1.Protective effect of the active component DMDD from Averrhoa carambola root on myocardial injury in diabetic mice and its correlation with the NCOA4/FTH1/ATG8 axis
Yongxin CHEN ; Yuxuan LI ; Kailei GU ; Jiajun YOU ; Xiaohan SUN ; Jing MA ; Yanping ZHOU ; Xiaojie WEI
China Pharmacy 2026;37(9):1141-1147
OBJECTIVE To investigate the protective effect of 2-dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione (DMDD), an active component from Averrhoa carambola root, on myocardial injury in diabetic mice based on the nuclear receptor coactivator 4/ferritin heavy chain 1/autophagy-related protein 8 (NCOA4/FTH1/ATG8) axis. METHODS The successfully modeled diabetic mice were randomly divided into model group and DMDD low-, medium-, and high-dose (12.5, 25, 50 mg/kg) groups, while an additional non-modeled control group was established, with 6 mice in each group. Each group received the corresponding drug solution or an equal volume of normal saline intragastically once daily for 21 consecutive days. After the administration, the levels of fasting blood glucose (FBG), serum lactate dehydrogenase (LDH), and creatine kinase isoenzyme MB (CK-MB) were measured. Myocardial pathological changes, degree of fibrosis, and myocardial cell ultrastructure were observed. Myocardial cell death index and NCOA4 protein positive index were detected. The protein expression levels of NCOA4, FTH1, ATG8, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in cardiac tissue were measured. RESULTS Compared with model group, each DMDD group showed significant alleviation of cardiac pathological injury and varying degrees of improvement in the myocardial cell ultrastructure. The FBG and serum LDH and CK-MB levels, the myocardial cell death index and NCOA4 protein positive index,the protein expression levels of NCOA4, FTH1, and ATG8 in cardiac tissue were significantly decreased ( P <0.001), while the protein expression levels of SLC7A11 and GPX4 were significantly increased ( P <0.001). CONCLUSIONS DMDD can reduce blood glucose levels, alleviate myocardial histopathological injury, and inhibit cell death in diabetic mice. The mechanism is associated with inhibiting excessive activation of the NCOA4/FTH1/ATG8 axis and reducing ferritinophagy.
2.Network meta-analysis of pneumonitis and interstitial lung disease associated with antibody-drug conjugates in the treatment of breast cancer
Xiaohan WANG ; Wei CHEN ; Fang YANG ; Keming CAO ; Jingxin WANG ; Wenxin XUE
China Pharmacy 2026;37(10):1370-1375
OBJECTIVE To compare the risk of pneumonitis and interstitial lung disease (ILD) associated with different antibody-drug conjugates (ADC) in the treatment of breast cancer. METHODS CNKI, VIP, PubMed, Embase and other Chinese and English databases, and ClinicalTrials.gov were searched from the inception to June 15, 2025. Randomized controlled trials (RCT) about pneumonitis and ILD associated with ADC (T-DM1, T-DXd, SG, Dato-DXd, SHR-A1811,ARX788, and T-Duo) in the treatment of breast cancer were included. After literature screening, data extraction, and quality assessment, a network meta-analysis was conducted using Stata 17.0 software, and the surface under the cumulative ranking curve(SUCRA) of all interventions were ranked. RESULTS A total of 19 RCTs involving 10 556 patients were included. The overall incidence of pneumonitis with ARX788 and T-DXd was significantly higher than that with T-DM1, T-DM1 plus TPC(T-DM1combined with pertuzumab or atezolizumab), TPC(treatment of primary care), and SG ( P <0.05), for grade 1-2 pneumonitis, ARX788 and T-DXd showed significantly higher incidence than T-DM1, T-DM1 plus TPC, and TPC ( P <0.05). For both indicators, ARX788 and T-Duo were ranked as the top two by SUCRA. For the incidence of grade ≥3 pneumonitis, T-DXd and T-DM1 were significantly higher than SG ( P <0.05), T-Duo and Dato-DXd were ranked as the top two by SUCRA. For overall incidence of ILD, ARX788 was significantly higher than T-DM1, SHR-A1811, TPC, and SG ( P <0.05), for the incidence of grade 1-2 ILD, ARX788 was significantly higher than T-DM1, SHR-A1811, and TPC ( P <0.05), for the incidence of grade ≥3 ILD, ARX788 was significantly higher than TPC ( P <0.05). For three indicators above, ARX788 and T-DXd combined with pertuzumab were ranked as the top two by SUCRA. CONCLUSIONS Compared with other ADCs, ARX788 and T-Duo are associated with a higher risk of pneumonitis and ILD in patients with breast cancer.
3.Discussion on processing time for Polygonatum kingianum based on analysis of correlation between sugar components and color changes
GUO Hong ; YAO Rui ; LI Zhe ; FAN Jing ; WANG Ying ; GUO Xiaohan ; CHEN Jia ; DUAN Baozhong ; YANG Jianbo ; JING Wenguang ; CHENG Xianlong ; WEI Feng
Drug Standards of China 2026;27(1):0083-0091
Objective: To investigate the correlation between color parameters (L*, a*, b*, Eab*) and the contents of reducing sugars, total polysaccharides, total oligosaccharides, as well as four saccharides (fructose, glucose, sucrose, and kestose) during the nine cycles of steaming and sun-drying processing of Polygonatum kingianum, and to preliminarily explore the optimal processing duration.
Methods: The color changes were objectively evaluated using a colorimeter. The anthrone-sulfuric acid method was employed to determine total polysaccharides and oligosaccharides. The 3,5-dinitrosalicylic acid (DNS) colorimetric method was used to measure total reducing sugar content. High-performance liquid chromatography coupled with charged aerosol detection (HPLC-CAD) was applied for quantitative analysis of fructose, glucose, sucrose, and kestose. Multivariate statistical analysis was conducted to assess samples from different processing stages.
Results: Significant variations in color and component contents were observed across processing stages. The herbal pieces progressively darkened with increased processing cycles: brightness (L*) and total color difference (Eab*) initially decreased then stabilized, while a* (red-green) and b* (yellow-blue) values first increased then declined. Total polysaccharides and oligosaccharides showed overall decreasing trends, whereas reducing sugars initially increased before stabilizing. Fructose and glucose levels rose continuously, while sucrose and kestose decreased progressively, becoming undetectable after five cycles.
Conclusion: The chromatic alteration and saccharide composition of P. kingianum showed significant correlation with processing duration. Both total color difference (Eab*) and reducing sugar content stabilized after four processing cycles (12 hours), suggesting that four cycles of steaming and sun-drying may represent the optimal processing duration.
4.Analytical research on processing techniques of Polygoni Multiflori Radix Praeparata based on chemical composition and color changes correlation
YAO Rui ; GUO Hong ; LI Zhe ; GUO Xiaohan ; ZHANG Xiaoshu ; DUAN Baozhong ; YANG Jianbo ; CHEN Jia ; JING Wenguang ; CHENG Xianlong ; WEI Feng
Drug Standards of China 2026;27(1):0100-0108
Objective: To investigate the correlation between the color parameters (L*, a*, b*, Eab* values) of Polygoni Multiflori Radix Praeparata powder prepared by different processing techniques and the contents of 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucopyranoside, emodin, physcion, emodin-8-O-β-D-glucopyranoside, physcion-8-O-β-D-glucopyranoside.
Methods: The L*, a*, b* and Eab* values of Polygoni Multiflori Radix Praeparata powder prepared by different processing techniques were determined by spectrophotometer, and the contents of the five components were determined by high performance liquid chromatography. Secondly, SPSS 26.0 software and Simca 14.1 software were used to analyze the correlation.
Results: Through the hierarchical cluster analysis (HCA), it was found that the steamed samples and black bean steamed samples could be obviously divided into two categories: raw products and processed products. The processed products could be further divided into 2-8 h and 12-48 h. Pearson correlation analysis showed that the content of stilbene glycoside was significantly positively correlated with L*, a* and b* values (P<0.01). The a* value was significantly positively correlated with the content of emodin and physcion (P<0.01). Emodin-8-O-β-D-glucoside was positively correlated with L* value and b* value, while physcion-8-O-β-D-glucoside was negatively correlated with a* value. Partial least squares discriminant analysis (PLS) showed that 2,3,5,4’-tetrahydroxystilbene-2-O-β-D-glucoside (VIP=1.69) and emodin-8-O-β-D-glucoside (VIP=1.06) were the key variables affecting chromaticity characteristics (P<0.01).
Conclusion: The three processes of steaming, black bean steaming and black bean stewing are consistent in composition transformation and chromaticity variation, and stilbene glycoside can be used as a specific index component to characterize the processed color. Chromatic parameters can effectively reflect the processing progression and serve as quality monitoring indicators during production.
5.Effects of Bushen Huoxue Formulation (补肾活血方) on Synaptic Vesicle-Associated Proteins in Neurons and the Intestinal Barrier in Parkinson's Disease Model Rats
Naxin WEI ; Yingfan CHEN ; Xiaorong QI ; Qian ZHANG ; Xiaohan GENG ; Yuzhi ZHANG ; Min LI
Journal of Traditional Chinese Medicine 2026;67(15):1640-1649
ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation (补肾活血方, BSHXF) in Parkinson's disease (PD) from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups, control group, model group, Madopar group, and BSHXF group, with 12 rats in each group. Except for the control group, rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling, rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/(kg·d), while rats in the Madopar group received Madopar tablet suspension at 2 g/(kg·d). Rats in the control group and the model group were administered distilled water by gavage at 10 ml/(kg·d). All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test (total distance traveled, average speed, and total distance traveled in the central zone), rotarod test (latency to fall), and balance beam test (traversal time). Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein (α-syn), phosphorylated serine 129 α-synuclein (pSer129-α-syn), vesicle-associated membrane protein 2 (VAMP2), and synaptophysin (SYP) in the substantia nigra and colon tissues. The mRNA expression levels of α-syn, VAMP2, and SYP were detected by RT-PCR, and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 (ZO-1) and occludin in colon tissues, as well as tyrosine hydroxylase (TH) levels in substantia nigra tissues. ResultsCompared with the control group, rats in the model group showed reduced total distance traveled, average speed, and central-zone distance in the open field test, decreased latency to fall in the rotarod test, and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn, as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues, whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased, while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased (P<0.05). HE staining showed focal necrosis in the mucosal layer of colon tissues, disappearance of some intestinal glands, extensive inflammatory cell infiltration, and proliferation of fibrous connective tissue in the submucosa. Compared with the model group, both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators (P<0.05). Pathological damage in colon tissues was also alleviated, with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group, rats in the BSHXF group exhibited increased average speed, central-zone distance, and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased, while VAMP2 protein expression was increased. In colon tissues, SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased (P<0.05). ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling, restoring intestinal barrier integrity, and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.
6.Effects of Bushen Huoxue Formulation (补肾活血方) on Synaptic Vesicle-Associated Proteins in Neurons and the Intestinal Barrier in Parkinson's Disease Model Rats
Naxin WEI ; Yingfan CHEN ; Xiaorong QI ; Qian ZHANG ; Xiaohan GENG ; Yuzhi ZHANG ; Min LI
Journal of Traditional Chinese Medicine 2026;67(15):1640-1649
ObjectiveTo investigate the potential mechanisms underlying the therapeutic effects of Bushen Huoxue Formulation (补肾活血方, BSHXF) in Parkinson's disease (PD) from the perspectives of synaptic vesicle cycling and intestinal barrier function. MethodsForty-eight male SD rats were randomly divided into four groups, control group, model group, Madopar group, and BSHXF group, with 12 rats in each group. Except for the control group, rats were administered rotenone by gavage once daily for 4 consecutive weeks to establish a PD rat model. After successful modeling, rats in the BSHXF group received concentrated BSHXF solution by gavage at a dose of 13.5 g/(kg·d), while rats in the Madopar group received Madopar tablet suspension at 2 g/(kg·d). Rats in the control group and the model group were administered distilled water by gavage at 10 ml/(kg·d). All groups received continuous gavage treatment for 2 weeks. Motor function was evaluated using the open field test (total distance traveled, average speed, and total distance traveled in the central zone), rotarod test (latency to fall), and balance beam test (traversal time). Histopathological changes in colon tissues were observed by HE staining. Western Blotting was used to detect the protein levels of α-synuclein (α-syn), phosphorylated serine 129 α-synuclein (pSer129-α-syn), vesicle-associated membrane protein 2 (VAMP2), and synaptophysin (SYP) in the substantia nigra and colon tissues. The mRNA expression levels of α-syn, VAMP2, and SYP were detected by RT-PCR, and α-syn expression was examined by immunohistochemistry. Immunofluorescence staining was performed to assess the levels of tight junction protein 1 (ZO-1) and occludin in colon tissues, as well as tyrosine hydroxylase (TH) levels in substantia nigra tissues. ResultsCompared with the control group, rats in the model group showed reduced total distance traveled, average speed, and central-zone distance in the open field test, decreased latency to fall in the rotarod test, and prolonged traversal time in the balance beam test. The protein levels of pSer129-α-syn and α-syn, as well as α-syn mRNA expression were increased in the substantia nigra and colon tissues, whereas the protein and mRNA expression levels of VAMP2 and SYP were decreased. The relative integrated optical density of α-syn in the substantia nigra and colon tissues was increased, while the relative fluorescence intensities of ZO-1 and occludin in colon tissues and TH in the substantia nigra were decreased (P<0.05). HE staining showed focal necrosis in the mucosal layer of colon tissues, disappearance of some intestinal glands, extensive inflammatory cell infiltration, and proliferation of fibrous connective tissue in the submucosa. Compared with the model group, both the Madopar group and BSHXF group showed varying degrees of improvement in the above indicators (P<0.05). Pathological damage in colon tissues was also alleviated, with only mild fibrous tissue proliferation and limited diffuse inflammatory cell infiltration observed in the mucosal layer. Compared with the Madopar group, rats in the BSHXF group exhibited increased average speed, central-zone distance, and latency to fall in the rotarod test. The levels of pSer129-α-syn and α-syn proteins in the substantia nigra were decreased, while VAMP2 protein expression was increased. In colon tissues, SYP protein levels and mRNA expression were elevated. The relative fluorescence intensity of ZO-1 in colon tissues and TH in substantia nigra tissues was also increased (P<0.05). ConclusionBSHXF may improve motor dysfunction in PD by regulating synaptic vesicle cycling, restoring intestinal barrier integrity, and improving neuronal synaptic function through modulation of synaptic vesicle-associated protein expression in the substantia nigra and colon tissues.
7.Analysis of Differential Compounds of Poria cocos Medicinal Materials by Integrated Qualitative Strategy Based on UPLC-Q-Orbitrap-MS
Jiayuan WANG ; Xiaohan FAN ; Xiaoxiao WEI ; Rong CAO ; Jin WANG ; Lei WANG ; Fengqing XU ; Shunwang HUANG ; Deling WU ; Hongsu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):148-156
ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Orbitrap-MS), combined with mass defect filtering(MDF) and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials, with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component, global natural product social molecular network(GNPS) was established, and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection(VIP) value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison, 8 compounds were newly identified by MDF, 28 compounds were newly identified by GNPS, and a total of 102 chemical compounds were identified, including 43 triterpenoids, 16 saccharides, 26 amino acids and peptides, 3 nucleosides, and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen, amino acids and peptides were the most abundant in Poria and cultivated Fushen, carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen, type Ⅲ triterpenoids were more abundant in Poriae Cutis, all four types of triterpenoids were higher in Fushenmu, and type Ⅰ, Ⅱ, and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened, including serine, guanosine, gallic acid, 2-octenal, maltotriose, trametenolic acid, dehydroeburicoic acid, dehydrotrametenolic acid, poricoic acid A, poricoic acid B, poricoic acid E and G, but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials, the types of constituents are generally similar, but their relative contents differed significantly among these medicinal materials, especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS, MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.
8.Analysis of Differential Compounds of Poria cocos Medicinal Materials by Integrated Qualitative Strategy Based on UPLC-Q-Orbitrap-MS
Jiayuan WANG ; Xiaohan FAN ; Xiaoxiao WEI ; Rong CAO ; Jin WANG ; Lei WANG ; Fengqing XU ; Shunwang HUANG ; Deling WU ; Hongsu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):148-156
ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Orbitrap-MS), combined with mass defect filtering(MDF) and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials, with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component, global natural product social molecular network(GNPS) was established, and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection(VIP) value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison, 8 compounds were newly identified by MDF, 28 compounds were newly identified by GNPS, and a total of 102 chemical compounds were identified, including 43 triterpenoids, 16 saccharides, 26 amino acids and peptides, 3 nucleosides, and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen, amino acids and peptides were the most abundant in Poria and cultivated Fushen, carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen, type Ⅲ triterpenoids were more abundant in Poriae Cutis, all four types of triterpenoids were higher in Fushenmu, and type Ⅰ, Ⅱ, and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened, including serine, guanosine, gallic acid, 2-octenal, maltotriose, trametenolic acid, dehydroeburicoic acid, dehydrotrametenolic acid, poricoic acid A, poricoic acid B, poricoic acid E and G, but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials, the types of constituents are generally similar, but their relative contents differed significantly among these medicinal materials, especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS, MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.
9.Effects of macrophage migration inhibitory factor on survival,proliferation,and differentiation of human embryonic stem cells
Ting HUANG ; Xiaohan ZHENG ; Yuanji ZHONG ; Yanzhao WEI ; Xufang WEI ; Xudong CAO ; Xiaoli FENG ; Zhenqiang ZHAO
Chinese Journal of Tissue Engineering Research 2025;29(7):1380-1387
BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.
10.Clinical efficacy of extended abdominal wall resection combined with reconstruction for abdo-minal wall aggressive fibromatosis
Zhen REN ; Lisheng WU ; Wenxiu HAN ; Bo HAO ; Xiaohan WEI ; Hu LIU ; Shuhan WANG ; Chen PAN ; Pengfei JI ; Baichuan ZHOU
Chinese Journal of Digestive Surgery 2025;24(9):1186-1190
Objective:To investigate the clinical efficacy of extended abdominal wall resec-tion combined with reconstruction for abdominal wall aggressive fibromatosis (AF).Methods:The retrospective and descriptive study was conducted. The clinical data of 70 patients with abdominal wall AF who were admitted to 3 medical centers, including The First Affiliated Hospital of the University of Science and Technology of China, between January 2009 and July 2024 were collected. There were 6 males and 64 females, aged (36±13)years. All patients underwent extended abdominal wall resection combined with abdominal wall reconstruction. Observation indicators: (1) surgical situations; (2) tumor recurrence and postoperative complications. Comparisons of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1)Surgical situations. All 70 patients underwent extended abdominal wall resection combined with abdominal wall recons-truction. The operation time was 90(91)minutes and duration of postoperative hospital stay was 10(6)days. Of the 70 patients, 41 patients underwent abdominal wall AF resection plus polypropylene mesh abdominal wall reconstruction, with a defect area of 60(54)cm2. The mesh placement method was uniformly Sublay repair. The remaining 29 patients underwent abdominal wall AF resection plus direct suture repair, with a defect area of 34(31)cm2. There was a significant difference in the abdominal wall defect area between the two groups ( U=291.00, P<0.05). All 70 patients achieved R 0 resection. The distance from surgical margin to tumor edge was 2-3 cm in 39 cases and >3 cm in 31 cases. (2) Tumor recurrence and postoperative complications. All 70 patients were followed up for 78(90)months. During follow-up, 10 patients developed tumor recurrence (5 cases with mesh reinforced abdominal wall reconstruction and 5 cases with direct suture repair). Among them, one case was monitored, one case underwent radiotherapy, and neither received further surgical treatment. The remaining 8 patients underwent repeat R 0 resection, and no further recurrence occurred. There was no significant difference in recurrence rate between the patients with mesh reconstruction and patients with direct suture repair ( χ2=0.06, P>0.05). The postoperative recurrence rate was 9.7%(3/31) in patients with the distance from surgical margin to tumor edge >3 cm, versus 17.9%(7/39) in patients with the distance from surgical margin to tumor edge of 2-3 cm, showing no significant difference between them ( χ2=0.97, P>0.05). Sixty patients had no tumor recurrence. During follow-up, none of the 70 patients developed incisional hernia. Two patients experienced postoperative wound infection, and 6 cases developed postoperative chronic pain. Conclusion:Extended abdominal wall resection combined with reconstruction is safe and feasible for abdominal wall AF.

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