1.The Role of Lysosomal Dysfunction in Hepatocellular Carcinoma: From Pathogenesis to Targeted Therapies
Yue-Yan WU ; Xin CHEN ; Ce-Fan ZHOU ; Jing-Feng TANG ; Rui ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):609-622
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.
2.Efficacy and safety of surgery-assisted transjugular intrahepatic portosystemic shunt in treatment of portal hypertension comorbid with complex portal vein thrombosis
Zhenhua FAN ; Chengbin DONG ; Qimei LI ; Yu ZHANG ; Yifan WU ; Dongfang LIU ; Guangzhong XU ; Dezhong WANG ; Jianfei CHEN ; Zhendong YUE ; Lei WANG
Journal of Clinical Hepatology 2026;42(3):586-592
ObjectiveTo investigate the feasibility, safety, and efficacy of surgery-assisted transjugular intrahepatic portosystemic shunt (SA-TIPS) in the treatment of portal hypertension comorbid with complex portal vein thrombosis, including cavernous transformation of the portal vein (CTPV). MethodsAn analysis was performed for the data of 36 patients with portal hypertension and complex portal vein thrombosis who underwent SA-TIPS in Beijing Shijitan Hospital, Capital Medical University, from November 2023 to January 2025, including general status, technical data of the surgical process (surgical success rate, puncture times, time of operation, the number of stents used, and the length of shunt), perioperative complications, and surgical recovery. The change in portal pressure gradient (PPG) after shunt was compared, and the rate of reaching the standard for PPG reduction was calculated, as well as stent patency rate within 1 week after surgery. The paired samples t-test was used for comparison of continuous data between two groups. ResultsAmong the 36 patients, 34 (94.4%) underwent SA-TIPS successfully. The incidence rate of perioperative complications was 16.7% (6/36), including 3 cases of thoraco-abdominal hemorrhage, 2 cases of intraoperative arrhythmia, and 1 case of incision infection. There was a significant reduction in PPG after SA-TIPS (t=19.85, P<0.01), and the patients achieving a ≥50% reduction in PPG accounted for 76.5% (26/34). Imaging reexamination within 1 week showed a shunt patency rate of 100%. ConclusionSA-TIPS has a high technical success rate, a favorable safety profile, and good efficacy in the treatment of portal hypertension comorbid with complex portal vein thrombosis (including CTPV), and therefore, it holds promise for clinical application.
3.Association between ambient particulate matter exposure and risk of benign prostatic hyperplasia in middle-aged and older men: A longitudinal cohort study based on CHARLS
Hanxiao HU ; Chuchu LIU ; Yuyuan HU ; Jiali CHEN ; Lingyi WANG ; Xiaobo LIU ; Yue WU
Journal of Environmental and Occupational Medicine 2026;43(5):630-636
Background Benign prostatic hyperplasia (BPH) is a common chronic urinary disease in middle-aged and older men, yet the impact of long-term exposure to atmospheric particulate matter (PM) on its pathogenesis remains unclear. Objective To investigate the association between PM exposure and the risk of incident BPH in middle-aged and older men. Methods Based on four waves of follow-up data (2011–2018) from the China Health and Retirement Longitudinal Study (CHARLS), 4766 participants were enrolled. Robust Poisson regression models were employed to assess the association between exposure to PM (PM1, PM2.5, and PM10) and the risk of incident BPH. Relative risks (RR) and their corresponding 95% confidence intervals (95%CI) were calculated. Dose-response relationships were fitted using restricted cubic splines (RCS). Subgroup analyses were performed to explore potential effect modifications, and multiple imputation was used to handle missing data. Results Over a mean follow-up of 6 years, 914 incident BPH cases were identified among the4766 participants (cumulative incidence: 19.18%). After adjusting for confounders, each 10 μg·m−3 increase in PM1, PM2.5, and PM10 concentrations was associated with a 13.1% (RR=1.131, 95%CI: 1.063, 1.203), 8.5% (RR=1.085, 95%CI: 1.050, 1.122), and 5.1% (RR=1.051, 95%CI: 1.034, 1.069) increased risk of BPH, respectively. RCS analysis showed that no nonlinear relationship was found between PM1 and PM2.5 and the risk of BPH (P>0.05); however, a nonlinear association was observed for PM10 (P=0.03), with the risk increment slowing beyond 100 μg·m−3. Subgroup and sensitivity analyses confirmed the robustness of these findings. Conclusion Long-term exposure to ambient particulate matter may be associated with an increased risk of incident BPH in middle-aged and older men.
4.Association between ambient particulate matter exposure and risk of benign prostatic hyperplasia in middle-aged and older men: A longitudinal cohort study based on CHARLS
Hanxiao HU ; Chuchu LIU ; Yuyuan HU ; Jiali CHEN ; Lingyi WANG ; Xiaobo LIU ; Yue WU
Journal of Environmental and Occupational Medicine 2026;43(5):630-636
Background Benign prostatic hyperplasia (BPH) is a common chronic urinary disease in middle-aged and older men, yet the impact of long-term exposure to atmospheric particulate matter (PM) on its pathogenesis remains unclear. Objective To investigate the association between PM exposure and the risk of incident BPH in middle-aged and older men. Methods Based on four waves of follow-up data (2011–2018) from the China Health and Retirement Longitudinal Study (CHARLS), 4766 participants were enrolled. Robust Poisson regression models were employed to assess the association between exposure to PM (PM1, PM2.5, and PM10) and the risk of incident BPH. Relative risks (RR) and their corresponding 95% confidence intervals (95%CI) were calculated. Dose-response relationships were fitted using restricted cubic splines (RCS). Subgroup analyses were performed to explore potential effect modifications, and multiple imputation was used to handle missing data. Results Over a mean follow-up of 6 years, 914 incident BPH cases were identified among the4766 participants (cumulative incidence: 19.18%). After adjusting for confounders, each 10 μg·m−3 increase in PM1, PM2.5, and PM10 concentrations was associated with a 13.1% (RR=1.131, 95%CI: 1.063, 1.203), 8.5% (RR=1.085, 95%CI: 1.050, 1.122), and 5.1% (RR=1.051, 95%CI: 1.034, 1.069) increased risk of BPH, respectively. RCS analysis showed that no nonlinear relationship was found between PM1 and PM2.5 and the risk of BPH (P>0.05); however, a nonlinear association was observed for PM10 (P=0.03), with the risk increment slowing beyond 100 μg·m−3. Subgroup and sensitivity analyses confirmed the robustness of these findings. Conclusion Long-term exposure to ambient particulate matter may be associated with an increased risk of incident BPH in middle-aged and older men.
5.Development of a postoperative recurrence prediction model for stage Ⅰ non-small cell lung cancer patients using multimodal data based on machine learning
Di ZHANG ; Yi WU ; Yu XU ; Shuai WANG ; Yue HU ; Huawei CHEN ; Nana HU ; Rong HE ; Xueling TONG ; Mengxia LI
Journal of Army Medical University 2025;47(14):1602-1611
Objective To develop a machine learning model integrating preoperative chest CT radiomic features with clinical data for predicting 5-year postoperative recurrence risk in stage Ⅰ non-small cell lung cancer(NSCLC)patients undergoing surgical resection.Methods A total of 217 patients with pathologically confirmed stage Ⅰ NSCLC(selected from 778 initially screened cases based on our inclusion and exclusion criteria)treated in Army Medical Center of PLA between January 2014 and December 2019 were retrospectively enrolled,including 53 recurrence cases and 164 non-recurrence cases within 5-year follow-up.They were randomly divided into a training set(n=173)and a validation set(n=44)in a ratio of 8:2.Radiomic models were established based on extracted features from tumor-dominant regions of interest(ROI)on CT images,while clinical models were developed using demographic characteristics and preoperative laboratory examinations.A combined model was further constructed by integrating both feature sets,and model performance was compared to identify the optimal predictive model.Results This study screened the features from non-contrast CT images and ultimately selected 7 radiomic features for constructing radiomic model.Among 6 machine learning algorithms,the adaptive boosting(Adaboost)model demonstrated the best overall predictive performance,with an area under the curve(AUC)of 0.866(95%CI:0.808~0.923;accuracy:0.832,specificity:0.884)in the training set and of 0.806(95%CI:0.630~0.983;accuracy:0.795,specificity:0.971)in the validation set.Univariate and multivariate logistic regression analyses identified 4 clinical features for clinical model construction.The clinical model achieved an AUC value of 0.874(95%CI:0.821~0.928;accuracy:0.827,specificity:0.891)in the training set and 0.813(95%CI:0.677~0.948;accuracy:0.636,specificity:0.600)in the validation set.By integrating the 7 radiomic features and 4 clinical features using a feature-level fusion strategy,the combined model exhibited further improved predictive performance,with an AUC value of 0.953(95%CI:0.924~0.983;accuracy:0.884,specificity:0.860)and 0.852(95%CI:0.729~0.976;accuracy:0.682,specificity:0.629),respectively in the training set and the validation set.Conclusion The combined model integrating preoperative CT radiomic features with clinical risk factors may provide an evidence-based framework for evaluating 5-year postoperative recurrence risk in stage Ⅰ NSCLC patients.
6.Analysis of dosimetric characteristics of proton radiotherapy in 3 cases of abdominal and pelvic tumors
Jinghao DUAN ; Jinbo YUE ; Cheng TAO ; Shizhang WU ; Chengqiang LI ; Tianyuan DAI ; Jinhu CHEN ; Tong BAI ; Jian ZHU
Journal of International Oncology 2025;52(7):455-461
Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT) and intensity modulated radiation therapy (IMRT) for typical abdominal and pelvic tumors.Methods:Three patients with abdominal and pelvic tumors (one case each of liver cancer, cervical cancer, and prostate cancer) admitted to Shandong Cancer Hospital and Institute from January to June 2024 were selected as the research subjects. IMPT and IMRT plans were designed for each case based on clinical target volume (CTV) and organs at risk (OARs) constraints. Dosimetric parameters, including conformity index (CI), homogeneity index (HI), and gradient index (GI) for target coverage, as well as OARs dose metrics, were evaluated. The volume of additional dose deposition in the body was compared by assessing regions receiving 10%, 30%, and 50% of the prescription dose.Results:For all three cases, IMRT plan demonstrated higher CI values (0.82, 0.81, and 0.86) compared to IMPT plan (0.61, 0.62, and 0.43). IMPT plan yielded lower HI values (0.053, 0.075, and 0.020) than IMRT plan (0.060, 0.120, and 0.080) and lower GI values (3.45, 2.63, and 3.80 vs. 7.28, 4.76, and 4.66 for IMRT plan). In liver cancer, IMPT plan reduced the D mean of normal liver tissues and right kidney by 37.8% and 78.5%, respectively, and decreased the D max of spinal cord by 13.2%. For cervical cancer, IMPT plan reduced the V 30 of the small bowel by 22.0%, D mean of the bladder, rectum and bone marrow by 15.7%, 14.3% and 12.6%, and spinal cord D max by 4.8%. In prostate cancer, IMPT plan lowered bladder and rectal D mean by 14.9% and 36.5%, respectively, but resulted in an increase of 35.3% and 6.1% in the D mean and V 40 of the left femoral head, respectively, and an increase of 23.6% and 10.8% in the D mean and V 40 of the right femoral head, respectively. IMPT plan reduced the volumes receiving 10%, 30%, and 50% of the prescription dose by 48.9%-64.8%, 22.0%-47.0%, and 22.0%-57.7%, respectively, compared to IMRT plan. Conclusions:Comparison between IMPT and IMRT plans for abdominopelvic tumors: IMPT plan offers advantages in reducing doses to normal organs such as the liver, kidneys, spinal cord, small intestine, rectum, and bladder. However, its advantage is less pronounced regarding the dose to the femoral heads. IMPT plan notably minimizes additional dose deposition within the body.
7.Pathological mechanisms and clinical significance of the association between metabolic syndrome and granulomatous mastitis based on intermingled phlegm-blood stasis theory
Lina Ma ; Jingjing Wu ; Meina Ye ; Yue Zhou ; Yifan Cheng ; Hongfeng Chen
Journal of Traditional Chinese Medical Sciences 2025;2025(4):542-551
ObjectiveTo examine the relationship between metabolic syndrome (MS) and its key components in granulomatous mastitis (GM), we explored potential pathological mechanisms through the lens of traditional Chinese medicine (TCM), particularly the concept of intermingled phlegm-blood stasis.MethodsIn this retrospective study, we enrolled 172 patients with GM and 164 patients with non-inflammatory benign breast masses. Metabolic indicators (waist circumference [WC], blood lipids, etc.), inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-α), and adipose tissue CD68 expression were measured. Logistic regression was used to analyze risk factors and receiver operating characteristic curves were used to evaluate diagnostic efficacy. The correlation between TCM pathogenesis and biomarkers was also examined.ResultsMS prevalence was significantly higher in the GM group than in the controls (26.16% vs. 6.10%, P .001). Multivariate analysis identified abdominal obesity (WC ≥ 80 cm, odds ratio [OR] = 1.065) and low levels of high-density lipoprotein cholesterol (HDL-C; 1.29 mmol/L, OR = 0.066) as independent risk factors for GM (P .001 for both). Among patients with GM, HDL-C levels were inversely correlated with inflammatory markers (r = −0.341 to −0.440), whereas patients with concurrent MS demonstrated greater CD68 macrophage infiltration (P .001). According to TCM, abdominal obesity corresponds to “spleen deficiency with phlegm-dampness accumulation,” and low HDL-C reflects “deficiency of vital qi,” which collectively lead to phlegm-blood stasis obstruction in the mammary collaterals; this aligns with the key MS driving mechanisms of chronic inflammation and immune dysregulation.ConclusionMS promotes GM development through chronic inflammation and immune dysregulation, with abdominal obesity and low HDL-C levels serving as core risk factors. The TCM theory of intermingled phlegm-blood stasis provides a novel interpretation of the metabolic-inflammatory mechanisms underlying GM. Accordingly, we propose phlegm-resolving and blood-activating strategies as potential therapeutic approaches for metabolic–immune axis regulation.
8.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
9.Herbal Textual Research on Malvae Semen in Famous Classical Formulas
Dongxue CHEN ; Yibo LIU ; Yangyang YU ; Guoshuai LYU ; Huili WU ; Xinle HAN ; Yue TAN ; Minhui LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):252-264
The medicinal use of Malvae Semen has a long history. In this paper, by consulting the ancient materia medica, prescription, agronomy, literature and other aspects of the classics, the name, origin, evolution of scientific name, quality, harvesting and processing, functions and indications and others of Malvae Semen were systematically sorted out and verified, so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shennong Bencaojing began to use Dongkuizi as the correct name, which was used in the past dynasties, and there were also aliases such as Kuicaizi, Huacai, and Kuizi. Through the original research, it can be seen that Kuicai is the mainstream original plant of Malvae Semen, that is, Malva verticillata var. crispa, the Alcea rosea and M. cathayensis are also used. In modern times, the seeds of Abutilon theophrasti have been passed off as Malvae Semen, while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties, the cultivation of Kuicai has been decreasing, while A. theophrasti is more common and easy to obtain, and Abutili Semen and Malvae Semen are similar in morphology and confused, which should be corrected. In addition, Malvae Fructus is a Mongolian customary medicinal herb, which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai, as an important vegetable in history, was widely cultivated and gradually shrunk after the Song dynasty, it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies, full grain, grayish brown color, no mud, and no impurities. The harvesting is generally in the autumn and winter. After drying, it is seeded, sieved peel and impurities, mashed, or slightly stir-fried to yellow-white color with gentle fire. It is sweet, cold and slippery in nature and taste, with the main effects of laxation, diuresis, lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity, promoting diuresis and removing nebula, the efficacy is quite different from that of Malvae Semen. Based on the results of textual research, it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas, the corresponding processing methods should be selected according to the requirements of drug processing in the formulas, while the raw products are recommended to be used if the processing is not specified.
10.Herbal Textual Research on Malvae Semen in Famous Classical Formulas
Dongxue CHEN ; Yibo LIU ; Yangyang YU ; Guoshuai LYU ; Huili WU ; Xinle HAN ; Yue TAN ; Minhui LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):252-264
The medicinal use of Malvae Semen has a long history. In this paper, by consulting the ancient materia medica, prescription, agronomy, literature and other aspects of the classics, the name, origin, evolution of scientific name, quality, harvesting and processing, functions and indications and others of Malvae Semen were systematically sorted out and verified, so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research, Shennong Bencaojing began to use Dongkuizi as the correct name, which was used in the past dynasties, and there were also aliases such as Kuicaizi, Huacai, and Kuizi. Through the original research, it can be seen that Kuicai is the mainstream original plant of Malvae Semen, that is, Malva verticillata var. crispa, the Alcea rosea and M. cathayensis are also used. In modern times, the seeds of Abutilon theophrasti have been passed off as Malvae Semen, while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties, the cultivation of Kuicai has been decreasing, while A. theophrasti is more common and easy to obtain, and Abutili Semen and Malvae Semen are similar in morphology and confused, which should be corrected. In addition, Malvae Fructus is a Mongolian customary medicinal herb, which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai, as an important vegetable in history, was widely cultivated and gradually shrunk after the Song dynasty, it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies, full grain, grayish brown color, no mud, and no impurities. The harvesting is generally in the autumn and winter. After drying, it is seeded, sieved peel and impurities, mashed, or slightly stir-fried to yellow-white color with gentle fire. It is sweet, cold and slippery in nature and taste, with the main effects of laxation, diuresis, lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity, promoting diuresis and removing nebula, the efficacy is quite different from that of Malvae Semen. Based on the results of textual research, it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas, the corresponding processing methods should be selected according to the requirements of drug processing in the formulas, while the raw products are recommended to be used if the processing is not specified.


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