1.Screening and quantitative analysis of Q-Marker for anti-renal fibrosis of Shenqi shenshuai mixture based on untargeted metabolomics and bioinformatics
Yuhang ZHOU ; Yuqi LI ; Zhuo GAO ; Qingfeng RUAN ; Xiaoxuan ZENG ; Hui WANG ; Chuanqi HUANG ; Hongfeng XU
China Pharmacy 2026;37(13):1716-1721
OBJECTIVE To screen and quantitatively analyze the quality marker (Q-Marker) associated with anti-renal fibrosis in Shenqi shenshuai mixture (SQSS), so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology, gene expression omnibus (GEO) and connectivity map (CMAP) databases, the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics,and 84 active ingredients with anti-renal fibrosis activity were further screened out, such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database, including berberine, quercetin, honokiol, nicotinamide, daidzein, coumarin, kaempferol, formononetin and amygdalin. The quantitative results showed that the average contents of the above components (excluding amygdalin) in 10 batches of SQSS were 2.523, 1.942, 26.848, 1.415, 0.692, 0.171, 0.374, 7.401 μg/mL, respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study, and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.
2.Screening and quantitative analysis of Q-Marker for anti-renal fibrosis of Shenqi shenshuai mixture based on untargeted metabolomics and bioinformatics
Yuhang ZHOU ; Yuqi LI ; Zhuo GAO ; Qingfeng RUAN ; Xiaoxuan ZENG ; Hui WANG ; Chuanqi HUANG ; Hongfeng XU
China Pharmacy 2026;37(13):1716-1721
OBJECTIVE To screen and quantitatively analyze the quality marker (Q-Marker) associated with anti-renal fibrosis in Shenqi shenshuai mixture (SQSS), so as to provide references for the analysis of pharmacodynamic substances and new drug transformation of SQSS. METHODS The chemical components of SQSS were characterized by untargeted metabolomics. Combined with network pharmacology, gene expression omnibus (GEO) and connectivity map (CMAP) databases, the anti-renal fibrosis Q-Markers of SQSS were screened. HPLC-MS/MS was applied to determine the contents of Q-Markers in 10 batches of SQSS. RESULTS A total of 1 319 compounds were identified from SQSS via untargeted metabolomics,and 84 active ingredients with anti-renal fibrosis activity were further screened out, such as formononetin. Nine anti-renal fibrosis Q-Markers were obtained by network pharmacology and GEO database, including berberine, quercetin, honokiol, nicotinamide, daidzein, coumarin, kaempferol, formononetin and amygdalin. The quantitative results showed that the average contents of the above components (excluding amygdalin) in 10 batches of SQSS were 2.523, 1.942, 26.848, 1.415, 0.692, 0.171, 0.374, 7.401 μg/mL, respectively. CONCLUSIONS Nine anti-renal fibrosis Q-Markers of SQSS were screened in this study, and the contents of eight among them were determined. The results can provide a basis for elucidating the pharmacodynamic material basis and promoting the new drug transformation of SQSS.
3.The Effect of Banxia Xiexin Decoction (半夏泻心汤) on the Expression of LXRα in Liver Tissue and the JAK2/STAT3 Signaling Pathway in Gastric Antrum Tissue of Diabetic Gastroparesis Model Rats
Qi XU ; Nuobing RUAN ; Jinju LI ; Xijuan LYU ; Zhaohui FANG
Journal of Traditional Chinese Medicine 2025;66(2):178-187
ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction (半夏泻心汤, BXD) in the treatment of diabetic gastroparesis (DGP). MethodsA total of 29 SD rats were randomly divided into four groups, blank group (5 rats) and model group, BXD group and metformin group (8 rats in each group). Except for the blank group, rats were administered intraperitoneally with 1% streptozotocin (STZ) solution and were fed a high-sugar, high-fat diet to establish the DGP rat model. After successful modeling, the BXD group was treated with BXD at 6.68 g/(kg·d) by gavage, the metformin group was treated with metformin hydrochloride at 105 mg/(kg·d) by gavage, and the blank group and the model group were treated with normal saline at 6.68 ml/(kg·d) by gavage, for 8 weeks. After the last administration, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG) were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin (MTL) and gastrin (GAS), as well as inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin (HE) staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α (LXRα) levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue, and of janus kinase 2 (JAK2), phospho-janus kinase 2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3) and phospho-signal transducer and activator of transcription 3 (p-STAT3) in gastric antrum tissue. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of LXRα in liver tissue and JAK2, STAT3 in gastric antrum tissue. ResultsCompared with the blank group, the model group showed significant hepatic fatty degeneration, gastric antrum tissue structure destruction, and increases in FBG, HbA1c, TC, and TG levels; the average fluorescence intensity, protein level, and mRNA expression of LXRα in liver tissue were reduced; the gastric emptying rate and gastric tissue GAS and MTL levels decreased; inflammatory factors including TNF-α, IL-6, IL-1β in gastric tissue increased, IL-10 decreased; in gastric antrum tissue, the mRNA expression of p-JAK2/JAK2, p-STAT3/STAT3, and JAK2 and STAT3 increased (P<0.01). Compared with the model group, both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology; FBG, HbA1c, TC, and TG levels decreased, while LXRα fluorescence intensity, protein level, and mRNA expression in liver tissue significantly increased; the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher; the levels of TNF-α, IL-6, and IL-1β decreased, whereas IL-10 levels increased, p-JAK2/JAK2, p-STAT3/STAT3, and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased (P<0.05 or P<0.01). The BXD group showed higher level than the metformin group in FBG, HbA1c, and TG levels, lower level in gastric emptying rate and gastric tissue GAS content, and higher level in gastric tissue TNF-α, IL-6, IL-1β levels; there was also a decrease in IL-10 levels, and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue, as well as in p-JAK2/JAK2 levels in gastric antrum tissue (P<0.05 or P<0.01). ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.
4.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
5.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
6.Diagnostic value of mediastinal lymph nodes CT imaging features in pulmonary sarcoidosis
Yuehong LI ; Ting RUAN ; Kun WEN ; Ying CHEN ; Yantian LYU ; Minghua JIN ; Li XU ; Guopeng XU
Chongqing Medicine 2025;54(1):168-171
Objective To explore the diagnostic value of mediastinal lymph nodes CT image features in pulmonary sarcoidosis.Methods The imageologic data of the patients with pulmonary sarcoidosis(pulmonary sarcoidosis group)and lung cancer complicating mediastinal lymph node metastasis(lung cancer group)con-firmed by EBUS-TBNA in this hospital from June 2015 to November 2023 were analyzed retrospectively.The chest plain scan CT and enhanced scan CT were performed in all cases,and the imaging characteristics were compared between the two groups.The receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated.The diagnostic value of CT imaging characteristics in pulmonary sar-coidosis was analyzed.Results The proportion of female patients in the lung sarcoidosis group was signifi-cantly higher than that in the lung cancer group,while the age was smaller than that in the lung cancer group,and the differences were statistically significant(P<0.05).The number of mediastinal lymph nodes,location,short diameter and CT enhancement value in the pulmonary sarcoidosis group had statistical difference(P<0.05).The ROC curve analysis showed that AUC of lymph node short diameter reciprocal,CT enhancement value and position in detection alone were 0.586,0.785 and 0.505 respectively,and AUC of the three combined reciprocal was the highest(0.789).Conclusion The lymph node short diameter,CT enhancement value and po-sition have certain value in clinical diagnosis of pulmonary sarcoidosis and the 3-indicator combination could increase the diagnostic efficiency of pulmonary sarcoidosis.
7.Preliminary application of MRI image fusion technology in guiding percutaneous balloon compression for trigeminal neuralgia
Tao AN ; Weiguo XU ; Kaihua WU ; Yong WANG ; Jianwen HUANG ; Changchun LIAO ; Kaijun LI ; Na RUAN
Journal of Interventional Radiology 2025;34(10):1099-1104
Objective To discuss the technical advantages of MRI image fusion technology in guiding percutaneous balloon compression(PBC)for trigeminal neuralgia(TN).Methods The clinical data of 13 patients with TN,who received MRI image fusion technology-guided PBC from November 2022 to July 2023,were retrospectively analyzed.The MRI images of the trigeminal nerve obtained one week before surgery were fused with the intraoperative DynaCT images of the skull base so as to simultaneously display the Meckel s cave and foramen ovale,and under the 3-D view the optimal puncture path was determined.The needle was positioned at the entry point of the skin,than the skin was cut open with a sharp surgical blade and the needle was inserted to the foramen ovale area to a predetermined depth.Lateral skull base fluoroscopy and DynaCT scan were used to check that the puncture needle tip was placed into the foramen ovale.Than the puncture needle was replaced by a fine guiding-needle and it was pushed into the Meckel's cave.Under the dual guidance of lateral fluoroscopy and fusion image,the balloon was push forward and was filled with iodine contrast media to compress the trigeminal ganglion within the Meckel's cave.After completion of the treatment,the balloon and puncture needle were removed and manual oppression was applied on the face to achieve hemostasis.Results Immediately after PBC,the pain was relieved in all patients.No permanent or serious complications occurred.One patient had a relapse 3 months after PBC and a second PBC procedure had to be carried out.No obvious pain recurrence was observed in the remaining patients during follow-up period.During the surgery,the mean number of foramen ovale puncturing was(1.31±0.46)times,the mean X-ray exposure time was(8.64±5.66)min,and the mean cumulative dose of X-ray was(570.29±257.15)mGy.After PBC,12 patients(92.31%)developed facial numbness and one patient(7.69%)developed facial pain,all of which were healed after treatment.Conclusion MRI image fusion technology can improve the visualization and accuracy of PBC procedure.It can also reduce the number of puncturing,decrease the radiation exposure dose,and improve the surgical ability of young doctors.Therefore,MRI image fusion technology should be further developed and applied in clinical practice.
8.Triglyceride-glucose index and homocysteine in association with the risk of stroke in middle-aged and elderly diabetic populations
Xiaolin LIU ; Jin ZHANG ; Zhitao LI ; Xiaonan WANG ; Juzhong KE ; Kang WU ; Hua QIU ; Qingping LIU ; Jiahui SONG ; Jiaojiao GAO ; Yang LIU ; Qian XU ; Yi ZHOU ; Xiaonan RUAN
Shanghai Journal of Preventive Medicine 2025;37(6):515-520
ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹
9.Diagnostic value of serum carcinoembryonic antigen-related cell adhesion molecule 6 in pancreatic cancer
Jie LI ; Liyuan LIN ; Xiang ZHENG ; Fuhai WANG ; Haoyu RUAN ; Jian XU
Chinese Journal of Clinical Laboratory Science 2025;43(5):351-355
Objective To investigate the diagnostic value of serum carcinoembryonic antigen-related cell adhesion molecule 6(CEACAM6)in pancreatic cancer.Methods A total of 188 patients admitted to the Pancreas Center of the First Affiliated Hospital of Nanjing Medical University from May to December 2024 were consecutively enrolled,including 112 patients in the pancreatic cancer group and 76 patients in the benign pancreatic disease group(43 with pancreatitis and 33 with benign pancreatic tumors).Additional-ly,76 healthy individuals were included in the health control group.Serum CEACAM6 and carbohydrate antigen 19-9(CA19-9)levels were detected by ELISA and chemiluminescence immunoassay(CLIA),respectively.The receiver operating characteristic(ROC)curve was drawn to evaluate the diagnostic efficacy of serum CEACAM6 for pancreatic cancer.The positive rate of serum CEACAM6 in CA19-9-negative pancreatic cancer patients was also investigated.Results The levels of serum CEACAM6 in the pancreatic cancer group(20.3[11.1,34.0]ng/mL)were significantly higher than those in the benign pancreatic disease group(6.2[2.6,10.5]ng/mL,Z=64.1,P<0.001)and healthy control group(0.8[0.4,4.4]ng/mL,Z=131.6,P<0.001).The areas under the ROC curve(AUCROC),sensitivity,and specificity of CEACAM6 and CA19-9 in the diagnosis of pancreatic cancer were 0.889(95%CI:0.854-0.924)and 0.819(95%CI:0.761-0.863),81.3%and 65.2%,and 84.9%and 86.2%,respectively.The AUCROC,sensitivity,and specificity of the combined detection of the two reached 0.916(95%CI:0.875-0.946),91.1%,and 82.2%,respectively,which were better than any single indicator(P<0.05).In addition,the positive rate of serum CEACAM6 in CA19-9-negative pancreatic canc-er patients was 83.3%,significantly higher than CEA and CA125(P<0.01).Conclusion The detection of serum CEACAM6 is help-ful to the diagnosis of pancreatic cancer,and its combination with serum CA19-9 can improve the diagnostic efficacy of pancreatic cancer.
10.Application research of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early gastric cancer
Zhi ZHENG ; Zimeng WANG ; Rui XU ; Haiqiao ZHANG ; Zheng ZHANG ; Guotian RUAN ; Jie YIN ; Xiaoye LIU ; Jun CAI ; Guangyong CHEN ; Xiujing SUN ; Shengtao ZHU ; Peng LI ; Jun ZHANG ; Shutian ZHANG
Chinese Journal of Surgery 2025;63(7):587-596
Objective:To evaluate the short-term efficacy of endoscopic-laparoscopic regional gastric resection combined with sentinel lymph node basin dissection in patients with early-stage gastric cancer.Methods:This is a retrospective case series study. Data of 17 consecutive early gastric cancer patients from a prospective cohort at Beijing Friendship Hospital,Capital Medical University were analyzed between August 2023 and August 2024. Sixteen cases were from the department of general surgery and 1 from the department of gastroenterology. The cohort included 9 males and 8 females,with a mean age of 61.4 years (range: 46 to 79 years). Clinical data,including demographics,pathological features,surgical procedures,and follow-up outcomes,were collected through medical records and databases. All patients were followed for over 3 months,with follow-up ending on December 5,2024.Results:A total of 17 patients were involved. Among them, 5 patients underwent endoscopic submucosal dissection (ESD) combined with laparoscopic sentinel lymph node dissection (LSBD),and another 3 patients who underwent complete ESD resection received LSBD due to pathological stage meeting the expanded indications. 6 patients who underwent non-curative ESD resection received laparoscopic gastric regional resection (LRG) combined with LSBD,and another 3 patients directly received LRG combined with LSBD. The average number of sentinel lymph nodes dissected before surgery ( M(IQR)) was 8.9 (4.5) (range: 4 to 21),and the detection rate and accuracy rate were both 100%. Postoperative pathology confirmed that there was no metastasis in the sentinel lymph nodes of 5 patients who underwent ESD combined with LSBD and 3 patients who underwent LSBD after complete ESD resection. The vertical and horizontal margins of ESD were all negative. One patient was an absolute indication for ESD. For the 6 patients who underwent non-curative ESD resection combined with LRG and LSBD,the horizontal margins were all negative. Two patients showed 1 metastasis in each of the 21 and 9 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed during the operation. Postoperatively,73 and 39 lymph nodes were retrieved respectively. The former had 1 additional metastasis,while the latter had no metastasis. Among the 3 patients who underwent direct LRG combined with LSBD,the horizontal margins were negative. One patient was confirmed as an absolute indication for ESD by postoperative pathology,and one patient had 1 metastasis in 8 sentinel lymph nodes during the operation,and additional distal gastrectomy was performed. Postoperatively,there was no metastasis in 54 lymph nodes. All patients had no complications such as infection,bleeding,perforation,or death after surgery. Among the 14 patients who did not receive additional radical surgery,they were able to pass gas and defecate within 3 days after surgery,with an average hospital stay of 6 days. The nutritional indicators and gastric radionuclide emptying imaging half-emptying time were similar to those before surgery at 3 months after surgery. Conclusions:Laparoscopic and endoscopic cooperative regional gastrectomy with sentinel lymph node basin dissection has the advantages of minimal invasiveness,preservation of gastric function,and precise treatment. It maybe suitable for patients with early-stage gastric cancer at high risk of lymph node metastasis and has good short-term efficacy.

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