ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Objective To conduct a cross-sectional study on the relationship between the serum uric acid(sUA)to high density lipoprotein-cholesterol(HDL-C)ratio(UHR)and female infertility.Methods We analyzed data from the National Health and Nutrition Examination Survey(NHANES)2013-2018 cycle,examining 2,963 women aged 18 to 45 years.A multivariable Logistic regression model was used to assess the association between UHR and infertility,adjusting for various confounding factors.The study also explored interactions and dose-response relationships through subgroup analyses and restricted cubic spline(RCS)models,and evaluated the predictive value of UHR for infertility by using receiver operating characteristic(ROC)curve analysis.Results The results showed that the prevalence of infertility was significantly higher among women with elevated UHR.Baseline characteristics revealed that the mean UHR in women with infertility(9.68±4.23)was significantly higher than in those without infertility(8.7±3.81,P<0.001).Multivariable Logistic regression analysis indicated that women in the highest quartile(Q4)of UHR had a significantly increased likelihood of infertility compared to those in the lowest quartile(Q1),with adjusted odds ratios(ORs)ranging from 1.61(95% CI:1.14-2.28)to 1.98(95% CI:1.42-2.78)across different models(P for trend<0.001).Subgroup analyses demonstrated that these associations were consistent across different age groups,body mass index(BMI)categories,and racial groups.The RCS model showed a significant linear dose-response relationship between UHR and infertility risk(nonlinear P=0.03,overall association P<0.001).Additionally,ROC analysis indicated that UHR had a moderate ability to discriminate infertility status,with an area under the curve(AUC)of 0.570.Conclusion A higher UHR is significantly associated with an increased risk of female infertility,and UHR has the potential to serve as a predictive biomarker for the risk of female infertility.

Objective To conduct a cross-sectional study on the relationship between the serum uric acid(sUA)to high density lipoprotein-cholesterol(HDL-C)ratio(UHR)and female infertility.Methods We analyzed data from the National Health and Nutrition Examination Survey(NHANES)2013-2018 cycle,examining 2,963 women aged 18 to 45 years.A multivariable Logistic regression model was used to assess the association between UHR and infertility,adjusting for various confounding factors.The study also explored interactions and dose-response relationships through subgroup analyses and restricted cubic spline(RCS)models,and evaluated the predictive value of UHR for infertility by using receiver operating characteristic(ROC)curve analysis.Results The results showed that the prevalence of infertility was significantly higher among women with elevated UHR.Baseline characteristics revealed that the mean UHR in women with infertility(9.68±4.23)was significantly higher than in those without infertility(8.7±3.81,P<0.001).Multivariable Logistic regression analysis indicated that women in the highest quartile(Q4)of UHR had a significantly increased likelihood of infertility compared to those in the lowest quartile(Q1),with adjusted odds ratios(ORs)ranging from 1.61(95% CI:1.14-2.28)to 1.98(95% CI:1.42-2.78)across different models(P for trend<0.001).Subgroup analyses demonstrated that these associations were consistent across different age groups,body mass index(BMI)categories,and racial groups.The RCS model showed a significant linear dose-response relationship between UHR and infertility risk(nonlinear P=0.03,overall association P<0.001).Additionally,ROC analysis indicated that UHR had a moderate ability to discriminate infertility status,with an area under the curve(AUC)of 0.570.Conclusion A higher UHR is significantly associated with an increased risk of female infertility,and UHR has the potential to serve as a predictive biomarker for the risk of female infertility.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells， and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma， amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention， showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy， its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice， in order to provide new ideas for immunotherapy for liver cancer.