1.The Combination of Gefitinib and Acetaminophen Exacerbates Hepatotoxicity via ROS-Mediated Apoptosis
Jiangxin XU ; Xiangliang HUANG ; Yourong ZHOU ; Zhifei XU ; Xinjun CAI ; Bo YANG ; Qiaojun HE ; Peihua LUO ; Hao YAN ; Jie JIN
Biomolecules & Therapeutics 2024;32(5):647-657
Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat.This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression.Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.
2.Investigation and analysis of thyroid nodules and goiter in school-age children in different water iodine areas of Jiangsu Province
Yuting XIA ; Li SHANG ; Yunjie YE ; Yang WANG ; Mao LIU ; Peihua WANG ; Yan XU
Chinese Journal of Endemiology 2022;41(10):819-823
Objective:To analyze the detection rate of thyroid nodules and goiter in school-age children in different water iodine regions and investigate the difference of thyroid nodule and goiter in school-age children with different age, gender and body mass index (BMI) in Jiangsu Province.Methods:In 2017, three villages with water iodine values of 8.1, 51.2 and 115.4 μg/L (iodine deficient group, iodine appropriate group and iodine high group) were selected as survey sites in Xuzhou City, Jiangsu Province, where the supply of iodized salt was suspended. One primary school was selected from each village, and children aged 8 to 10 years old (age balance, half male and half female) were selected from each primary school as the survey subjects. Urine sample were collected, urinary iodine level was determined, height and weight were measured, and neck B ultrasound was performed.Results:A total of 131, 140 and 138 school-age children aged 8 to 10 years old were investigated in the iodine deficient group, iodine appropriate group and iodine high group, respectively, with a total of 409 children. The detection rates of thyroid nodules were 6.9% (9/131), 15.0% (21/140) and 16.7% (23/138), respectively, and the detection rates of goiter were 1.5% (2/131), 1.4% (2/140) and 6.5% (9/138) in the three groups, respectively. There were statistically significant differences in the detection rates of thyroid nodules and goiter in different water iodine groups (χ 2 = 6.92, 6.37, P < 0.05). The detection rates of thyroid nodules in different age groups were 9.5% (12/126), 11.3% (16/142) and 17.7% (25/141), the differences were statistically significant (χ 2 = 9.05, P < 0.05). The detection rates of thyroid nodules were 11.6% (24/207), 14.4% (29/202), and 12.5% (39/313), 16.9% (14/83), 0/9 and 0/4 in the subjects of different gender and BMI, the differences were not statistically significant (χ 2 = 0.69, P > 0.05). The detection rates of goiter in the subjects of different gender, age and BMI were 1.4% (3/207), 5.0% (10/202); 2.4% (3/126), 6.3% (9/142), 0.7% (1/141); 1.6% (3/313), 4.8% (4/83), 3/9 and 1/4. The differences were statistically significant (χ 2 = 4.07, 7.66, P < 0.05). Conclusion:The detection rate of thyroid nodules in school-age children in different water iodine regions in Jiangsu Province may have a certain relationship with age, and the detection rate of goiter may have a certain relationship with age, gender and BMI.
3.Practice and thinking of Otorhinolaryngology Clinical Skill Competition
Bing LIANG ; Yuqin FAN ; Peihua WANG ; Yan LIU ; Hao WU
Chinese Journal of Medical Education Research 2021;20(10):1157-1160
This paper introduces the clinical skill competition organized by the faculty of Otolaryngology Department of Shanghai Jiao Tong University School of Medicine, and analyzes the main problems in implementing items of basic life support, single ear compression bandage, debridement and suturing, foreign body removal from pharynx and larynx area, nasal packing and hemostasis and comprehensive skills. According to contestants' performances, their abilities in clinical analysis and operating skills have been tested, and their professional humanities have been cultivated. Thus, the aim of "promoting learning through examination and substituting competition for practice" is achieved through the competition. Clinical skill competitions can be used widely as supplement form of medical education for its practicability, entertainment, innovation and interaction.
4. Using metabolism related factors constructing a predictive model for the risk of cardiovascular diseases in Xinjiang Kazakh population
Shuxia GUO ; Lei MAO ; Peihua LIAO ; Rulin MA ; Xianghui ZHANG ; Heng GUO ; Jia HE ; Yunhua HU ; Xinping WANG ; Jiaolong MA ; Jiaming LIU ; Lati MU ; Yizhong YAN ; Jingyu ZHANG ; Kui WANG ; Yanpeng SONG ; Wenwen YANG ; Wushoer PUERHATI
Chinese Journal of Endocrinology and Metabolism 2020;36(1):51-57
Objective:
To construct and confirm a predictive model for the risks of cardiovascular diseases (CVD) with metabolic syndrome (MS) and its factors in Xinjiang Kazakh population.
Methods:
A total of 2 286 Kazakh individuals were followed for 5 years from 2010 to 2012 as baseline survey. They were recruited in Xinyuan county, Yili city, Xinjiang. CVD cases were identified via medical records of the local hospitals in 2013, 2016 and 2017, respectively. Factor analysis was performed on 706 MS patients at baseline, and main factors, age, and sex were extracted from 18 medical examination indexs to construct a predictive model of CVD risk. After excluding the subjects with CVD at baseline and incomplete data, 2007 were used as internal validation, and 219 Kazakhs in Halabra Township were used as external validation. Logistic regression discriminations were used for internal validation and external validation, as well as to calculate the probability of CVD for each participant and receiver operating characteristic curves.
Results:
The prevalence of MS in Kazakh was 30.88%. Seven main factors were extracted from the Kazakh MS population, namely obesity factor, blood lipid and blood glucose factor, liver function factor, blood lipid factor, renal metabolic factor, blood pressure factor, and liver enzyme factor. The area under the curve (AUC) for predicting CVD in the internal validation was 0.773 (95%
5.Analysis of water iodine content in Jiangsu rural water factory
Yuting XIA ; Kuikui LU ; Li SHANG ; Yunjie YE ; Peihua WANG ; Yang WANG ; Mao LIU ; Yan XU ; Ran LIU
Chinese Journal of Endemiology 2019;38(10):818-822
Objective To further understand and master the distribution and influencing factors of water iodine in Jiangsu Province.Methods From 2012 to 2014,half of the water plants in rural centralized water supply monitoring plants in 63 counties (cities,districts) of Jiangsu Province were selected as survey sites,and the types of monitoring,types of water plants,types of water sources,self-inspection ability,disinfection situation,water treatment methods were investigated and analyzed.One sample of peripheral water was collected from each survey site to determine the water iodine content.Results From 2012-2014,there were 938 samples of river water were monitored,and the median water iodine was 5.9 μg/L.There were 57 samples of lake water were monitored,the median water iodine was 6.8 μg/L.There were 228 samples of reservoir water were monitored,and the median water iodine was 7.1 μg/L.There were 43 samples of gully pond water were monitored,and the median water iodine was 6.9 μg/L.There were 5 474 samples of deep well water were monitored,and the median water iodine was 28.2 μg/L.There were 162 samples of shallow well water were monitored,and the median water iodine was 30.9 μg/L.There was a statistically significant difference in the median iodine content of water samples from different water sources (x2 =844.9,P < 0.05).The differences of median iodine of lake water,reservoir water,gully pond water,deep well water and shallow well water among different monitoring types were significant (x2 =9.6,6.3,9.7,121.2,38.1,P < 0.05).The differences of median iodine of river water,reservoir water,deep well water and shallow well water among different types of water plants were significant (x2 =109.5,39.0,153.3,7.6,P < 0.05).The iodine contents of fiver water,lake water,deep well water and shallow well water had significant difference in selfinspection ability of different water plants (x2 =62.5,5.1,29.9,10.1,P < 0.05).The iodine content of reservoir water,deep well water and shallow well water were significandy different in different disinfection situation (x2 =12.1,12.4,35.7,P < 0.05).The medians iodine of river water,reservoir water,deep well water and shallow well water had significant difference in different water treatment methods (x2 =9.5,21.2,102.4,46.9,P < 0.05).Conclusions The water iodine contents of water samples in different types of water sources in rural area of Jiangsu Province are different.The level of water iodine is affected by factors such as monitoring type,type of water plant,self-inspection ability,disinfection situation and water treatment method.
6.A light stimulation device and optical control experiment method for carp robots.
Yong PENG ; Xiaoxiao HAN ; Tingting WANG ; Yang LIU ; Yanhong YAN ; Yang ZHAO ; Aidi WANG ; Peihua SU ; Fan ZHANG
Journal of Biomedical Engineering 2018;35(5):720-726
In order to solve the problems that the injury, hemorrhage, infection and edema of the brain tissue caused by brain electrodes implantation for aquatic animal robots, a light stimulation device and an optical control experiment method for carp robots are proposed in this paper. According to the shape of the carp skull, the device is a structure of Chinese character " cut by a printed circuit board which can provide three groups of A, B and C bridge platforms for the light stimulation source. The two ends of a bridge in every group are welded with a jumper board, and the light emitting diodes (LED) are inserted into the jumper boards as the light stimulation source, and all negative poles of the jumper boards are connected to the console by the wire. A LED light can be replaced by another LED light according to the need of the wavelength of the LED light, and various combinations of the light stimulation modes can be also selected. This device was mounted on the carp robot's head, the carp robot was placed in a water maze, and the optical control experiment method was observed to control the forward movement and steering movement of the carp robots ( = 10) under the dark light condition. The results showed that the success rates of the three groups of red light control experiments were 53%-87%, and the success rates of the three groups of blue light control experiments were 50%-80%. This study shows that the apparatus and the method are feasible.
7.Expression of cytokine and Toll-like receptor in children with bacterial infection and its clinical application
Qiong WANG ; Peihua ZHANG ; Shunfeng MAO ; Yan LU
Chinese Journal of Postgraduates of Medicine 2017;40(12):1069-1072
Objective To explore the expression of cytokine and Toll- like receptors(TLRs) in children′s bacterial infection and its clinical significance. Methods Sixty children patients with systemic inflammatory response syndrome(SIRS)were enrolled in this study from December 2014 to June 2016.They were infected by Gram-positive bacteria(G+), Gram-negative bacteria(G+), and regarded as G+group (30 cases) and G- group (30 cases). In addition, 20 healthy subjects were selected as control group.The levels of tumor necrosis factor(TNF)-α, interferon(IFN)-γ, interleukin(IL)-2, IL-4, IL-6, IL-10 and TLR2, TLR4 in peripheral blood were compared.Results The levels of TNF-α,IFN-γ,IL-2, IL-6 and IL-10 in G+group and G-group were significantly higher than those in the control group, and the levels of IFN-γ,IL-6,IL-10 in G+group were significantly lower than those in G+group(P<0.05). The level of TLR2 in G+group was significantly higher than that in G+group and control group(P<0.05).The level of TLR4 in G+group was significantly higher than that in G+group and control group(P<0.05). After treatment, the levels of TNF-α, IFN-γ, IL-2,IL-4, IL-6,IL-10,TLR2 and TLR4 in SIRS were significantly lower than those before treatment: (5.42 ± 1.34) ng/L vs. (9.13 ± 2.91) ng/L, (3.91 ± 1.26)ng/L vs.(6.69 ± 2.13)ng/L,(2.42 ± 0.34)ng/L vs.(3.28 ± 0.62)ng/L,(3.57 ± 0.69)ng/L vs.(4.55 ±1.17) ng/L, (18.82 ± 3.32) ng/L vs. (253.32 ± 38.21) ng/L, (14.32 ± 2.57) ng/L vs. (45.27 ± 8.24) ng/L, 0.366 ± 0.015 vs.1.084 ± 0.053, 0.424 ± 0.029 vs.0.824 ± 0.068,P<0.01.Conclusions Cytokine spectroscopy and TLRs is involved in the process of bacterial infection. Combined detection has great significance in the diagnosis of bacterial infection and identification of infection in children and can provide reference for clinic.
8.Comparison of three kinds of nutritional screening tools in clinical application of general surgery patients application
Xiaoming GAO ; Chunyan HAO ; Peihua ZHU ; Junjing WANG ; Peng YAN ; Rong CHEN
Chinese Journal of Current Advances in General Surgery 2017;20(6):454-457
Objective:To compare the applicability and consistency of NRS2002,SGA and MNA in general surgery hospitalized patients and analyze the effect in clinical outcomes of NRS resuits with respect to each tool.Method:The 150 patients hospitalized in our hospital were chosen as object of study,to screen and evaluate nutritional risk of patients by NRS 2002,SGA and MNA,respectively,on the second hospital day,then to compare the consistency of NRS results with respect to the four tools on clinical outcomes.Results:The applicabilities of hospital NRS2002,SGA and MNA were alternatively 97.25,97.25% and 98.35%.The evaluation of patients' NRS corresponding to different four tools was consistent.The effects of screening results of MNA,NRS2002 and SGA on clinical outcomes were most closely related.Conclusion:The three nutritional evaluation tools can be applied to the screening of malnutrition in General Surgery.The effects of screening results of NRS2002 and SGA on clinical outcomes were most closely related.
9.Application of echocardiography in percutaneous left atrial appendage closure in patients with nonvalvular atrial fibrillation
Zhenhui ZHU ; Jiande WANG ; Hao WANG ; Yan YAO ; Peihua FANG
Chinese Journal of Ultrasonography 2014;23(12):1026-1029
Objective To explore the value and methods of echocardiographic application in percutaneous left atrial appendage(LAA) closure for stroke prevention in patients with nonvalvular atrial fibrillation.Methods 6 male patients with nonvalvular atrial fibrillation were enrolled for percutaneous LAA closure,the mean age was (68.7 ± 5.6) years old,the mean CHADS2 (congestive heart failure,hypertension,age≥75 years,diabetes mellitus,and prior stroke or transient ischemic attacks) score was 3.2 ± 1.0.Rheumatic valvular diseases were excluded by transthoracic eehocardiography(TTE) before closure procedure.Transesophageal echocardiography(TEE) was performed to guide the punctures of the atrial septum and then monitored the operation all through the closure procedure.Diameter of LAA orifice was measure by TEE to help choosing the closure device.Immediate results of closure and complications were inspected by TEE simultaneously.24 hours,7 days,3 months,6 months and 1 year follow-up were performed using TTE.Results All the 6 patients underwent LAA closure successfully.3 LAmbre(Lifetech Scientific,Shenzhen) devices and 3 Watchman(Boston Scientific,Natick,Massachusetts) devices were implanted respectively in the 6 patients.Mean diameter of the LAA orifice was (22.4 ± 3.3)mm,and mean size of the closure devices was (28.0 ± 2.9) mm.2 mm in width residual flow at the inferior edge of closure device existed in 1 ease.No complication was observed.Post-procedure 24 hours and 7 days post-procedure followup showed optimal results in all cases.Conclusions Implantation of both LAA closure devices can be performed with high success rates in patients with nonvalvula ratrial fibrillation,with high risk for stroke,and who either had contraindication or were not willing to accept oral antieoagulation.Echocardiography plays a core role all through the closure procedure and can make it safer and more efficient.
10.Analgesic effects of parecoxib sodium after orthopedic subarachnoid block anesthesia
Liqiu CHEN ; Dun DENG ; Haibo YAN ; Zhaohui WANG ; Wenbin ZHANG ; Weikang ZHANG ; Limin ZHU ; Xiaoyu CHEN ; Peihua YAN ; Dengfei LI ; Huafang HUANG
Chinese Journal of Trauma 2012;28(4):353-356
Objective To investigate the analgesic effects of parecoxib sodium combined with patient controlled epidural analgesia (PCEA) after orthopedic subarachnoid block anesthesia surgery.Methods Two hundred patients undergone orthopedic subarachnoid block anesthesia surgery were randomly and equally divided into two groups:Group P (treated intravenously with 40 mg parecoxib sodium combined with PCEA at the end of operation) and Group C ( treated intravenously with 0.5 g tramadol combined with PCEA at the end of operation).The visual analog scale (VAS) was performed at 6,12,24,48 and 72 hours postoperatively in two groups.Meanwhile,the press frequency of analgesic pump,effective frequency,side effects and satisfaction degree were recorded. Results The VAS sore of Group P was lower than that of Group C at 6,12,24,48 and 72 hours postoperatively ( P < 0.05 ).Group P showed a less number in aspects of the press frequency of analgesic pump,effective frequency,and side effects at 12 and 24 hours,but a higher satisfactory degree,compared with Group C (P <0.05). Conclusion Combined use of parecoxib sodium and PCEA can exert a better analgesic effect and have a low incidence rate of side effects following orthopedic subarachnoid block anesthesia.

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