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.Research progress on the intervention of sarcopenia with traditional Chinese medicine based on the AMPK signaling pathway
Wenyu FAN ; Bairong HUANG ; Congmin HONG ; Yan CHEN ; Jiayin WANG ; Jing GAO ; Xiaodong FENG
China Pharmacy 2026;37(9):1229-1235
arcopenia is a systemic skeletal muscle disorder characterized by a decrease in skeletal muscle mass and progressive decline in function, with multiple signaling pathways involved in its occurrence and development. Among them, the AMP-activated protein kinase (AMPK) signaling pathway, as a key pathway regulating cellular energy homeostasis, plays an important role in the regulation of skeletal muscle metabolism and functional maintenance by improving abnormalities in glucose and lipid metabolism, balancing skeletal muscle protein synthesis and degradation, improving mitochondrial function, promoting autophagy, and inhibiting inflammatory responses and oxidative stress. This article reviews the research progress on how various traditional Chinese medicine (TCM) monomers, including polyphenols, flavonoids, and terpenoids; various traditional Chinese medicine extracts, such as those from Lycium barbarum , Asini Corii Colla, and Panax quinquefolium , and TCM compounds, such as Guiqi zhuangjin decoction, Jianpi qiangji granules, and Qigu capsules, intervene in sarcopenia by regulating the AMPK signaling pathway to promote muscle protein synthesis, inhibit protein degradation, improve mitochondrial function, and alleviate inflammation and oxidative stress. Additionally, their molecular mechanisms are explored. The aim is to deeply elucidate the basis of TCM in the prevention and treatment of sarcopenia and to provide theoretical support for the development of related innovative drugs.
3.Clinical cohort study of non inflated subclavian approach,axillary approach,and traditional open surgery for unilateral thyroid cancer
Mingchuang LI ; Xuan FAN ; Zheng CHEN ; Yatong ZHAO ; Hua ZHANG ; Guo CHEN ; Jing LYU ; Wen TIAN ; Qingsong ZHANG
Chinese Journal of Surgery 2025;63(7):611-617
Objective:To compare surgical-related indicators between non-inflated subclavian endoscopic surgery and axillary and traditional open surgery for the treatment of right lobe thyroid cancer,as well as their effects on postoperative anterior cervical function and cosmetic outcomes.Methods:This retrospective cohort study analyzed 151 cases of thyroid cancer patients who underwent surgical treatment at the Department of Thyroid Surgery,Zhengzhou Central Hospital Affiliated to Zhengzhou University from June 2024 to October 2024. Based on the surgical approach,patients were divided into three groups:56 cases of traditional open surgery group, 44 cases of non-inflated axillary approach group,and 51 cases of non-inflated subclavian approach group. Comparative indicators included surgical time, parathyroid autotransplantation rate,complete exposure rate of central area, number of lymph node dissections, number of positive lymph nodes, anterior cervical function, and satisfaction with incision beauty. One-way analysis of variance,non-parametric test,Kruskal-Wallis test,Pearson χ2 test and Fisher′s exact probability method were used to compare the results of the three groups and subsequent pairwise comparisons,respectively. Results:All laparoscopic surgeries were successfully completed without conversion to open surgery. (1) Surgical time:the traditional open surgery group had the shortest operative time ( M(IQR))(71.5(16.0)minutes), significantly shorter than both endoscopic groups (both P<0.01); among the endoscopic approaches, the non-inflated subclavian approach group (97.0(10.0)minutes) had a significantly shorter operative time than the non-inflated axillary approach group (115.0(11.0)minutes)( P<0.01). (2) Parathyroid autotransplantation rate:the rates were 53.6%(30/56) in the traditional group, 70.5%(31/44) in the non-inflated axillary approach group, and 66.7%(34/51) in the non-inflated subclavian approach group, with no statistically significant differences ( P>0.05). (3) Complete exposure rate of the central area:the exposure rate was 100%(56/56) in the traditional open surgery group, 86.4%(38/44) in the non-inflated axillary approach group, and 96.1%(49/51) in the non-inflated subclavian approach group. A significant difference was observed between the traditional open surgery group and the non-inflated axillary approach group ( χ2=8.124, P<0.01), but not observed between other groups. (4) Number of lymph node dissection:no significant difference was found among the three groups (8(6)(range:2 to 17) in the traditional open surgery group,7(3)(range:2 to 16) in the non-inflated axillary approach group,7(4)(range:2 to 16) in the non-inflated subclavian approach group)( P=0.078).(5) Number of positive lymph nodes:no significant differences were observed among the three groups( P=0.923). (6) Postoperative anterior cervical function:① Visual analogue scale: there was no significant difference between the non-insufflation transaxillary approach group and the non-insufflation subclavian approach group at 3 days and 1 month postoperatively ( P>0.017). However, the two groups had significantly lower scores than the traditional open group (both P<0.01). ② Neck disability index:at 3 days post-surgery, there were significantly lower in the axillary and subclavian groups compared to the traditional open group ( P<0.01), with no significant difference between the two endoscopic groups( P>0.017); at 1 month postoperatively, the traditional open surgery group, gasless axillary approach group, and gasless subclavian approach group, with statistically significant differences between each group (both P<0.01). ③ Swallowing disorder index: no significant differences were observed at 3 days post-surgery( P>0.05); however, at 1 month post-surgery, the endoscopic groups showed significantly lower scores compared to the traditional open group(both P<0.01).(7) Satisfaction with incision beauty:significant differences were found among the three groups in terms of vancouver scar scores, patient scar assessment scores, and observer scar assessment scores(all P<0.01). Conclusions:Compared to the non-inflated axillary endoscopic thyroidectomy, the non-inflated subclavian approach offers a technically simpler procedure, better exposure of the central lymph node dissection area, and superior protection of anterior cervical function, although it results in less favorable cosmetic outcomes. Under strict preoperative evaluation and appropriate indications,both non-inflated subclavian and axillary approaches can achieve outcomes comparable to traditional open surgery for cN0 thyroid cancer,demonstrating good clinical application value.
4.Erosive pustular dermatosis of the scalp
Qitao CHEN ; Yuqian LI ; Guanghui SHAO ; Jing ZHU ; Qilin ZHU ; Zhongming LI ; Xufeng DU ; Weixin FAN
Chinese Journal of Dermatology 2025;58(3):272-275
Erosive pustular dermatosis of the scalp (EPDS) is a rare superficial skin inflammatory disease that occurs on the scalp, and its pathogenesis is still unclear. Its clinical manifestations are similar to those of infective inflammation and malignant tumors, and its diagnosis is highly dependent on non-specific pathological changes, so the diagnosis is relatively difficult. Clinically, topical glucocorticoids are the main treatment method, but treatment outcomes vary greatly among individuals, and patients with refractory EPDS need other treatment methods. EPDS generally requires long-term topical glucocorticoid therapy, and adverse drug reactions are common. This review summarizes research progress in EPDS in recent years, in order to improve clinicians' understanding of this disease.
5.Congenital triangular alopecia
Guanghui SHAO ; Yuqian LI ; Qitao CHEN ; Qilin ZHU ; Jing ZHU ; Zhongming LI ; Xufeng DU ; Weixin FAN
Chinese Journal of Dermatology 2025;58(7):668-671
Congenital triangular alopecia is a kind of non-inflammatory and non-cicatricial alopecia, and most cases develop this disease at the ages of 2 - 9 years. The pathogenesis of congenital triangular alopecia is still unclear, and there is a lack of effective treatments. Congenital triangular alopecia is rather liable to be misdiagnosed and erroneously treated, and dermoscopy helps confirm the diagnosis. This review summarizes the progress in the epidemiology, pathogenesis, clinical diagnosis, and treatment of congenital triangular alopecia.
6.Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex ? for patients with premenopausal breast cancer
Xiying SHAO ; Qingyuan ZHANG ; Zhaofeng NIU ; Man LI ; Jingfen WANG ; Zhanhong CHEN ; Ruizhen LUO ; Guangdong QIAO ; Jianguo WANG ; Liyuan QIAN ; Ronghua YANG ; Zhendong CHEN ; Jian WANG ; Yumin YAO ; Jianghua OU ; Tao SUN ; Qiao CHENG ; Yongsheng WANG ; Jian HUANG ; Hongying ZHAO ; Wuyun SU ; Zhong OUYANG ; Yu DING ; Lilin CHEN ; Sumei YANG ; Mengsheng CUI ; Aimin ZANG ; Enxiang ZHOU ; Peizhi FAN ; Jing ZHANG ; Qiang LIU ; Yuee TENG ; Hui LI ; Jianyun NIE ; Jin YANG ; Xiaojia WANG ; Zefei JIANG
Chinese Journal of Oncology 2025;47(4):340-348
Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.
7.The correlation of serum hypoxia-inducible factor-1α level with cerebral microbleeds and cognitive impairment
Qing LI ; Xiaowen ZHAO ; Jing REN ; Miao YU ; Hanfang CUI ; Fangyuan DING ; Hao LIU ; Qiong LI ; Fan WANG ; Qing LI ; Xiyan CHEN ; Chengbiao LU ; Shaomin LI ; Jianhua ZHAO
Journal of Capital Medical University 2025;46(2):216-227
Objective To explore the correlation between serum hypoxia-inducible factor-1α(HIF-1α)levels and cerebral microbleeds(CMBs)and cognitive impairment and to assess the predictive value of HIF-1α for CSVD-related cognitive impairment.Methods A total of 104 patients with CSVD who attended the Department of Neurology,First Affiliated Hospital of Xinxiang Medical University from June 2022 to November 2023 were enrolled.All enrolled patients were subjected to basic statistics,cranial nuclear magnetic resonance examination,cognitive function assessment,and serum HIF-1α test,and the number and location of CMBs were counted.Based on the above data the enrolled patients were grouped.The correlation between HIF-1α and cognitive function and CMBs was studied the influencing factors of CMBs and cognitive impairment were analyzed,and the predictive value of HIF-1α on the occurrence of cognitive impairment was evaluated.Results There were statistically significant differences in HIF-1α levels and cognitive function among different CMBs groups.Serum HIF-1α levels were significantly negatively correlated with overall cognitive function,visuospatial and executive function,attention,and delayed recall,and serum HIF-1α was positively correlated with the number of CMBs.HIF-1α may be a risk factor for CMBs and cognitive impairment associated with CSVD,and serum HIF-1α has potential in predict the cognitive impairment caused by CSVD.Conclusion Serum levels of HIF-1α were associated with the number of CMB and CSVD-related cognitive impairment,and serum levels of HIF-1α may have a predictive value for CSVD-related cognitive impairment.
8.Comparison of left ventricular reverse remodeling and prognosis after transcatheter aortic valve replacement in aortic stenosis and mixed aortic valve disease
Meng SUN ; Lu-lin CHEN ; Jing-yun BAI ; Li-jie YAN ; Jing-jing LIU ; Xian-wei FAN ; Xue-jie LI ; Juan HU ; Jin-tao WU ; Hai-tao YANG
Chinese Journal of Interventional Cardiology 2025;33(2):71-78
Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P<0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.
9.Distribution and exposure assessment of enrofloxacin residues in freshwater fish
Chenyue FAN ; Hongxin NIU ; Ying PAN ; Yan CHEN ; Jing CHEN ; Shenliang LYU ; Ying MEI ; Linan HOU ; Renping TONG
Shanghai Journal of Preventive Medicine 2025;37(9):765-767
ObjectiveTo understand the distribution of enrofloxacin (ENR) residues in freshwater fish, to evaluate the dietary exposure risk to ENR for consumers through the consumption of different freshwater fish in Shanghai, and to provide a reference for controlling antibiotic residues in freshwater fish. MethodsGrass carp, Wuchang bream, pond loach, and Asian swamp eels were purchased from the markets in Shanghai. After being fed with ENR, the fish were divided into 42 batches according to their species and weight, and thereafter ENR residues in the muscles and skin of the fish were measured. In addition, a total of 44 batches of Wuchang bream, pond loach, Asian swamp eels were purchased from the markets, and the ENR residues in the muscles with or without the fish skin were measured, and the exposure risk was evaluated. ResultsThe average residues of ENR in skin of the freshwater fish after being fed with drugs in the 42 groups were higher than those in muscles (M=659.38 μg·kg-1, M=460.83 μg·kg-1; z=-2.212, P=0.027). The over-standard rates of ENR residues in the muscles with or without skin 44 batches of freshwater fish of sold in Shanghai were 36.36% and 29.55%, respectively. The median exposure, P95 exposure, and maximum exposure to ENR through the consumption of the muscles with the skin for adults and children in Shanghai were higher than those through the consumption of muscles without the skin. For children, the margin of safety (MOS) for the max exposure to ENR by consuming the muscles with the skin was more than 1, while the MOS was less than 1 in all other cases for both children and adults. ConclusionThe ENR residues in the skin of freshwater fish are generally higher than those in the muscles. The risk of ENR residues in freshwater fish sold in Shanghai is within a controllable range. However, there might be a certain risk of acute exposure to ENR for children by consuming muscles with the skin of freshwater fish.
10.Efficacy of volar locking plates combined with dorsal mini-plates for treatment of complex distal radius fractures
Jing PENG ; Ji WANG ; Shiyang CHEN ; Xiaotao LONG ; Jun FAN ; Ge WAN
Journal of Chongqing Medical University 2025;50(8):1103-1108
Objective:To investigate the efficacy of volar anatomical locking plates combined with dorsal mini-plates in treating com-plex distal radius fractures.Methods:We retrospectively included patients with complex distal radius fractures who had been treated with volar locking plates and dorsal mini-plates at Chongqing General Hospital from January 2019 to June 2023.The quality of articu-lar surface fragment reduction was assessed through image analysis.Follow-up data included the Mayo wrist score,Disabilities of the Arm,Shoulder,and Hand Questionnaire(DASH)score,wrist range of motion,time to fracture healing,and complications.Results:Twenty-eight patients[19 males,9 females;mean age,(45.4±11.9)years]were included,with a mean follow-up of 1(4.9±3.6)months.Their injury mechanisms included falls from height(11 cases),traffic accidents(9 cases),and simple falls(8 cases).After op-eration,the volar tilt was(5.1±4.9)°,and the ulnar inclination was(19.8±2.8)°;at the final follow-up,the angles were(5.2±4.8)° and(19.3±2.5)°,respectively,neither showing any significant change(P>0.05).At the final follow-up,all fractures healed,with a mean healing time of 3.6 months.At 1 year after operation,the wrist extension was(50.7±6.3)°;the wrist flexion was(49.4±6.1)°;the DASH score was 15.0±6.3;the Mayo wrist scores were excellent or good in 24 cases;the grip strength of the affected side averaged 84.4%of that of the contralateral side.No implant loosening occurred.Two cases of superficial wound infection and one case of exten-sor tendon irritation were reported.Conclusion:Locked volar plat-ing combined with dorsal mini-plating provides stable fixation for comminuted articular surface fragments in complex distal radius fractures,enabling early functional rehabilitation with favorable wrist recovery and low rates of dorsal tendon irritation.

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