1.Prognostic Factors of Liposarcoma in Head and Neck
Shuo DING ; Zhigang HUANG ; Jugao FANG ; Yang ZHANG ; Lizhen HOU ; Wei GUO ; Gaofei YIN ; Qi ZHONG
Cancer Research on Prevention and Treatment 2025;52(1):31-35
Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.
2.Mechanism of Shexiang Tongxin Dripping Pills in Ameliorating AngⅡ-induced Vascular Smooth Muscle Cell Dysfunction
Yueyao HU ; Wei WANG ; Mingyue HUANG ; Shujuan GUO ; Junkai YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):97-106
ObjectiveTo study the mechanism of Shexiang Tongxin Dripping pills-containing serum (STDP) in ameliorating angiotensinⅡ (AngⅡ)-induced cell phenotype transformation, proliferation, migration, and dysfunction of vascular smooth muscle cells. MethodsAn AngⅡ-induced proliferation and migration model of vascular smooth muscle cells was established. The cells were treated with STDP at 5%, 10%, and 20% for 24 h. The immunofluorescence assay was employed to detect the expression of α smooth muscle actin (α-SMA) and matrix metalloproteinase-2 (MMP-2). The cell-counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) staining were employed to detect the proliferation of vascular smooth muscle cells, and the scratch assay was employed to detect the migration of the cells. Western blot was employed to determine the expression levels of pathway proteins such as angiotensin-converting enzyme 2 (ACE2), angiotensin Ⅱ type 2 (AT2), angiotensin Ⅱ type 1 (AT1), as well as proliferation and migration proteins such as typeⅠ collagen (ColⅠ) and osteopontin (OPN). ResultsCompared with the model group, STDP increased the expression of α-SMA, reduced the expression of MMP-2, and inhibited the proliferation and migration of vascular smooth muscle cells (P<0.05). Furthermore, STDP up-regulated the expression levels of ACE2, AT2, and MAS1, while down-regulating the expression level of AT1, PCNA, ColⅠ, MMP-9, Rock1, Rock2, and SRF (P<0.05). Compared with the STDP group, the ACE2 inhibitor reversed the regulatory effects of STDP. ConclusionSTDP inhibits the phenotype transformation, proliferation, and migration of vascular smooth muscle cells and regulates the expression of cell proliferation and migration-related proteins to ameliorate the dysfunction of vascular smooth muscle cells. It exerts the effects by up-regulating the expression of proteins in the ACE2-AT2/MAS pathway and down-regulating the expression of proteins in the AT1-Rock signaling pathway.
3.The mechanism of Laggerae Herba in improving chronic heart failure by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway
Jinling XIAO ; Kai HUANG ; Xiaoqi WEI ; Xinyi FAN ; Wangjing CHAI ; Jing HAN ; Kuo GAO ; Xue YU ; Fanghe LI ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):343-353
Objective:
To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice.
Methods:
Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue.
Results:
Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group.
Conclusion
Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.
4.Shexiang Tongxin Dropping Pills Ameliorate Dysfunction of Cardiac Microvascular Endothelial Cells in Rat Model of Heart Failure
Junkai YAO ; Shujuan GUO ; Mingyue HUANG ; Chun LI ; Yong WANG ; Wei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):87-95
ObjectiveTo study the mechanism by which Shexiang Tongxin dropping pills (STDP) ameliorate the dysfunction of coronary microvascular endothelial cells in the rat model of heart failure. MethodsThe heart failure model was established by ligation of the left anterior descending coronary artery in rats, which were then allocated into sham, model, STDP, and telmisartan (TLM) groups and treated for 21 days. The heart function was detected by echocardiography, and the levels of myocardial injury markers, nitric oxide (NO), endothelin-1 (ET1), and angiotensinⅡ (AngⅡ) were determined by enzyme-linked immunosorbent assay (ELISA). The protein levels of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) were determined by Western blot. The model of cardiac microvascular endothelial cell injury was established by AngⅡ induction and then treated with the STDP-containing serum (5%, 10%, and 20%) for 24 h. The levels of NO and ET1 were measured by ELISA. Western blot was employed to determine the protein levels of eNOS, iNOS, angiotensin-converting enzyme 2 (ACE2), and angiotensinⅡ receptor 2 (AT2). MLN-4760, an ACE2 inhibitor, was used to explore the mechanism underpinning the regulatory effect of STDP on the ACE2-AT2/MAS pathway. ResultsCompared with the sham group, the model group showed decreases in left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.05), a decline in serum NO level, elevations in serum AngⅡ and ET1 levels, a reduction in p-eNOS/eNOS ratio, and up-regulation in iNOS expression (P<0.05). Compared with the model group, STDP increased LVEF, LVFS, and cardiac output (P<0.05), raised the level of NO and lowered the levels of AngⅡ and ET1 in the serum (P<0.05), increased the p-eNOS/eNOS value, and inhibited iNOS expression (P<0.05). Compared with the AngⅡ group, STDP increased the NO content and decreased the ET1 content in endothelial cells (P<0.05), increased the p-eNOS/eNOS ratio, and inhibited the iNOS expression (P<0.05). The ACE2 inhibitor MLN-4760 reversed the regulatory effects of STDP on p-eNOS, eNOS, and iNOS. ConclusionSTDP improves the cardiac function in the rat model of heart failure, enhances the synthesis and release of NO in cardiac microvascular endothelial cells, reduces AngⅡ and ET1 levels, and regulates the expression of p-eNOS and eNOS, thereby ameliorating the dysfunction of microvascular endothelial cells in heart failure. This mechanism is related to the upregulation of the expression of proteins in the ACE2-AT2/MAS pathway.
5.Relationship Between Gastroesophageal Reflux Disease-Related Symptoms and Clinicopathologic Characteristics and Long-Term Survival of Patients with Esophageal Adenocarcinoma in China
Kan ZHONG ; Xin SONG ; Ran WANG ; Mengxia WEI ; Xueke ZHAO ; Lei MA ; Quanxiao XU ; Jianwei KU ; Lingling LEI ; Wenli HAN ; Ruihua XU ; Jin HUANG ; Zongmin FAN ; Xuena HAN ; Wei GUO ; Xianzeng WANG ; Fuqiang QIN ; Aili LI ; Hong LUO ; Bei LI ; Lidong WANG
Cancer Research on Prevention and Treatment 2025;52(8):661-665
Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of
6.Mechanism on Banxia Xiexintang Inducing Ferroptosis in Gastric Cancer Cells Based on Nrf2/GPX4 Signaling Pathway
Ling LI ; Yaxing LI ; Xue WANG ; Xiao QIU ; Wei GUO ; Hailiang HUANG ; Xijian LIU ; Tao HAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):10-19
ObjectiveTo observe the effect of Banxia Xiexintang (BXT) on the proliferation of human gastric cancer HGC-27, MKN-45, and AGS cells and its mechanism. MethodCell counting kit-8 (CCK-8) was used to detect the effects of different concentrations of BXT-containing serum (5%, 10%, and 20%) on the proliferation of HGC-27, MKN-45, and AGS cells. A mitochondrial membrane potential probe (TMRE) was used to detect the expression of mitochondrial membrane potential in cells. A kit was used to detect iron ion (Fe2+) content, lipid peroxide (LPO), and superoxide dismutase (SOD) activity. Western blot was used to detect the protein expression levels of glycogen synthase3β (GSK3β), phosphorylated GSK3β (p-GSK3β), nuclear factor E2 related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4). The real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of member 11 of the cystine/glutamic acid reverse transporter solute vector family 7 (SLC7A11), member 2 of the heavy chain solute vector family 3 (SLC3A2), transferrin receptor 3 (TFRC), and tumor protein (TP)53. ResultCCK-8 results showed that BXT and capecitabine could significantly reduce the survival rate of three kinds of gastric cancer cells after treatment with drug-containing serum for 24 h (P<0.01). After 48 h of intervention with drug-containing serum, the survival rate of three kinds of gastric cancer cells was significantly decreased in both the capecitabine group and the BXT group compared with the blank group. The BXT group was dose-dependent, with 20% BXT having the most significant effect (P<0.01). In terms of biochemical indicators of ferroptosis, compared with the blank group, BXT and capecitabine significantly decreased the expression of mitochondrial membrane potential (P<0.01) and SOD activity (P<0.01) and significantly increased the contents of LPO and Fe2+ (P<0.01), so as to improve the sensitivity of gastric cancer cells to ferroptosis. In terms of the Nrf2/GPX4 pathway, compared with the blank group, the BXT group could reduce the protein expressions of p-GSK3β, Nrf2, and GPX4 (P<0.01) in gastric cancer cells and increase mRNA expressions of SLC7A11 and SLC3A2 (P<0.05). It could also increase the protein expression of GSK3β (P<0.01) and mRNA expression of TP53 and TFRC (P<0.05, P<0.01) in gastric cancer cells. Inhibition of the Nrf2/GPX4 pathway induces ferroptosis in gastric cancer cells. Compared with the capecitabine group, the 20% BXT group showed a more obvious effect. ConclusionBanxia Xiexintang can induce ferroptosis in gastric cancer cells HGC-27, MKN-45, and AGS by inhibiting the Nrf2/GPX4 pathway.
7.Bionic design,preparation and clinical translation of oral hard tissue restorative materials
Han ZHAO ; Yan WEI ; Xuehui ZHANG ; Xiaoping YANG ; Qing CAI ; Chengyun NING ; Mingming XU ; Wenwen LIU ; Ying HUANG ; Ying HE ; Yaru GUO ; Shengjie JIANG ; Yunyang BAI ; Yujia WU ; Yusi GUO ; Xiaona ZHENG ; Wenjing LI ; Xuliang DENG
Journal of Peking University(Health Sciences) 2024;56(1):4-8
Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.
8.Detection of germline variants in pancreatic cancer by next-generation sequencing and correlation analysis of clinical factors
Hui-Qin JIANG ; Li ZHANG ; Fei HUANG ; Xin-Ning CHEN ; Li YU ; Min-Na SHEN ; Bei-Li WANG ; Bai-Shen PAN ; Wei GUO
Fudan University Journal of Medical Sciences 2024;51(1):19-24
Objective To investigate the rate of germline variants in patients with pancreatic cancer and clinical characteristics related with germline variants.Methods A total of 271 patients diagnosed with pancreatic cancer were enrolled in this study.Germline variants of 21 tumor susceptibility genes were detected by next-generation sequencing,and the relationship between germline variants and clinical factors such as age of onset,family history and personal history was analyzed.Results The rate of germline P/LP variants was 6.3%in unselected pancreatic cancer patients,but was high as 17.1%in genetic high-risk group patients(those with a family or personal history of cancer,or early-onset).Genes with higher frequency of germline variants in pancreatic cancer patients were PALB2,BRCA2,and ATM.Conclusion The rate of germline variants in overall pancreatic cancer patients is not high,but it increases significantly in genetic high-risk group,proving the importance of clinical factors in the screening of hereditary pancreatic cancer.
9.The value of high-throughput sequencing data reanalysis in identifying ERBB2 amplification in colorectal cancer patients
Min-Na SHEN ; Li ZHANG ; Xin-Ning CHEN ; Fei HUANG ; Chao-Gang BAI ; Li-Meng CHEN ; Hai-Xiang PENG ; Yan ZHOU ; Bei-Li WANG ; Bai-Shen PAN ; Wei GUO
Fudan University Journal of Medical Sciences 2024;51(2):166-171
Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.
10.Prenatal diagnostic value of MRI in fetal Chiari malformation
Yan ZHUANG ; Chang-An CHEN ; He ZHANG ; Xiao-Wei HUANG ; Guo-Fu ZHANG
Fudan University Journal of Medical Sciences 2024;51(2):191-197,217
Objective To evaluate the value of magnetic resonance imaging(MRI)in prenatal diagnosis of fetal Chiari malformation.Methods The prenatal MRI findings of 27 cases of Chiari malformation confirmed by follow-up in Obstetrics and Gynecology Hospital,Fudan University from Feb 2010 to Feb 2022 were retrospectively analyzed and compared with ultrasound findings.Results Twenty-seven pregnant women,aged from 16-36 years(average 28.0 years)and 27 fetuses with gestation from 15.3-38.4 weeks(average 24.3 weeks)were studied.There were 18 cases of Chiari Ⅱ(Chiari malformation type Ⅱ,CMⅡ),3 cases of Chiari Ⅲ(CMⅢ),6 cases of Chiari Ⅳ(CMⅣ).CMⅡ and CMⅢ images showed brain herniation,descending pons,narrowing or disappearance of the posterior fossa cistern and the fourth ventricle,the subarachnoid space disappears.There were 17 cases of hydrocephalus,2 cases of cerebrospinal fluid loss,17 cases of"lemon head"and"banana cerebellar"signs,4 cases of encephalocele,15 cases of spinal bifida,3 cases of lower spinal cord and 2 cases of spinal cavity,4 cases of spinal angular deformity and 6 cases of other malformations.In CMⅣ,there were 2 cases of undeveloped cerebellum and 4 cases of cerebellum and brainstem dysplasia,hydrocephalus in 5 cases,posterior fossa cistern widening in 4 cases,and other malformations in 4 cases.MRI showed the posterior fossa structure and spinal cord more clearly than ultrasound,and could find lesions not detected by ultrasound.Conclusion Prenatal MRI can be used as a complementary examination of ultrasound,which can improve the accuracy of diagnosis of Chiari malformation,reduce the rate of missed diagnosis,and clarify the classification of Chiari malformation.


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