public Health Science Data Center to analyze the time trend of hepatitis B incidence by joinpoint regression. The age-period-cohort model was used to analyze the age, period, and cohort effects of hepatitis B onset. Spatial autocorrelation analysis was used to explore the spatial distribution characteristics of hepatitis B in China. Results: From 2004 to 2020, China reported a total of 17,449,842 cases of hepatitis B, with an average annual incidence rate of 76.30/100,000. The incidence of hepatitis B in China showed an increasing trend from 2004 to 2007, with an average annual percentage change (AAPC) of 9.49 (95% CI 2.12-17.39), and a decreasing trend from 2007 to 2014, with an AAPC of -3.77 (95% CI -5.93 to -1.55). The incidence of hepatitis B in China tended to be stable from 2014 to 2020, with an AAPC of -0.46 (95% CI -2.86 to 2.01). Age, period, and cohort effect significantly affect the incidence of hepatitis B. The age effect showed that the incidence rate of hepatitis B reached its peak at the age of 22 years, with an average incidence rate of 176.173/100,000. The period effect showed that the highest level during the study period occurred during 2004-2006. The cohort effect showed that the risk of hepatitis B increased first and then decreased, with the turning point of 1924-1974. The incidence of hepatitis B varies significantly among regions. The incidence in the northeast and northwest regions has decreased, that in the south and southwest regions has increased, and that in other regions has remained stable. Conclusions: China has achieved remarkable results in the prevention and control of hepatitis B, but there are still differences in the incidence rate among different age groups and regions. These results suggest the need to further strengthen the identification and screening of high-risk populations and promote supplementary adult hepatitis B vaccination. Future intervention strategies should fully consider regional differences, implement precise intervention measures based on the epidemic trends and spatial distribution characteristics of each region, optimize resource allocation, and enhance the overall effectiveness of hepatitis B prevention and control.

Introduction Meteorological factors and air pollutants are two important factors affecting hospitalisation for coronary heart disease. This study aims to investigate the effects of meteorological factors and air pollutants on the risk of coronary heart disease hospitalisation and their interactions in rural areas with heavy particulate matter pollution at the edge of the desert in southern Xinjiang. Methods In this study, patients with coronary heart disease who were hospitalized in Tangyi Town, Tumushuke City, Xinjiang Province, were selected as the study subjects, and the lagged effects of meteorological factors and air pollutants on the risk of coronary heart disease hospitalisation and their interactions were analysed by combining the distributional lag nonlinear model and the quasi-Poisson regression model. Results The results showed that the associations between meteorological factors and air pollutant concentrations with the risk of coronary heart disease hospitalisation both showed non-linear and lagged effects. There was an antagonistic effect between mean daily temperature and PM 2.5 and PM 10 on the effect of coronary heart disease hospitalisation, with RERIs of −0.73 (95% CI: −2.63, −0.04), and −1.14 (95% CI: −1.93, −0.60), respectively. The relative risk of coronary heart disease hospitalisation in the low-temperature, high PM10 concentration environment was 1.53 (95% CI: 1.09, 2.13). The risk of hospitalization for coronary heart disease is increased by 30 and 19% in environments with low humidity and high PM 2.5 and PM 10 concentrations, respectively. There are also interactions between particulate matter and gaseous pollutants and between different gaseous pollutants. Discussion This study suggests the need to necessity of management of multiple air pollutants and response to climate change, as well as the importance of implementing targeted preventive and control measures by the relevant authorities in according to meteorological and air pollution conditions, which can effectively reduce the hospitalization rate of patients with coronary heart disease.