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Issue 4 ， 2023
- Abstract：Objective： To evaluate the clinical efficacy of Yanghe Decoction in patients with breast cancer receiving neo-adjuvant chemotherapy （NAC） and its impact on inflammatory factors of the patients.MethodsSixty-two female patients with breast cancer， confirmed by biopsy， who were scheduled to undergo preoperative NAC for the first time were selected and randomly divided into the study group and control group， 31 cases in each group. The patients in the study group were treated with Yanghe Decoction orally based on routine NAC， and the patients in the control group were treated with placebo orally based on routine NAC. The administration of Chinese medicine followed the NAC cycles， and the treatment duration covered the entire NAC period of the patients. The clinical efficacy and pathological chemotherapy response ［including Miller-Payne （MP） grade and residual cancer burden （RCB） grade） of the two groups were evaluated. Before and after NAC and in the middle of NAC， the levels of serum inflammatory factors including interleukin （IL）-2R， IL-6， IL-8 and tumor necrosis factor-α （TNF-α） were detected. Meanwhile， safety events and common adverse reactions during NAC were recorded in order to evaluate the safety of Yanghe Decoction applied in NAC.Results①The objective response rate （ORR） was 90.3% in the study group and 87.1% in the control group， with no statistically significant difference between the two groups （P>0.05）. In the aspect of time to response （TTR）， the proportion of patients who achieved complete or partial response in the first 4 cycles of NAC was 67.7% in the study group and was 41.9% in the control group， with statistically significant difference between the two groups （P<0.05）. ②After treatment， 21 patients （67.7%） in the study group reached MP grade 4 or grade 5， and 13 patients （41.9%） in the control group reached MP grade 4 or grade 5， with statistically significant difference between the two groups （P<0.05）. ③In the middle of NAC and after NAC， the levels of IL-6 and IL-8 in the study group were lower than those in the control group （P<0.05）. After NAC， the level of TNF-α in the study group was lower than that in the control group （P<0.05）. ④During NAC， no serious safety events occurred in both groups， and there was no statistically significant difference in the incidence of safety events between the two groups （P>0.05）. In the aspect of the incidence of adverse reactions， the incidence of fatigue in the study group was significantly lower than that in the control group （P<0.05）.ConclusionYanghe Decoction can enhance the tumor regression rate during NAC in patients with breast cancer， improve the efficacy of pathological chemotherapy response， reduce the levels of serum inflammatory factors， and improve the adverse reactions during NAC， which was safety.Keywords：breast cancer;Yanghe Decoction;neo-adjuvant chemotherapy;inflammatory factors;clinical efficacy;safety;adverse reactions
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Published：2023-08-04 - Abstract：Objective： To evaluate the clinical efficacy of maintenance therapy involved in Chinese medicine in patients with advanced colorectal cancer （ACC） after first-line chemotherapy， in order to provide an evidence-based basis for Chinese medicine intervention in ACC maintenance therapy.MethodsA retrospective cohort study design was applied. The clinical data of ACC patients were collected， and the patients were divided into the intervention group and control group according to whether taking Chinese medicine during the maintenance therapy. The patients in the control group were given conventional maintenance therapy with western medicine， and the patients in the intervention group were given Chinese medicine orally based on the treatment of the control group. Propensity score matching （PSM） was used to further balance the covariates between the two groups， the progression-free survival （PFS） and overall survival （OS） were taken as outcome indicators， and the influences of Chinese medicine on oral fluorouracil maintenance therapy and the observation strategy maintenance therapy were analyzed.ResultsA total of 850 patients with ACC were included， and 670 patients were included after PSM and divided into the intervention group （335 cases） and the control group （335 cases）. The median PFS was 10 months （95%CI 8.05~11.95） in the intervention group and 7 months （95%CI 6.15~7.85） in the control group， with a hazard ratio（HR） of 0.75 （95%CI 0.64~0.88， P=0.000） for progression or death. The median OS was 32 months （95%CI 26.15~37.85） in the intervention group and 21 months （95%CI 17.24~24.76） in the control group， with a HR of 0.62 （95%CI 0.53~0.73， P=0.000） for death. In patients treated with oral fluorouracil maintenance therapy， the median PFS was 13 months in the intervention group and 10 months in the control group （HR=0.80， 95%CI 0.61~1.06， P=0.098）， and the median OS was 31 months in the intervention group and 22 months in the control group （HR=0.65， 95%CI 0.52~0.81， P=0.000）. In patients treated with observation strategy maintenance therapy， the median PFS was 10 months in the intervention group and 6 months in the control group （HR=0.78， 95%CI 0.63~0.96， P=0.013）， and the median OS was 27 months in the intervention group and 17 months in the control group （HR=0.65， 95%CI 0.52~0.81， P=0.000）.ConclusionMaintenance therapy containing Chinese medicine after first-line chemotherapy can prolong the PFS and OS in patients with ACC， meanwhile Chinese medicine can prolong the OS in patients treated with fluorouracil maintenance therapy and prolong the PFS and OS in patients treated with observation strategy maintenance therapy.Keywords：advanced colorectal cancer;maintenance treatment;Chinese medicine;progression-free survival;overall survival
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Published：2023-08-04
Clinical Research
- Abstract：Objective： To explore the influence and mechanism of the effective traditional Chinese medcine nitidine chloride on A549 MLN4924 drug-resistant lung cancer cell lines.MethodsA549 cells were treated with low dose of MLN4924 for 6 months， and half maximal inhibitory concentration （IC50） analysis and Western blot analysis were performed to ensure the successful induction of MLN4924 drug-resistant cell lines （A549-MR）. A549-MR was treated with the concentration gradient and time gradient of nitidine chloride， and the effect of nitidine chloride on A549-MR growth was detected by ATPLite cell proliferation analysis and cell counting. Meanwhile， the total protein of A549 cells was collected for Western blot analysis to detect the molecular mechanism of inhibition of A549-MR growth by nitidine chloride.ResultsIC50 analysis and Western blot analysis showed that after low-dose and long-time treatment of A549 cells， the IC50 of MLN4924 on A549 cells was increased from 0.355 μmol/L to 10.643 μmol/L， and the neddylation modification of Cullins family proteins wasn't significantly inhibited. Cell proliferation analysis showed that the proliferation of MLN4924 drug-resistant lung cancer cells was significantly inhibited by nitidine chloride， Western blot results showed that the expression of Cullins protein in A549-MR cells was down-regulated by nitidine chloride and its tumor suppressor substrate protein p21 and p27 were induced to accumulate.ConclusionBy inhibiting the activity of the CRLs （cullin-RING ligases） complex， nitidine chloride can induce the accumulation of downstream tumor suppressor protein substrates， which can inhibit the proliferation of the drug-resistant lung cancer cells induced by the neddylation inhibitor MLN4924.Keywords：nitidine chloride;MLN4924;drug resistance;cullin-RING ligases complex
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Published：2023-08-04 - Abstract：Objective： To investigate the effect of polydatin （PD） on human neuroblastoma SH-SY5Y cell damage induced by hydrogen peroxide （H2O2） and its mechanism.MethodsSH-SY5Y cells were treated with different concentrations of H2O2 for 24 h， and cell viability was detected by cell counting kit-8（CCK-8） method to determine the induced concentration of H2O2. After 2 h of PD pretreatment， then induced with H2O2 for 22 h， and the cell viability was detected by CCK-8 method to determine the concentration of PD. Cells were divided into DMSO group， H2O2 group， H2O2+PD 20 μmol/L group and H2O2+PD 40 μmol/L group. Apoptosis was detected with annexin V-fluorescein isothiocyanate/propidium iodide （Annexin V-FITC/PI） apoptosis kit. Total intracellular reactive oxygen species （ROS） were determined by flow cytometry. Glutathione peroxide （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） in cells were detected by ELISA. Mitochondrial membrane potential was detected by JC-1 mitochondrial fluorescence probe. B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， cysteine protein-3 （Caspase-3）， cleaved poly（adenosine diphosphate-ribose） polymerase （Cleaved-PARP）， nuclear factor E2 associated factor 2 （Nrf2）， Kelch-like epichlorohydrin associated protein 1 （Keap1） and heme oxygenase 1 （HO-1） protein contents were detected by Western blot.Results①CCK-8 experiment results showed that viability of SH-SY5Y cells was 60% after 400 μmol/L H2O2 treatment， so 400 μmol/L H2O2 was selected as the subsequent stimulation condition of SH-SY5Y cells； 20， 40， 50， 80 μmol/L PD could significantly inhibit the H2O2-induced viability decrease in SH-SY5Y cells （P<0.05）. ②Annexin V-FITC/PI apoptosis experiment results showed that 20， 40 μmol/L PD could inhibit SH-SY5Y cell apoptosis induced by H2O2 （P<0.05）. Western blot results showed that 20， 40 μmol/L PD could inhibit the expression of apoptosis-related proteins Bax and Caspase-3 in H2O2-induced SH-SY5Y cells （P<0.05）， and promote the expression of anti-apoptosis protein Bcl-2 （P<0.05）. ③20， 40 μmol/L PD could reduce H2O2-induced ROS， MDA contents， and increase GPH and SOD content in SH-SY5Y cells. ④The results of JC-1 mitochondrial membrane potential assay indicated that 20， 40 μmol/L PD could alleviate H2O2-induced mitochondrial damage in SH-SY5Y cells. ⑤Western blot results showed that 20， 40 μmol/L PD could significantly inhibit the down-regulation of Keap1， Nrf2 and HO-1 proteins in H2O2-induced SH-SY5Y cells （P<0.05）.ConclusionPD can protect H2O2-induced apoptosis， oxidative stress， and mitochondrial damage in SH-SY5Y cells， and its mechanism may be related to the activation of Keap1/Nrf2/HO-1 signal pathway.Keywords：polydatin;human neuroblastoma cells;oxidative stress;mitochondria damage;peroxide;Keap1/Nrf2/HO-1 signal pathway
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Published：2023-08-04 - Abstract：Objective： To investigate effect and mechanism of Fructus Psoraleae on lung adenocarcinoma using network pharmacology， molecular docking and experimental validation.MethodsActive ingredients of Fructus Psoraleae and the potential targets related to lung adenocarcinoma （LUAD） were searched in Symptom Mapping （SymMap）， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine （BATMAN-TCM）， Traditional Chinese Medicine Integrated Database （TCMID） and Gene Expression Profiling Interactive Analysis （GEPIA）； Venn diagram was used to obtain the targets of the active ingredient of Fructus Psoraleae acting on LUAD， Cystoscape 3.7.2 software was used to construct the network diagram of active ingredient from Fructus Psoraleae on LUAD targots. STRING database was used for protein-protein interaction analysis； Database for Annotation， Visualization and Integrated Discovery （DAVID） was used for enrichment analysis， and Origin 2021 software was used for constructing “active ingredient-target-pathway” network diagram. AutoDockTools 1.5.6 and PyMOL was used for molecular Docking.Results①Fifty-five intersection targets of Fructus Psoraleae for lung adenocarcinoma treatment were obtained， involving core targets such as β1-adrenoceptor （ADRB1） and β2-adrenoceptor （ADRB2）， as well as signaling pathways such as cyclic guanosine monophosphate （cGMP）-protein kinase G （PKG） and hypoxia inducible factor-1 （HIF-1）. ②The molecular docking results suggested that bakuchiol had low binding energy with ADRB1 and ADRB2， which were core therapeutic targets of lung adenocarcinoma. ③The experimental validation results confirmed that bakuchiol could inhibit tumor cell proliferation and expression levels of genes such as adrenergic receptor subtypes ADRB1， ADRB2 and α1A-adrenoreceptor （ADRA1A）， which were consistent with results of the network pharmacology analysis.ConclusionFructus Psoraleae and its active ingredient bakuchiol may exert anti-lung adenocarcinoma effects by intervening with β-adrenergic receptors and their signaling pathways.Keywords：Fructus Psoraleae;lung adenocarcinoma;network pharmacology;molecular docking;β-adrenergic receptors
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Published：2023-08-04 - Abstract：Objective： To explore the mechanism of Baitouweng Decoction against colorectal adenoma based on network pharmacology analysis and experimental verification.MethodsCytoscape 3.9.0 software， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and GeneCards database were used to construct a “disease-drug chemical component-target” network to predict the effective chemical components of Baitouweng Decoction in the treatment of colorectal adenoma. Gene Ontology（GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were carried out to construct a “signal pathway-target” network and predict the core targets. Finally， the predicted core targets were validated in a mouse colorectal adenoma model.Results①The network pharmacological analysis showed that there are 129 potential targets of Baitouweng Decoction active ingredients in the treatment of colorectal adenoma， among which 10 active ingredients were corresponding to 40 key potential targets. And Baitouweng Decoction may exert therapeutic effects on colorectal adenoma by regulating the interleukin-17 （IL-17） signaling pathway and p53 signaling pathway to affect biological processes such as the DNA-binding transcription factor binding， DNA polymerase type Ⅱ specific DNA-binding transcription factor binding， nuclear factor receptor activity. ②Experimental validation was carried out on 12 targets that exceeded the mean value of degree values， and the results showed that the expression of estrogen receptor 1 （ESR1） and caspase-8 （CASP8） genes after the intervention of Baitouweng Decoction was significantly decreased compared with that of the model group （P<0.05）， which is presumed to be the key targets of Baitouweng Decoction in the treatment of colorectal adenoma.ConclusionBaitouweng Decoction may exert anti-colorectal adenoma effect through multiple components， multiple targets and multiple pathways.Keywords：Baitouweng Decoction;colorectal adenoma;network pharmacology;IL-17 signaling pathway;p53 signaling pathway;ESR1;CASP8
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Published：2023-08-04 - Abstract：Objective： To evaluate the inhibitory effects of Jianpi Bushen Jiedu Recipe （JBJR） on hepatocellular xenograft tumor and angiogenesis-related factors in nude mice through hypoxia-inducible factor-1α （HIF-1α）.MethodsThe nude mice vaccinated with subcutaneous transplantation tumor of liver cancer were randomly divided into the blank group， sorafenib group， and JBJR high， medium and low dose groups. The mice were given corresponding drug intervention for four consecutive weeks. The transplantation tumor size was compared among the groups. The microvessel density （MVD） of tumor was detected by immunohistochemistry， the HIF-1α mRNA was detected by real-time PCR， and the influences of different drugs on nitric oxide synthase （NOS）， vascular endothelial growth factor （VEGF） and basic fibroblast growth factor （bFGF） were detected by enzyme linked immunosorbent assay （ELISA）.ResultsCompared with the blank group， the tumor volume in each dose group of JBJR was significantly reduceed （P<0.05）， the MVD were significantly decreased （P<0.01）， and the MVD of the sorafenib group was decreased （P<0.05）. Compared with the blank group， the HIF-1α mRNA expression in the high dose group of JBJR and sorafenib group were significantly reduced （P<0.05）. Compared with the blank group， the expression of VEGF in the high dose group of JBJR and sorafenib group was significantly down-regulated （P<0.05）， and the expression of bFGF in above two groups were also significantly reduced compared with the blank group （P<0.05）.ConclusionJBJR can reduce the transplantation tumor of liver cancer in nude mice， and inhibit the angiogenesis of transplantation tumor. Its mechanisms may be reducing the expressions of VEGF and bFGF， meanwhile decreasing the activity of NOS in transplantation tumor， thereby inhibiting angiogenesis of liver cancer through down-regulating the expression of HIF-1α in HCCLM3 cells.Keywords：Jianpi Bushen Jiedu Recipe;liver cancer;angiogenesis;hypoxia-inducible factor-1α;vascular endothelial growth factor
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Published：2023-08-04
Experiment Research
- Abstract：With the improvement of people's health awareness and the popularization of low-dose CT as a means of pulmonary cancer screening， the detection rate of pulmonary ground-glass nodule （GGN） is gradually increasing. While the pulmonary GGN is closely related to pulmonary adenocarcinoma， so timely diagnosis and treatment of pulmonary GGN in clinical practice play an important role in blocking the transformation of inflammatory to cancer. This paper summarizes the current status of traditional Chinese medicine and western medicine in diagnosis and treatment of pulmonary GGN from the following aspects： understanding of traditional Chinese medicine， risk factors， mechanisms of malignancy， diagnosis and traditional Chinese medicine and western medicine treatment. In view of the fact that western medicine treatment of GGN is mainly based on follow-up observation， and traditional Chinese medicine has no mature diagnosis and treatment standard， so it is urgent to establish an effective and feasible plan for diagnosis and treatment of GGN with the integration of traditional Chinese medicine and western medicine.Keywords：pulmonary ground-glass nodule;traditional Chinese medicine;western medicine;diagnosis;treatment
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Published：2023-08-04
Theoretical Research
- Abstract：Tongguanteng Injection is a traditional Chinese medicine injection made from the extract of Marsdeniae tenacissima caulis. It has the functions of clearing heat and detoxifying， resolving phlegm and softening lump， etc. It is widely used for the treatment of digestive tract， respiratory tract and other tumors in clinic. When combined with other antitumor drugs， it can improve the therapeutic efficiency and reduce toxicity. Tongguanteng Injection contains a variety of chemical components， mainly steroids and phenolic acids. The content of phenolic acids is 6.0~13.0 mg/mL based on chlorogenic acid， and the content of steroid saponins is not less than 8.0 mg/mL based on tenacissoside A. In this paper， the research progress of the chemical composition， pharmacological effects， quality evaluation， pharmacokinetics， clinical application and adverse reactions of Tongguanteng Injection were reviewed， and some suggestions were proposed for its further study.Keywords：Tongguanteng Injection;chemical composition;pharmacological effects;quality evaluation;pharmacokinetics;clinical application;adverse reaction
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Published：2023-08-04 - Abstract：N6-methyladenosine （m6A） modification is a dynamic and reversible chemical modification found commonly in the RNA of eukaryotic cells， which can regulate the splicing， metabolism， translation and stability of various RNAs （including lncRNA， mRNA， snRNA， rRNA and tRNA）. m6A can promote the growth and proliferation of tumor cells and exert a certain resistance to radiotherapy and chemotherapy， therefore， m6A as a target for cancer therapy may be a new therapeutic approach. This paper reviews the roles of m6A RNA methylated modification in the proliferation， invasion and metastasis， drug resistance， and poor prognosis of non-small cell lung cancer （NSCLC）， as well as the inhibition of NSCLC by Chinese medicine through regulating m6A RNA methylated modification， in order to provide the new theoretical basis and response strategies for the pathogenesis exploration and clinical treatment of NSCLC.Keywords：m6A RNA methylated modification;non-small cell lung cancer;tumor proliferation;targeted drug resistance;Chinese medicine intervention;review
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Published：2023-08-04 - Abstract：Compared with other types of breast cancer， triple-negative breast cancer （TNBC） has strong invasion and high drug resistance， due to the lack of targets of endocrine and targeted therapy. Tumor-associated macrophages （TAMs） are the most abundant cells in the tumor microenvironment （TME）. The classic M1 type and the selective M2 type polarized by TAMs have anti-tumor and pro-tumor activities， respectively. The studies of recent years find that TAMs play an important role in the occurrence and development of TNBC， which can promote the proliferation of TNBC， the migration and invasion of TNBC， the formation of tumor vessels of TNBC， and the immunosuppression and escape of TNBC. The correlative studies indicate that the active components or compounds of traditional Chinese medicine can enhance the phagocytic function of TAMs， further promote the polarization of TAMs into M1 type， promote the repolarization of M2 type into M1 type， and inhibit the polarization of TAMs into M2 type. The advantages of traditional Chinese medicine in TNBC intervention by regulating the polarization of TAMs have been gradually found， and it plays an important role in the treatment of TNBC.Keywords：triple-negative breast cancer;polarization of tumor-associated macrophages;traditional Chinese medicine
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Published：2023-08-04 - Abstract：Malignant tumors have high morbidity and mortality. Although a large number of anti-tumor drugs have been developed， their clinical efficacy is unsatisfactory， which is closely related to the complex tumor microenvironment （TME）. It is difficult to simulate the interaction of various cells in the spatial structure of TME by traditional two-dimensional （2D） culture models of a single cell type， which hinders the drug research and development based on the real world. In vitro multicellular co-culture three-dimensional （3D） tumor spheroid models have gradually become the most promising approaches for tumor biology and anti-tumor drug research because it can better simulate in vivo TME. Traditional Chinese medicine has the characteristics of synergistic anti-tumor effects through multi-component， multi-level and multi-target. However， 2D models of a single cell type often cannot reflect the overall effects of traditional Chinese medicine， making multicellular co-culture 3D tumor spheroid models more suitable for its research. This article reviews the classification and construction methods of 3D multicellular co-culture models.Keywords：multicellular;co-culture;tumor spheroid;microfluidics;tumor microenvironment
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Published：2023-08-04 - Abstract：Cervical cancer （CC） is a common female malignant tumor. Epithelial-mesenchymal transition （EMT） is closely related to the occurrence， development， metastasis and dissemination of CC， and inhibiting EMT course is of great significance in reducing the recurrence and mortality rates of CC. By summing up the effect of different kinds of active components of traditional Chinese medicine on EMT of CC， this paper clarifies the reverse effect of active components of traditional Chinese medicine on EMT of CC， and finds that the clearing heat Chinese medicine， tonifying deficiency Chinese medicine， promoting blood circulation and removing blood stasis Chinese medicine， and the methods of tonifying liver and kidney， and dredging and regulating down Jiao has potential therapeutic effects in the intervention of EMT of CC， which should be further verified by relevant experiments， in order to provide a new idea for the precise study of Chinese medicine in the prevention and treatment of EMT of CC， and to provide a new reference for the prevention and treatment of CC metastasis and the enrichment of existing treatment methods.Keywords：cervical cancer;active ingredients of traditional Chinese medicine;epithelial-mesenchymal transition;transforming growth factor-β1;review
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Published：2023-08-04
Review
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