1.Shashen Maidong Tang Enhances Efficacy of Chemotherapy in Mouse Model of Lewis Lung Cancer by Modulating JAK2/STAT3 Signaling Pathway
Lin YU ; Yaoyao WANG ; Limin LIU ; Zuowei HU ; Yanping ZHOU ; Shang WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):1-10
ObjectiveTo predict the mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer via network pharmacology and validate the prediction results in animal experiments. MethodsThe potential mechanism through which Shasheng Maidong Tang enhances the efficacy of chemotherapy for lung cancer was predicted by network pharmacology, liquid chromatography-mass spectrometry (LC-MS), and molecular docking methods. C57/BL6 mice were assigned into normal, model, cisplatin, and Shasheng Maidong Tang+cisplatin groups. In addition to the normal group, the remaining groups were injected subcutaneously with 0.2 mL of 1×107 cells·mL-1 Lewis lung cancer cells to establish the Lewis lung cancer model. The daily gavage dose of Shasheng Maidong Tang was 3.58 g·kg-1, and the concentration of cisplatin intraperitoneally injected on every other day was 2 mg·kg-1. Drugs were administered for 14 d. The changes in the tumor volume and the rate of tumor suppression were monitored, and the tumor histopathological changes were observed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay was employed to measure the interleukin (IL)-6 and interferon (IFN)-γ levels in peripheral blood. Real-time PCR was performed to quantify the mRNA levels of Janus kinase 2 (JAK2), signal transducer and activator of transcription 1 (STAT1), and signal transducer and activator of transcription 3 (STAT3) in the tumor tissue of mice. Western blot was employed to determine the protein levels of JAK2, STAT3, B-cell lymphoma-2 (Bcl-2), cysteinyl aspartate-specific proteinase-3 (Caspase-3), and Pim-1 proto1 (PIM1) in the tumor tissue. Immunohistochemistry was employed to detect the expression of Bcl-2 and PIM1 in the tumor tissue. ResultsNetwork pharmacological predictions indicated that Shasheng Maidong Tang might enhance the efficacy of chemotherapy for lung cancer by regulating nitrogen metabolism, AGE-RAGE signaling pathway, cancer pathway, and JAK/STAT signaling pathway. The experimental results demonstrated that tumor volume in the cisplatin group and Shasheng Maidong Tang+cisplatin group was reduced compared with the model group, with statistically distinct differences observed on days 14, 17, 20 post modeling (P<0.05). Notably, the Shasheng Maidong Tang+cisplatin therapy further decreased tumor volume compared with the cisplatin group, showing marked reductions on days 17 and 20 (P<0.05), consistent with trends visualized in tumor volume comparison charts. The Shasheng Maidong Tang+cisplatin group exhibited higher tumor inhibition rate than the cisplatin group (P<0.05). Histopathological analysis via HE staining revealed that the tumors in the model group displayed frequent nuclear mitosis, densely arranged cells, hyperchromatic nuclei, and no necrosis. Cisplatin treatment induced partial necrosis and vacuolization, while the Shasheng Maidong Tang+cisplatin group exhibited extensive necrotic regions, maximal vacuolization, disarranged tumor cells, and minimal mitotic activity. Compared with the model group, the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed elevated level of IFN-γ (P<0.01) and declined level of IL-6 (P<0.01) in the peripheral blood. Compared with the cisplatin group, the Shasheng Maidong Tang+cisplatin group presented elevated level of IFN-γ (P<0.01) and lowered level of IL-6 (P<0.01) in the peripheral blood. Compared with the model group, the cisplatin group and the Shasheng Maidong Tang+cisplatin groups showed down-regulated mRNA levels of JAK2 and STAT3 (P<0.01) and up-regulated mRNA level STAT1 (P<0.01). Compared with the cisplatin group, the Shasheng Maidong Tang+cisplatin group presented down-regulated mRNA levels of JAK2 and STAT3 (P<0.01) and up-regulated mRNA level of STAT1 (P<0.01). Compared with the model group, the cisplatin group and the Shasheng Maidong Tang+cisplatin group showed down-regulated protein levels of JAK2 (P<0.01), Bcl-2 (P<0.01), PIM1 (P<0.01), and STAT3 (P<0.05), and up-regulated protein level of Caspase-3 (P<0.01). Compared with the cisplatin group, Shasheng Maidong Tang+cisplatin group presented down-regulated protein levels of JAK2 (P<0.01), Bcl-2 (P<0.01), PIM1 (P<0.01), STAT3 (P<0.05), and up-regulated protein level of Caspase-3 (P<0.01). The Bcl-2 and PIM1 expression results obtained by immunohistochemistry were consistent with those of Western blot. ConclusionShasheng Maidong Tang may enhance the efficacy of chemotherapy in the mouse model of Lewis lung cancer by regulating the JAK2/STAT3 signaling pathway.
2.Mechanisms of Gegen Qinlian Tang-containing Serum in Improving 5-FU Sensitivity by Inhibiting Glycolysis in Colorectal Cancer Cells Based on CDK16/MYC Pathway
Rong CAI ; Shang WANG ; Fuqing CHENG ; Yanping ZHOU ; Zuowei HU ; Yunhai LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):1-9
ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang (GQT) inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil (5-FU)-resistant colorectal cancer (CRC) cells based on the cyclin-dependent kinase 16 (CDK16)/MYC proto-oncogene (MYC) pathway. MethodsHCT-116/5-FU cells were treated with different concentrations (5%, 10%, 20%, 30%) of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 (CCK-8) assay, and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU, GQT, and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine (EDU) staining and annexin V-FITC/PI double staining, respectively. Glucose consumption, adenosine triphosphate (ATP) production, and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins, CDK16, MYC, and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation (CoIP) was used to examine the protein interaction between CDK16 and MYC, and cycloheximide (CHX) treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells, significant inhibition was observed only at 5 mg·L-1 5-FU (P<0.05), which was used for model establishment. Compared with 5-FU alone, addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability (P<0.05), with stronger inhibition at higher serum concentrations. Thus, 5% GQT-containing serum was used in subsequent experiments. Compared with the control group, 5-FU, GQT, and 5-FU + GQT treatments all significantly reduced cell proliferation (P<0.05) and increased apoptosis (P<0.01). The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone (P<0.01), accompanied by more pronounced reductions in glucose consumption, ATP production, and lactate generation (P<0.01). Additionally, compared with control, 5-FU, and GQT groups, the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms (P<0.01) and greater inhibition of glycolytic enzymes, including hexokinase 2 (HK2), 3-phosphoinositide-dependent protein kinase 1 (PDK1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) (P<0.01). CDK16, MYC, and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group (all P<0.01). MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group (P<0.05), which was rescued by CDK16 overexpression (P<0.05). ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU, potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.
3.Mechanisms of Gegen Qinlian Tang-containing Serum in Improving 5-FU Sensitivity by Inhibiting Glycolysis in Colorectal Cancer Cells Based on CDK16/MYC Pathway
Rong CAI ; Shang WANG ; Fuqing CHENG ; Yanping ZHOU ; Zuowei HU ; Yunhai LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):1-9
ObjectiveTo explore the molecular mechanisms by which serum containing Gegen Qinlian Tang (GQT) inhibits glycolysis and enhances chemotherapy sensitivity in 5-fluorouracil (5-FU)-resistant colorectal cancer (CRC) cells based on the cyclin-dependent kinase 16 (CDK16)/MYC proto-oncogene (MYC) pathway. MethodsHCT-116/5-FU cells were treated with different concentrations (5%, 10%, 20%, 30%) of GQT-containing serum. Cell viability and 5-FU sensitivity were assessed using the cell counting kit-8 (CCK-8) assay, and the experimental concentrations of 5-FU and GQT for subsequent experiments were determined. Cell proliferation and apoptosis under individual 5-FU, GQT, and combined 5-FU + GQT treatments were evaluated using 5-ethynyl-2′-deoxyuridine (EDU) staining and annexin V-FITC/PI double staining, respectively. Glucose consumption, adenosine triphosphate (ATP) production, and lactate levels were measured by colorimetric assays. Expression levels of glycolysis-related proteins, CDK16, MYC, and phosphorylated MYC were detected by Western blot. Co-immunoprecipitation (CoIP) was used to examine the protein interaction between CDK16 and MYC, and cycloheximide (CHX) treatment was applied to assess the effect of CDK16 overexpression on MYC protein stability. ResultsCCK-8 assays showed that 2.5 mg·L-1 5-FU significantly inhibited HCT-116 cell viability in a dose-dependent manner. In HCT-116/5-FU cells, significant inhibition was observed only at 5 mg·L-1 5-FU (P<0.05), which was used for model establishment. Compared with 5-FU alone, addition of 5% GQT-containing serum significantly suppressed HCT-116/5-FU cell viability (P<0.05), with stronger inhibition at higher serum concentrations. Thus, 5% GQT-containing serum was used in subsequent experiments. Compared with the control group, 5-FU, GQT, and 5-FU + GQT treatments all significantly reduced cell proliferation (P<0.05) and increased apoptosis (P<0.01). The 5-FU + GQT combination showed superior inhibition of proliferation compared with 5-FU or GQT alone (P<0.01), accompanied by more pronounced reductions in glucose consumption, ATP production, and lactate generation (P<0.01). Additionally, compared with control, 5-FU, and GQT groups, the 5-FU + GQT group exhibited stronger suppression of MYC and its phosphorylated forms (P<0.01) and greater inhibition of glycolytic enzymes, including hexokinase 2 (HK2), 3-phosphoinositide-dependent protein kinase 1 (PDK1), lactate dehydrogenase A (LDHA), and pyruvate kinase M2 (PKM2) (P<0.01). CDK16, MYC, and MYC phosphorylation expression levels were significantly downregulated in the 5-FU + GQT group compared with the 5-FU group (all P<0.01). MYC protein stability decreased in a time-dependent manner in the 5-FU + GQT group (P<0.05), which was rescued by CDK16 overexpression (P<0.05). ConclusionGQT significantly enhances the sensitivity of HCT-116/5-FU cells to 5-FU, potentially by inhibiting CDK16 and thereby reducing MYC-mediated glycolysis.
4.Predictors of delayed function independence in patients with acute vertebrobasilar artery occlusion achieved successful recanalization after endovascular therapy
Haiying HU ; Yingjie XU ; Pan ZHANG ; Zuowei DUAN ; Yong LIANG ; Chen JIA
International Journal of Cerebrovascular Diseases 2023;31(2):81-86
Objective:To investigate the prevalence and predictors of delayed function independence (DFI) in patients with acute vertebrobasilar artery occlusion (VBAO) achieved successful recanalization after endovascular therapy.Methods:Patients with acute VBAO received endovascular treatment in the Departments of Neurology, the First Affiliated Hospital of University of Science and Technology and General Hospital of Eastern Theater Command, PLA from December 2015 to December 2018 were retrospectively enrolled. The demographic, clinical, laboratory and imaging data were collected. Early functional independence (EFI) was defined as the modified Rankin Scale score 0-2 at discharge, and DFI was defined as the modified Rankin Scale score 0-2 at 90 d after discharge for non-EFI patients. Multivariate logistic regression analysis was used to determine the independent predictors of DFI. Results:A total of 122 patients with acute VBAO were included. Their age was 61.8±11.9 years old and 91 (74.6%) were male. The median Glasgow Coma Scale (GCS) score was 7, the median National Institutes of Health Stroke Scale (NIHSS) score was 26.5, and the median posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) score was 9. Twenty-four patients (20.0%) had EFI; of the 98 patients with non-EFI, 18 (18.4%) had DFI. Multivariate logistic regression analysis showed that male (odds ratio [ OR] 0.038, 95% confidence interval [ CI] 0.002-0.658; P=0.025), cardiogenic embolism ( OR 0.116, 95% CI 0.023-0.579; P=0.009), baseline NIHSS score ( OR 1.136, 95% CI 1.040-1.242; P=0.005) and lung infection ( OR 6.089, 95% CI 1.451-25.562; P=0.014) were the independent predictors of DFI. Conclusions:Nearly 1/5 of the non-EFI patients have DFI. Male, cardiogenic embolism, lower baseline NIHSS score and without pulmonary infection are the independent predictors of DFI.
5.Prescription Regularity of Chinese Herbs on Treating Cancer-related Fatigue in 1999 - 2017
Bing WANG ; Wei HOU ; Zuowei HU
Herald of Medicine 2019;38(2):248-252
Objective To analyze the prescription regularity of Chinese herbs in the treatment of cancer-related fatigue by TCM inheritance platform system software. Methods A total of documents on treating cancer-related fatigue by Chinese herbs were collected in CNKI database, Wanfang database, VIP database, CBM database from 1999 to 2017. According to the inclusion and exclusion criteria, the eligible prescriptions were selected to establish the database for summing up and analysing prescription regularity. Results A total of 33 articles were included in the analysis of 38 prescriptions, involving 108 kinds of Chinese herbs, of which the most common kinds were hot nature herb, sweetish taste, spleen meridian. Atractylodes, Poria, Licorice, Astragalus, Angelica, Tangerine peel, Codonopsis,Rehmannia had a high frequency of usage. It eventually formed 45 commonly used drug models, evolved into 16 core combinations of 3 to 4 herbs, and clustered into 5 new prescriptions. Conclusion The modern Chinese medicine in treatment of cancer-related fatigue is mainly focused on the spleen and kidney, what' s more, according to the unique nature of cancer treatment, more experts emphasize on the regulation of spleen and stomach function, which provides a useful reference for clinical syndrome differentiation and treatment.
6.Comparative study of clinical features between different subtype bipolar patients with first mania episode
Rubai ZHOU ; Wu HONG ; Guoqing ZHAO ; Jia HUANG ; Yousong SU ; Yong WANG ; Yingyan HU ; Lan CAO ; Chengmei YUAN ; Daihui PENG ; Zhiguo WU ; Zuowei WANG ; Mengjuan XING ; Jun CHEN ; Yiru FANG
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(4):490-495
Objective·To compare the clinical features between different subtype bipolar patients with first mania episode, and to contribute to early identification of bipolar disorder. Methods·This study was based on the database named as National Bipolar Mania Pathway Survey (BIPAS). From November 2012 to January 2013, bipolar patients from 26 mental health facilities in China were enrolled in current study. The clinical features were compared between mania patients of different subtypes, including hypomania (groupⅠ), mania without psychotic symptoms (groupⅡ), mania with psychotic symptoms (group Ⅲ) and mixed state (group Ⅳ). Results·There was significant difference in the percentage of clinical symptoms between different subtype bipolar patients with first mania episode, especially the mania and anxiety related symptoms. Group Ⅰ, Ⅲ , Ⅳ were further compared with groupⅡ, which was considered as the typical bipolar disorder. The results showed that the mania related symptoms was significantly higher in group Ⅱ, but anxiety related symptoms was significantly higher in group Ⅰ, Ⅲ, Ⅳ. Moreover, Logistic regression analysis revealed that more eloquent or humor and unusually restless could be in favor of the diagnosis of hypomania; younger and mania or hypomania as first episode might be in favor of the diagnosis of mania with psychotic symptoms; older, national minorities and unusually restless could be in favor of the diagnosis of mixed state. Conclusion·The clinical features between different subtype bipolar patients with first mania episode are various, and analysis of the clinical features can contribute to early identification of bipolar disorder.
7.Determination of Release Rate and in vitro Transdermal Rate of Asarinin in Cancer Pain Cataplasm
Yanping ZHOU ; Jiao QU ; Quanwei YANG ; Hongfeng XU ; Geng ZHANG ; Zuowei HU
China Pharmacy 2016;(4):482-484
OBJECTIVE:To determinate the release rate and in vitro transdermal rate of asarinin in Cancer pain cataplasm. METHODS:Using homemade devices and modified France diffusion,isolated skin of rats as barrier,normal saline as solvent,the content of asarinin was determined by HPLC. Release rate of Cancer pain cataplasm within 20,50,80 and 120 min and transder-mal amount within 2,4,8,12,24 h were investigated,and accumulative release rate and accumulative transdermal rate were cal-culated. RESULTS:Accumulative release rate by 120 min of asarinin in Cancer pain cataplasm was 73.01%;24 h in vitro transder-mal rate was 26.01%,and transdermal kinetics equation of asarinin was Q=5.717 7t1/2-0.385 4(r=0.979). CONCLUSIONS:Cancer pain cataplasm has good release and transdermal performance. Its transdermal kinetics is in line with Higuchi equation.
8.Effects of gefitinib combined with DC-CIK on advanced lung adenocarcinoma
Zuowei HU ; Xia ZHAO ; Jiangfeng GUAN ; Wenling SONG ; Hui ZENG
Journal of Chinese Physician 2016;18(1):56-59,62
Objective To investigate the short-term efficacy and safety of gefitinib combined with dendritic cells-cytokine induced killer (DC-CIK) cells in the treatment of advanced lung adenocarcinoma.Methods Fifty patients with lung adenocarcinoma who in previous had underwent radiotherapy and first-line chemotherapy failure received DC-CIK in combination with gefitinib treatment,blood count changes,imaging data,carcinoembryonic antigen and changes in the quality of life before and after treatment were compared and evaluated.Results DC-CIK could improve effectively and relieve bone marrow suppression response after chemotherapy and significantly increase the WBC content of blood (P < 0.01).After treatment,the tumor carcinoembryonic antigen (CEA) was significantly lower in patients (P < 0.01).Fifty cases of patients in complete remission (CR) were 0 cases,partial remission (PR) were 24 cases,stable disease (SD) were 17 cases and progression (PD) were 9 cases,and the response rates (RR) were 48%;The quality of life of patients was significantly improved (P < 0.05).Common adverse reactions were rash,diarrhea,chill and fever,but mild symptoms could be relieved after symptomatic treatment.Conclusions Gefitinib with autologous DC-CIK cell infusion second-line treatment of advanced lung cancer have a certain short-term efficacy,without significant adverse reactions.Gefitinib with autologous DC-CIK cell therapy can mitigate the response of bone marrow suppression in patients with advanced lung cancer and improve the quality of life of patients.Long-term effect remains to be investigated.
9.Optimization of Ethanol Reflux Extraction Process for Aitong Cataplasm by Weighted Score Orthogonal Test
Hongfeng XU ; Quanwei YANG ; Geng ZHANG ; Nancai YU ; Zuowei HU
China Pharmacist 2016;19(7):1252-1254
Objective:To optimize the ethanol reflux extraction process for Aitong cataplasm .Methods: Orthogonal design was used to investigate the effect of solid-liquid ratio,extraction time and times on the extraction technology of Aitong cataplasm with the content of asarinin and dry extract yield as the indices .Results:The best extraction conditions were as follows:extracted 3 times with 8-fold amount of 70%ethanol, and 1 hour for each time.Conclusion: The optimized extraction process is stable and feasible , which can be used to extract Aitong cataplasm .
10.The effect of assertive case management on relapse and health economic evaluation in schizophrenics living in communities
Jing ZHAO ; Qinyu LV ; Xiangqin GUO ; Guoqin HU ; Zuowei WANG ; Yaqin JIANG ; Jian CHEN ; Jubao LU ; Yi WU ; Hongtao XIE ; Zhenghui YI
Chinese Journal of Nervous and Mental Diseases 2014;(11):666-672
Objective To evaluate the effect of assertive case management on relapse and health economic evalua?tion in schizophrenics living in communities. Methods Two hundred outpatients were randomly divided into the study group (107 enrolled, 107 completed) which received assertive case management and the control group (93 enrolled, 91 completed) which received normal management treatment for 12 months. Clinical global impression scale (CGI) and the cost of treatment were assessed every three months. Medication adherence and family burden were evaluated before treat?ment and 3, 6 and 12 months after the treatment using Medication Adherence Rating Scale (MARS) and Family Burden Instructing, respectively. Results The study group was less likely to relapse compared with the control group over the 12-month follow-up and the relapse rates were 1.9%and 11.0%in study and control groups, respectively (P<0.01). The repeated-measures analysis of variance indicated that time main effect was significant in severity of illness factor score of CGI (P<0.01). The time main effect and group main effect in factor 1 and factor 3 scores of MARS were significant (all P<0.05) and there was an interaction effect in factor1 score of MARS (P<0.01). In the study group, time effect were signifi?cant in factor 1 score of MARS (P<0.01). The time main effects in indirect cost and total cost were significant and so were interaction effects in direct cost and total cost (P<0.05). In the study group, time effects were significant in direct cost and total cost (P<0.01). Comparison of FBI dimensions before and after the intervention showed that family relation?ship was much more decreased in the study group than in the control group (P<0.01). Conclusions Assertive Case Man?agement can reduce the recurrence of schizophrenia living in communities, improve compliance medication and family re?lationship as well as reduce the cost of treatment.

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