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.The role of bile acid dynamics in inflammatory bowel disease and metabolic dysfunction-associated steatotic liver disease
Si-Rui Yu ; Run Sun ; Mei-Ya Shi ; Mei Yang ; Kun Chen ; Qiong Pan ; Ling Zhao ; Ming-Yue Wu ; Jin Chai
Liver Research 2026;10(1):35-50
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.
6.Construction of a COPD risk prediction model based on machine learning and the COPD-SQ questionnaire
Lin CHEN ; Luna ZHAO ; Yue ZHOU ; Panpan WANG ; Jingkun LI ; Wenwen ZHANG ; Xinxin ZHANG ; Chao WU ; Dong LIU
Acta Universitatis Medicinalis Anhui 2026;61(7):1261-1268
ObjectiveTo construct and evaluate various machine learning models for predicting the risk of chronic obstructive pulmonary disease (COPD) in individuals, thereby providing data support for early screening and intervention. MethodsA total of 823 subjects were selected for this study, comprising 142 individuals in the high-risk group for COPD and 681 individuals in the low-risk group. Data collected included demographic characteristics, smoking history, symptoms (such as cough and shortness of breath), and scores from the Chronic obstructive pulmonary disease screening questionnaire. Four machine learning algorithms—Logistic regression, random forest, support vector machine, and XGBoost—were utilized to construct risk prediction models. The performance of these models was assessed using 5-fold cross-validation, with evaluation metrics including accuracy, precision, recall, F1-score, area under the receiver operating characteristic curve (AUC), and average precision (AP). Furthermore, a feature importance analysis was performed. ResultsThe Logistic Regression model exhibited superior performance, achieving an AUC of 0.982 and an AP of 0.939. This was closely followed by the Random Forest model, which recorded an AUC of 0.975 and an AP of 0.890. Feature importance analysis revealed that smoking history, symptoms of shortness of breath, and body weight were significant predictors. All models demonstrated robust performance in identifying low-risk populations; however, variations were observed in their efficacy in identifying high-risk populations. ConclusionMachine learning models have proven effective in identifying individuals at high risk for COPD. Among these, the Logistic regression model exhibits the best overall performance, efficiently identifying high-risk populations and serving as a valuable clinical auxiliary screening tool. Various models, each with distinct performance characteristics, are suited to different clinical screening scenarios, thereby offering targeted decision-making support for the establishment of a hierarchical and intelligent COPD screening pathway.
7.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.
8.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.
9.Study on the epidemiological characteristics and influencing factors of long COVID among previously infected individuals in two communities in Shanghai
Junhong YUE ; Chen CHEN ; Qingqing JIA ; Xiaoxia LIU ; Huiting WANG ; Fei WU ; Yanlu YIN ; Jiajie ZANG ; Yanfei GUO ; Fan WU
Shanghai Journal of Preventive Medicine 2025;37(7):597-605
ObjectiveTo analyze the epidemiological characteristics of long COVID and to investigate its main influencing factors by examining individuals infected with SARS-CoV-2 between March and June 2022 in two communities in Shanghai, to lay the foundation for further research on the mechanism and clinical treatment of long COVID, and to provide the basis for the development of inexpensive, convenient, and feasible prevention and intervention strategies. MethodsA cross-sectional study was conducted, enrolling 6 410 individuals infected with SARS-CoV-2. Data were collected through a questionnaire survey. The incidence and common symptoms of long COVID were analyzed, along with their associations with demographic characteristics, medical history, and behavioral factors. A logistic regression model was used to identify the major factors associated with the development of long COVID symptoms. ResultsThe overall incidence rate of long COVID among the study population was 13.9%. The most commonly reported symptoms included fatigue (65.1%), attention disorders (23.1%), and cough (16.9%). The analysis showed that having underlying chronic diseases (OR=2.580, 95%CI: 2.165‒3.074), a history of allergies (OR=1.418, 95%CI: 1.003‒1.971), current smoking (OR=1.461, 95%CI: 1.013‒2.079), ever smoking (OR=2.462, 95%CI: 1.687‒3.551), a greater number of symptoms during the acute phase [1 symptom (OR=1.778, 95%CI: 1.459‒2.162), 2 symptoms (OR=2.749, 95%CI: 2.209‒3.409), ≥3 symptoms (OR=7.792, 95%CI: 6.333‒9.593)] and aggravated symptoms during the acute phase (OR=1.082, 95%CI: 1.070‒1.094) were factors associated with a higher risk of developing long COVID symptoms. Additionally, individuals who had consumed alcohol in the past year (OR=1.914, 95%CI: 1.344‒2.684) were more prone to objective long COVID symptoms. Among individuals under 50 years of age, females (OR=1.427, 95%CI: 1.052‒1.943) were more likely to develop objective long COVID symptoms. ConclusionThis study has identified the diversity of long COVID symptoms, which involve multiple organs and systems, including fatigue, attention disorders, cough, and joint pain. It has also revealed associations between long COVID and various demographic factors (e.g., age, gender), personal medical history (e.g., underlying chronic diseases, history of allergies), acute-phase characteristics (e.g., number and severity of symptoms), and behavioral factors (e.g., smoking, alcohol consumption). These findings highlight the need for further research and ongoing surveillance of long COVID and may inform the development of more targeted health management strategies for specific populations.
10.Expert consensus on the positioning of the "Three-in-One" Registration and Evaluation Evidence System and the value of orientation of the "personal experience"
Qi WANG ; Yongyan WANG ; Wei XIAO ; Jinzhou TIAN ; Shilin CHEN ; Liguo ZHU ; Guangrong SUN ; Daning ZHANG ; Daihan ZHOU ; Guoqiang MEI ; Baofan SHEN ; Qingguo WANG ; Xixing WANG ; Zheng NAN ; Mingxiang HAN ; Yue GAO ; Xiaohe XIAO ; Xiaobo SUN ; Kaiwen HU ; Liqun JIA ; Li FENG ; Chengyu WU ; Xia DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):445-450
Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.


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