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.Single-center analysis of unplanned reoperation case after liver transplantation
Zhi CHEN ; Qingqing DAI ; Fan HUANG ; Guobin WANG ; Xiaojun YU ; Ruolin WU ; Liujin HOU ; Zhenghui YE ; Xinghua ZHANG ; Wei WANG ; Xiaoping GENG ; Hongchuan ZHAO
Organ Transplantation 2026;17(3):452-459
Objective To analyze the main causes and risk factors of unplanned reoperation after liver transplantation. Methods The clinical data of 242 liver transplant recipients in the First Affiliated Hospital of Anhui Medical University from January 2015 to December 2024 were retrospectively analyzed. According to whether unplanned reoperation was performed during the same hospitalization after surgery, the recipients were divided into the reoperation group (n=36) and the non-reoperation group (n=206). The preoperative, intraoperative and postoperative data of the two groups, as well as donor and graft-related data, were compared to analyze the risk factors of unplanned reoperation after liver transplantation and the survival status of the two groups. Results Among the 242 liver transplant recipients, 36 underwent unplanned reoperations, with a total of 54 procedures including various laparotomies, endoscopic and interventional surgeries, among which there were 20 laparotomies, 18 endoscopic surgeries and 16 interventional surgeries. The most common cause of unplanned reoperation was biliary complications (20 times), followed by vascular complications (17 times). Compared with the non-reoperation group, the reoperation group had longer graft cold ischemia time, higher postoperative fatality rate of recipients, longer length of stay in the intensive care unit and postoperative hospital stay, and higher total hospitalization costs (all P<0.05). The incidence of unplanned reoperation was higher in recipients who underwent split liver transplantation (P<0.05). Multivariate analysis showed that intraoperative blood loss ≥1 000 mL, positive culture of graft perfusate and split liver transplantation were independent risk factors for unplanned reoperation (all P<0.05). The postoperative 7-day, 1-month, 3-month and 6-month survival rates of recipients in the reoperation group and the non-reoperation group were 100% vs. 98.1%, 88.9% vs. 94.2%, 69.4% vs. 90.8% and 66.7% vs. 90.8%, respectively, and the postoperative survival rate of recipients in the reoperation group was lower than that in the non-reoperation group (P<0.05). Conclusions The main causes of unplanned reoperation after liver transplantation are biliary complications, vascular complications, abdominal incision infection and intra-abdominal hemorrhage. Intraoperative massive blood loss, positive culture of graft perfusate and split liver transplantation are the risk factors associated with unplanned reoperation after liver transplantation.
4.Analysis of the application status of prescription pre-review systems in Yunnan province
Fan XU ; Wenjie YIN ; Kejia LI ; Zhengfu LI ; Jie CHEN ; Meixian WU ; Ruixiang CHEN ; Songmei LI ; Guowen ZHANG ; Te LI
China Pharmacy 2026;37(1):6-10
OBJECTIVE To investigate the application status of prescription pre-review systems in healthcare institutions of Yunnan province, evaluate their system functions and management capabilities, and provide a practical basis for promoting rational drug use. METHODS A questionnaire survey was conducted among public healthcare institutions at or above the secondary level in Yunnan province to investigate the deployment status of the systems. A capability maturity assessment framework was constructed, encompassing 6 dimensions and 39 indicators, including real-time prescription review, prescription correlation review, rule setting, evidence-based information support, prescription authority management, and system operation management. This framework was then used to evaluate the institutions that had implemented the pre-review systems. RESULTS A total of 100 valid questionnaires were collected, with 37 institutions having adopted prescription pre-review systems, mainly tertiary hospitals. The system predominantly adopted a modular architecture and was embedded into the hospital information system through application programming interfaces and middleware, providing certain capabilities for real-time prescription risk identification. Evaluation results indicated that basic functions such as reviewing indications, contraindications, and drug compatibility performed well, while deficiencies remained in functions related to parenteral nutrition prescription, review of drug dosage for specific diseases, individual patient characteristic recognition, and rule setting. Moreover, the construction of review centers and establishment of management systems were also not well-developed. CONCLUSIONS The overall application rate of prescription pre-review systems in Yunnan province remains low. System functions and management mechanisms require further improvement. It is recommended to enhance information infrastructure in lower-level institutions and explore regionally unified review models to promote standardized and intelligent development of prescription review practices.
5.Jingmaiyan Granules Combined with External Application of Jinhuang Ointment in Treatment of Acute Stage Blood Heat Stasis Type Superficial Thrombophlebitis of Lower Extremities: A Randomized, Double-blind, Placebo-controlled Clinical Trial
Qiaoyilan LIANG ; Hong CHEN ; Weijing FAN ; Hongshuo SHI ; Fangfang WU ; Guobin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):196-202
ObjectiveTo evaluate the clinical efficacy and safety of Jingmaiyan granules (composed of Lonicerae Japonicae Flos, Sedi Herba, Paeoniae Radix Rubra, Moutan Cortex, Rhei Radix et Rhizoma Praeparata, and Glycyrrhizae Radix et Rhizoma) combined with external application of Jinhuang Ointment in treating acute-stage blood heat stasis type superficial thrombophlebitis (ST) of lower extremities, and to explore their effects on hemorheology and serum inflammatory factors. MethodsA randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 124 patients with lower extremity ST were randomized into two groups(62 cases in each group). The control group received external application of Jinhuang ointment and oral placebo treatment, while the observation group received external application of Jinhuang ointment and oral Jingmaiyan granules. Both groups were treated for 2 weeks. The clinical symptom scores, therapeutic efficacy of traditional Chinese medicine (TCM) syndrome, pain visual analog scale (VAS) scores, hemorheological indices [including whole blood high-shear, medium-shear, and low-shear viscosity, as well as plasma viscosity (PV)], and inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] were compared before and after treatment. ResultsAfter 2 weeks of treatment, the total effective rate in the observation group (98.3%, 60/62) was significantly higher than that in the control group (83.8%, 52/62), with a statistically significant difference (Z=3.512 1, P<0.05). Compared with pre-treatment scores, the scores for skin color, skin temperature, swelling, pain, and cord or nodules were significantly reduced in both groups (P<0.05), with more pronounced improvement in the observation group (P<0.05). Additionally, compared with pre-treatment levels, the whole blood viscosity (low-, medium-, and high-shear) significantly improved in both groups after treatment (P<0.05), with more marked improvement in the observation group (P<0.05). Furthermore, the plasma viscosity, CRP, IL-6, and TNF-α levels were significantly reduced in both groups after treatment (P<0.05), with more pronounced improvement observed in the observation group (P<0.05). ConclusionThe combination of external application of Jinhuang ointment and oral Jingmaiyan granules effectively improves clinical symptoms, hemorheological abnormalities, and inflammatory responses in patients with acute stage blood heat stasis type ST of lower extremities. The treatment is safe and holds clinical promotion value.
6.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
7.Clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists in China
Yunjin ZHANG ; Xiaorong WU ; Zhiyun HUANG ; Meiyan ZHANG ; Fan ZHANG ; Hongtao LIU
China Pharmacy 2026;37(2):142-148
OBJECTIVE To conduct a clinical comprehensive evaluation of five marketed thrombopoietin receptor agonists (TPO-RA) approved in China, providing quantitative evidence for drug selection and therapeutic decision-making in medical institutions. METHODS Relevant data on Romiplostim for injection, Eltrombopag olamine tablets, Herombopag olamine tablets, Avatrombopag maleate tablets, and Lusutrombopag tablets were collected. Based on the Chinese Rapid Guide for Drug Evaluation and Selection in Medical Institutions (Second Edition), 12 formulations of these five TPO-RA were scored quantitatively and comparatively across five dimensions: pharmacological characteristics, efficacy, safety, cost-effectiveness, and other attributes. RESULTS The comprehensive scores of the 12 formulations ranged from 62.56 to 75.50 points, with most scoring ≥70 points. Using the highest-scoring formulation for each generic name as a representative, the overall rankings of the five TPO-RA were as follows: Lusutrombopag tablets (75.50 points), Eltrombopag olamine tablets (75.10 points), Avatrombopag maleate tablets (70.40 points), Romiplostim for injection (63.93 points), and Herombopag olamine tablets (63.52 points). Lusutrombopag tablets scored relatively high in pharmacological characteristics, safety, and cost-effectiveness, while Eltrombopag olamine tablets performed well in efficacy and cost-effectiveness. The other formulations showed varying scores across evaluation dimensions. CONCLUSIONS The five TPO-RA demonstrate favorable overall clinical value, with Lusutrombopag tablets and Eltrombopag olamine tablets ranking higher in comprehensive scores, these two drugs should be prioritized in drug selection and formula optimization by medical institutions.
8.Screening of Lu(a-b-) phenotype in Shenzhen and a comparative study on the population polymorphism of genes related to the Lutheran blood group system
Tong LIU ; Fan WU ; Liyan SUN ; Jin QIU ; Shuang LIANG
Chinese Journal of Blood Transfusion 2026;39(2):217-223
Objective: To investigate the distribution frequency and molecular mechanism of the rare blood type Lu(a-b-) in Shenzhen, and to compare the polymorphisms of the Lutheran blood group system encoding gene LU and the In (Lu) phenotype-related gene KLF1 among Han Chinese, Indian, and Uyghur populations in Xinjiang. Methods: Serological methods were used to screen the Lu(a-b-) phenotype of blood donors in Shenzhen. Third-generation sequencing was employed to sequence the full-length of the LU and KLF1 genes in Lu (a-b-) phenotype samples as well as the samples from the Han Chinese, Indians, and Uyghur population, followed by analysis of gene haplotypes frequencies. Results: Ten individuals with the Lu(a-b-) phenotype were screened out of 14 367 blood donors in Shenzhen, yielding a frequency of approximately 0.07%. Only 2 cases showed mutations in the coding region of the LU gene, while all individuals showed heterozygous mutations in the coding region of the KLF1 gene. The highest mutation frequencies of the LU and KLF1 genes were observed in the Uyghur population in Xinjiang and the Han Chinese in Shenzhen, respectively. Conclusion: All Lu(a-b-) phenotypes are of the In (Lu) type, and their formation mechanism is mainly related to KLF1 gene mutations. Both the LU and KLF1 genes exhibit significant polymorphism in the Han Chinese, Indians, and Uyghur populations.
9.Mechanisms of Liuwei Buqi Prescription in Regulating Macrophage Efferocytosis for Treatment of Lung-kidney Qi Deficiency Syndrome in COPD Based on Nrf2/MARCO Signaling Pathway
Jiankang JIANG ; Hui WANG ; Lu ZHANG ; Zegeng LI ; Jiabing TONG ; Fan WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):222-229
ObjectiveTo investigate the mechanisms by which Liuwei Buqi prescription (LWBQ) regulates alveolar macrophage efferocytosis and improves inflammatory responses in rats with chronic obstructive pulmonary disease (COPD) characterized by lung-kidney Qi deficiency based on the nuclear factor erythroid 2-related factor 2 (Nrf2)/macrophage receptor with collagenous structure (MARCO) pathway. MethodsSuccessfully modeled rats were randomly divided into a model group, low-dose LWBQ group (LWBQ-L, 2.25 g·kg-1·d-1), medium-dose LWBQ group (LWBQ-M, 4.5 g·kg-1·d-1), high-dose LWBQ group (LWBQ-H, 9 g·kg-1·d-1), and aminophylline group (AMIN, 50 mg·kg-1·d-1), with 8 rats in each group. Another 8 healthy rats were included as the blank group. Except for the blank group, rats in the remaining groups were subjected to smoke exposure combined with forced swimming, intratracheal lipopolysaccharide (LPS) instillation, and subcutaneous hydrocortisone injection to establish a COPD model with lung-kidney Qi deficiency. After successful modeling, rats were administered different doses of LWBQ or AMIN by gavage. Body weight, fur condition, and oral secretions were observed. Pulmonary function was measured using an animal lung function analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF) and serum (SER). Hematoxylin-eosin (HE) staining was used to examine pathological changes in lung tissue. Giemsa staining was performed to detect eosinophils, basophils, and neutrophils in BALF. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used to detect apoptosis in lung tissue. Western blot and real-time polymerase chain reaction (Real-time PCR) were employed to determine the protein and mRNA expression levels of efferocytosis-related proteins growth arrest-specific gene 6 (GAS6), milk fat globule-epidermal growth factor 8 (MFG-E8), and pathway-related proteins Nrf2 and MARCO in lung tissue. ResultsCompared with the blank group, the model group showed reduced food intake, nasal and oral secretions with sputum, and decreased body weight (P<0.01), decreased peak expiratory flow (PEF) (P<0.01), increased forced vital capacity (FVC) (P<0.01), and decreased forced expiratory volume in 0.3 s/forced vital capacity [FEV0.3/FVC (%)] (P<0.01). The expression levels of IFN-γ, IL-6, IL-1, and TNF-α in BALF and SER were increased (P<0.01). Lung tissue exhibited structural destruction, hyperplasia, inflammatory exudation, increased apoptotic cells, and increased mean optical density (P<0.01). The protein and mRNA expression levels of GAS6, MFG-E8, and MARCO, as well as Nrf2 mRNA expression, were increased (P<0.01). Compared with the model group, the LWBQ groups showed increased food intake, reduced nasal and oral secretions with sputum, and increased body weight (P<0.05, P<0.01). PEF was increased (P<0.01). FVC was increased in rats treated with low- and medium-dose LWBQ (P<0.01), and FEV0.3/FVC (%) was increased in rats treated with medium- and high-dose LWBQ (P<0.05, P<0.01). The expression levels of IFN-γ, IL-6, IL-1, and TNF-α in BALF and SER were decreased (P<0.01). Lung tissue structure was relatively intact, with improvement in hyperplasia and inflammatory exudation. The number of apoptotic cells in lung tissue was reduced, and mean optical density was decreased (P<0.05, P<0.01). The protein and mRNA expression levels of efferocytosis-related proteins GAS6 and MFG-E8 and pathway-related proteins Nrf2 and MARCO were increased (P<0.01). ConclusionLWBQ can alleviate pulmonary and systemic inflammation, improve lung function, and reduce lung tissue damage in rats with COPD characterized by lung-kidney Qi deficiency. The mechanism may be related to enhancement of alveolar macrophage efferocytosis through regulation of the Nrf2/MARCO pathway.
10.Analysis of thermal environment and students thermal comfort in primary and secondary school classrooms in winter
Chinese Journal of School Health 2026;47(2):168-172
Objective:
To evaluate the current situation of thermal environment in primary and secondary school classrooms during winter, and to analyze students thermal comfort needs, so as to provide a basis for improving classroom thermal environment.
Methods:
From December 16 to 26, 2024, a stratified cluster random sampling method was used to select 90 classrooms from 15 primary and secondary schools in centralized/air conditioned heating areas(Liaoning Province, Tianjin City, Shanghai City) and naturally ventilated areas(Anhui Province and Jiangxi Province)for on site environmental measurement. A questionnaire survey was conducted among 743 students. The differences between groups using the χ 2 test were compared. Based on actual measurement data, a predicted mean vote prepared percentage of dissatisfied (PMV-PPD) model for centralized/air conditioned classrooms and an adaptive model for naturally ventilated classrooms were established, and the thermal neutral temperature and comfort interval were calculated.
Results:
The average outdoor temperature during on site measurement was 4.00(0.20,7.00)℃. In classrooms with centralized or air conditioned heating systems, the measured average temperature was (19.33±2.59)℃, with a thermal comfort range of 20.35-25.35 ℃ and a thermal neutral temperature of 22.85 ℃. And 13.92% of students reported feeling cold, while 80.80% felt comfortable. In classrooms with natural ventilation, the measured average temperature was (12.26±1.83)℃, with a thermal neutral temperature of 19.67 ℃ and a thermal comfort range of 16.17-23.17 ℃. About 48.33% of students reported feeling cold, and 49.81 % felt comfortable.The results of univariate analysis showed that there were statistically significant differences in shoe thickness, temperature sensation, relative humidity sensation and wind speed sensation between centralized/air conditioned heating areas ( χ 2= 7.01 , 31.47, 13.57, 13.80,all P <0.05). There were also statistically significant differences in school stage for primary and secondary school students, body mass index, classroom location for seat, temperature sensation, relative humidity sensation and wind speed sensation between naturally ventilated areas ( χ 2=42.13, 11.13, 11.04, 60.39, 29.27, 38.46,all P <0.05).
Conclusions
There are differences in thermal environment and students subjective thermal comfort in primary and secondary schools under different ventilation modes in winter. The temperature standards for heated classrooms should be revised, and differentiated environmental regulation strategies should be adopted based on different ventilation methods to improve students health and comfort levels.


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