1.Influencing factors for recompensation and its impact on the prognosis in patients with decompensated liver cirrhosis
Danqing XU ; Haiwen LI ; Huan MU ; Yingyuan ZHANG ; Caifen SA ; Li LIU ; Yongrui YANG
Journal of Clinical Hepatology 2026;42(1):90-100
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated liver cirrhosis, as well as the impact of recompensation on the prognosis of such patients, and to provide a basis for early identification of high-risk patients in clinical practice. MethodsA retrospective analysis was performed for the clinical data of patients who attended The Third People’s Hospital of Kunming from January 2016 to December 2022 and were diagnosed with decompensated liver cirrhosis due to hepatitis B, hepatitis C, alcoholic hepatitis, and autoimmune hepatitis, and they were divided into recompensation group and persistent decompensation group. To control for confounding factors, whether recompensation occurred was used as the rouping variable,and BMI, alcohol consumption history, HIV infection history, TG, CHOL, LDL, and HDL were used as covariates. The propensity score was calculated, and 1:1 nearest neighbor matching was performed with a caliper value of 0.1. After propensity score matching, the recompensation group and the persistent decompensation group with relatively balanced covariates were obtained. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for recompensation; the “rms” package was used to establish a nomogram; the receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC); the Hosmer-Lemeshow test was used to assess the goodness of fit of the model; the “Calibration Curves” package was used to plot calibration curves for model assessment. The Kaplan-Meier method was used to plot survival curves, and the Log-rank test was used for comparison of survival curves. ResultsAmong the 863 patients with decompensated liver cirrhosis, 305 experienced recompensation, resulting in an incidence rate of 35.3%. After PSM, 610 cases were successfully matched, with 305 cases in each group. The univariate and multivariate Cox regression analyses showed that etiology (hepatitis C: hazard ratio[HR]=0.288, P=0.002); male(HR=0.701, P=0.016), age(HR=0.988, P=0.047), hemoglobin (HGB)(HR=1.006, P=0.017), and CD4 T cell(HR=1.001,P=0.047), TIPS procedure (HR=1.808,P=0.042) were independent influencing factors for recompensation in patients with decompensated liver cirrhosis. During follow-up, 116 patients died of liver disease-related causes, with 27 patients (8.85%) in the recompensation group and 89 (15.95%) in the persistent decompensation group; 109 patients developed HCC, with 23 patients (7.54%) in the recompensation group and 86 (15.41%) in the persistent decompensation group. The Kaplan-Meier survival curves showed significant separation between the patients with different states of compensation in terms of liver disease-related mortality rate and the incidence rate of HCC, and the Log-rank test showed that there were significant differences between the two groups in liver disease-related mortality rate (χ2=9.023, P=0.003) and the incidence rate of HCC (χ2=10.526, P=0.001). ConclusionEtiology,sex,age,TIPS,HGB,and CD4 T cell are independent influencing factors for recompensation in patients with decompensated liver cirrhosis. There is a significant difference in the incidence rate of recompensation between decompensated liver cirrhosis patients with different etiologies, and female patients and patients with a younger age,a history of TIPS, a higher HGB level, and a higher CD4 lymphocyte count are more likely to experience recompensation. Recompensation is the key to improving the long-term prognosis of patients and can significantly reduce long-term liver disease-related mortality rate and the incidence rate of HCC.
2.Construction of a nomogram model for clinical cure of chronic hepatitis B with a low level of hepatitis B surface antigen treated with pegylated interferon α-2b
Yingyuan ZHANG ; Huan MU ; Lixian CHANG ; Danqing XU ; Yuanzhen WANG ; Chunyun LIU ; Weikun LI ; Huangchenghao ZHANG ; Chunyan MOU ; Li LIU
Journal of Clinical Hepatology 2026;42(5):1038-1047
ObjectiveTo investigate the predictive factors for HBsAg clearance in chronic hepatitis B (CHB) patients with a low level of hepatitis B surface antigen (HBsAg) treated with pegylated interferon α-2b (PEG-IFN-α-2b), to establish a combined predictive model and a nomogram based on multiple factors, and to provide a reference for formulating individualized treatment regimens and predicting treatment outcome in clinical practice. MethodsA retrospective analysis was performed for 167 CHB patients with HBsAg <1 500 IU/mL who attended The Third People’s Hospital of Kunming from January 2022 to January 2024 and were treated with PEG-IFN-α-2b. According to whether clinical cure was achieved, the patients were divided into HBsAg clearance group and HBsAg non-clearance group. Related data were collected, including general information and serological/biochemical/virological indicators at different time points during treatment. The independent samples t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the chi-square test was used for comparison of categorical data. The multivariate logistic regression analysis was used to identify independent influencing factors. The receiver operating characteristic (ROC) curve was used to assess the value of indicators used alone or in combination in predicting clinical cure, and calibration curves were plotted to assess the risk prediction model. ResultsThe univariate analysis showed that there were significant differences between the two groups in age (t=-6.839, P<0.05), history of nucleos(t)ide analogue treatment for over 1 year (χ2=59.339, P<0.05), genotype (χ2=4.610, P<0.05), nonalcoholic fatty liver disease (χ2=5.319, P<0.05), hepatitis B virus DNA status before treatment (χ2=60.861, P <0.05), compensated liver cirrhosis (χ2=10.960, P<0.05), HBeAg status before treatment (χ2=19.060, P<0.05), a history of interferon treatment (χ2=8.162, P<0.05), presence of interferon antibodies after treatment (χ2=12.858, P<0.05), HBsAg level before treatment (Z=-7.412, P<0.05), alanine aminotransaminase (ALT) level at baseline (Z=-6.117, P<0.05), ALT level at 12 weeks of treatment (Z=-7.171, P<0.05), platelet count (PLT) at 24 weeks of treatment (Z=-3.622, P<0.05), and thyroid stimulating hormone (TSH) level at 24 weeks of treatment (Z=-2.830, P<0.05). The multivariate logistic regression analysis showed that age (odds ratio [OR]=1.230, P=0.007), history of nucleos(t)ide analogue treatment for over 1 year (OR=0.008, P=0.011), HBeAg status before treatment (OR=0.003, P=0.012), HBsAg level before treatment (OR=1.005, P=0.014), ALT level at baseline (OR=0.949, P=0.014), ALT level at 12 weeks of treatment (OR=0.969, P=0.016), PLT at 24 weeks of treatment (OR=0.969, P=0.022), and TSH level at 24 weeks of treatment (OR=3.608, P=0.045) were independent influencing factors for HBsAg clearance at 48 weeks of treatment in CHB patients with HBsAg <1 500 IU/mL. The Hosmer-Lemeshow goodness-of-fit test yielded χ2=1.398, P=0.994, indicating that the model had good fitting. The Bootstrap method was used to perform internal validation of the nomogram model, and there was a good degree of fitting between the calibration curve and the ideal curve, with a mean absolute error of 0.029. The ROC curve analysis showed that the combination of predictive factors had an area under the ROC curve of 0.982 (95% confidence interval: 0.961 — 0.999), with a sensitivity of 94.10% and a specificity of 93.10%, suggesting that the nomogram model had a good discriminatory ability. For the CHB patients with HBsAg <1 500 IU/mL and different features, further analysis of HBsAg clearance rate at 48 weeks of treatment showed an HBsAg clearance rate of 69.60% for those with HBsAg ≤67.65 IU/mL before treatment, 58.30% for those with a baseline ALT level of ≥62.50 U/L, 68.30% for those with an ALT level of ≥92.50 U/L at 12 weeks of treatment, 42.40% for those with PLT ≥104×109/L at 24 weeks of treatment, and 48.30% for those with a TSH level of ≤1.38 μIU/mL at 24 weeks of treatment, with significant differences between the two groups (all P<0.001). ConclusionAge, history of nucleos(t)ide analogue treatment for over 1 year, HBeAg status before treatment, HBsAg level before treatment, baseline ALT level, ALT level at 12 weeks of treatment, PLT level at 24 weeks, and TSH level at 24 weeks of treatment are independent predictive factors. The combined prediction nomogram model constructed in this study has a relatively high value in predicting clinical cure at 48 weeks of PEG-IFN-α-2b treatment in CHB patients with HBsAg<1 500 IU/mL, thereby providing a reference for selecting suitable treatment population and predicting clinical cure.
3.Pharmaceutical care for a patient with missed abortion after aortic mechanical valve replacement surgery
Huan CHEN ; Baian WANG ; Qingqing DU ; Yao MU
China Pharmacy 2026;37(13):1751-1754
OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery, and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio (INR) after taking mifepristone, clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes; for the selection of sex hormones after missed abortion, clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment, supplemented by Xian yimucao capsules, to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge, and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery, mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans, identification of drug-drug interactions, assessment of bleeding risks, and selection of postoperative sex hormones. Through full pharmaceutical monitoring, they ensure the safety of patients’ medication.
4.Pharmaceutical care for a patient with missed abortion after aortic mechanical valve replacement surgery
Huan CHEN ; Baian WANG ; Qingqing DU ; Yao MU
China Pharmacy 2026;37(13):1751-1754
OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery, and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio (INR) after taking mifepristone, clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes; for the selection of sex hormones after missed abortion, clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment, supplemented by Xian yimucao capsules, to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge, and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery, mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans, identification of drug-drug interactions, assessment of bleeding risks, and selection of postoperative sex hormones. Through full pharmaceutical monitoring, they ensure the safety of patients’ medication.
5.Diagnostic value of cytokines combined with Model for End-Stage Liver Disease score in predicting hepatic encephalopathy in end-stage liver disease
Jinyu XIANG ; Lixian CHANG ; Yingyuan ZHANG ; Huan MU ; Wenyan LI ; Hongyan WEI ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2026;42(7):1638-1647
ObjectiveTo construct and validate a predictive model for hepatic encephalopathy (HE) in patients with end-stage liver disease (ESLD) by combining key indicators such as cytokines and Model for End-Stage Liver Disease (MELD) score, and to provide evidence-based support for the early identification of high-risk populations and the optimization of intervention strategies in clinical practice. MethodsA retrospective analysis was performed for 2 167 patients with ESLD who were admitted to The Third People’s Hospital of Kunming from January 2022 to December 2024, the patients were divided into a training set with 1 517 patients and a validation set with 650 patients at a ratio of 7∶3 using the stratified random sampling method. A univariate analysis and a least absolute shrinkage and selection operator (LASSO) regression analysis were performed for the training set to identify potential influencing variables, and then a binary Logistic regression model was constructed to investigate the independent influencing factors for HE in ESLD patients. A nomogram prediction model was established based on this regression model, and the Hosmer-Lemeshow goodness-of-fit test was performed. The receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis, and clinical impact curve were used to comprehensively evaluate the degree of fit, accuracy, consistency, and clinical practicability of the predictive model derived from the training set. The Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups. The chi-square test or Fisher exact test was used for comparison of categorical data between two groups. ResultsThe univariate analysis showed that there were significant differences between the study group and the control group in age, sex, blood ammonia, lymphocytes, hemoglobin, platelet count, prothrombin time, fibrinogen, international normalized ratio, total bilirubin, aspartate aminotransferase, total protein, albumin, prealbumin, alkaline phosphatase, cholinesterase, total bile acid, triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, blood glucose, CD3+ T cells, CD4+ T cells, CD8+ T cells, high-sensitivity C-reactive protein, carcinoembryonic antigen, triiodothyronine, thyroxine, free triiodothyronine, free thyroxine, interleukin-1β, interleukin-5, interleukin-6, interleukin-8, interleukin-12p70, interleukin-17, interferon-γ, and MELD score (all P<0.05). The LASSO regression analysis identified nine variables of age, blood ammonia, albumin, prealbumin, cholinesterase, total cholesterol, thyroxine, interleukin-17, and MELD score, and the binary Logistic regression analysis showed that blood ammonia, interleukin-17, and MELD score were independent risk factors for HE in ESLD patients, while age and thyroxine were independent protective factors (all P<0.05). A nomogram model was constructed based on these five variables. The Hosmer-Lemeshow goodness-of-fit test in the training set showed a good degree of fit (P=0.207), with a McFadden’s pseudo-R2 of 0.184, suggesting that the model had acceptable explanatory power; the Hosmer-Lemeshow goodness-of-fit test in the internal validation set further confirmed the calibration stability of the model (P=0.067), suggesting that the model had a good degree of fit in independent data. The model had an area under the ROC curve of 0.784 in the validation set, with a sensitivity of 0.710 and a specificity of 0.752. The mean absolute error of the calibration curve was 0.067, and decision curve analysis and clinical impact curve showed that the nomogram model had positive net benefit and good clinical practicability. ConclusionThe nomogram model constructed based on age, blood ammonia, thyroxine, interleukin-17, and MELD score for predicting HE in patients with ESLD has a good degree of fit, high accuracy and consistency, and excellent clinical practicability.
6.Influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis
Danqing XU ; Huan MU ; Yingyuan ZHANG ; Lixian CHANG ; Yuanzhen WANG ; Weikun LI ; Zhijian DONG ; Lihua ZHANG ; Yijing CHENG ; Li LIU
Journal of Clinical Hepatology 2025;41(2):269-276
ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January, 2019 to December, 2022 were enrolled, among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group, and 154 patients without recompensation were enrolled as control group. Related clinical data were collected, and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis, and the receiver operating characteristic (ROC) curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis, 63 (29.03%) had recompensation. There were significant differences between the recompensation group and the control group in HIV history (χ2=4.566, P=0.034), history of partial splenic embolism (χ2=6.687, P=0.014), Child-Pugh classification (χ2=11.978, P=0.003), grade of ascites (χ2=14.229, P<0.001), albumin (t=4.063, P<0.001), prealbumin (Z=-3.077, P=0.002), high-density lipoprotein (t=2.854, P=0.011), high-sensitivity C-reactive protein (Z=-2.447, P=0.014), prothrombin time (Z=-2.441, P=0.015), carcinoembryonic antigen (Z=-2.113, P=0.035), alpha-fetoprotein (AFP) (Z=-2.063, P=0.039), CA125 (Z=-2.270, P=0.023), TT3 (Z=-3.304, P<0.001), TT4 (Z=-2.221, P=0.026), CD45+ (Z=-2.278, P=0.023), interleukin-5 (Z=-2.845, P=0.004), tumor necrosis factor-α (Z=-2.176, P=0.030), and portal vein width (Z=-5.283, P=0.005). The multivariate analysis showed that history of partial splenic embolism (odds ratio [OR]=3.064, P=0.049), HIV history (OR=0.195, P=0.027), a small amount of ascites (OR=3.390, P=0.017), AFP (OR=1.003, P=0.004), and portal vein width (OR=0.600, P<0.001) were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history, grade of ascites, history of partial splenic embolism, AFP, portal vein width, and the combined predictive model of these indices had an area under the ROC curve of 0.556, 0.641, 0.560, 0.589, 0.745, and 0.817, respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis, those with a history of partial splenic embolism, a small amount of ascites, and an increase in AFP level are more likely to experience recompensation, while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.
7.The Mechanisms of Quercetin in Improving Alzheimer’s Disease
Yu-Meng ZHANG ; Yu-Shan TIAN ; Jie LI ; Wen-Jun MU ; Chang-Feng YIN ; Huan CHEN ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2025;52(2):334-347
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.
8.Value of albumin-bilirubin, easy albumin-bilirubin, and platelet-albumin-bilirubin scores in predicting the prognosis of patients with HCV-associated hepatocellular carcinoma
Huan MU ; Yingyuan ZHANG ; Danqing XU ; Yuanqiang HE ; Chunyan MOU ; Chunyun LIU ; Li LIU
Journal of Clinical Hepatology 2025;41(5):921-926
ObjectiveTo investigate the value of albumin-bilirubin (ALBI), easy albumin-bilirubin (EZ-ALBI), and platelet-albumin-bilirubin (PALBI) scores in predicting 2-year survival in patients with HCV-associated hepatocellular carcinoma (HCV-HCC). MethodsA retrospective analysis was performed for the clinical data of 174 patients with HCV-HCC who were admitted to The Third People’s Hospital of Kunming from January 2020 to January 2022, and the patients were followed up till 2 years after admission. According to the follow-up results, the patients were divided into survival group with 95 patients and death group with 79 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for the survival of HCV-HCC patients. The Kaplan-Meier method was used to plot survival curves and analyze the 2-year survival rate of HCV-HCC patients with different EZ-ALBI grades, and the log-rank test was used for comparison between groups. ResultsThere were significant differences between the survival group and the death group in platelet count, aspartate aminotransferase (AST), total bilirubin, albumin (Alb), alpha-fetoprotein (AFP), prealbumin, prothrombin time, international normalized ratio, PALBI score, ALBI score, EZ-ALBI score, Model for End-Stage Liver Disease (MELD) score, HCV genotype, peritoneal effusion, and vascular invasion (all P<0.05). The univariate Cox regression analysis showed that AST, Alb, AFP, ALBI score, EZ-ALBI score, PALBI score, MELD score, Barcelona Clinic Liver Cancer Staging, and peritoneal effusion were influencing factors for the survival of patients (all P<0.05), and the multivariate Cox regression analysis showed that EZ-ALBI score (hazard ratio [HR]=1.850, 95% confidence interval [CI]: 1.054 — 3.247, P=0.032) and peritoneal effusion (HR=1.993, 95%CI: 1.030 — 3.858, P=0.041) were independent risk factors for the survival of HCV-HCC patients. The survival curve analysis showed that the patients with EZ-ALBI grade 1/2/3 had a 2-year survival rate of 90.9%, 60.2%, and 32.2%, respectively, and there was a significant difference in cumulative survival rate between the patients with different EZ-ALBI grades (χ2=26.294, P<0.001). ConclusionEZ-ALBI score and the presence or absence of peritoneal effusion can be used as predictors of the survival of HCV-HCC patients.
9.Value of FibroScan, gamma-glutamyl transpeptidase-to-platelet ratio, S index, interleukin-6, and tumor necrosis factor-α in the diagnosis of HBeAg-positive chronic hepatitis B liver fibrosis
Yingyuan ZHANG ; Danqing XU ; Huan MU ; Chunyan MOU ; Lixian CHANG ; Yuanzhen WANG ; Hongyan WEI ; Li LIU ; Weikun LI ; Chunyun LIU
Journal of Clinical Hepatology 2025;41(4):670-676
ObjectiveTo investigate the value of noninvasive imaging detection (FibroScan), two serological models of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) score and S index, and two inflammatory factors of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B (CHB), as well as the consistency of liver biopsy in pathological staging, and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients, and related examinations were performed before liver biopsy, including total bilirubin, alanine aminotransferase, platelet count, gamma-glutamyl transpeptidase, albumin, IL-6, TNF-α, liver stiffness measurement (LSM), and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy, and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic (ROC) curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis, and the Delong test was used for comparison of the area under the ROC curve (AUC). ResultsIn the consistency check, inflammation degree based on liver biopsy had a Kappa value of 0.807 (P<0.001), and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 (P<0.001), suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM, GPR score, S index, IL-6, and TNF-α (all P<0.05), and GPR score, S index, IL-6, and TNF-α were positively correlated with LSM (all P<0.05). GPR score, S index, IL-6, and TNF-α were all independent risk factors for diagnosing significant liver fibrosis (≥S2) and progressive liver fibrosis (≥S3) (all P<0.05). As for each indicator alone, GPR score had the highest value in the diagnosis of significant liver fibrosis (≥S2), followed by S index, IL-6, and TNF-α, while S index had the highest value in the diagnosis of progressive liver fibrosis (≥S3), followed by GPR score, TNF-α, and IL-6. The joint model had a higher predictive value than each indicator alone (all P<0.05). ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score, S index, IL-6, and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB, and the combined prediction model established by them can better diagnose liver fibrosis.
10.Application of Engineered Exosomes in Tumor-targeted Therapy
Jia-Lu SONG ; Yi-Xin JIN ; Xing-Yu MU ; Yu-Huan JIANG ; Jing WANG
Progress in Biochemistry and Biophysics 2025;52(5):1140-1151
Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.

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