1.Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis
Ting XU ; Xicheng WANG ; Ying XIN ; Zhenghang WANG ; Jifang GONG ; Xiaotian ZHANG ; Yanyan LI ; Congcong JI ; Yu SUN ; Feilong ZHAO ; Depei HUANG ; Yuezong BAI ; Jian LI ; Lin SHEN
Cancer Research and Treatment 2023;55(2):626-635
Purpose:
The human epidermal growth factor receptor 2 (HER2) is an established therapeutic target for various kinds of solid tumors. HER2 amplification occurs in approximately 1% to 6% of colorectal cancer. In this study, we aimed to assess the efficacy and safety of trastuzumab in combination with chemotherapy in HER2-positive metastatic colorectal cancer (mCRC).
Materials and Methods:
An open-label, phase II trial (Clinicaltrials.gov: NCT03185988) was designed to evaluate the antitumor activity of trastuzumab and chemotherapy in HER2-positive digestive cancers excluding gastric cancer in 2017. Patients from this trial with HER2-positive, KRAS/BRAF wild-type, unresectable mCRC were analyzed in this manuscript. Eligible patients were treated with trastuzumab (8 mg/kg loading dose and then 6 mg/kg every 3 weeks) and irinotecan (120 mg/m2 days 1 and 8 every 3 weeks). The primary endpoint was the objective response rate.
Results:
Twenty-one HER2-positive mCRC patients were enrolled in this study. Seven patients (33.3%) achieved an objective res-ponse, and 11 patients (52.4%) had stable disease as their best response. The median progression-free survival (PFS) was 4.3 months (95% confidence interval, 2.7 to 5.9). Four of the 21 patients (19.0%) had grade 3 adverse events, including leukopenia, neutropenia, urinary tract infection, and diarrhea. No treatment-related death was reported. Exploratory analyses revealed that high tumor tissue HER2 copy number was associated with better therapeutic response and PFS. Alterations in the mitogen-activated protein kinase pathway, HER2 gene, phosphoinositide 3-kinase/AKT pathway, and cell cycle control genes were potential drivers of trastuzumab resistance in mCRC.
Conclusion
Trastuzumab combined with chemotherapy is a potentially effective and well-tolerated therapeutic regimen in mCRC with a high HER2 copy number.
2.Content determinnation of chlorogenic acid and linarin in Yejuhua Granules
Weiguang SUN ; Manling DU ; Ji WANG ; Zhiyun HUANG ; Anfeng WAN ; Jiansheng GAO ; Xiaotian ZHONG
International Journal of Traditional Chinese Medicine 2023;45(2):197-200
Objective:To establish a method for determintation of chlorogenic acid and linarin in Yejuhua granules by HPLC.Methods:We applied HPLC methods. The Kromasil 100-5 C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.4%H 3PO 4 solution (gradient elution), the flow rate was 1.0 ml/min, the dection wavelenghth was 334 nm and the column temperture was 32 ℃. Results:Chlorogenic acid and buddleoside had good linearity in the ranges of 0.30-1.50 μg ( r2=0.999 1) and 0.12-0.62 μg ( r2=0.999 8), respectively. The average recoveries were 99.70% and 96.67%, with RSD<2%, respectively. Conclusion:The method is simple, rapid, reliable, efficient, and can be used for determination of chlorogenic acid and buddleoside in Yejuhua Granules.
3.Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.
Ji DONG ; Xinglong WU ; Xin ZHOU ; Yuan GAO ; Changliang WANG ; Wendong WANG ; Weiya HE ; Jingyun LI ; Wenjun DENG ; Jiayu LIAO ; Xiaotian WU ; Yongqu LU ; Antony K CHEN ; Lu WEN ; Wei FU ; Fuchou TANG
Protein & Cell 2023;14(6):433-447
Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans
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Epigenesis, Genetic
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Gastric Mucosa/metabolism*
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Chromatin/metabolism*
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Stem Cells
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Epithelium/metabolism*
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Fatty Acid-Binding Proteins/metabolism*
4.Analysis of perioperative complications and influencing factors of complications in 1 000 cases of robotic gynecological surgery
Xiaotian HUANG ; Mei JI ; Zhao ZHAO ; Nannan HE ; Yue LI ; Penglin XU ; Jingfang ZHANG
Chinese Journal of Obstetrics and Gynecology 2021;56(5):341-348
Objective:To investigate the occurrence and influencing factors of perioperative complications after robotic gynecologic surgery.Methods:The clinical data and occurrence of perioperative complications in 1 000 cases robotic surgery completed in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:(1) Clinical data: the average age of the patients was (50.2±10.4) years old, and the average body mass index (BMI) was (24.4±3.6) kg/m 2. Among 1 000 cases, 811 cases of them were malignant tumors, including 405 cases of cervical cancer, 279 cases of endometrial carcinoma, 112 cases of epithelial ovarian cancer (EOC), 15 cases of vulvar cancer; 189 cases of them were benign diseases, including 43 cases of uterine prolapse, 57 cases hysterectomy of uterine leiomyoma and adenomyosis of the uterus ≥12 weeks, 84 cases myomectomy of uterine leiomyoma, and 5 cases of fallopian tubal ligation requiring anastomosis. Surgical methods: in patients with malignant tumors, cervical cancer, hysterectomy plus salpingectomy or salpingo-oophorectomy for stage Ⅰa1, and radical hysterectomy plus pelvic lymphatic dissection plus salpingectomy or salpingo-oophorectomy for stage Ⅰa2-Ⅱb. Endometrial carcinoma, performed by staging surgery. Staging surgery for EOC with early stage and cytoreductive surgery with advanced EOC. Vulvar cancer, extensive vulvar resection plus inguinal lymphadenectomy. In patients with benign diseases, uterine prolapse, hysterectomy plus salpingectomy or salpingo-oophorectomy plus sacrocolpopexy. Uterine leiomyoma or adenomyosis with uterus ≥ 12 weeks, hysterectomy plus salpingectomy or salpingo-oophorectomy. Myomectomy for patients requiring uterine preservation with uterine leiomyoma. Tubal anastomosis for patients with fallopian tubal ligation. (2) Surgical complications: intraoperative complications occurred in 25 patients (2.5%, 25/1 000), including 11 patients with vascular laceration, 11 patients with ureteral injury, 2 patients with bladder injury, and 1 patient with intestinal injury. Postoperative complications occurred in 130 patients (13.0%, 130/1 000), including 66 cases of lower limb venous thrombosis, 20 cases of lymphatic cyst, 8 cases of hydronephrosis, 9 cases of ileus, 16 cases with infection, 6 cases with genital fistula, 4 cases with trocar site herniation and 1 case with subcutaneous emphysema. The incidence of intraoperative complications was 3.1% (25/811) in malignant tumors and no case in benign diseases, the incidence rate in malignant tumors was significantly higher than that in benign diseases ( χ2=4.778, P=0.029). The incidence rate in cervical cancer (4.2%, 17/405) and EOC (3.6%, 4/112) were significantly higher than those in endometrial carcinoma (1.4%, 4/279) and vulvar cancer (0/15; P<0.05). The incidence of postoperative complications was 15.2% (123/811) in malignant tumors and 3.7% (7/189) in benign diseases. The incidence rate in malignant tumors was significantly higher than that in benign diseases ( χ2=17.807, P<0.01), but there were no significant difference among different malignant tumors ( χ2=4.318, P=0.229). (3) The correlative factors affecting the occurrence of surgical complications: patient′s age, BMI, previous pelvic or abdominal surgery history, the nature of disease (malignant or benign), operation time, and comorbidities had a significant impact on the incidence of postoperative complications ( P<0.05). Multivariate logistic regression analysis showed that the patient′s age ≥40 years old, BMI ≥25 kg/m 2, previous pelvic or abdominal surgery history, malignant tumors and comorbidities were independent influential factors of the postoperative complications ( P<0.05). Conclusions:Perioperative complications vary according to the type of the surgery. The age, BMI, previous pelvic or abdominal surgery history, malignant tumors, and comorbidities are influential factors of postoperative complications.
5.Analysis of research status and development countermeasures of clinical key specialties in Henan Province
Chenxi LV ; Jinling GUO ; Xiaotian LIU ; Zhilong WANG ; Kun JI ; Jiyi LV ; Chenhui CAI ; Kaixuan WANG
Chinese Journal of Medical Science Research Management 2020;33(5):372-376
Objective:To understand the output of research and education of clinical key Specialties in Henan Province, to analyze the current situation and existing problems, and to provide scientific evidence and suggestions for the improvement of specialist ability.Methods:Through the questionnaire survey to collect the scientific research data of key specialties from 2015 to 2019, apply Epidata 3.0 to input the data, use SPSS 21.0 software to carry out test and Mann Whitney U test, and carry out a comparative analysis of the national and provincial clinical key specialty discipline leaders, medical talent team, academic, scientific research and education output in Henan Province. Results:Academic literacy and scientific research ability of leaders of national and provincial key clinical specialties in Henan Province are equal. However, there is still a big gap in scientific research and education ability between national and provincial key clinical specialties in Henan Province.Conclusions:The provincial key clinical specialties need to improve the ability of scientific research and education in a more holistic way, further strengthen the medical talents team, and focus on the exchange of high-level academic platform and the cultivation of research talents.
6.Analysis of influencing factors of comprehensive strength of key medical specialties based on TOPSIS evaluation
Chenxi LYU ; Jinling GUO ; Xiaotian LIU ; Zhilong WANG ; Kun JI ; Jiyi LYU ; Chenhui CAI ; Kaixuan WANG
Chinese Journal of Hospital Administration 2020;36(6):520-524
Objective:To evaluate the comprehensive strength of the specialties included in the medical service capacity improvement project of Henan provincial medical and health institutions, analyze the influencing factors, and provide scientific basis for the specialty construction.Methods:A total of 52 specialties were included in the project. According to the content of construction assessment and acceptance, the questionnaire was designed and filled in by the persons in charge of the specialties from the aspects of basic conditions, medical technical team, medical service ability, medical quality, scientific research and teaching ability. TOPSIS method was used to evaluate the comprehensive strength of specialty, and the main influencing factors were analyzed by single factor analysis, Mann-Whitney U test, correlation analysis and multiple stepwise regression analysis. Results:The research and teaching ability of the specialties had the strongest correlation with the comprehensive strength of the specialties. The scientific research and teaching ability was strongly related to the medical service ability. The number of people holding the post of academic institutes at or above provincial level, the number of industry standards or national guidelines, the number of academic conferences hosted at or above the provincial level, the number of postgraduate training, the number of papers published in SCI and core journals were the main influencing factors of scientific research and teaching ability.Conclusions:It is necessary to improve the level of scientific research and teaching in key specialty to promote the improvement of medical service ability. We should pay more attention to the construction of high-level talents, the cultivation of research-oriented talents, the application of new medical technology and original research.
7.Inactivation of TFEB and NF-B by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion.
Huanmin NIU ; Lilin QIAN ; Bin SUN ; Wenjian LIU ; Fang WANG ; Qian WANG ; Xiaotian JI ; Yanhai LUO ; Effat Un NESA ; Hongxiang LOU ; Huiqing YUAN
Acta Pharmaceutica Sinica B 2019;9(5):923-936
It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.
8.Analysis of general survey results of iodine content in drinking water of Shanxi Province
Baisuo GUO ; Xiangdong ZHANG ; Fengfeng ZHANG ; Yanting REN ; Yongping WANG ; Yulan JING ; Jing JI ; Jie HUAN ; Hongyun CHEN ; Xiaotian CHENG ; Qingzhen JIA
Chinese Journal of Endemiology 2018;37(2):128-131
Objective To understand the distribution of water iodine in the external environment of Shanxi Province, and to provide a basis for redefining and implementation of scientific iodine supplementation in iodine deficiency, iodine adequate or iodine high areas. Methods In 2012 - 2016, administrative villages (neighborhood committees)in 119 counties(cities,districts)in 11 cities of Shanxi Province were selected as the investigation units, and 1 to 5 drinking water samples were collected. Water iodine content was detected using arsenic-cerium catalytic spectrophotometry. Areas standard was designated: water iodine content < 10 μg/L as iodine deficiency areas, > 100 μg/L as iodine high areas. Results A total of 26 213 administrative villages (neighborhood committees) of 1 362 townships (towns) of 119 counties (cities, districts) were surveyed, covering 2 850.94 ten thousand people. A total of 32 766 water samples were collected and the median iodine was 5.2 μg/L. There were 18 199 villages with water iodine < 10 μg/L, accounting for 69.4% (covering 1 812.17 ten thousand people, accounting for 63.6%), 6 471 villages with water iodine 10-<50 μg/L,accounting for 24.7%(covering 787.44 ten thousand people,accounting for 27.6 %),1 166 villages with water iodine 50 - < 100 μg/L,accounting for 4.4% (covering 181.46 ten thousand people, accounting for 6.4%), 377 villages with water iodine ≥100 μg/L, accounting for 1.4%(covering 69.87 ten thousand people, accounting for 2.5%).In 1 362 townships (towns), 71.1% (969)water iodine median was<10 μg/L,24.2%(330)water iodine median was in 10-<50 μg/L,3.4%(46)water iodine median was in 50-<100 μg/L,and 1.2%(17) water iodine median was ≥100 μg/L. In 119 counties(cities,districts),there were 90 counties(accounting for 75.6%) with the water median < 10 μg/L, there were 26 counties (accounting for 21.8%) with the water median 10 - < 50 μg/L. Conclusions Most parts of Shanxi Province(or the resident population) are iodine deficiency areas, the external environment water iodine contents in the rest of the regions are different, we should adopt different iodine supplement or iodine reduction measures in regions with different water iodine levels.
9.Recent advances in biomarkers for the targeted therapy of metastatic colorectal cancer
Lingling ZHAO ; Guobin XU ; Guohong WANG ; Lianhai ZHANG ; Xiaotian ZHANG ; Shuqin JIA ; Jiafu JI
Chinese Journal of Laboratory Medicine 2017;40(4):326-330
Colorectal Cancer (CRC) is a kind of molecular diversified neoplasm.For nonmetastatic early CRC patients who received surgery based systemic treatment,the 5 years survival rate is as high as 50%-80%.However,only chemotherapy is available for majority of metastatic advanced CRC patients.The effect of chemotherapy is disappointing.Numerous studies have demonstrated that some patients with metastatic advanced CRC can benefit from anti-EGFR and anti-VEGF monoclonal antibodies.Here,we give a brief overview about the clinical research of the detection of KRAS,BRAF,MSI and HER2in guiding treatment with targeted drugs in metastatic advanced CRC
10.Multidisciplinary treatment for a patient with locally advanced esophagogastric junc-tion cancer
Ziyu JIA ; Tao FU ; Zhaode BU ; Xiaotian ZHANG ; Yongheng LI ; Lei TANG ; Zhongwu LI ; Jiafu JI
Chinese Journal of Clinical Oncology 2016;(1):42-46
Since the biological characteristics of esophageal gastric junction (EGJ) cancer are different from those of gastric cancer and esophageal cancer, the choice of initial treatment is particularly important. This article introduces a case of locally advanced EGJ can-cer with single metastasis factor treated with preoperative radiochemotherapy in the Beijing Cancer Hospital. Through the multidisci-plinary team, we aim to achieve a better prognosis for this patient and propose new treatment practices for EGJ cancer.

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