The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]₄P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.
Cadmium/metabolism* ; Adenosine Triphosphatases/metabolism* ; Ophiopogon/drug effects* ; Soil Pollutants/toxicity* ; Plant Proteins/metabolism* ; Stress, Physiological ; Multigene Family ; Gene Expression Regulation, Plant

ObjectiveTo investigate the value of prealbumin-to-total bilirubin （PA/TBil） ratio on admission in predicting 90-day mortality or liver transplantation in patients with HBV-related acute-on-chronic liver failure （HBV-ACLF）， as well as the effect of its combination with Model for End-Stage Liver Disease （MELD） score on the predictive performance for short-term prognosis. MethodsA retrospective analysis was performed for the clinical data of 216 HBV-ACLF patients who were admitted to Department of Infectious Diseases in the First Affiliated Hospital of Soochow University from April 2020 to May 2025， and the patients were followed up for 3 months. According to the outcome， the patients were divided into survival group with 104 patients and death/transplantation group with 112 patients. The Kolmogorov-Smirnov test was used to check whether the continuous data was in accordance with the normal distribution； the two-independent-samples t test was used for comparison of normally distributed continuous data between two groups， while the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups. The chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate binary Logistic regression analyses were used to investigate the influencing factors for prognosis， and the receiver operating characteristic （ROC） curve was used to analyze the performance of each indicator in predicting the prognosis of ACLF. The area under the ROC curve （AUC） was calculated， and the Delong test was used for comparison of AUC. ResultsA total of 216 patients were enrolled in this study， with a 90-day survival rate of 48.15% （104/216）. Compared with the death/transplantation group， the survival group had significantly higher platelet count， lymphocyte count， albumin， and PA/TBil ratio （all P<0.05） and significantly lower age， white blood cell count， neutrophil count， prothrombin time， international normalized ratio， aspartate aminotransferase， total bilirubin， creatinine， and MELD score （all P<0.05）. The multivariate Logistic regression analysis showed that age （odds ratio ［OR］=1.05， 95% confidence interval ［CI］： 1.02 — 1.09， P<0.001）， PA/TBil ratio （OR=0.16， 95%CI： 0.05 — 0.46， P<0.001）， and MELD score （OR=1.09， 95%CI： 1.01 — 1.17， P=0.024） were independent influencing factors for 90-day prognosis in HBV-ACLF patients. PA/TBil ratio and MELD score used alone or in combination had an AUC of 0.760， 0.779， and 0.811， respectively， in predicting the prognosis of HBV-ACLF patients， and PA/TBil ratio combined with MELD score had a better AUC than PA/TBil ratio or MELD score used alone （Z=-2.058 and 2.017， both P<0.05）. ConclusionBoth serum PA/TBil ratio and MELD score can effectively predict the prognosis of patients with HBV-ACLF， and a combination of the two indicators had a better predictive performance than MELD score alone， which provides an important reference for clinical risk stratification management and timely intervention.

Mitophagy is an evolutionarily highly conserved selective autophagy process that maintains cellular homeostasis and mitochondrial quality control by specifically recognizing and removing damaged or superfluous mitochondria. During tumorigenesis， mitophagy eliminates damaged mitochondria and reduces the accumulation of reactive oxygen species （ROS）， thereby helping to sustain cellular homeostasis. Energy metabolism refers to the core biological process through which cells convert chemical energy from nutrients into adenosine triphosphate （ATP） via biochemical pathways such as glycolysis and oxidative phosphorylation， providing energy for cellular activities. While research on gastrointestinal tumors is advancing rapidly， a major bottleneck lies in their complex metabolic adaptations and therapeutic resistance. Targeting the interplay between mitophagy and energy metabolism has emerged as a promising therapeutic strategy for this disease. Current research on mitophagy and energy metabolism in gastrointestinal tumors， including the molecular mechanisms of their bidirectional regulatory network and applications in targeted therapies， remains to be systematically elucidated. Therefore， this review summarizes the implications of the mitophagy-energy metabolism interplay in gastrointestinal tumors， with the aim of providing insights for future research.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.

Objective:To analyze the immediate risk and 5-year cumulative risk of high-grade cervical lesions in high-risk human papillomavirus(Hr-HPV)positive patients with minor cytological abnormalities and to validate the local applicability of clinical management strategies in the 2019 American Society for Colposcopy and Cervical Pathology Guidelines.Methods:A total of 565 patients with positive Hr-HPV,cytology result of atypical squamous cells of undetermined significance(ASC-US)or low-grade squamous intraepithelial lesion(LSIL)and also under-went colposcopy and biopsy were selected from the gynecological clinic of Peking Union Medical College Hospital from February 2017 to November to analyze the immediate risk of high-grade cervical lesions(CIN2 and above).Besides,a total of 193 patients with histological results of CIN1 or below and 5-year follow-up data available were further analyzed for the 5-year cumulative risk of high-grade cervical lesions.Results:①In the 565 patients,the immediate incidence of CIN2+and CIN3+was 32.21%and 12.39%,respectively.Multivariate Logistic regression showed that the immediate risk of CIN2+in the LSIL group(35.54%)was 1.62 times that in the ASC-US group(28.78%)(95%CI 1.12-2.36,P＜0.05);the immediate risk of CIN2+in HPV 16/18+group(45.29%)was 2.89 times that in Hr-HPV other+group(23.68%)(95%CI 1.99-4.20,P＜0.05).② Among 193 patients with 5-year long-term follow-up,the 5-year cumulative incidence of CIN2+and CIN3+was 6.2%and 2.6%,respectively.Cox regression analysis results showed that there were no statistically significant differences in 5-year cumulative risk of CIN2+and CIN3+among different ages,Hr-HPV infection types and cytological results(P＞0.05).Conclu-sions:LSIL had a higher detection rate of CIN2+than ASC-US patients only in the first colposcopy biopsy;the immediate risk of high-grade cervical lesion was significantly higher in HPV16/18+patients than in Hr-HPV oth-er+patients,but no significant difference in the 5-year cumulative incidence of high-grade lesions after colposco-py was found.Age was not an independent risk factor for the development of high-grade lesions.