1.Evaluation Value of Blood Biomarker Tests for Efficacy of EGFR-TKI in Advanced NSCLC Treatment
Rui FAN ; Yonghui WU ; Zhan GU ; Yanbin PENG ; Lixin WANG
Cancer Research on Prevention and Treatment 2025;52(5):382-387
Objective To analyze the levels of serum CTCs and ctDNA in NSCLC patients receiving first-line EGFR-TKI treatment, and to explore the clinical value of CTCs and ctDNA detection in assessing the efficacy of treatment for advanced lung cancer. Methods A total of 109 NSCLC patients receiving first-line EGFR-TKI treatment were enrolled. Serum tumor markers CEA, CTCs, and ctDNA were detected at baseline and after one month of treatment. Chest CT scans were performed, and treatment efficacy was evaluated based on RECIST1.1 criteria. CTCs were counted by enrichment-staining-computational algorithm to analyze malignant features, while ctDNA was assessed using digital PCR. Results Survival rate was low in patients with abnormal CEA and ctDNA tests at baseline and in patients with reduced serum CTCs after treatment. In the SD subgroup of patients with brain metastases and advanced stage, the PFS benefit was low. Conclusion Patients in the SD subgroup have significantly higher recurrence risks than those in the PR or CR subgroups. Therefore, CTC and ctDNA testing should be applied to patients in the SD subgroup to identify high-risk patients with poor response to EGFR-TKI treatment, intervene with additional treatment promptly, and obtain long progression-free survival.
2.Immunoinfiltration correlation analysis of secreted phosphoprotein SPP1 in multiple tumors
Jie CHEN ; Lin CHEN ; Yan-Lun GU ; Mo ZHANG ; Zhan-Yu MEN ; Lu WANG ; Xiao-Cong PANG
The Chinese Journal of Clinical Pharmacology 2024;40(13):1968-1971
Objective To utilize bioinformatic approaches to elucidate the correlation between secreted phosphoprotein 1(SPP1)and immune infiltration in various malignancies,elucidating the mechanism of gene function in cancer-immune cell interplay.Methods Cancer samples were derived from the Cancer Genome Atlas(TCGA)and Genotype-tissue Expression(GTEx)database,examining SPP1 expression difference between tumors and normal tissues using Gene Expression Profiling Interactive Analysis(GEPIA2),and its correlation with different immune cells in extracellular matrix via TIMER2 Database.SPP1's association with interacting molecules was scrutinized on the STRING website,followed by assessment of its distinct functional state across various cancers from Cancer Single-cell State Atlas Database(Cancer SEA).Results In 32 tumor types,SPP1 mRNA is significantly elevated in 23 types of cancers and correlates heavily with fibroblast,integrin family,and CD44.Furthermore,the SPP1 gene exhibits profound specificity in tumor functions such as vascular invasion,metastasis,DNA damage,and repair.Conclusion Specific expression of SPP1 in tumors signifies a significant correlation with tumor immune cells in the extracellular matrix,promoting tumor progression and invasion.This suggests that targeted monitoring of SPP1 could serve as a prospective cancer diagnostics/therapeutics biomarker.
3.Phylostratigraphy Study of Cancer-related Genes
Siqi WANG ; Xun GU ; Zhan ZHOU
Chinese Journal of Modern Applied Pharmacy 2024;41(2):177-191
OBJECTIVE
To analyze the evolution of the transition from unicellular organisms to multicellular organisms from a phylogenetic stratigraphy perspective, combining the "cancer atavism hypothesis". To investigate the evolutionary chronology of cancer-related genes to guide research on cancer mechanisms and the development of treatment strategies.
METHODS
Phylostratr was used to identify the systematic evolutionary strata of all human protein-coding genes, housekeeping genes, cancer driver genes, tumor suppressor genes, oncogenes, neutral genes, and differentiation genes. Differential distribution of genes from different functional categories and human protein-coding genes was analyzed using log-odds ratios and hypergeometric distributions. TCGA was utilized to investigate transcriptional expression datas in cancer tumor samples and normal samples, and calculations and analysis were performed using transcriptome age index.
RESULTS
A total of 20291 protein-coding genes were classified into 27 different strata based on the farthest homologous species in the sequence alignment results. Within the phylogenetic stratigraphic structure, the datasets of 4159 housekeeping genes, 527 cancer driver genes, 87 tumor suppressor genes, 134 oncogenes, 10755 neutral genes, and 4274 differentiation genes exhibit distinct distribution patterns. The overall distribution of these genes significantly differs from that of all human protein-coding genes. Cancer-related genes exhibited a more ancient phylogenetic stratigraphic distribution. Transcriptome age index results for bile duct cancer, colon cancer, lung cancer, liver cancer, head and neck cancer, and kidney chromophobe samples showed strong expression of highly conserved and ancient genes within the tumors.
CONCLUSION
Cancer-related genes exhibit older evolutionary origins within the phylogenetic context suggesting a more conserved function during species evolution. And the phenomenon of enhanced expression of highly conserved ancient genes in tumor tissues can be used to explore tumor gene expression patterns, and provide new ideas for the discovery of new anti-tumor drug targets and drug research.
4.Bacterial community diversity in human Demodex mites
Renren HAN ; Dacun ZHANG ; Lan WANG ; Feifan TANG ; Jiacheng CAO ; Jingxuan WANG ; Xiaodong ZHAN ; Shengli GU
Chinese Journal of Schistosomiasis Control 2024;36(2):174-178
Objective To investigate the bacterial community diversity in human Demodex mites, so as to provide insights into unraveling the role of human Demodex mites in them caused infectious diseases. Methods From June to July 2023, Demodex mites were collected from the faces of college students in a university in Wuhu City using the adhesive tape method, and the V4 region of 16S ribosomal RNA (16S rRNA) gene and the internal transcribed spacer (ITS) gene of nuclear ribosomal DNA were amplified on an Illumina PE250 high-throughput sequencing platform. Sequencing data were spliced according to the overlapping relations and filtered to yield effective sequences, and operational taxonomic units (OTUs) was clustered. The diversity index of obtained OUTs was analyzed, and the structure of the bacterial community was analyzed at various taxonomic levels. Results A total of 57 483 valid sequences were obtained using 16S rRNA gene sequencing, and 159 OUTs were classified according to similarity. Then, OUTs at a 97% similarity were included for taxonomic analyses, and the bacteria in Demodex mites belonged to 14 phyla, 20 classes, 51 orders, 72 families, and 94 genera. Proteobacteria was the dominant phylum, and Vibrio, Bradyrhizobium and Variovorax were dominant genera. A total of 56 362 valid sequences were obtained using ITS gene sequencing, and 147 OTUs were obtained, which belonged to 5 phyla, 17 classes, 34 orders, 68 families, and 93 genera and were annotated to Ascomycota, Basidiomycota and Chytridiomycota, with Ascomycota as the dominant phylum, and Alternaria alternata, Epicoccum, Penicillium, and Sarocladium as dominant genera. Conclusions There is a high diversity in the composition of bacterial communities in human Demodex mites, with multiple types of microorganisms and high species abundance.
5.Surgical strategy for treatment of complex aortic coarctation
Xiaohan XU ; Miti WU ; Faliang ZHAN ; Tao YE ; Yizhou GAO ; Weidong GU ; Qun GU ; Yongfeng SHAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(05):776-781
Objective To summarize the clinical experience of the treatment for complex aortic coarctation with extra anatomic bypass and anatomic correction techniques. Methods The clinical data of patients with complex aortic coarctation treated in the First Affiliated Hospital of Nanjing Medical University and Friendship Hospital of Ili Kazakh Autonomous Prefecture between April 2012 and November 2020 were retrospectively reviewed. Results A total of 12 patients were enrolled, including 5 males and 7 females aged 11-54 (34.3±16.2) years. Extra anatomic bypass grafting was performed in 8 patients and anatomic correction was performed in 4 patients. The operations were successful in all patients. There was no perioperative death. The average cardiopulmonary bypass time was 203.0±46.0 min (7 median incision patients), and the average intraoperative blood loss was 665.0±102.0 mL. The average postoperative ventilator support time was 32.3±7.5 h, and the average postoperative hospital stay time was 10.2±4.3 d. The mean drainage volume of median incision was 1 580.0±360.0 mL, and the mean drainage time was 9.3±2.7 d. The mean drainage volume of left thoracotomy was 890.0±235.0 mL, and the mean drainage time was 4.8±2.5 d. One patient had a transient hoarse after operation and recovered 6 months later. The follow-up period ranged from 2 to 10 years with an average time of 81.0±27.0 months. All patients had a recovery of hypertension, cardiac afterload after 2 years postoperatively. One patient who received an artificial blood vessel replacement in situ was examined stenosis recurrence at the third year after discharge. Others were asymptomatic during the follow-up period. There were no death or other complications. Conclusion The treatment strategy for complex aortic coarctation should be individualized according to the anatomical features and concomitant heart diseases. Extra anatomic bypass technique is a safe and feasible choice.
6.Herbal Textual Research on Paridis Rhizoma in Famous Classical Formulas
Jingjing GU ; Tianmei YANG ; Meiquan YANG ; Zhilai ZHAN ; Jinyu ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):186-199
This article systematically analyzes the historical evolution of the name, origin, scientific name evolution, medicinal parts, producting area, harvesting and processing, clinical efficacy of Paridis Rhizoma by consulting the ancient materia medica, medical books and prescription books, combined with modern literature, in order to provide a reference for the development of famous classical formulas containing Paridis Rhizoma. According to research, it can be verified that Paridis Rhizoma was first recorded in Shennong Bencaojing with the name of Zaoxiu, and this name has been used for ancient materia medica in the past generations. The name of Chonglou was first appeared in Xinxiu Bencao of the Tang dynasty, and has gradually become the rectification of name, with it being the correct name in modern legal names at all levels. The mainstream source of Paridis Rhizoma used in ancient times was the dried rhizomes of Paris polyphylla var. chinensis, but due to the similarity plant morphology of the genus Paris, there was much confusion, and the same genus of plants with thick rhizomes were also used as Paridis Rhizoma, such as P. polyphylla, P. polyphylla var. stenophylla. Since modern times, P. polyphylla var. yunnanensis has also been included as one of the mainstream sources of Paridis Rhizoma. The origin recorded in ancient materia medica are mainly in Shandong, Anhui, Jiangsu, Jiangxi, Yunnan and other regions, which are collected in the wild for medicinal purposes, modern cultivation is more prevalent in southwestern regions, such as Yunnan, Sichuan, Guizhou and Guangxi. In ancient times, the harvest time was mostly root harvesting in April and May of the lunar calendar, while in modern times, they are mostly harvested throughout the year or in autumn. Autumn harvesting is the best choice, with roots removed from the production area, washed, and dried in the sun. In ancient times, Paridis Rhizoma was processed by baking, grinding and other methods, but in modern times, sliced raw products were mainly used as medicine. Paridis Rhizoma has a slightly cold nature, a bitter taste, and a small toxicity. It can regulate the liver meridian, clear heat and detoxify, reduce swelling and pain, cool the liver and calm convulsions. It is used for symptoms such as boils and carbuncles, throat swelling and pain, snake and insect bites, and its flavor and efficacy are basically consistent in ancient and modern records. Based on the results of the textual research, it is recommended that the dried rhizomes of P. polyphylla var. chinensis or P. polyphylla var. yunnanensis should be used in the development of famous classical formulas containing Paridis Rhizoma, the processing method is selected according to the requirements of the formula, and the raw product is recommended to be used as medicine if not specified.
7.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
8.Effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα in blood CD4+Th1 cells of patients with allergic rhinitis
Junling WANG ; Mengmeng ZHAN ; Fangqiu GU ; Yifei LI ; Zhaolong ZHANG ; Congyi ZHAO ; Danyang ZHAO ; Hui ZHENG ; Yijie ZHANG ; Bingyu QIN
The Journal of Practical Medicine 2024;40(11):1513-1518
Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.
9.Effect of percutaneous endoscopic foraminal discectomy on clinical outcome of L5-S1 lumbar disc hernia-tion and influence of iliac crest height on clinical efficacy
Deta CHEN ; Xinhua ZHAN ; Xiaoping SHENG ; Wu RAO ; Jingliang GU ; Yan YU
The Journal of Practical Medicine 2024;40(12):1690-1695
Objective To investigate the effect of percutaneous endoscopic transforaminal discectomy(PETD)on L5-S1 lumbar disc herniation(LDH)and the influence of iliac crest height on the clinical efficacy.Methods A total of 86 patients treated with PETD for LDH(L5-S1 segment)from February 2019 to February 2018 were selected and grouped according to the relationship between the highest point of the iliac crest and the position of the L4-5 pedicle.Forty-eighty patients with the highest point of the iliac crest located below the upper edge of the L5 pedicle were included in group A;thirty-three patients with the highest point of the iliac crest located between the lower edge of the L4 pedicle and the upper edge of the L5 pedicle were included in group B,and five patients with the highest point of the iliac crest located above the lower edge of the L4 pedicle were included in group C.The operation indexes of the three groups were compared.The visual analogue score(VAS)and Oswestry Disability index(ODI)before and after surgery[preoperative(T0),1 week after surgery(T1),1 month,6 months and 12 months after surgery(T2,T3,T4)]were compared among the three groups.Results There was no difference in operation time and blood loss among the three groups(P>0.05).At T0,there was no difference in VAS score and ODI among the three groups(P>0.05).At T1-T4,when VAS score and ODI of the three groups were lower than that at T0,VAS in group A and B was lower than that in group C(P<0.05),but there was no difference between group A and B(P>0.05).Conclusion PETD has significantly clinical efficacy in the treatment of L5-S1 LDH,and whether the iliac crest height is higher than the level of the lower edge of the L4 pedicle will affect its clinical efficacy.
10.Exploration of the Mechanism of Icariin on Prostate Cancer Based on Network Pharmacology and Animal Experiments
Wenli LIN ; Yanran ZHAN ; Yanfen CHEN ; Jiahui HE ; Yuanjun WEI ; Taofen CHEN ; Xiangtao WENG ; Chiming GU
Herald of Medicine 2024;43(12):1874-1880
Objective To investigate the intervention effects and mechanism of icariin on prostate cancer based on network pharmacology and animal experiments.Methods The targets of icariin were predicted using the SwissTargetPrediction database.Protein-protein interaction networks were constructed with the String database,and core targets were screened using Cytoscape 3.9.1.GO and KEGG enrichment analysis on core targets were conducted with the Metascape database to predict the mechanism of action.A PC-3 tumor-bearing mouse model of prostate cancer was established to observe the inhibitory effects of icariin alone and in combination with paclitaxel on tumor growth.Results Network pharmacology predictions suggested that icariin has potential therapeutic effects on prostate cancer,with core targets potentially including serine/threonine kinase 1(AKT1),B-cell lymphoma-2(BCL2),epidermal growth factor receptor(EGFR),heat shock protein 90 alpha family class A member 1(HSP90AA1),heat shock protein 90 alpha family class B member 1(HSP90AB1),nuclear factor kappa B subunit 1(NF-κB1),tumor protein p53,etc.Animal experiments found that compared with the model control group,the tumor volume growth in the icariin group and the paclitaxel group was significantly inhibited,and the serum tumor necrosis factor content was significantly reduced,while testosterone levels did not change significantly.Both groups significantly downregulated the mRNA expression of Notch1,Jagged1 and Hes1(P<0.05),with the combined treatment group showing a more significant inhibitory effect.Conclusions Both network pharmacology and animal experimental results confirmed that icariin has a significant inhibitory effect on prostate cancer.One of the mechanisms of its anti-tumor effects may be the significant inhibition of the activated Notch signaling pathway in tumors.


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