1.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
2.Correlation Analysis of Huanglian Jiedu Wan on Syndrome Improvement and Clinical Biomarkers of "Excess Heat-Toxicity" Based on Machine Learning Model
Qi LI ; Keke LUO ; Baolin BIAN ; Hongyu YU ; Mengxiao WANG ; Mengyao TIAN ; Wen XIA ; Yuan MA ; Xinfang ZHANG ; Pengyue LI ; Nan SI ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):162-173
ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally, the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome, such as oral ulcers, sore throat, and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation, oxidative stress, and energy metabolism in the early phase, Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting (XGBoost) algorithm was used to develop a prediction model for main symptom classification, with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers, sore throat, and overall symptoms, with significant effects observed especially in sore throat and overall symptom analyses (P<0.01). Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement, were also called "heat-related biomarkers", including succinic acid, α-ketoglutaric acid, glycine, lactic acid, adenosine monophosphate (AMP), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), and so on. Conversely, clinical biomarkers negatively correlated with symptom severity, were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan, including malic acid, fumaric acid, cis-aconitic acid, adrenocorticotropic hormone (ACTH), IL-1β, IL-4, IL-8, succinic acid, and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables, with importance scores of 0.081 and 0.080, respectively. After screening out 14 key variables and optimizing the parameters, model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables, confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established, achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.
3.Impacts of external fixation of different durations on rehabilitation outcomes after open repair of acute Achilles tendon rupture
Yuan CAO ; Xiuzhi LI ; Zengzhen CUI ; Yuliang FU ; Liangyu BAI ; Jixing FAN ; Tengjiao ZHU ; Gao SI ; Yang LYU ; Fang ZHOU
Chinese Journal of Trauma 2025;41(4):360-368
Objective:To compare the impacts of external fixation of different durations on rehabilitation outcomes after open repair of acute Achilles tendon rupture.Methods:A prospective cohort study was conducted to analyze the clinical data of patients with unilateral acute closed Achilles tendon rupture admitted to Peking University Third Hospital from August 2020 to August 2023. Patients were divided into Group A ( n=96), Group B ( n=347), Group C ( n=346), and Group D ( n=105) based on different postoperative immobilization durations (0, 2, 4 and 6 weeks, respectively). After all the patients received identical open repair procedure, Group A was rehabilitated immediately but the other groups were rehabilitated with the same protocol after removal of the external fixation. Four groups were compared in terms of recovery time of one-leg heel-rise height (OHRH), recovery time of light exercise (LE) in brisk walking and jogging and recovery time of range of motion (ROM). Visual analogue scale (VAS) scores were also compared at 2, 4, 6 and 8 weeks postoperatively. Achilles tendon total rupture score (ATRS) and American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores were evaluated at 6, 8, 10, 12, 14 and 16 weeks postoperatively. Complications were recorded. Results:A total of 894 patients including 869 males and 25 females were included, aged 18-60 years [(35.0±6.3)years]. All the patients were followed up for 14-25 months [(19.0±3.0)months]. The recovery time of OHRH in Group A and B was 12.0(12.0, 12.0)weeks and 12.0(10.0, 12.0)weeks, shorter than those in Group C [14.0(14.0, 16.0)weeks] and D [14.0(14.0, 14.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of LE in Group A and B was 18.0(18.0, 18.0)weeks and 18.0(16.0, 18.0)weeks, shorter than those in Group C [20.0(20.0, 20.0)weeks] and D [20.0(20.0, 20.0)weeks] ( P<0.05), with no significant difference between Group A and B ( P>0.05) and between Group C and D ( P>0.05). The recovery time of ROM in Group A and B was 6.0(6.0, 6.0)weeks and 6.0(6.0, 6.0)weeks, shorter than those in Group C [8.0(8.0, 10.0)weeks] and D [10.0(10.0, 10.0)weeks)] ( P<0.05), with no significant difference between Group A and B, and between Group C and D ( P>0.05). At 2 weeks postoperatively, the VAS scores were 2.0(1.0, 2.0)points, 2.0(1.0, 2.0)points, and 2.0(1.5, 2.0)points in Group B, C and D, lower than 5.0(5.0, 5.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 4 weeks postoperatively, the VAS scores were 1.0(0, 1.0)points, 1.0(0, 1.0)points, and 1.0(0.5, 1.0)points in Group B, C and D, lower than 2.0(1.0, 2.0)points in Group A ( P<0.05), with no significant difference among Group B, C, and D ( P>0.05). At 6 weeks postoperatively, the VAS score was 0(0, 0)points in all the 4 groups, with no significant difference among them ( P>0.05). At 8 weeks postoperatively, the VAS score was 0(0, 0)points, with lower scores in Group A and B than those in Group C and D ( P<0.05) but with no significant difference between Group A and B and between Group C and D ( P>0.05). At 6 weeks postoperatively, the ATRS scores were 52.0(52.0, 53.8)points and 52.0(50.0, 53.0)points in Group A and B, higher than 41.0(38.0, 43.0)points and 19.0(18.0, 20.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the ATRS scores were 66.0(66.0, 68.0)points in Group A, higher than 63.0(62.0, 64.0)points, 52.0(50.0, 53.0)points, and 39.0(37.0, 40.0)points in Group B, C and D ( P<0.05), with a higher score in Group B than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the ATRS score was 75.0(74.0, 76.0)points in Group B, higher than 69.0(69.0, 70.0)points, 72.0(66.0, 74.0)points, and 62.0(58.5, 63.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the ATRS score was 84.0(82.0, 85.0)points in Group B, higher than 75.0(75.0, 77.0)points, 79.0(72.0, 81.0)points, and 72.0(71.0, 73.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 14 weeks postoperatively, the ATRS score was 87.0(86.0, 87.0)points in Group B, higher than 82.0(82.0, 84.0)points, 83.0(80.0, 85.0)points, and 79.0(77.5, 80.0)points in Group A, C and D ( P<0.05), with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 16 weeks postoperatively, the ATRS scores were 87.0(87.0, 88.0)points and 88.0(87.0, 88.0)points in Group A and B, higher than 86.0(85.0, 87.0)points and 84.0(83.0, 85.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 6 weeks postoperatively, the AOFAS ankle-hindfoot scores were 94.0(94.0, 95.0)points and 95.0(94.0, 96.0)points in Group A and B, higher than 85.0(83.0, 86.0)points and 74.0(72.0, 75.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05) but with no significant difference between Group A and B ( P>0.05). At 8 weeks postoperatively, the AOFAS ankle-hindfoot scores were 100.0(99.0, 100.0)points in Group B, higher than 94.0(94.0, 95.0)points, 92.0(90.0, 93.0)points, and 83.0(82.0, 84.0)points in Group A, C and D ( P<0.05), with a higher score in Group A than those in Group C and D ( P<0.05) and a higher score in Group C than that in Group D ( P<0.05). At 10 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in Group B, higher than 98.0(98.0, 98.0)points, 98.0(96.8, 99.0)points, and 96.0(95.0, 97.0)points in Group A, C and D, with higher scores in Group A and C than that in Group D ( P<0.05) but with no significant difference between Group A and C ( P>0.05). At 12 weeks postoperatively, the AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points in both Group A and B, with no significant difference between them ( P>0.05), which was higher than 100.0(98.0, 100.0)points and 99.0(98.0, 99.0)points in Group C and D ( P<0.05), with a higher score in Group C than that in Group D ( P<0.05). At 14 and 16 weeks postoperatively, AOFAS ankle-hindfoot score was 100.0(100.0, 100.0)points, with no significant difference among all the groups ( P>0.05). Superficial wound infection occurred in 12 patients [5.2%(5/96) in Group A, 0.6%(2/347) in Group B, 0.6%(2/346) in Group C and 2.9%(3/105) in Group D] ( P<0.01) while rerupture occurred in 16 [9.4%(9/96) in Group A, 1.2% (4/347) in Group B, 0.9%(3/105) in Group C, and 0 patient in Group D] ( P<0.01). Conclusion:For patients with unilateral acute Achilles tendon rupture, two weeks of postoperative external fixation after open repair can shorten the time of returning sports, alleviate pain, and promote functional recovery, without increasing the risk of complications.
4.The Effects of the Combination of Curcumin,Berberine,and Puerarin on Lipid Levels in Hyperlipidemic Mice
Zhi-yuan FAN ; Yi-zhou XU ; Si-wei XU ; Xiong-hua XING ; Mao-lin LIU ; Xia YI
Progress in Modern Biomedicine 2025;25(13):2100-2109,2099
Objective:To investigate the effects of curcumin,berberine,and puerarin combination therapy on lipid levels in hyperlipidemic mice.Methods:A total of 40 male C57BL/6J mice were randomly divided into eight groups:normal control group(A),high-fat control group(B),curcumin group(C),berberine group(D),puerarin group(E),low-dose combination group of curcumin,berberine,and puerarin(F),high-dose combination group of curcumin,berberine,and puerarin(G),and positive control group(H),with 5 mice in each group.The normal control group was fed a standard diet,while the other groups were given a high-fat diet.After establishing the hyperlipidemic model,the mice were administered with physiological saline,curcumin(200 mg/kg),berberine(200 mg/kg),puerarin(300 mg/kg),low-dose combination of curcumin(50 mg/kg),berberine(50 mg/kg),and puerarin(100 mg/kg),high-dose combination of curcumin(200 mg/kg),berberine(200 mg/kg),and puerarin(300 mg/kg),or simvastatin(6 mg/kg)via gavage for three weeks.After treatment,serum was collected from the mice for biochemical analysis of lipid levels and liver function.Liver tissues were subjected to HE staining,Western blot analysis and real-time quantitative PCR.Results:Curcumin,berberine,and puerarin,whether administered individually or in combination,can reduce the body weight of hyperlipidemic mice(P<0.01).Treatment with curcumin,berberine,and puerarin individually significantly reduced lipid levels in hyperlipidemic mice(P<0.05)and alleviated liver damage caused by hyperlipidemia(P<0.05).Furthermore,the high-dose combination of curcumin,berberine,and puerarin exhibited a more pronounced effect on improving lipid levels(P<0.01)and provided greater protective effects on the liver compared to the positive control group(P<0.05).Additionally,curcumin,berberine,and puerarin administered individually can each promote the expression of the LDLR gene in high-fat diet mice(increased by 90%,85%,and 98%,respectively)and reduce the expression of the ACC gene(decreased by 42%,45%,and 43%,respectively).The combination of all three compounds enhances the expression of the LDLR gene in high-fat diet mice(increased by 90%with low-dose combination and 169%with high-dose combination)and reduces the expression of the ACC gene(decreased by 38%with low-dose combination and 42%with high-dose combination).Conclusion:The combination of curcumin,berberine,and puerarin significantly improves lipid levels in hyperlipidemic mice and mitigates liver damage associated with hyperlipidemia.
5.Application progress of micro-CT and finite element analysis techniques in scaphoid bone research
Yuan LYU ; De-zhou ZHANG ; Hai-long QIAN ; Si-min WANG ; Chao-qun WANG ; Kun LI ; Jie CHEN ; Xue BAI ; Hai-long ZHAO ; Shao-jie ZHANG ; Yuan MA ; Zhi-jun LI ; Jun SHI ; Xing WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(2):168-173
The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.
6.Dosimetry effect of fluence smoothing in Monaco Treatment Planning System for short-course volumetric modulated arc therapy of preoperative rectal cancer
Yao XIAO ; De-li ZHOU ; Kun-pu SU ; Lin-shan LI ; Meng-yuan SI ; Yan-hai LIU ; Chuan CHEN
Chinese Medical Equipment Journal 2025;46(5):48-53
Objective To investigate the dosimetric differences in preoperative short-course volumetric modulated arc therapy(VMAT)for rectal cancer using different fluence smoothing(FS)levels in the Monaco Treatment Planning System(Monaco TPS).Methods Twenty rectal cancer patients who received preoperative neoadjuvant short-course VMAT at some hospital from September 2021 to December 2022 were retrospectively selected.Four groups of radiotherapy plans were formulated using the Monaco TPS for each case,which were classified into an off group,a low group,a medium group and a high group based on the FS levels.Then the four groups were compared in terms of the dosimetric parameters,monitor unit and number of the segments in the planning target volume(PTV)and organ at risk(OAR).Statistical analysis was performed using SPSS 27.0 software.Results All the four groups had the doses to the target volume meeting clinical requirements,which had no significant differences in the doses to 5%(D5%)and 95%(D95%)to the target volume and the maximum dose(Dmax),minimum dose(Dmin),mean dose(Dmean)and conformity index(all P>0.05).Statistical differences were found between the homogeneity indexes of the four groups(P<0.05),with the medium group behaving the best.The number of the segments rose while the mornitor units decreased siginificantly with the increase of FS levels,with the differences being statistically significant(P<0.05).There were no significant differences between the V25,V20,V15 and V10 of the small intestine,the V25 and V20 of the bladder and the V15 and V10 of the left and right femur(all P>0.05).Conclusion In preoperative short-course VMAT for rectal cancer,clinical requirements can be met with different FS levels in the Monaco TPS,and medium-level FS results in optimal overall dose distribution in terms of treatment planning.[Chinese Medical Equipment Journal,2025,46(5):48-53]
7.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
8.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
9.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.
10.Expert consensus on evaluation index system construction for new traditional Chinese medicine(TCM) from TCM clinical practice in medical institutions.
Li LIU ; Lei ZHANG ; Wei-An YUAN ; Zhong-Qi YANG ; Jun-Hua ZHANG ; Bao-He WANG ; Si-Yuan HU ; Zu-Guang YE ; Ling HAN ; Yue-Hua ZHOU ; Zi-Feng YANG ; Rui GAO ; Ming YANG ; Ting WANG ; Jie-Lai XIA ; Shi-Shan YU ; Xiao-Hui FAN ; Hua HUA ; Jia HE ; Yin LU ; Zhong WANG ; Jin-Hui DOU ; Geng LI ; Yu DONG ; Hao YU ; Li-Ping QU ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2025;50(12):3474-3482
Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards*
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Humans
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Consensus
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Drugs, Chinese Herbal/therapeutic use*
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Surveys and Questionnaires

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