1.Efficacy Mechanism of Xianlian Jiedu Prescription Against Colorectal Cancer Recurrence vias Regulating Angiogenesis
Yanru XU ; Lihuiping TAO ; Jingyang QIAN ; Weixing SHEN ; Jiani TAN ; Chengtao YU ; Minmin FAN ; Changliang XU ; Yueyang LAI ; Liu LI ; Dongdong SUN ; Haibo CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):79-87
ObjectiveTo explore effect of Xianlian Jiedu prescription on the recurrence of colorectal cancer (CRC) and investigate the related mechanisms. MethodsA postoperative recurrence model was established in 25 Balb/c mice by injecting CT26 cells subcutaneously into the armpit, followed by surgical removal of 99% of the subcutaneous tumor. The mice were randomly divided into model group, low-dose Xianlian Jiedu prescription (XLJDP-L) group (6.45 g·kg-1·d-1), medium-dose Xianlian Jiedu prescription (XLJDP-M) group (12.9 g·kg-1·d-1), high-dose Xianlian Jiedu prescription (XLJDP-H) group (25.8 g·kg-1·d-1), and 5-fluorouracil (5-FU) group (1×10-3 g·kg-1·d-1). The mice were euthanized after 14 days of continuous intervention, and recurrent tumor tissue was harvested. Hematoxylin and eosin (HE) staining was used to observe pathological and morphological changes in the recurrent tumor tissue. Immunohistochemistry (IHC) was employed to assess the expression of proliferating cell nuclear antigen (Ki67), vascular endothelial growth factor (VEGF), and platelet-endothelial cell adhesion molecule (CD31) in recurrent tumor tissue. The Western blot was used to detect the protein expression levels of angiopoietin-2 (ANG-2), VEGF, phosphorylated-protein kinase B (p-Akt), protein kinase B (Akt), phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), and phosphatidylinositol 3-kinase (PI3K) in recurrent tumor tissue. ResultsBefore treatment, there were no statistical differences in tumor volume, tumor weight, and body mass among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group, indicating model stability. After treatment, compared with those in the model group, the tumor volume and tumor weight in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01), showing dose dependency. Meanwhile, there were no significant differences in body weight among the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group compared to the model group. HE staining showed that compared with that in the model group, tumor tissue in the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group had loosely arranged cells, increased intercellular spaces, small and shriveled nuclei, light staining, fewer mitotic figures and atypical nuclei, and increased necrotic areas. IHC showed that compared with those of the model group, the positive rates of Ki67, VEGF, and CD31 in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly reduced (P<0.01) in a dose-dependent manner. Western blot results showed that compared with those of the model group, the protein expression levels of ANG-2 and VEGF in the recurrent tumor tissue of the XLJDP-L, XLJDP-M, and XLJDP-H groups and the 5-FU group were significantly downregulated (P<0.05, P<0.01), and the p-Akt/Akt and p-PI3K/PI3K ratios were significantly decreased in a dose-dependent manner (P<0.05, P<0.01). ConclusionXianlian Jiedu prescription significantly inhibits the recurrence of CRC in mice after subcutaneous tumor surgery. The mechanism may involve regulating the PI3K/Akt pathway and downregulating key angiogenic proteins such as ANG-2, VEGF, and CD31.
2.Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants
Sha ZHU ; Jing XU ; Ranran SHI ; Xiaokang WANG ; Maomao SUN ; Shina LI ; Lingling GAO ; Yuanyuan LI ; Huimin WEN ; Changliang ZHAO ; Shuai LI ; Juan JI ; Cuihong YANG ; Yonghui YU
Chinese Journal of Pediatrics 2024;62(1):29-35
Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
3.Influence of diabetes and obesity on the risk of recurrence or anal fistula in patients with perianal abscess after simple incision and drainage
Honglan SUN ; Deming YU ; Huifeng LIU ; Changliang CHEN ; Nan LI
Chinese Journal of Endocrine Surgery 2024;18(3):358-362
Objective:To explore the interaction effect of diabetes and obesity on recurrence or anal fistula in patients with perianal abscess after simple incision and drainage.Methods:The clinical data of 163 patients with perianal abscess who underwent simple incision and drainage from Jun. 2021 to Jun. 2023 were analyzed retrospectively. The incidence of recurrence or anal fistula in 6 months after surgery was calculated. Multivariate Logistic regression model was used to analyze the influencing factors of postoperative recurrence or anal fistula. The multiplicative and additive models were used to analyze the interaction effect of diabetes and obesity on the risk of postoperative recurrence or anal fistula.Results:In 6 months after simple incision and drainage, the incidence of recurrence or anal fistula was 28.22% (46/163). Univariate analysis results showed that gender, obesity, and diabetes were related to recurrence of perianal abscess or incidence of anal fistula ( P<0.05). Multivariate Logistic regression analysis results showed that obesity ( OR=2.447, 95% CI: 1.320-4.538) and diabetes ( OR=2.162, 95% CI: 1.187-3.938) were independent risk factors for postoperative recurrence or anal fistula ( P<0.05). Interaction effect analysis found that after adjusting for confounding factors, diabetes and obesity had additive interaction effect on the risk of postoperative recurrence or anal fistula. The relative excess risk due to interaction (RERI), attribution percentage (AP), and interaction effect index (S) were 1.829 (95% CI: 0.605-3.007), 0.405 (95% CI: 0.143-0.597), and 2.098 (95% CI: 1.201-3.172), respectively. There was no multiplicative interaction effect between the two ( P>0.05) . Conclusions:Diabetes and obesity are independent risk factors for recurrence or anal fistula in patients with perianal abscess after simple incision and drainage. The two may have synergistic effect on the risk of postoperative recurrence or anal fistula.
4.Construction and verification of a nomogram model for postoperative recurrence risk in patients with complex anal fistula
Deming YU ; Changliang CHEN ; Honglan SUN ; Huifeng LIU ; Guodan JIANG ; Nan LI
Chinese Journal of Endocrine Surgery 2023;17(6):686-691
Objective:To explore the influencing factors of postoperative recurrence in patients with complex anal fistula, and to construct a nomogram model to predict the risk of postoperative recurrence and verify it.Methods:Clinical data of 310 patients with complex anal fistula who underwent fistulectomy in the hospital from Aug. 2019 to Mar. 2023 were retrospectively selected and divided into modeling group (93 cases) and validation group (217 cases) in a 3∶7 ratio according to system randomization method. Hospital electronic medical record system was used to collect patient baseline data and calculate the recurrence rate of patients 6 months after surgery. According to the data of the modeling group, multivariate Logistic regression was used to analyze the influencing factors of postoperative recurrence in patients with complex anal fistula. Based on the influencing factors, a nomogram model was established to predict the risk of postoperative recurrence, and external verification was performed based on the data of the validation group.Results:The recurrence rate at 6 months after operation was 20.43% (19/93) in the modeling group and 17.51% (38/217) in the validation group. There was no significant difference in recurrence rate between the two groups ( χ2=0.370, P=0.543) . The proportion of male, smoking history, diabetes mellitus, high anal fistula and unclear position of internal orifice in the recurrence group was higher than that in the non-recurrence group, and the body mass index and course of disease were higher than those in the non-recurrence group ( P<0.05) . Based on the above seven influencing factors, a nomogram model of the risk of recurrence of complex anal fistula after surgery was established. C index of the modeling group and the validation group was 0.984 and 0.798 respectively, the calibration curve was close to the ideal curve, and the Receiver operating characteristic AUC of the nomogram prediction model was>0.70, indicating that model consistency, prediction efficiency and differentiation were good. Conclusion:The nomogram prediction model based on gender, body mass index, smoking history, diabetes mellitus, course of disease, high anal fistula and internal orifice position can effectively predict the risk of postoperative recurrence in patients with complex anal fistula.
5.Efficacy and Mechanism of Shenbai Jiedu Prescription Against Proliferation of HCT116 Cells
Dong JIANG ; Haibo CHENG ; Weixing SHEN ; Changliang XU ; Jiani TAN ; Yueyang LAI ; Dongdong SUN ; Liu LI ; Minmin FAN ; Chengtao YU ; Jun XIAO
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(13):34-41
ObjectiveTo investigate the mechanism by which Shenbai Jiedu prescription (SBJDF) inhibits the proliferation of colorectal cancer (CRC) HCT116 cells. MethodAfter 48 h treatment of HCT116 cells with SBJDF (0, 0.25, 0.5, 1, 2, 4 g·L-1), the viability of HCT116 cells were determined by methyl thiazolyl tetrazolium (MTT) colorimetry. Following the classification of cells into blank control group and SBJDF (1, 2, 4 g·L-1) groups, the effect of SBJDF on HCT116 cell morphology was observed under an inverted microscope. The effects of SBJDF on the proliferation of HCT116 cells and mitochondrial membrane potential (Δψm) were detected by colony formation assay and JC-1 probe, respectively. The flow cytometry was then performed for determining cell cycle distribution and apoptosis. The effects of SBJDF on cell cycle-, apoptosis-, and nuclear factor kappa-B (NF-κB) signaling pathway-related proteins were determined by Western blot. ResultSBJDF effectively inhibited the vitality of HCT116 cells and changed their morphology in a concentration-dependent manner. Compared with the blank control group, SBJDF at 1, 2, 4 g·L-1 significantly reduced cell colony formation (P<0.05, P<0.01),and SBJDF at 2 and 4 g·L-1 arrested the HCT116 cell cycle at G0/G1 phase (P<0.05, P<0.01). Compared with the blank control group, SBJDF at 1, 2, 4 g·L-1 remarkably down-regulated the protein expression of CyclinD1 (P<0.05, P<0.01). SBJDF at 2 and 4 g·L-1 lowered the CyclinA2 and cyclin-dependent kinase 4 (CDK4) (P<0.05, P<0.01). SBJDF at 4 g·L-1 reduced the cyclin-dependent kinase 1 (CDK1) (P<0.01). Compared with the blank control group, SBJDF at 2 and 4 g·L-1 induced HCT116 cell apoptosis, down-regulated the protein expression of anti-apoptosis-related proteins Bcl-2 and Bcl-xl as well as the NF-κB signaling pathway-related proteins IκB kinase α (IKKα),inhibitor α of NF-κB (IκBα),and phospho-NF-κB p65 (p-p65) (P<0.05, P<0.01), and diminished the mitochondrial membrane potential of HCT116 cells. ConclusionSBJDF inhibits the proliferation of HCT116 cells, which may be related to its inhibition of the activation of NF-κB signaling pathway and the induction of cell cycle arrest and apoptosis.
6.Shenbai Jiedu Prescription Inhibits Proliferation of Colorectal Cancer Cells by Regulating PTEN/PI3K/Akt Signaling Pathway
Jianrong LIU ; Min HUANG ; Minmin FAN ; Haibo CHENG ; Weixing SHEN ; Jun XIAO ; Changliang XU ; Jiani TAN ; Yueyang LAI ; Chengtao YU ; Dongdong SUN ; Liu LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(14):36-43
ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer (CRC) cells by regulating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro, and treated with different concentrations of Shenbai Jiedu prescription (2, 4, 8, 16 g·L-1). The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium (MTT). Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN, PI3K, Akt, glycogen synthase kinase-3β (GSK-3β), c-Myc, survivin and Cyclin D1. Western blot was employed to measure the protein expression levels of PTEN, phosphorylated PTEN (p-PTEN), PI3K, Akt, phosphorylated Akt (p-Akt), GSK-3β, phosphorylated GSK-3β (p-GSK-3β), c-Myc, survivin and Cyclin D1, β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group, Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner (P<0.01). Compared with the control group, the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K, Akt, c-Myc, survivin and CyclinD1 were down-regulated after treatment with Shenbai Jiedu prescription (P<0.01). The protein expression levels of PTEN, p-PTEN and GSK-3β were up-regulated whereas those of PI3K, Akt, p-Akt, GSK-3β, p-GSK-3β, c-Myc, survivin and CyclinD1 were down-regulated (P<0.05, P<0.01). Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.
7.Preliminary study on prediction of hematoma expansion in hypertensive intracerebral hemorrhage based on cranial radiomics
Chuan Ding ; Xiaohu Li ; Jun Wang ; Hongwen Li ; Yuping Wang ; Changliang Yu ; Yaqiong Ge ; Haibao Wang ; Bin Liu
Acta Universitatis Medicinalis Anhui 2022;57(1):161-164
Objective :
To study the best machine learning method for early prediction of hematoma expansion in hypertensive intracerebral hemorrhage based on head CT plain scan.
Methods :
The CT images of 130 patients with cerebral hemorrhage were retrospectively analyzed , and the texture features of the head CT plain scan were extracted. The classifier was trained by selecting the features , and the six classic machine learning methods were crossvalidated to evaluate the stability and performanceof predicting cerebral hemorrhage hematoma expansion.
Results:
The prediction performance of support vector machine (SVM⁃Radial) (AUC 0. 714 ± 0. 144 , accuracy 0. 723 ± 0. 109) , generalized linear model ( GLM) prediction performance ( AUC 0. 643 ± 0. 125 , accuracy 0. 587 ± 0. 136) , random forest (RF) prediction performance (AUC 0. 686 ± 0. 128 , accuracy 0. 680 ± 0. 130) , k ⁃nearest neighbor (kNN) prediction performance ( AUC 0. 657 ± 7C 15 , accuracy 0. 639 ± 39 performance 19) , gradient boosting tree algorithm (GBM) Prediction performance ( AUC 0. 718 ± 0. 141 , accuracy 0. 670 ± 0. 126) , neural network (NNet) prediction performance (AUC 0. 659 ± 0. 162 , accuracy 0. 680 ± 0. 130) , in which support vector machines showed high prediction performance , generalized linear model showed low predictive performance.
Conclusion
Among the six machine learning methods based on cranial CT radiomics to predict early hematoma expansion in hypertensive intracerebral hemorrhage , support vector machine (SVM⁃Radial) has the best predictive performance and has potential clinical application value.
8.Insight into chemical basis of traditional Chinese medicine based on the state-of-the-art techniques of liquid chromatography-mass spectrometry.
Yang YU ; Changliang YAO ; De-An GUO
Acta Pharmaceutica Sinica B 2021;11(6):1469-1492
Traditional Chinese medicine (TCM) has been an indispensable source of drugs for curing various human diseases. However, the inherent chemical diversity and complexity of TCM restricted the safety and efficacy of its usage. Over the past few decades, the combination of liquid chromatography with mass spectrometry has contributed greatly to the TCM qualitative analysis. And novel approaches have been continuously introduced to improve the analytical performance, including both the data acquisition methods to generate a large and informative dataset, and the data post-processing tools to extract the structure-related MS information. Furthermore, the fast-developing computer techniques and big data analytics have markedly enriched the data processing tools, bringing benefits of high efficiency and accuracy. To provide an up-to-date review of the latest techniques on the TCM qualitative analysis, multiple data-independent acquisition methods and data-dependent acquisition methods (precursor ion list, dynamic exclusion, mass tag, precursor ion scan, neutral loss scan, and multiple reaction monitoring) and post-processing techniques (mass defect filtering, diagnostic ion filtering, neutral loss filtering, mass spectral trees similarity filter, molecular networking, statistical analysis, database matching, etc.) were summarized and categorized. Applications of each technique and integrated analytical strategies were highlighted, discussion and future perspectives were proposed as well.
9.Clinical application of deep inferior epigastric perforator flap in repair of soft tissue defects of the calf
Changliang OU ; Xing ZHOU ; Xuchao LUO ; Yonggen ZOU ; Yu HUANG ; Jian WU ; Bo HUANG
Chinese Journal of Microsurgery 2018;41(4):339-342
Objective To investigate the clinical efficacy of deep inferior epigastric perforator (DIEP) flap in the repair of soft tissue defects of the calf.Methods From January,2015 to January,2017,the DIEP flap was used to repair the soft tissue defect of calf in 11 patients,which were 7 males and 4 females,aged 23-62 years,with an average age of 42 years.Among them,there were 5 cases of anterior tibial soft tissue defect and 6 cases of posterior tibial soft tissue defect.The size of soft tissue defects ranged from 9.0 cm×5.0 cm to 32.0 cm×12.0 cm.The wounds were heavily polluted and debridement exploration combined VSD surgery in emergency.After 7 to 14 days,free deep inferior epigastric perforator flap was used to repaire.The flap was cut in the range of 10.0 cm×6.0 cm-34.0 cm×13.0 cm.Nine cases of abdominal donor sutured direct,and a small part of 2 cases to take thigh thick skin graft repair.Results All the flaps survived.In only 1 patient,the distal part of the flap was necrotic and healed after appropriate treatment.Eleven patients were followed-up for 3-18 months (average of 10 months).The shape of the flap was similar to that of the affected area.The texture was soft and not bloated.Conclusion The DIEP flap can provide reliable blood supply,large cutting area and flexible design.It can be used to repair soft tissue defect of calf and obtain satisfactory clinical results.
10.Effect of Xiang-Qi-Tang on coagulation factors in mice with endotoxemia
Yuting ZHANG ; Yu MA ; Lizi YIN ; Yangping OU ; Gang YE ; Gang SHU ; Bendong FU ; Haiqing SHEN ; Changliang HE
Chinese Journal of Veterinary Science 2017;37(8):1583-1588
To study the anticoagulant effect of Xiang-Qi-Tang (XQT),the mice model of endotoxemia was established to detect the expression of coagulation factors and their regulatory proteins in serum and aorta.The results showed that XQT could decrease the expression of TF and increase the expression of tPA in the aorta of mice with endotoxemia,and also decrease the expression of sEPCR in the serum.We further found that XQT caused the decrease of sEPCR through the regulation of PKC δ and ADAM17 to contribute the anticoagulation in mice.This study may provide a new strategy for treating endotoxin-induced disease and provide evidences for further researching the pharmacological action of XQT.


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