Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

To interpret the evidence-to-decision （EtD） framework and to illustrate its application in traditional Chinese medicine （TCM） guideline development using the example of the Pharmacovigilance Guideline of Chinese Patent Medicine， thereby providing methodological references for TCM guideline standardization. Based on the core three stages of the EtD framework （formulating the question， making an assessment of the evidence， and drawing conclusions）， critical decision points and evaluation evidence within the evidence-translation process were systematically addressed， aligning with the purpose， scope， and key questions of the guideline. Qualitative research methods， such as the nominal group technique， were employed to formulate recommendations. The analysis was conducted based on the EtD framework. During question formulation， the specific characteristics and practical needs of pharmacovigilance for Chinese patent medicines were clarified， focusing on the core objective of safety assurance throughout the product lifecycle. In the evidence assessment， multi-source evidence was integrated， including policy documents， literature research， and expert consensus， completing the evidence evaluation. Finally， in recommendation-forming， dispersed research evidence and expert experience were synthesized into consensus， culminating in the guideline's completion through solicitation of opinions and peer review. The EtD framework provides a structured tool for evidence-to-decision translation in TCM guideline development， effectively enhancing the transparency and scientific rigor of the process. Therefore， it is recommended that TCM guideline development adopt the EtD framework to improve the evidence-to-decision process with TCM characteristics.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

Objective To observe the value of MRI quantified uterine indictors in late pregnancy for predicting uterine inertia in delivery.Methods A total of 182 pregnant women were retrospectively collected and were divided into uterine inertia group(inertia group,n=67)and non-uterine inertia group(non-inertia group,n=115)based on delivery or cesarean section records.MRI quantified uterine indicators were compared between groups,and those being statistically different were included to build a multivariate logistic regression model for predicting uterine inertia in delivery.The predictive performance of this model was evaluated using receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results The inertia group had more previous uterine surgeries,also higher proportion of in vitro fertilization and embryo transfer(IVF-ET)and cesarean sections compared to the non-inertia group(all P＜0.05).In late pregnancy,the longitudinal diameter of the uterus,cervical length and the thickness of the myometrium at the placental attachment site in inertia group were larger than those in non-inertia group(all P＜0.05).Increased times of previous uterine surgeries,undergoing IVF-ET,as well as increased longitudinal diameter of the uterus and cervical length in late pregnancy were all independent predictors of uterine inertia in delivery(all P＜0.05).AUC of the multivariate logistic regression model established based on the above factors for predicting uterine inertia in delivery was 0.733.Conclusion MRI quantified uterine indictors in late pregnancy could be used to predict uterine inertia in delivery.

Objective To observe the value of MRI quantified uterine indictors in late pregnancy for predicting uterine inertia in delivery.Methods A total of 182 pregnant women were retrospectively collected and were divided into uterine inertia group(inertia group,n=67)and non-uterine inertia group(non-inertia group,n=115)based on delivery or cesarean section records.MRI quantified uterine indicators were compared between groups,and those being statistically different were included to build a multivariate logistic regression model for predicting uterine inertia in delivery.The predictive performance of this model was evaluated using receiver operating characteristic(ROC)curve and the area under the curve(AUC).Results The inertia group had more previous uterine surgeries,also higher proportion of in vitro fertilization and embryo transfer(IVF-ET)and cesarean sections compared to the non-inertia group(all P＜0.05).In late pregnancy,the longitudinal diameter of the uterus,cervical length and the thickness of the myometrium at the placental attachment site in inertia group were larger than those in non-inertia group(all P＜0.05).Increased times of previous uterine surgeries,undergoing IVF-ET,as well as increased longitudinal diameter of the uterus and cervical length in late pregnancy were all independent predictors of uterine inertia in delivery(all P＜0.05).AUC of the multivariate logistic regression model established based on the above factors for predicting uterine inertia in delivery was 0.733.Conclusion MRI quantified uterine indictors in late pregnancy could be used to predict uterine inertia in delivery.

AIM To investigate the effects of Modified Baitouweng Decoction and Lizhong Decoction on mouse ulcerative colitis(UC).METHODS The mouse model of UC was established by 3％dextran sulfate sodium(DSS)induction.The C57BL/6 mice were randomly divided into the blank group,the model group,the low,medium and high dose Modified Baitouweng Decoction and Lizhong Decoction groups(3,6,12 g/kg),and sulfasalazine group(300 mg/kg),for 7 days gavage of the appropriate drugs,with 10 mice in each group.The mice had their disease activity index(DAI)and colonic mucosal damage index(CMDI)calculated;their colonic length and unit colonic weight measured;their histopathologic changes of colon observed by HE;their colonic ROS,MDA levels and GSH-Px,SOD activities detected by superoxide anion fluorescent probes and kits;their colonic levels of TNF-α,IL-6 and IL-1β detected by ELISA;their colonic LC3 expression detected by immunofluorescence method;and their colonic AMPK,mTOR and p70S6K protein expressions detected by Western blot method.RESULTS Compared with the blank group,the model group displayed significantly higher DAI score,CMDI score,unit colon weight,pathology score,ROS and MDA content,TNF-α,IL-6,and IL-1β levels,and mTOR and p70S6K protein expression(P＜0.01);and significantly lower colon length,GSH-Px and SOD activity,LC3 level,and phosphorylated AMPK protein expression(P＜0.01).Compared with the model group,the groups intervened with Modified Baitouweng Decoction and Lizhong Decoction or sulfasalazine shared decreased DAI score,CMDI score,unit colon mass,pathology score,ROS,MDA,TNF-α,IL-6,IL-1β levels,mTOR,p70S6K protein expressions(P＜0.01);and significantly improved symptomsin terms of the elevated colonic length,GSH-Px,SOD activities,LC3 level,AMPK protein expression(P＜0.01).CONCLUSION Modified Baitouweng Decoction and Lizhong Decoction may attenuate inflammatory response and oxidative damage in UC mouse models via AMPK/mTOR/p70S6K signaling pathway.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

AIM To explore the relieving effect of Er Miao Wan on atopic dermatitis in mice.METHODS In vivo experiment:BALB/c mice were randomly divided into normal group,model group,dexamethasone group(2 mg/kg)and high,medium and low dose groups of Er Miao Wan(4.68,2.34 and 1.17 g/kg).The mouse model of atopic dermatitis was established by repeatedly smearing DNCB solution,and the model was given orally for 21 days.The skin lesion condition on the back of mice,ear swelling degree,and the weight difference between ear lobes were observed and recorded.HE staining was used to observe the histopathological changes in the skin lesion tissues of mice.Toluidine blue(TB)staining was used to observe the infiltration of mast cells in skin lesions.The expression of macrophage marker F4/80 in skin lesions was detected by IHC.The serum levels of TSLP,IL-4,IL-5 and total IgE were detected by ELISA.In vitro experiment:RAW264.7 cells in logarithmic growth period were given 400,200 and 100 μg/mL Er Miao Wan for intervention.Cell proliferation was detected by CCK-8 method.NO level in cell supernatant was detected by Griess method.TNF-α,IL-1 β and IL-6 levels in cell supernatant were detected by ELISA method.The expressions of proteins related to the MAPK/NF-κB signaling pathway in cells was detected by Western blot.RESULTS In vivo experiment:Compared with the model group,the scores of back skin lesions,the swelling degree of right ear and the weight difference between left and right ear pieces in the high-dose group of Er Miao Wan decreased(P＜0.05,P＜0.01),the thickness of skin lesions decreased,the infiltration of mast cells and macrophages decreased(P＜0.05,P＜0.01),and the inflammatory factors TSLP,IL-4,IL-5 and total IgE levels in serum decreased(P＜0.05,P＜0.01),and the expression of F4/80 in the skin lesions decreased(P＜0.01).In vitro experiment:Compared with the model group,the levels of NO,TNF-α,IL-1 β and IL-6 in Er Miao Wan 400 and 200 μg/mL groups decreased(P＜0.05,P＜0.01),and the phosphorylation levels of P38,JNK and P65 proteins decreased(P＜0.05,P＜0.01).CONCLUSION Er Miao Wan can alleviate skin lesion inflammation in DNCB-induced atopic dermatitis mice,and its mechanism may be related to inhibiting the activation of MAPK/NF-κB signaling pathway of macrophage,reducing macrophage infiltration and reducing Th2 cytokines.

Objective:To analyze the dynamic changes of serum exosome miR-552 and miR-653 levels in pa-tients with gastric cancer before and after chemotherapy and their relationship with clinical benefit.Methods:IA total of 128 patients with gastric cancer received chemotherapy from January 2022 to January 2024.According to the chemo-therapy effect,the two groups were divided into disease progression group and disease remission group.The levels of serum exosome miR-552 and miR-653 before and after chemotherapy were detected in the two groups,the risk fac-tors affecting the chemotherapy effect of gastric cancer patients were screened,the risk nomogram model was con-structed,and the efficacy was evaluated.Results:The proportion of TNM stage(Ⅲ+Ⅳ),lymph node metastasis,dis-tant metastasis,tumor size(>5 cm),invasion depth(T3/T4)and tumor growth pattern(invasive type)in disease progres-sion group was higher than that in disease remission group(P<0.05).The levels of serum exosomes miR-552 and miR-653 in disease progression group were higher than those in remission group before and after chemotherapy(P<0.05).Compared with before chemotherapy,miR-552 and miR-653 levels in both groups decreased(P<0.05).Logistic regres-sion analysis showed that TNM stage,lymph node metastasis,distant metastasis,tumor size,invasion depth,miR-552 and miR-653 were all risk factors affecting the chemotherapy efficacy of gastric cancer(P<0.05).ROC curve results showed that the AUC,95%CI,sensitivity and specificity of risk nomogram model to predict chemotherapy efficacy of gastric cancer were 0.867,0.672～0.991,92.80%and 80.40%,respectively(P<0.001).Calibration curve results showed that both predicted and actual predicted values were near the ideal curve,and the Hosmer-Lemeshow goodness of fit curve test χ2=1.869,P=0.782.Conclusion:The levels of serum exosomes miR-552 and miR-653 are closely related to the chemotherapy efficacy of gastric cancer,and dynamic monitoring of the above indexes is helpful for the evaluation of the disease and prognosis of gastric cancer.In this study,the risk nomogram model constructed based on the above indexes and other risk factors has high predictive value and clinical practicability for chemotherapy efficacy in patients with gastric cancer.