1.Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma
Shou-Wu WU ; Shao-Kun LIN ; Zhong-Zhu NIAN ; Xin-Wen WANG ; Wei-Nian LIN ; Li-Ming ZHUANG ; Zhi-Sheng WU ; Zhi-Wei HUANG ; A-Min WANG ; Ni-Li GAO ; Jia-Wen CHEN ; Wen-Ting YUAN ; Kai-Xian LU ; Jun LIAO
Progress in Biochemistry and Biophysics 2024;51(9):2182-2193
ObjectiveTo investigate the effect of mucin 1 (MUC1) on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) and its regulatory mechanism. MethodsThe 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital. The expression of MUC1 was measured by real-time quantitative PCR (qPCR) in the patients with PNC. The 5-8F and HNE1 cells were transfected with siRNA control (si-control) or siRNA targeting MUC1 (si-MUC1). Cell proliferation was analyzed by cell counting kit-8 and colony formation assay, and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells. The qPCR and ELISA were executed to analyze the levels of TNF-α and IL-6. Western blot was performed to measure the expression of MUC1, NF-кB and apoptosis-related proteins (Bax and Bcl-2). ResultsThe expression of MUC1 was up-regulated in the NPC tissues, and NPC patients with the high MUC1 expression were inclined to EBV infection, growth and metastasis of NPC. Loss of MUC1 restrained malignant features, including the proliferation and apoptosis, downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells. ConclusionDownregulation of MUC1 restrained biological characteristics of malignancy, including cell proliferation and apoptosis, by inactivating NF-κB signaling pathway in NPC.
2.A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers
Qiong Wei HU ; Guang Wei ZHOU ; Wei Guang ZHOU ; Xi Jia LIAO ; Xing Jia SHI ; FengYang XIE ; Heng Shou LI ; Yong WANG ; Hong Xian FENG ; Li Xiu GU ; Feng Bi CHEN
Biomedical and Environmental Sciences 2024;37(5):445-456
Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis. Results After Bonferroni correction,the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population. Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.
3.Recent Progress in Detection Techniques of Thyroglobulin
Yue WU ; Yong-Jie SHAN ; Shou-Ji CAO ; Shi-Qi JI ; Bo-Wen CHEN ; Xian-Ying MENG ; Zhen-Xin WANG
Chinese Journal of Analytical Chemistry 2024;52(9):1234-1243
Thyroglobulin(Tg)is a glycoprotein with large molecular weight,which is synthesized and secreted into the bloodstream by thyroid follicular cells.The concentration level of Tg in blood is one of the important biomarkers for diagnosis of thyroid diseases such as differentiated thyroid cancer(DTC),subacute thyroiditis,etc..Radioimmunoassay(RIA),immunoradiometric assay(IRMA),and immunochemiluminescence assay(ICMA)are the main clinical methods for detecting Tg.Recently,for meeting the requirement of detecting low concentration of Tg in blood after thyroid clearance surgery,researchers have developed various high-performance analysis methods for detecting Tg concentration in blood samples,providing new assays for thyroid disease screening and efficacy evaluation.This review summarized the analysis methods of Tg,especially the new progresses in the biosensors for monitoring low concentration of Tg in blood during the past five years.The current technical challenges of these methods in clinical applications were briefly discussed,which might provide useful information for developing new liquid biopsy methods of DTC.
4.Long-term outcome of EVAHEART I implantable ventricular assist device for the treatment of end stage heart failure: clinical 3-year follow-up results of 15 cases.
Hai Bo CHEN ; Xian Qiang WANG ; Juan DU ; Jia SHI ; Bing Yang JI ; Li SHI ; Yi Sheng SHI ; Xing Tong ZHOU ; Xiao Han YANG ; Sheng Shou HU
Chinese Journal of Cardiology 2023;51(4):393-399
Objective: To evaluate the long-term efficacy and safety of the implantable ventricular assist system EVAHEART I in clinical use. Methods: Fifteen consecutive patients with end-stage heart failure who received left ventricular assist device therapy in Fuwai Hospital from January 2018 to December 2021 were enrolled in this study, their clinical data were retrospectively analyzed. Cardiac function, liver and kidney function, New York Heart Association (NYHA) classification, 6-minute walk distance and quality of life were evaluated before implantation and at 1, 6, 12, 24 and 36 months after device implantation. Drive cable infection, hemolysis, cerebrovascular events, mechanical failure, abnormally high-power consumption and abnormal pump flow were recorded during follow up. Results: All 15 patients were male, mean average age was (43.0±7.5) years, including 11 cases of dilated cardiomyopathy, 2 cases of ischemic cardiomyopathy, and 2 cases of valvular heart disease. All patients were hemodynamically stable on more than one intravenous vasoactive drugs, and 3 patients were supported by preoperative intra aortic balloon pump (IABP). Compared with before device implantation, left ventricular end-diastolic dimension (LVEDD) was significantly decreased ((80.93±6.69) mm vs. (63.73±6.31) mm, P<0.05), brain natriuretic peptide (BNP), total bilirubin and creatinine were also significantly decreased ((3 544.85±1 723.77) ng/L vs. (770.80±406.39) ng/L; (21.28±10.51) μmol/L vs. (17.39±7.68) μmol/L; (95.82±34.88) μmol/L vs. (77.32±43.81) μmol/L; P<0.05) at 1 week after device implantation. All patients in this group were in NYHA class Ⅳ before implantation, and 9 patients could recover to NYHA class Ⅲ, 3 to class Ⅱ, and 3 to class Ⅰ at 1 month after operation. All patients recovered to class Ⅰ-Ⅱ at 6 months after operation. The 6-minute walk distance, total quality of life and visual analogue scale were significantly increased and improved at 1 month after implantation compared with those before operation (P<0.05). All patients were implanted with EVAHEART I at speeds between 1 700-1 950 rpm, flow rates between 3.2-4.5 L/min, power consumption of 3-9 W. The 1-year, 2-year, and 3-year survival rates were 100%, 87%, and 80%, respectively. Three patients died of multiple organ failure at 412, 610, and 872 d after surgery, respectively. During long-term device carrying, 3 patients developed drive cable infection on 170, 220, and 475 d after surgery, respectively, and were cured by dressing change. One patient underwent heart transplantation at 155 d after surgery due to bacteremia. Three patients developed transient ischemic attack and 1 patient developed hemorrhagic stroke events, all cured without sequelae. Conclusion: EVAHEART I implantable left heart assist system can effectively treat critically ill patients with end-stage heart failure, can be carried for long-term life and significantly improve the survival rate, with clear clinical efficacy.
Humans
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Male
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Adult
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Middle Aged
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Female
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Heart Failure/complications*
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Follow-Up Studies
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Retrospective Studies
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Heart-Assist Devices
;
Quality of Life
5.Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease.
Sheng Xian FAN ; Jian WANG ; Qiang LI ; You Sheng LI ; Wen Xian GUAN ; Jie Shou LI
Chinese Journal of Gastrointestinal Surgery 2021;24(1):94-100
Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.
Bacterial Infections/physiopathology*
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Bile Acids and Salts/physiology*
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Cholestasis/physiopathology*
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Enteral Nutrition
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Gastrointestinal Microbiome/physiology*
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Humans
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Intestinal Diseases/physiopathology*
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Intestines/physiopathology*
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Liver/physiopathology*
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Liver Diseases/physiopathology*
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Parenteral Nutrition/adverse effects*
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Short Bowel Syndrome/physiopathology*
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Signal Transduction
6.A multicenter study on the establishment and validation of autoverification rules for coagulation tests
Linlin QU ; Jun WU ; Wei WU ; Beili WANG ; Xiangyi LIU ; Hong JIANG ; Xunbei HUANG ; Dagan YANG ; Yongzhe LI ; Yandan DU ; Wei GUO ; Dehua SUN ; Yuming WANG ; Wei MA ; Mingqing ZHU ; Xian WANG ; Hong SUI ; Weiling SHOU ; Qiang LI ; Lin CHI ; Shuang LI ; Xiaolu LIU ; Zhuo WANG ; Jun CAO ; Chunxi BAO ; Yongquan XIA ; Hui CAO ; Beiying AN ; Fuyu GUO ; Houmei FENG ; Yan YAN ; Guangri HUANG ; Wei XU
Chinese Journal of Laboratory Medicine 2020;43(8):802-811
Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.
7.Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China.
Yan MA ; Dong Shan ZHU ; Ren Bo CHEN ; Nan Nan SHI ; Si Hong LIU ; Yi Pin FAN ; Gui Hui WU ; Pu Ye YANG ; Jiang Feng BAI ; Hong CHEN ; Li Ying CHEN ; Qiao FENG ; Tuan Mao GUO ; Yong HOU ; Gui Fen HU ; Xiao Mei HU ; Yun Hong HU ; Jin HUANG ; Qiu Hua HUANG ; Shao Zhen HUANG ; Liang JI ; Hai Hao JIN ; Xiao LEI ; Chun Yan LI ; Min Qing LI ; Qun Tang LI ; Xian Yong LI ; Hong De LIU ; Jin Ping LIU ; Zhang LIU ; Yu Ting MA ; Ya MAO ; Liu Fen MO ; Hui NA ; Jing Wei WANG ; Fang Li SONG ; Sheng SUN ; Dong Ting WANG ; Ming Xuan WANG ; Xiao Yan WANG ; Yin Zhen WANG ; Yu Dong WANG ; Wei WU ; Lan Ping WU ; Yan Hua XIAO ; Hai Jun XIE ; Hong Ming XU ; Shou Fang XU ; Rui Xia XUE ; Chun YANG ; Kai Jun YANG ; Sheng Li YUAN ; Gong Qi ZHANG ; Jin Bo ZHANG ; Lin Song ZHANG ; Shu Sen ZHAO ; Wan Ying ZHAO ; Kai ZHENG ; Ying Chun ZHOU ; Jun Teng ZHU ; Tian Qing ZHU ; Hua Min ZHANG ; Yan Ping WANG ; Yong Yan WANG
Biomedical and Environmental Sciences 2020;33(12):893-905
Objective:
Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.
Methods:
A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio (
Results:
Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks.
Conclusion
Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult
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Aged
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COVID-19/virology*
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China/epidemiology*
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Comorbidity
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Female
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Humans
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Male
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Middle Aged
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Retrospective Studies
;
Severity of Illness Index
;
Treatment Outcome
8.Current Status of Antithrombotic Strategy for Elderly Patients With Atrial Fibrillation and Acute Coronary Syndrome After Stent Implantation in Beijing Area
Bo-Yang ZHANG ; Peng-Fei LIU ; Nan-Nan WANG ; Yu-Bin WANG ; Ru-Chen LIU ; Ge WANG ; Xiu-Feng XIE ; Hai-Feng YUAN ; Hai-Hong TANG ; Li ZHAO ; Yun-Dai CHEN ; Kang-Xing SONG ; Yi-Da TANG ; Cheng-Jun GUO ; Yun-Tian LI ; Zhi-Min MA ; Xian WANG ; Dang-Sheng HUANG ; Shou-Li WANG ; Tian-Chang LI
Chinese Circulation Journal 2018;33(1):30-35
Objective: To investigate the current status of antithrombotic strategy for elderly patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) after stent implantation in Beijing area and to study the safety and efficacy of different therapeutic strategy. Methods: A total of 467 relevant patients were enrolled by re-travelling electronic medical records from 12 hospitals in Beijing area. The patients' mean age was (78.70±3.32) years and they were divided into 2 groups by antithrombotic therapy condition: Triple therapy group, n=17 (3.64%), Double therapy group, n=450 (96.36%). The incidence of major adverse cardiac and cerebral events (MACCE) including all-caused death, non-fatal myocardial infarction, stent thrombosis, target vessel revascularization (TVR), stoke and bleeding was compared between Triple therapy group and Double therapy group.Results: The medication in Double therapy group included aspirin+ticagrelor, aspirin+clopidogrel, clopidogrel+warfarin and cilostazol+clopidogrel; in Triple therapy group was aspirin+clopidogrel+warfarin. Patient with HAS-BLED score≥3 was defined as high risk of bleeding and they were all treated by double therapy; HAS-BLED<3 was defined as low risk of bleeding, only 5.03% patients were treated by triple therapy. 3 patients in Triple therapy group and 33 in Double therapy group suffered from gastrointestinal bleeding, P=0.338; 6 patients in Triple therapy group and 128 in Double therapy group had MACCE, P=0.589; 3 and 80 patients died in Triple therapy group and Double therapy group, P=0.766. Conclusion: Triple therapy was rarely used in elderly AF and ACS patients after stent implantation, double therapy was the main strategy; the incidence of MACCE and mortality were similar between triple and double therapies; patients with triple therapy had the higher incidence of gastrointestinal bleeding.
9.Clinical Value of Extravascular Lung Water Monitoring for Rapid Recovery in Pediatric Patients After Complete Repair of Tetralogy of Fallot
Ju-Xian YANG ; Xu WANG ; Shou-Jun LI ; Jun YAN ; Sheng-Li LI ; Min ZENG ; Lei-Lei DUAN ; Xia LI ; Li-Wei LIU ; Zhong-Yuan LU ; Xue-Fang YANG ; Lin ZHENG ; Dan LI
Chinese Circulation Journal 2018;33(3):270-274
Objective: To explore the clinical value of extravascular lung water monitoring for rapid recovery in pediatric patients after complete repair of tetralogy of Fallot (TOF). Methods: A total of 43 pediatric patients received complete repair of TOF were studied. The pulse contour cardiac index (PCCI), global end diastolic volume index (GEDI), stroke volume variation (SVV), systemic vascular resistance index (SVRI), global ejection fraction (GEF), maximum of pressure increase in aorta (dPmax), extravascular lung water index (EVWI) and pulmonary vascular permeability index (PVPI) were recorded by pulse-indicated continuous cardiac output (PICCO) monitoring at immediately enter pediatric ICU (PICU) and 6h, 12h, 18h, 24h post-operation. Meanwhile, the heart rate, blood pressure, central venous pressure (CVP), left atrium pressure (LAP) and balance of liquid were monitored; mechanical ventilation time, PICU stay time, re-intubation,re-occlusion of major aortopulmonary collateral arteries (MAPCAs) and other complications were recorded. Based on post-operative mechanical ventilation time, the patients were divided into 2 groups: Rapid recovery (R) group, patients with mechanical ventilation≤24h, n=29 and Delayed recovery (D) group, patients with mechanical ventilation>24h, n=14. Results: Compared with group D, group R had the shorter mechanical ventilation time (14.2±8.0) h vs (86.3±44.5) h and PICU stay time (2.5±1.7) days vs (5.3±3.6) days, both P<0.05; decreased PVPI at immediately enter PICU and 6h, 12h, 18h, 24h post-operation as (4.9±1.3 vs 6.4±1.5),(5.1±1.8 vs 6.5±1.3),(4.8±2.0 vs 6.5±1.6),(4.4±1.1vs 6.9±1.8), (4.4±2.5 vs 6.5±2.2) respectively, all P<0.05; Lower ELWI at 12h and 18h post-operation as(20.9±6.1) ml/kg vs (26.8±5.7) ml/kg and(19.1±5.5) ml/kg vs (26.7±5.5)ml/kg, both P<0.05. Group R had no patient received re-occlusion of MAPCAs after operation, while Group D had 3. No death, no catheter-related complication occurred in either group. Conclusion: MAPCAs may increase extravascular lung water, pulmonary vascular permeability and cause lung perfusion, therefore affect the early recovery of complete repair of pediatric TOF. PICCO monitoring may conduct bedside quantitative observation of lung perfusion, combining with ELWI and PVPI, clinicians may identify and manage MAPCAs as necessity for rapid recovery in relevant patients.
10. Relationship between catecholamine level and gene polymorphism of β1 adrenergic receptor G1165C in children with EV71 infection in hand foot and mouth disease
Zhi-Xian LEI ; Bang-Tao LI ; Ya-Zhou WANG ; Qiu-Yu LIN ; Li-Rong ZHOU ; Xin LI ; Wei XIANG ; Hong-Ai LI ; Xiao-Ming LI ; Man-Fang XIE ; Qi WANG ; Nai-Chao FENG ; Dao-Mou ZHU ; Yuan-Ping HAI ; Lan CUI ; Ya-Qin ZHANG ; Zhi-Wen LIU ; Shou-Ye WU ; Yong-Zhao CHEN ; Hong-Ai LI ; Ting HUANG ; Lan CUI ; Ke-Qing ZHU ; Xiao-Jie HE
Asian Pacific Journal of Tropical Medicine 2017;10(5):473-477
Objective To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). Methods The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). Results The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P < 0.05); however, the levels of plasma adrenaline in two groups had no statistical differences (P > 0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). Conclusions As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of β1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.

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