1.Construction and Preliminary Application of Animal Disease Model Digital Atlas Database Platform
Huiping LI ; Hongbin GAO ; Jinyin WEN ; Jinchun YANG
Laboratory Animal and Comparative Medicine 2025;45(3):300-308
Objective Domestic research institutions and researchers have established a wide variety of animal disease models and accumulated a wealth of specialized, distinctive, and targeted atlas data during the model development process. These atlas data are of great value for development and application. Therefore, it is necessary to develop a professional and complete digital atlas database platform for animal models, which can achieve the open sharing of animal model atlas data and the integration and optimization of atlas resources related to disease animal models held by relevant domestic institutions. Methods Based on the B/S architecture, the authors' institution built a digital atlas database of animal models, using Java as the main development language and Oracle database system along with related auxiliary tools. The database platform ran in a Linux environment and could be accessed by users through a web browser. At present, the data on this platform mainly came from the atlas resources submitted by animal model resource units within Guangdong Province. Results In August 2024, a digital atlas database platform for animal models was constructed based on the classification structure of three dimensions: systemic diseases, animal species, and resource units. This platform provided functions such as collection, management, retrieval, and viewing of atlas data. As of January 2025, four resource units had submitted 61 atlas data entries of animal models to the platform, totalling 610 data items. Conclusion The animal model digital atlas database platform has been constructed and put into preliminary use. Although the amount of data on the platform is still limited, it is capable of integrating and openly sharing animal model atlas data. It is believed that with the continuous enrichment of atlas data in the future, this platform is expected to provide important data support for the development of laboratory animal science and comparative medicine research, thereby promoting the efficient utilization of scientific research resources.
2.Construction and Preliminary Application of Animal Disease Model Digital Atlas Database Platform
Huiping LI ; Hongbin GAO ; Jinyin WEN ; Jinchun YANG
Laboratory Animal and Comparative Medicine 2025;45(3):300-308
Objective Domestic research institutions and researchers have established a wide variety of animal disease models and accumulated a wealth of specialized, distinctive, and targeted atlas data during the model development process. These atlas data are of great value for development and application. Therefore, it is necessary to develop a professional and complete digital atlas database platform for animal models, which can achieve the open sharing of animal model atlas data and the integration and optimization of atlas resources related to disease animal models held by relevant domestic institutions. Methods Based on the B/S architecture, the authors' institution built a digital atlas database of animal models, using Java as the main development language and Oracle database system along with related auxiliary tools. The database platform ran in a Linux environment and could be accessed by users through a web browser. At present, the data on this platform mainly came from the atlas resources submitted by animal model resource units within Guangdong Province. Results In August 2024, a digital atlas database platform for animal models was constructed based on the classification structure of three dimensions: systemic diseases, animal species, and resource units. This platform provided functions such as collection, management, retrieval, and viewing of atlas data. As of January 2025, four resource units had submitted 61 atlas data entries of animal models to the platform, totalling 610 data items. Conclusion The animal model digital atlas database platform has been constructed and put into preliminary use. Although the amount of data on the platform is still limited, it is capable of integrating and openly sharing animal model atlas data. It is believed that with the continuous enrichment of atlas data in the future, this platform is expected to provide important data support for the development of laboratory animal science and comparative medicine research, thereby promoting the efficient utilization of scientific research resources.
3.Finite element simulation and experimental test of normal coracoclavicular ligament and flexible reconstruction
Guizhu JI ; Qiu ZHENG ; Wuxiang WANG ; Guan WANG ; Wen LI ; Xiaobo LU ; Ke DUAN ; Zhong LI ; Hongbin YANG ; Cheng LIANG
Chinese Journal of Tissue Engineering Research 2024;28(5):706-711
BACKGROUND:For dislocation of acromioclavicular joint induced by coracoclavicular ligament fracture,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are common repair methods.Further study on the stress distribution and fracture risk of the two repair methods is of great significance. OBJECTIVE:To study the biomechanical properties of the coracoclavicular ligament,and compare the fixation effect,stress distribution and failure mode of single and double EndoButton Plates reconstruction. METHODS:(1)Finite element simulation analysis:Mimics,Wrap and SolidWorks were used to establish normal coracoclavicular ligament,single EndoButton Plate reconstruction and double EndoButton Plates reconstruction.Ansys software was used to analyze the stress and deformation of the scapula and clavicle of each model under vertical load.(2)Sample experiment:Fifteen intact scapular-clavicle specimens were randomly grouped into five groups,with three specimens in each group.In group A,the acromioclavicular ligament was severed and the coracoclavicular ligament remained intact.In group B,acromioclavicular ligaments and trapeoid ligaments were severed,leaving intact conical ligaments.In group C,acromioclavicular ligaments and conical ligaments were cut off,and the intact traprex ligaments were retained.In group D,acromioclavicular and coracoclavicular ligaments were severed,and coracoclavicular ligaments were repaired by single EndoButton Plate reconstruction.In group E,acromioclavicular and coracoclavicular ligaments were severed,and the coracoclavicular ligaments were repaired by double EndoButton Plates reconstruction.The mechanical experiment was carried out by a mechanical testing machine to analyze the biomechanical status,stress distribution and failure patterns of the scapular-clavicle and clavicle. RESULTS AND CONCLUSION:(1)Finite element simulation analysis:The average stress of coracoclavicular ligament attached specimens was the lowest,and the risk of coracoclavicular fracture was less than that of single and double EndoButton Plates reconstruction.The mean stress of the coracoid process was similar in single and double EndoButton Plates reconstruction,and the fracture risk was similar.(2)Sample experiment:In groups A,B,C,D and E,the stiffness of specimens was(26.4±3.5),(19.8±2.8),(21.3±3.2),(57.7±4.1),and(46.2±2.8)N/mm,respectively;the ultimate loads were(545.5±53.7),(360.1±42.1),(250.9±44.4),(643.5±39.1),and(511.9±31.7)N,respectively;global stiffness in groups D and E was higher than that in group A(P=0.000 06,0.000 3);ultimate load in group D was higher than that in group A(P<0.05);the ultimate load was not significantly different between the group E and group A(P>0.05).Ligament fracture was observed in groups A,B and C and coracoid process fracture was found in groups D and E.(3)These results suggest that from the biomechanical analysis,Single EndoButton Plate reconstruction and double EndoButton Plates reconstruction are effective treatment techniques for coracoclavicular ligament fracture in acromioclavicular joint dislocation,but increase the risk of fracture.The double EndoButton Plates reconstruction dispersed the stress of the steel plate and reduced the contact force between the steel plate and bone,but slightly reduced the ultimate bearing capacity.Single and double EndoButton Plates reconstruction should be selected according to the actual clinical situation.
4.Clinical application of digital subtraction angiography in treatment of iatrogenic vascular injury caused by central venous catheterization
Zhenzhen CHEN ; Xue CHEN ; Xuegang WEN ; Anming CUI ; Xianzhong WANG ; Hongbin ZHANG
Chinese Journal of Digestive Surgery 2024;23(9):1227-1230
Central venous catheterization plays an important role in the rescue of critically patients. Commonly used central veins in clinical practice include subclavian vein, internal jugular vein, and femoral vein. Serious complications after catheterization can endanger patients′ lives in severe cases. It is necessary to improve the understanding and treatment of serious complications of central vein catheterization in clinical work. A case of iliac vein dissection caused by right femoral vein catheterization was summarized in this article, and the catheter was successfully removed under digital subtraction angiography direct vision after the distal end of the catheter penetrated the vascular wall and reached the peritonea, which provided reference for the treatment of iatrogenic injury caused by central vein catheterization.
5.Human 8-cell embryos enable efficient induction of disease-preventive mutations without off-target effect by cytosine base editor.
Yinghui WEI ; Meiling ZHANG ; Jing HU ; Yingsi ZHOU ; Mingxing XUE ; Jianhang YIN ; Yuanhua LIU ; Hu FENG ; Ling ZHOU ; Zhifang LI ; Dongshuang WANG ; Zhiguo ZHANG ; Yin ZHOU ; Hongbin LIU ; Ning YAO ; Erwei ZUO ; Jiazhi HU ; Yanzhi DU ; Wen LI ; Chunlong XU ; Hui YANG
Protein & Cell 2023;14(6):416-432
Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans
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Apolipoprotein E4/genetics*
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Cytosine
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Mutation
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Blastocyst
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Heterozygote
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Gene Editing
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CRISPR-Cas Systems
6.Ten-year experience of mitral valve surgery in infants
Xiafeng YU ; Wen ZHANG ; Wei DONG ; Renjie HU ; Lisheng QIU ; Hongbin ZHU ; Haibo ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(8):449-453
Objective:To summarize the experience and effect of mitral valvuloplasty in the treatment of mitral valve disease in infants.Methods:The clinical data of 140 infants with mitral valve disease from June 2010 to June 2020 were retrospectively analyzed. There were 62 males and 78 females, with body weight of(6.4±1.4)kg and age of(196.6±80.1)days. Among them, 131 cases were moderately or above mitral insufficiency, and 9 cases were mitral stenosis. The perioperative and follow-up clinical data were recorded, and the therapeutic effect and prognostic factors of mitral valve plastic surgery were analyzed.Results:All 140 children were received surgery of mitral valve repair under cardiopulmonary bypass. Cardiopulmonary bypass time was(79.1±41.9)min, aortic cross clamp time was(46.8±20.0)min, 7(5%)early death. Mechanical ventilation time was(74.2±149.8)h. After surgery, mild mitral regurgitation was found in 48 cases, mild-moderate regurgitation in 53 cases, moderate regurgitation in 32 cases, moderate-severe regurgitation in 6 cases, severe regurgitation in 1 case, with no mitral stenosis. During the follow-up period of 6-126 months, 3 cases died in the long term, and 11 cases were reoperated. Freedom from >moderate mitral regurgitation at 5 years after surgery was 81.2%. Longer cardiopulmonary bypass time and postoperative mitral regurgitation were risk factors for death and moderate or above regurgitation at the follow-up.Conclusion:Mitral valvuloplasty can effectively treat the mitral regurgitation and stenosis in infants. The prognosis of children with short cardiopulmonary bypass time and good valve plastic effect is better. For infants with Carpentier type I, good shaping effect can be achieved by mitral annuloplasty alone, while for type Ⅱ and type Ⅲ, treatment should be tailored to deal with the problems at all levels of the valve, and additional annuloplasty should be performed.
7.Surgical experience of pediatric cardiac fibromas
Wen ZHANG ; Qi JIANG ; Renjie HU ; Wei DONG ; Hongbin ZHU ; Lisheng QIU ; Haibo ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(10):596-598
Objective:To summarize single-center experience and short-term outcomes of surgical treatment of pediatric cardiac fibromas.Methods:There was a retrospective study of 10 patients who underwent surgical treatment of cardiac fibromas between January 2018 and October 2021. Fibromas were located in the left ventricle in 7 cases, and in the right ventricle in 3 cases. Mean tumor diameter was(5.6±2.0) cm.Results:Median age at surgery was 3.1 years old(5 months-9 years old). Nine patients received complete resection, and the other one received partial resection. One patient with giant left ventricular fibroma required extracorporeal membrane oxygenation support for ventricular fibrillation after weaning from cardiopulmonary bypass, and was successfully weaned on the third postoperative day. There was no early mortality. Median follow-up time was 6 months(1 month-3 years). No tumor recurrence nor ventricular arrhythmia was documented during the follow-up period.Conclusion:Pediatric cardiac fibromas can be usually treated by complete resection, with relief of cardiac dysfunction and ventricular arrythmia after surgery, and with satisfactory results.
8.Surgical outcomes of interrupted aortic arch with ventricular septal defect in neonates and infants
Wen ZHANG ; Qi JIANG ; Yifan ZHU ; Renjie HU ; Xiafeng YU ; Wei DONG ; Hongbin ZHU ; Haibo ZHANG
Chinese Journal of Thoracic and Cardiovascular Surgery 2021;37(6):321-325
Objective:To summarize the surgical outcomes of interrupted aortic arch with ventricular septal defect (IAA/VSD) in neonates and infants.Methods:This was a retrospective review of clinical data of 123 neonates and infants who received surgery for IAA/VSD from Jan 2009 to Jan 2019. Median age at repair was 48 days. Forty-four patients (36%) were neonates. One-hundred-and-twenty-two patients (99%) underwent standard aortic arch reconstruction with VSD closure, and one neonate (1%) underwent staged Yasui operation. Risk factors for early mortality was analyzed by decision tree model.Results:Early mortality after surgery was 13%. Duration of cardiopulmonary bypass longer than 135 min, surgery received during neonatal period and before 2016 was identified as higher risk group for mortality. Median follow-up time was 3.5 years (range, 1-10 years). Freedom from aortic arch obstruction at 6 months, 1 year, 5 years after surgery was 75%, 72% and 72% respectively. Freedom from left ventricular outflow tract (LVOT) obstruction at 6 months, 1 year, 5 years after surgery was 91%, 83% and 73% respectively. A total of 17 patients received 21 reoperations. The patient who received Yasui operation experienced no residual obstruction during the follow-up.Conclusion:Early outcomes after surgery for IAA/VSD in neonates and infants are satisfactory. However, patients with standard aortic arch reconstruction have a higher risk for aortic and LVOT obstruction, and require multiple reoperations.
9.Application value of Clavien-Dindo classification in evaluation of postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy
Weikai CHEN ; An ZHANG ; Jinling WU ; Aimin ZHU ; Xuan ZHANG ; Nan LI ; Wenfang ZHAO ; Xinping WANG ; Wen′an WANG ; Jing WANG ; Jianping YU ; Ruiyu TAO ; Zhengkai LI ; Kun LI ; Le LI ; Long YAN ; Tingbao CAO ; Dengwen WEI ; Hongbin LIU
Chinese Journal of Digestive Surgery 2020;19(9):976-982
Objective:To investigate the application value of Clavien-Dindo classification in evaluation of postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Methods:The retrospective cohort study was conducted. The clinicopathological data of 262 patients with gastric cancer who were admitted to the 940th Hospital of Joint Logistic Support Force of Chinese People′s Liberation Army from January 2016 to January 2019 were collected. There were 214 males and 48 females, aged (58±11) years, with a range from 17 to 81 years. Of 262 patients, 120 cases undergoing Da Vinci robotic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into robotic group, and 142 cases undergoing laparoscopic-assisted total gastrectomy + D 2 lymphadenectomy + Roux-en-Y anastomosis were divided into laparoscopic group. Observation indicators: (1) intraoperative and postoperative situations; (2) postoperative pathological examination; (3)complications; (4) stratified analysis; (5) follow-up. Follow-up using outpatient examination and telephone interview was performed to detect complications, tumor recurrence and survival of patients within postoperative 2 months. The follow-up was up to May 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ranked data between groups was analyzed using the rank sum test. Results:(1) Intraoperative and postoperative situations: cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, the number of lymph node dissected, time to first flatus, time to initial fluid diet intake, duration of postoperative hospital stay of the robotic group were 1, (243±42)minutes, 100 mL(range, 100-150 mL), 38±15, (2.8±1.0)days, 3 days(range, 3-4 days), 11 days(range, 9-13 days), respectively. The above indicators of the laparoscopic group were 2, (244±38)minutes, 100 mL(range, 100-150 mL), 34±14, (3.2±1.0)days, 4 days(range, 3-5 days), 10 days(range, 9-13 days), respectively. There were significant differences in the number of lymph node dissected, time to first flatus, time to initial fluid diet intake between the two groups ( t=2.068, -3.030, Z=-3.370, P<0.05), and there was no significant difference in cases undergoing conversion to open surgery, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay between the two groups ( χ2=0.000, t=-0.158, Z=-1.824, -0.088, P>0.05). (2) Postoperative pathological examination: cases with well differentiated tumor, moderately differentiated tumor, poorly differentiated tumor, signet ring cell carcinoma or other types of tumor, cases in stage T1b, T2, T3 or T4a (pT staging), cases in stage N0, N1, N2, N3a or N3b (pN staging), cases in stage ⅠB, ⅡA, ⅡB, ⅢA, ⅢB or ⅢC (pTNM staging) of the robotic group were 6, 50, 55, 9, 10, 22, 63, 25, 42, 19, 19, 24, 16, 17, 22, 23, 20, 23, 15, respectively. The above indicators of the laparoscopic group were 4, 42, 84, 12, 6, 18, 81, 37, 39, 27, 32, 19, 25, 13, 19, 28, 39, 16, 27, respectively. There was no significant difference in the above indicators between the two groups ( Z=-1.880, -1.827, -0.140, -1.460, P>0.05). (3) Complications: cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death, cases with overall complications, cases with severe complications of the robotic group were 9, 6, 3, 2, 2, 0, 0, 22, 7, respectively. The above indicators of the laparoscopic group were 12, 15, 9, 6, 3, 1, 1, 47, 20, respectively. There were significant differences in cases with overall complications, cases with severe complications between the two groups ( χ2=7.309, 4.790, P<0.05), and there was no significant difference in cases with complication classified as grade Ⅰ, grade Ⅱ, grade Ⅲa, grade Ⅲb, grade Ⅳa, grade Ⅳb of Clavien-Dindo classification, cases with death between the two groups ( χ2=0.080, 2.730, 1.042, 0.704, 0.000, 0.000, 0.000, P>0.05). (4) Stratified analysis: of the patients with overall complications in robotic group, cases of male or female, cases aged ≥65 years or <65 years, cases with body mass index (BMI) ≥24 kg/m 2 or <24 kg/m 2, cases with tumor diameter ≥5 cm or <5 cm, cases with or without abdominal surgery, cases with tumor located at upper stomach or middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of American Society of Anesthesiologists (ASA) classification, cases with well differentiated tumor or undifferentiated tumor, cases in stage Ⅰ-Ⅱ or stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes or <250 minutes, cases with volume of intraoperative blood loss ≥150 mL or <150 mL, cases with the number of lymph node dissected ≥25 or <25 were 15, 7, 14, 8, 11, 11, 16, 6, 4, 18, 19, 3, 15, 7, 7, 15, 8, 14, 12, 10, 12, 10, 14, 8, respectively. The above indicators of patients with overall complications in the laparoscopic group were 33, 14, 17, 30, 16, 31, 36, 11, 11, 36, 27, 20, 31, 16, 13, 34, 14, 33, 24, 23, respectively. Of the patients with overall complication, there were significant differences in cases of male, cases aged ≥65 years or <65 years, cases with BMI<24 kg/m 2, cases with tumor diameter≥5 cm, cases without abdominal surgery, cases with tumor located at middle stomach, cases in Ⅰ-Ⅱ grade or Ⅲ grade of ASA classification, cases with well differentiated tumor, cases in stage Ⅲ (pTNM staging), cases with operation time ≥250 minutes, cases with volume of intraoperative blood loss <150 mL, cases with the number of lymph node dissected ≥25 between the two groups ( χ2=6.683, 4.207, 6.761, 7.438, 4.297, 6.325, 9.433, 3.970, 4.850, 4.911, 3.952, 3.915, 6.865, 4.128, P<0.05) and there was no significant difference in cases of female, cases with BMI≥24 kg/m 2, cases with tumor diameter <5 cm, cases with abdominal surgery, cases with tumor located at upper stomach, cases with undifferentiated tumor, cases in stage Ⅰ-Ⅱ (pTNM staging), cases with operation time < 250 minutes, cases with volume of intraoperative blood loss ≥150 mL, cases with the number of lymph node dissected <25 between the two groups ( χ2=0.277, 1.052, 1.996, 1.552, 2.172, 2.594, 2.244, 3.771, 1.627, 3.223, P>0.05). (5) Follow-up: 262 patients were followed up postoperatively for 2 months. During the follow-up, no patient was diagnosed with tumor recurrence, and one patient in the laparoscopic group died of severe infection. Conclusions:The Clavien-Dindo classification can be used in evaluating postoperative short-term complications of Da Vinci robotic-assisted or laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy. Compared with laparoscopic-assisted total gastrectomy with D 2 lymphadenectomy, Da Vinci robotic-assisted total gastrectomy with D 2 lymphadenectomy has the advantages of minimally invasiveness, low incidence of overall and severe complication.
10.Synergistic antitumor activity of artesunate and HDAC inhibitors through elevating heme synthesis synergistic upregulation of ALAS1 expression.
Cai-Ping CHEN ; Kun CHEN ; Zhiqi FENG ; Xiaoan WEN ; Hongbin SUN
Acta Pharmaceutica Sinica B 2019;9(5):937-951
Artemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. studies revealed that combination of ARS and HDACi exerted synergistic tumor inhibition by inducing cell death. Moreover, this combination exhibited more effective antitumor activity than either ARS or HDACi monotherapy in xenograft models without apparent toxicity. Importantly, mechanistic studies revealed that HDACi coordinated with ARS to increase 5-aminolevulinate synthase (ALAS1) expression, and subsequent heme production, leading to enhanced cytotoxicity of ARS. Notably, knocking down significantly blunted the synergistic effect of ARS and HDACi on tumor inhibition, indicating a critical role of ALAS1 upregulation in mediating ARS cytotoxicity. Collectively, our study revealed the mechanism of synergistic antitumor action of ARS and HDACi. This finding indicates that modulation of heme synthesis pathway by the combination based on ARTs and other heme synthesis modulators represents a promising therapeutic approach to solid tumors.

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