1.Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor.
Qian LI ; Tao SUN ; Hua ZHANG ; Wei LIU ; Yu XIAO ; Hongqi SUN ; Wencheng YIN ; Yanhong YAO ; Yangchun GU ; Yan'e LIU ; Fumei YI ; Qiqi WANG ; Jinyu YU ; Baoshan CAO ; Li LIANG
Chinese Journal of Lung Cancer 2022;25(3):137-146
BACKGROUND:
The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear.
METHODS:
A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization.
RESULTS:
There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not.
CONCLUSIONS
In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use*
;
Glucuronosyltransferase/genetics*
;
Humans
;
Lung Neoplasms/drug therapy*
;
Mutation
;
Polymorphism, Genetic
;
Retrospective Studies
2.Effects of broad-spectrum antibiotics on the efficacy of 5-fluorouracil treatment of CT26 tumor-bearing mice
Yanhong WU ; Zhigang ZHANG ; Aiping XU ; Tao ZHU ; Hui LIU ; Xiaoxuan ZUO ; Xiaolei TANG
Chinese Journal of Microbiology and Immunology 2021;41(12):934-943
Objective:To study the effects of broad-spectrum antibiotics and induced antibiotic-resistant bacteria on the efficacy of 5-fluorouracil (5-FU) chemotherapy for mice with colon cancer and to investigate the underlying mechanisms associated with anti-tumor immune responses.Methods:BALB/c mice were subcutaneously injected with CT26 colon cancer cells and randomized into four groups: tumor-bearing control group, antibiotic group treated with ampicillin, streptomycin and colistin, 5-FU group and anitibiotic+ 5-FU group. Tumor volumes and body weights were measured and recorded. Seven days after the last 5-FU treatment, the percentages of splenic immune cell subpopulations and proliferated CD8 + T cells after co-culturing with CT26 were analyzed by flow cytometry. Gut microbiota composition was detected by 16S rRNA sequencing and the bacteria in mesenteric lymph nodes (mLN) were isolated and cultured. Bone marrow-derive macrophages were stimulated with identified bacteria and the expression of M1 and M2 polarization markers were assessed by quantitative PCR. The proliferation of CD8 + T cells co-cultured with bacteria-treated macrophages was analyzed by flow cytometry. In addition, tumor-bearing mice were treated with 5-FU and oral gavage of bacteria isolated from antibiotic+ 5-FU group or PBS. Tumor volumes, gut microbiota composition and the percentages of proliferated CD8 + T cells co-cultured with CT26 were assessed. Results:Tumor volumes were larger and body weights were lower in the antibiotic+ 5-FU group than in the 5-FU group. The percentages of CD4 + T cells, CD8 + T cells and neutrophils did not varied significantly after using antibiotics, however, the percentage of monocytes was increased in the antibiotic group. The percentage of proliferated tumor-specific CD8 + T cells in the antibiotic+ 5-FU group was decreased compared with that in the 5-FU group. Compared with the control group and 5-FU group, antibiotic usage was associated with the changes in gut microbiota composition with decreased α diversity indexes. Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis were isolated from mLNs of the antibiotic group, 5-FU group and antibiotic+ 5-FU group, respectively. Bone marrow-derived macrophages stimulated with Proteus mirabilis expressed arginase at a high level, which was a M2 polarization marker of macrophage, and associated with the decreased percentage of proliferated CD8 + T cells after co-culturing. Bacteria of the genus Proteus were enriched in the gut microbiota of 5-FU-treated tumor-bearing mice with the oral gavage of Proteus mirabilis. Although no significant inhibitory effect on tumor growth was observed, the oral gavage of Proteus mirabilis was associated with the decreased percentage of proliferated tumor-specific CD8 + T cells in vitro. Conclusions:Broad-spectrum antibiotics inhibited the efficacy of chemotherapy and the proliferation of tumor-specific CD8 + T cells, in which antibiotic-resistant bacteria might be involved.
3.Proper use of examination of intraocular fluid to assist precise diagnosis and treatment of vitreoretinal diseases
Chinese Journal of Ocular Fundus Diseases 2021;37(7):497-502
There are many types of fundus diseases and their causes are complex. They can be caused by metabolic factors or inflammatory factors. Fundus examination and imaging examination tools are the main methods for diagnosing fundus diseases. However, in terms of determining the cause and early diagnosis, if the intraocular fluid detection technology can be reasonably combined, the advantages will be greater. Intraocular fluid is the general term for fluid in the eyeball, including aqueous humor, vitreous humor, etc. The molecular components that can be tested include DNA, RNA, antigens, antibodies, and cytokines. With the advancement of molecular testing technology and equipment, intraocular fluid testing as an evidence-based method has gradually been incorporated into the consensus and guidelines of more fundus disease experts, and is mainly used for infectious fundus diseases and camouflage syndromes. Reasonable use of intraocular fluid testing can help improve the personalized diagnosis and treatment of fundus diseases and reduce unnecessary drug overuse. However, it is worth noting that intraocular fluid detection is only one of many tools and cannot replace other examinations and clinical experience. Excessive intraocular fluid testing not only increases the risk of clinical infections because of invasiveness, but also increases the burden on patients.
4.Advance care planning acceptance and its influencing factors in heart failure patients
Yuan LIU ; Lin TAO ; Yongju PEI ; Yinping YI ; Yanhong SHEN ; Yu SHAN ; Yuefei HAO
Chinese Journal of Practical Nursing 2021;37(5):363-367
Objective:To investigate the acceptance of advance care planning and its influencing factors in heart failure patients.Methods:A total of 208 patients with heart failure were surveyed by general data questionnaires and advance care planning acceptance questionnaires.Results:The total score of advance care planning acceptance of heart failure patients was (44.26 ± 11.73), the score of feeling dimension was (13.67 ± 5.72), the score of attitude dimension was (30.59 ± 6.33). 53.4%(111/208) of patients were willing to accept the talking about advance care planning. Regression analysis results showed that education level, New York Heart Association (NYHA) classification, communication status with medical staff and whether they had received life-sustaining treatment were important factors influencing of the acceptance of advance care planning in patients with heart failure.Conclusion:Patients with heart failure had higher acceptance of advance care planning. In clinical work, it is necessary to strengthen the scientific popularization of advance care planning in patients with low education level, low NYHA grade and no exposure to life-sustaining treatment. And strengthen the daily communication with patients to prepare for the follow-up advance care planning related communication.
5. Expert consensus on prevention and cardiopulmonary resuscitation for cardiac arrest in COVID-19
Wei SONG ; Yanhong OUYANG ; Yuanshui LIU ; Heping XU ; Feng ZHAN ; Wenteng CHEN ; Jun ZHANG ; Shengyang YI ; Jie WEI ; Xiangdong JIAN ; Deren WANG ; Xianjin DU ; Ying CHEN ; Yingqi ZHANG ; Shuming XIANYU ; Qiong NING ; Xiang LI ; Xiaotong HAN ; Yan CAO ; Tao YU ; Wenwei CAI ; Sheng'Ang ZHOU ; Yu CAO ; Xiaobei CHEN ; Shunjiang XU ; Zong'An LIANG ; Duohu WU ; Fen AI ; Zhong WANG ; Qingyi MENG ; Yuhong MI ; Sisen ZHANG ; Rongjia YANG ; Shouchun YAN ; Wenbin HAN ; Yong LIN ; Chuanyun QIAN ; Wenwu ZHANG ; Yan XIONG ; Jun LV ; Baochi LIU ; Xiaojun HE ; Xuelian SUN ; Yufang CAO ; Tian'En ZHOU
Asian Pacific Journal of Tropical Medicine 2021;14(6):241-253
Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.
6.Methodological analysis of different types of reviews
Xiaodan NIU ; Hongxia TAO ; Haihui RUAN ; Junting CHI ; Jing ZHANG ; Yanhong WANG
Chinese Journal of Modern Nursing 2021;27(10):1391-1396
Literature review is an essential link in nursing research. A systematic and rigorous literature review can transform the existing primary research into evidence that effectively guides nursing practice, thereby promoting the development of nursing specialization. This article introduces common review types such as the systematic review, Meta-analysis, overview of systematic reviews, Meta-synthesis, scoping review, and integrative review, and distinguishes the similarities and differences of different types of reviews, and analyzes their advantages and limitations, in order to improve the scientific and professional level of nursing practice, and promote the development of evidence-based and nursing disciplines.
7.Risk factors for surgical site infection after emergency abdominal surgery: a multicenter cross-sectional study in China
Ze LI ; Junru GAO ; Li SONG ; Peige WANG ; Jian'an REN ; Xiuwen WU ; Suming LUO ; Qingjun ZENG ; Yanhong WENG ; Xinjian XU ; Qingzhong YUAN ; Jie ZHAO ; Nansheng LIAO ; Wei MAI ; Feng WANG ; Hui CAO ; Shichen WANG ; Gang HAN ; Daorong WANG ; Hao WANG ; Jun ZHANG ; Hao ZHANG ; Dongming ZHANG ; Weishun LIAO ; Wanwen ZHAO ; Wei LI ; Peng CUI ; Xin CHEN ; Haiyang ZHANG ; Tao YANG ; Lie WANG ; Yongshun GAO ; Jiang LI ; Jianjun WU ; Wei ZHOU ; Zejian LYU ; Jian FANG
Chinese Journal of Gastrointestinal Surgery 2020;23(11):1043-1050
Objective:Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence.Methods:Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS.Results:A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ 2=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ 2=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ 2=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ 2=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ 2=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ 2=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ 2=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions:For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.
8.Risk factors for surgical site infection after emergency abdominal surgery: a multicenter cross-sectional study in China
Ze LI ; Junru GAO ; Li SONG ; Peige WANG ; Jian'an REN ; Xiuwen WU ; Suming LUO ; Qingjun ZENG ; Yanhong WENG ; Xinjian XU ; Qingzhong YUAN ; Jie ZHAO ; Nansheng LIAO ; Wei MAI ; Feng WANG ; Hui CAO ; Shichen WANG ; Gang HAN ; Daorong WANG ; Hao WANG ; Jun ZHANG ; Hao ZHANG ; Dongming ZHANG ; Weishun LIAO ; Wanwen ZHAO ; Wei LI ; Peng CUI ; Xin CHEN ; Haiyang ZHANG ; Tao YANG ; Lie WANG ; Yongshun GAO ; Jiang LI ; Jianjun WU ; Wei ZHOU ; Zejian LYU ; Jian FANG
Chinese Journal of Gastrointestinal Surgery 2020;23(11):1043-1050
Objective:Surgical site infection (SSI) is the most common infectious complication after emergency abdominal surgery (EAS). To a large extent, most SSI can be prevented, but there are few relevant studies in China. This study mainly investigated the current situation of SSI occurrence after EAS in China, and further explored risk factors for SSI occurrence.Methods:Multi-center cross-sectional study was conducted. Clinical data of patients undergoing EAS in 33 hospitals across China between May 1, 2019 and June 7, 2019 were prospectively collected, including perioperative data and microbial culture results from infected incisions. The primary outcome was the incidence of SSI after EAS, while the secondary outcomes were postoperative hospital stay, ICU occupancy rate, length of ICU stay, hospitalization cost, and mortality within postoperative 30 days. Univariate and multivariate logistic regression models were used to analyze the risk factors of SSI after EAS.Results:A total of 660 EAS patients aged (47.9±18.3) years were enrolled in this study, including 56.5% of males (373/660). Forty-nine (7.4%) patients developed postoperative SSI. The main pathogen of SSI was Escherichia coli [culture positive rate was 32.7% (16/49)]. As compared to patients without SSI, those with SSI were more likely to be older (median 56 years vs. 46 years, U=19 973.5, P<0.001), male [71.4% (35/49) vs. 56.1% (343/611), χ 2=4.334, P=0.037] and diabetes [14.3% (7/49) vs. 5.1% (31/611), χ 2=5.498, P=0.015]; with-lower preoperative hemoglobin (median: 122.0 g/L vs. 143.5 g/L, U=11 471.5, P=0.006) and albumin (median: 35.5 g/L vs. 40.8 g/L, U=9452.0, P<0.001), with higher blood glucose (median: 6.9 mmol/L vs. 6.0 mmol/L, U=17 754.5, P<0.001); with intestinal obstruction [32.7% (16/49) vs. 9.2% (56/611), χ 2=25.749, P<0.001], with ASA score 3-4 [42.9% (21/49) vs. 13.9% (85/611), χ 2=25.563, P<0.001] and with high surgical risk [49.0% (24/49) vs. 7.0% (43/611), χ 2=105.301, P<0.001]. The main operative procedure resulting in SSI was laparotomy [81.6%(40/49) vs. 35.7%(218/611), χ 2=40.232, P<0.001]. Patients with SSI experienced significantly longer operation time (median: 150 minutes vs. 75 minutes, U=25 183.5, P<0.001). In terms of clinical outcome, higher ICU occupancy rate [51.0% (25/49) vs. 19.5% (119/611), χ 2=26.461, P<0.001], more hospitalization costs (median: 44 000 yuan vs. 15 000 yuan, U=24 660.0, P<0.001), longer postoperative hospital stay (median: 10 days vs. 5 days, U=23 100.0, P<0.001) and longer ICU occupancy time (median: 0 days vs. 0 days, U=19 541.5, P<0.001) were found in the SSI group. Multivariate logistic regression analysis showed that the elderly (OR=3.253, 95% CI: 1.178-8.985, P=0.023), colorectal surgery (OR=9.156, 95% CI: 3.655-22.937, P<0.001) and longer operation time (OR=15.912, 95% CI:6.858-36.916, P<0.001) were independent risk factors of SSI, while the laparoscopic surgery (OR=0.288, 95% CI: 0.119-0.694, P=0.006) was an independent protective factor for SSI. Conclusions:For patients undergoing EAS, attention should be paid to middle-aged and elderly patients and those of colorectal surgery. Laparoscopic surgery should be adopted when feasible and the operation time should be minimized, so as to reduce the incidence of SSI and to reduce the burden on patients and medical institutions.
9.Mechanism study of sanguinarine inhibiting tumor growth of ovarian cancer by apoptosis induction
Beilei ZHANG ; Yi LI ; Tao WU ; Feng JIANG ; Hongxi ZHAO ; Yanhong LI
Practical Oncology Journal 2019;33(4):305-309
Objective The aim of this study was to investigate the mechanism of sanguinarine(SANG)on the inhibitory pro-liferation in ovarian cancer SKOV3 cells. Methods CCK-8 assay was used to detect proliferation of SKOV3 cells. Flow cytometry was used to detect the effect of SANG on apoptosis in SKOV3 cells. The spectrophotometer was used to detect the production of reac-tive oxygen species(ROS)by SANG. The mouse ovarian cancer xenograft model was used to detect the inhibitory effect of SANG on tumor growth. Results SANG promoted apoptosis in SKOV3 cells in a dose-and time-dependent manner. The SANG-induced ap-optosis was associated with the production of ROS,Activated the c-Jun-N-terminal kinase( JNK) and nuclear factor-κB( NF-κB)signaling pathways. In mouse model of ovarian cancer xenografts,after intravenous injection of mice with SANG,SANG was signifi-cantly inhibited the growth of ovarian cancer xenografts when compared to the control group. SANG also significantly induced apoptosis in ovarian cancer xenografts. Conclusion SANG can significantly inhibit the proliferation of ovarian cancer SKOV3 cells,induce ap-optosis,increase the production of ROS,and inhibit the growth of ovarian cancer.
10.Application of FMEA regulated drug supply chain collaborative service platform for drug-receiving in outpatient pharmacy
Yanhong CHEN ; Jingxia WANG ; Xia TAO ; Wansheng CHEN ; Rong WU
Journal of Pharmaceutical Practice 2019;37(1):86-90
Objective To strengthen the system of drug supply chain collaborative service platform in drug supply, decrease drug inventory backlog, and improve the outpatient pharmacy management capacity in outpatient pharmacy.Methods Failure mode and effects analysis (FMEA) method was used to discover the potential risks in the drug supply chain collaborative service platform and formulate the corresponding improvement measures.Results The number of drug-receiving errors dropped from 137times to 32times and the risk reduction rate was 76.64%after improving the procurement process of the supply chain service platform, which significantly reduced the risk of contracting errors.Conclusion FMEA method could help to figure out the loopholes and hidden dangers of the pharmacy system, which made the outpatient pharmacy more reasonable and accurate by constantly improving the measures of the drug supply chain collaborative service platform.

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