1.Treatment of Pulmonary Nodules based on the Theory of "Two Colds Interacting,and Disturbance of Pivots"
Jingrui WANG ; Kexin DUAN ; Junjie HUANG ; Shujing WANG ; Zhiqiang CHEN ; Ying WANG ; Yanlong LI ; Xiangjun QI ; Lizhu LIN
Journal of Traditional Chinese Medicine 2024;65(23):2487-2491
Based on the discussions in the The Inner Canon of Yellow Emperor (《黄帝内经》), it is proposed that in the course of the disease, "bind" represents the initial stage of pulmonary nodules, while "accumulation" represents the final form. In terms of the pathogenesis, "two colds interacting" represented by "body cold" and "cold fluid retention" are the prerequisites for the formation of pulmonary nodules, while "disorder of qi" represented by "fainting" is the core of the formation. The specific manifestation is the disturbance of pivot of shaoyang (少阳) or shaoyin (少阴), resulting in a complex of cold and heat, and then phlegm and stasis are suddenly generated and further formed into nodules. Therefore, the treatment principle should be to regulate the cardinal mechanism, dissolve phlegm and blood stasis. Depending on the complex degree of cold and heat, it is suggested to use Chaihu Guizhi Decoction (柴胡桂枝汤), Chaihu Guizhi Ganjiang Decoction (柴胡桂枝干姜汤), or Chaihu Xianxiong Decoction (柴胡陷胸汤) for disturbance of shaoyang pivot, while for shaoyin pivot dysfunction, modified Mahuang Fuzi Xixin Decoction (麻黄附子细辛汤) or Shengjiang Powder (升降散) can be used.
2.Effect of Yifei Sanjie Pills (益肺散结丸) Combined with Cisplatin on Plasma Exosomal miRNAs in Lewis Lung Cancer Tumor-derived Mice
Lingling SUN ; Xiangjun QI ; Yanlong LI ; Leihao HU ; Lizhu LIN
Journal of Traditional Chinese Medicine 2024;65(19):2032-2040
ObjectiveTo investigate the tumor inhibition effect and mechanism of Yifei Sanjie Pills (益肺散结丸, YSP) on lung cancer. MethodsLewis lung cancer tumor-derived mice were established and divided into four groups including model control group, cisplatin group, cisplatin + YSP low-dose group and cisplatin + YSP high-dose group, with 12 mice in each group. The corresponding interventions were given for 14 days. The tumor volume was measured on the 0th, 3rd, 7th, 10th and 14th days of administration to evaluate the tumor growth. The plasma and tumor tissue were collected on the 15th day. Plasma from the model group, the cisplatin group and the cisplatin+YSP high-dose group were selected, and plasma exosomes were extracted; the differences in miRNA expression among the groups were detected and analyzed by second-generation sequencing technology, and the potential mechanism of action of YSP was investigated by principal component analysis, biofunctional enrichment analysis and miRNA-target gene regulatory network analysis. Quantitative real-time PCR was used to detect the expression of miRNA-615-3p in tumor tissues, and the relationship between miRNA-615-3p and overall survival of lung cancer were analyzed using the Kaplan-Meier plotter (kmplot.com) database. ResultsCompared to that of the model control group, the tumor volume of the cisplatin group on day 10, and the cisplatin + YSP low- and high-dose groups on day 7, 10, and 14 were significantly reduced (P<0.05 or P<0.01). Compared to that of the cisplatin group, the tumor volume of the cisplatin + YSP low- and high-dose groups on day 10 and 14 was significantly reduced (P<0.05). The principal component analysis of miRNA expression profiles showed significant differences in miRNA expression between different intervention groups. There were 21 differentially expressed miRNAs between the model control group and the cisplatin group, 50 differentially expressed miRNAs between the model control group and the cisplatin+ YSP high-dose group, and 6 differentially expressed miRNAs between the cisplatin group and the cisplatin+ YSP high-dose group. Biological function enrichment analysis showed that the differentially expressed miRNAs were mainly involved in the regulation of signaling pathways related to cell growth, proliferation, differentiation, autophagy and other biological activities. The miRNA-target gene regulatory network showed the top 20 genes that were targeted, among which there were proven miRNAs and genes related to lung cancer, and miRNAs that needed further investigation. The expression of miRNA-615-3p in tumor tissues decreased significantly in the cisplatin group and cisplatin+YSP high-dose group compared to that of the model group(P<0.05 or P<0.01). The miRNA-615-3p was negatively correlated with the survival prognosis of lung cancer(P<0.05). ConclusionCisplatin combined with YSP can effectively inhibit the proliferation of Lewis lung cancer tumors, and the tumor-suppressive effect is related to the regulation of multiple miRNAs, especially the downregulation of miRNA-615-3p expression.
3.Mechanism of Inducing Ferroptosis in Hepatocellular Carcinoma Cells by Shugan Quyu Jiedu Prescription Based on p53/SLC7A11/GPX4 Pathway
Xiaojun CAI ; Renyi YANG ; Zhibin WANG ; Yilin GONG ; Ke WANG ; Lizhu LIN ; Chong ZHONG ; Jing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):74-82
ObjectiveTo investigate the effect of Shugan Quyu Jiedu prescription (SGQYJDF) on inducing ferroptosis in hepatocellular carcinoma cells based on the tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway. MethodMHCC97H cells were divided into the blank serum group (10% blank serum medium), SGQYJDF-containing serum low concentration group (5% SGQYJDF-containing serum and 5% blank serum medium), SGQYJDF-containing serum medium concentration group (7.5% SGQYJDF-containing serum and 2.5% blank serum medium), SGQYJDF-containing serum high concentration group (10% SGQYJDF-containing serum medium) and sorafenib group (sorafenib concentration of 10 μmol·L-1 in 10% blank serum medium). After 24 hours of intervention, the cell survival rate was detected by cell counting kit-8 (CCK-8) assay. The cell proliferation ability was detected by 5-ethynyl-2′-deoxyuridine (EdU) staining. The intracellular ferrous ion (Fe2+) level was detected by ferrous ion fluorescent probe (FerroOrange) staining. The intracellular malondialdehyde (MDA) and glutathione (GSH) levels were detected by colorimetric assays. The ultrastructure of mitochondria was observed by transmission electron microscopy. The expression levels of ferroptosis-related proteins p53, SLC7A11 and GPX4 were detected by Western blot. ResultIn terms of cell viability, compared with the blank serum group, the SGQYJDF group showed a dose-dependent decrease in the survival rate of MHCC97H cells. Effect of the medium and high concentrations of SGQYJDF on the survival rate of MHCC97H cells were significantly decreased (P<0.01). Additionally, the results of the EdU assay showed that both the medium and high concentrations of SGQYJDF were able to inhibit the proliferation ability of MHCC97H cells (P<0.05, P<0.01). Regarding the biochemical indicators of ferroptosis, compared to the blank serum group, the medium and high concentrations of SGQYJDF were able to dose-dependently increase the intracellular Fe2+ level (P<0.01). The low, medium, and high concentrations of SGQYJDF were able to dose-dependently decrease the level of GSH in MHCC97H cells (P<0.01) and increase the level of MDA in the cells (P<0.05, P<0.01). In terms of pathway-related protein expression, compared to the blank serum group, the medium and high concentrations of SGQYJDF could significantly increase the expression of p53 (P<0.01). The low, medium, and high concentrations of SGQYJDF could significantly decrease the expression of GPX4 (P<0.01). The high concentration of SGQYJDF could decrease the expression of SLC7A11 (P<0.01). In terms of the cell morphology of ferroptosis, compared with the blank serum group, transmission electron microscopy revealed that the low concentration of SGQYJDF caused mitochondrial deformation, while the medium and high concentrations of SGQYJDF resulted in reduced mitochondrial volume, increased double-layer membrane density, and decreased mitochondrial cristae. These features were similar to those of sorafenib-induced ferroptosis. Furthermore, compared with the sorafenib group, the high concentration of SGQYJDF showed no statistically significant differences in cell survival rate, proliferation ability, Fe2+ level, MDA level, and GSH level. ConclusionThe results suggest that SGQYJDF may induce ferroptosis and inhibit proliferation in hepatocellular carcinoma MHCC97H cells by upregulating the expression of p53, suppressing the expressions of GPX4 and SLC7A11, downregulating the level of GSH, and leading to the accumulation of intracellular Fe2+ and MDA.
4.Preliminary study on the diagnostic efficacy of contrast-enhanced ultrasound in breast solid ductal papilloma
Lizhu HOU ; Yan ZHENG ; Ying SONG ; Mengqi ZHOU ; Lin ZHU ; Dan ZHAO ; Wei WANG ; Fenglin DONG
Chinese Journal of Ultrasonography 2024;33(5):378-384
Objective:To evaluate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of solid intraductal papilloma (sIDP) of breast by comparing with fibronenoma of breast (FA).Methods:The CEUS data of 62 cases of sIDP patients and 94 cases of FA patients that confirmed by pathology in the First Affiliated Hospital of Soochow University from October 2016 to January 2021 were retrospectively analyzed. The patients were divided into sIDP group and FA group according to the pathological results. The enhancement speed, enhancement degree, enhancement uniformity, whether the edge after enhancement was polished, whether the enhancement range was enlarged, whether there was a ring unenhanced area in the inner edge of the lesion and whether the inner edge of the unenhanced area was polished were observed in the two groups. SonoLiver software was used to perform offline analysis of the dynamic process of CEUS in the two groups respectively, the enhancement sequence diagram of the lesions was obtained. The pathological result was taken as the gold standard, univariate analysis was applied, and the parameters with statistical significance between the two groups were included in multivariate Logistic regression analysis to establish a differential diagnosis model. The diagnostic efficiency of sIDP was analyzed by ROC curve and diagnostic model.Results:Compared with the FA group, CEUS in the sIDP group mostly showed fast forward, high enhancement, and the enhancement sequence was mostly centrifugal. After CEUS, the lesion edges in the sIDP group were mostly accompanied by unenhanced areas and the inner edges of the unenhanced areas were not intact, and the differences between the two groups were statistically significant (all P<0.05). Binary Logistic regression showed that age, enhancement degree and enhancement order were independent risk factors for sIDP diagnosis. The ROC curve showed that the area under the ROC curve of age, enhancement degree and enhancement sequence combined for the diagnosis of sIDP was 0.874 (95% CI=0.812-0.922), the accuracy was 76.9%, the sensitivity was 67.7%, the specificity was 83.0%, the positive predictive value was 72.4%, and the negative predictive value was 79.6%. Conclusions:There are significant differences in age, enhancement degree and enhancement sequence between sIDP and FA patients. The three-parameter combination can improve the diagnostic efficiency of sIDP.
5.Clinical characteristics of 16 patients with nucleotide excision repair disorders and literature review
Lizhu HU ; Jing WANG ; Qiuhong WANG ; Zhou YANG ; Yu HUANG ; Jing GAO ; Jian CHEN ; Bin WANG ; Rui LIU ; Xian XU ; Nan PENG ; Hui WANG ; Yujiao DENG ; Liqiang WANG ; Haixu CHEN ; Lin MA ; Liping ZOU
Chinese Journal of Applied Clinical Pediatrics 2022;37(22):1730-1735
Objective:To summarize the clinical manifestations and gene mutation features of patients with nucleotide excision repair (NER) disorders.Methods:A retrospective analysis was made on clinical data of patients with NER disorders who were admitted to the Chinese People′s Liberation Army General Hospital from October 2008 to February 2022 and diagnosed in the Outpatient Department of Beijing Children′s Hospital, Capital Medical University from October 2015 to February 2022.Literature on previously reported Chinese patients with NER disorders was reviewed.Results:(1)A total of 16 patients with NER disorders were enrolled, including 6 males and 10 females.The onset age was 7.5 (4.0, 12.0) months and the age at diagnosis was 42.0 (21.5, 77.0) months.There were 3 types of NER disorders: Cockayne syndrome (CS) in 13 cases, Xeroderma Pigmentosum (XP) in 2 cases and Cerebro-Oculo-Facio-Skeletal syndrome (COFS) in 1 case.Four disease-causing genes were detected: CSA gene in 11 cases, CSB gene in 3 cases, XPG gene in 1 case, and XPD gene in 1 case.The first symptoms of the 16 patients were photosensitivity and developmental delay, and neurological symptoms were observed in all the 3 NER disorder types.XP and CS patients had skin symptoms.CS patients presented typical facial features, visual and auditory impairment, microcephaly and changes in neuroimaging features.COFS patients showed intrauterine growth retardation.(2)Results of literature review: a total of 96 Chinese patients reported were retrieved, involving 6 disease types, including CS in 45 cases, XP in 44 cases, trichothiodystrophy in 4 cases, COFS in 1 case, XP-CS in 1 case, and ultraviolet sensitive syndrome in 1 case.Nine mutated genes were identified: CSA in 33 cases, XPA in 15 cases, CSB in 13 cases, XPV in 10 cases, XPC in 9 cases, XPG in 7 cases, XPD in 7 cases, XPF in 1 case, and MPLKIP in 1 case.The common symptoms were growth failure (62 cases), skin photosensitivity (61 cases), typical facial features (52 cases), mental retardation (49 cases) and microcephaly (48 cases). Among 36 cases had imaging data 33 cases(91.7%)had calcification of basal nucleus or globus pallidus.Three cases had intrauterine growth retardation and microcephaly during pregnancy. Conclusions:Patients with such prenatal manifestations as intrauterine growth retardation and microcephaly or with typical symptoms like skin photosensitivity, typical facial features, growth failure, mental retardation, hypertonia, and calcifications of basal ganglia should be suspected of NER disorders.Early genetic testing is recommended to confirm the diagnosis.
6.Mechanism of action of Sini powder in treatment of liver cancer based on network pharmacology and molecular docking
Jing LI ; Jiahao MO ; Hongbin XU ; Junxia ZHU ; Peiyu SHI ; Wanli XING ; Chong ZHONG ; Lizhu LIN
Journal of Clinical Hepatology 2020;36(9):1998-2004
ObjectiveTo investigate the mechanism of action of Sini powder in the treatment of liver cancer based on network pharmacology and molecular docking. MethodsTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to obtain the compound and target of Sini powder, and the corresponding gene Symbol was obtained through Uniprot. The disease genes of liver cancer were obtained from Human Genome Database, and the genes with intersection with the target genes of Sini powder were screened out. Cytoscape3.7.1 software was used to draw the map of “traditional Chinese medicine (TCM)-compound-target” network. STRING was used to construct a protein-protein interaction (PPI) network, R studio software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on therapeutic targets, and then the results were visualized. The active component with the highest number of targets was selected as the ligand, and the target with the highest degree in the PPI network was selected as the receptor, so as to predict the structure of receptor-ligand complex and the amino acid residues that bind to each other. ResultsIn this study, 91 core targets and 141 relevant active components of Sini powder were screened out, among which quercetin and kaempferol were the main active components in the treatment of liver cancer. TP53 and HSP90AA1 were the main therapeutic targets. The GO enrichment analysis obtained 1007 items which met the screening criteria, which were mainly involved in the biological processes of antioxidation reaction, activity regulation of protein serine and threonine kinase, and cellular stress response. The KEGG enrichment analysis obtained 102 pathways, which mainly regulated the hepatitis B pathway and the PI3K-Akt signaling pathway in the prevention and treatment of liver cancer. The results of molecular docking showed a synergistic antitumor effect between the crystal structure domains VAL147, CYS220, GLU221, and PRO222 of quercetin-TP53. ConclusionThis study reveals the mechanism of action of Sini powder in the treatment of liver cancer by acting on multiple targets and signaling pathways, which provides a theoretical basis for biological experiments.
7.Expressions of human epidermal growth factor receptor 2 in recurrent patients after radical gastrectomy and its significance
Ling CHEN ; Jing LIN ; Xiaojie WANG ; Yu CHEN ; Lizhu CHEN ; Zengqing GUO ; Jiami YU ; Jingxian ZHENG
Cancer Research and Clinic 2020;32(3):178-181
Objective:To investigate the expressions of human epidermal growth factor receptor 2 (HER2) in recurrent patients after radical gastrectomy and its correlation with clinicopathologic features and prognosis.Methods:The clinical data of 116 recurrent patients after radical gastrectomy between December 2011 and March 2019 in Fujian Cancer Hospital were retrospectively analyzed. The relationship between HER2 expression of the tissues after radical gastrectomy and clinicopathological features as well as prognosis was also analyzed.Results:HER2 positive rate was 19.8% (23/116) in gastric cancer specimens of 116 patients after radical gastrectomy. HER2 positive rate in highly and moderately differentiated patients with gastric cancer was higher than that in those with poorly differentiated gastric cancer [33.3% (11/33) vs. 14.5% (12/83), χ2 = 5.292, P < 0.05]. HER2 positive rate in patients with lung metastasis was higher than that in patients without lung metastasis [42.1% (8/19) vs. 15.5% (15/97), χ2 = 5.517, P < 0.05]. There were no statistical differences in HER2 positive rate among gastric cancer patients with different gender, age, tumor location, recurrent site, TNM stage, number of metastasis, neurovascular invasion, liver metastasis, local recurrence (all P > 0.05). HER2 expression was not associated with disease-free survival time ( P > 0.05). Conclusion:HER2 expression is associated with the differentiation degree of gastric cancer and the location of distant metastasis, but it can not be used as a predictor for recurrence of gastric cancer.
8.Meta-analysis of Efficacy and Safety of Endostar Combined with Gemcitabine and Cisplatin in the Treatment of Advanced Non-small Cell Lung Cancer
Zhiqiang CHEN ; Zeyun LI ; Ruiting LIN ; Weipeng SUN ; Lizhu LIN ; Lingling SUN
China Pharmacy 2019;30(14):1990-1996
OBJECTIVE: To systematically evaluate the efficacy and safety of Endostar combined with gemcitabine and cisplatin in the treatment of non-small cell lung cancer (NSCLC), and to provide evidence-based reference for clinical drug use. METHODS: Retrieved from Cochrane Library, PubMed, Embase, ClinicalTrials, CNKI, Wanfang and VIP database, randomized controlled trials (RCT) about Endostar combined with gemcitabine and cisplatin(trial group) vs. gemcitabine combined with cisplatin (control group) for NSCLC were collected. After literature screening, data extraction and quality evaluation with Cochrane 5.1.0 bias risk evaluation tool and Jadad scale, Meta-analysis was performed by using Rev Man 5.3 software. RESULTS: A total of 27 RCTs were included, involving 1 646 patients. Results of Meta-analysis showed that response rate [RR=1.67, 95%CI(1.48,1.89),P<0.000 01] and clinical benefit rate [RR=1.26, 95%CI (1.20, 1.33),P<0.000 01] of trial group were significantly higher than those of control group. There was no statistical significance in the incidence of leucopenia [RR=0.98,95%CI(0.88, 1.11),P=0.79], thrombocytopenia [RR=1.07, 95%CI(0.91, 1.26),P=0.39] and gastrointestinal reaction [RR=1.01, 95%CI(0.90, 1.14),P=0.85] between 2 groups. CONCLUSIONS: Endostar combined with gemcitabine and cisplatin can improve therapeutic efficacy of NSCLC patients, without increasing the incidence of ADR.
9.Risk factors for postoperative hypoxemia in patients undergoing Stanford type A aortic dissection surgery
Lizhu LIN ; Beiwei LIANG ; Dongke LIANG ; Yizhi LU ; Bingdong ZHANG
Chinese Journal of Postgraduates of Medicine 2018;41(1):25-29
Objective To explore the risk factors for postoperative hypoxemia in patients undergoing Stanford type A aortic dissection surgery.Methods The clinical data of 77 patients with Stanford type A aortic dissection surgery were analyzed retrospectively.Among the patients, 40 patients occurred hypoxemia(hypoxemia group),and 37 patients did not occur hypoxemia(non-hypoxemia group).The preoperative,intraoperative and postoperative clinical data were compared between 2 groups,and the independent risk factors for postoperative hypoxemia were analyzed by multiple Logistic regression analysis.Results The incidence of postoperative hypoxemia in patients with Stanford type A aortic dissection was 51.9% (40/77).The multiple Logistic regression analysis result showed that age (OR =1.088,95% CI 1.018-1.164,P=0.013),body mass index≥25 kg/m2(OR=6.495,95% CI 1.327-31.789,P=0.021),pericardial effusion(OR=6.384,95% CI 1.426-28.576,P=0.015),white blood cell count(OR=1.289,95% CI 1.033-1.609,P=0.024)and using recombinant human coagulationⅦa (OR = 23.757, 95% CI 2.849 - 198.085, P = 0.003) were the independent predictive factors for postoperative hypoxemia in patients with Stanford type A aortic dissection.Conclusions The postoperative hypoxemia in patients with Stanford type A aortic dissection is related with perioperative systemic inflammation, especially in obese patients who should be given anti-inflammatory treatment during perioperative period.Control of bleeding and reducing the recombinant human coagulationⅦa as far as possible can reduce the incidence of postoperative hypoxemia.
10.Effectiveness and safety of Kang′ai injection combined with single agent chemotherapy in treatment of el-derly patients with advanced NSCLC
Hanrui CHEN ; Huaqin TIAN ; Zhiming CHEN ; Xuewu HUANG ; Xinting ZHENG ; Xuezhang CHEN ; Lizhu LIN
The Journal of Practical Medicine 2018;34(2):316-319
Objective To observe the effectiveness and safety of Kang′ai injection combined with docetaxel or gemcitabine chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer(NSCLC). Methods A multi-center,randomized and parallel control study was carried out in 150 elderly patients with ad-vanced NSCLC treated in 3 hospitals during the period from June 2013 to August 2014.The patients were randomly divided into platinum-based group(platinum-based doublet chemotherapy)and Kang′ai group(Kang′ai injection combined with single agent chemotherapy). The clinical efficacy,quality of life and adverse reactions were ob-served and compared between the two groups. Results There was no significant difference in the disease control rate between the two groups group(79.66% vs 81.82%)(χ2=0.101,P=0.751)while the effective rate of Kang′ai group was significantly higher than that of platinum-based group(30.51% vs 14.29%)(χ2=5.240,P=0.022). The effective rate of clinical symptom relief in Kang′ai group after treatment was significantly higher than that in platinum-based group(69.49% vs 48.05%)(χ2=6.278,P=0.012),and the increase rate of PS score in Kang′ai group after the treatment was also significantly higher than that in platinum-based group(18.64% vs 3.90%)(χ2=7.868,P=0.005).There was no significant difference in quality of life between two groups(P>0.05).The quali-ty of life score of Kang′ai group was significantly higher than that of platinum-based group at the second course of treatment(P<0.05).The incidence of adverse reactions in Kang′ai group was significantly lower than that in the platinum-based group(47.46% vs 71.42%)(χ2= 8.070,P < 0.05). Conclusion Kang′ai injection combined with single agent chemotherapy can effectively relieve clinical symptoms and reduce the tumor size in elderly patients with advanced NSCLC,with high safety.

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