1.Interpretation and Elaboration for the ARRIVE Guidelines 2.0—Animal Research: Reporting In Vivo Experiments (V)
Zhengwen MA ; Xiaying LI ; Xiaoyu LIU ; Yao LI ; Jian WANG ; Jin LU ; Guoyuan CHEN ; Xiao LU ; Yu BAI ; Xuancheng LU ; Yonggang LIU ; Yufeng TAO ; Wanyong PANG
Laboratory Animal and Comparative Medicine 2024;44(1):105-114
Improving the reproducibility of biomedical research results is a major challenge. Transparent and accurate reporting of the research process enables readers to evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist that is applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as enhance the reliability, repeatability, and clinical translation of animal experimental results. The use of the ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and completeness of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. This article is based on the best practices following the ARRIVE 2.0 guidelines in international journals, and it interprets, explains, and elaborates in Chinese the fifth part of the comprehensive version of the ARRIVE 2.0 guidelines published in PLoS Biology in 2020 (the original text can be found at
2.Establishment of irritable bowel syndrome model in rats by chronic water avoidance stress method and its evaluation
Tingting LIU ; Qingyu ZHANG ; Xiangshun ZHAO ; Yunlai SHI ; Yannan YU ; Zhengwen WANG ; Shaozong CHEN ; Chuwen FENG ; Tiansong YANG
Journal of Jilin University(Medicine Edition) 2024;50(3):840-846
Objective:To discuss the method for establishing the rat models of irritable bowel syndrome(IBS)by chronic water avoidance stress(WAS)method,and to evaluate its feasibility.Methods:Thirty male Wistar rats were randomly divided into control group(n=10)and model group(n=20).The rats in model group were induced by WAS method for 1 h everyday,lasting for 10 consecutive days;the rats in control group underwent no interventions.After modeling,the general conditions and body weights of the rats in two groups were observed and recorded.The elevated plus maze(EPM)test was used to detect the percentages of the number of open arm entries(OE)and the time spent in open arms(OT)of the rats in two groups;the abdominal withdrawal reflex(AWR)test was used to assess the visceral sensitivity of the rats in two groups;electrocardiography was used to detect the heart rate variability(HRV)of the rats in two groups;electromyography(EMG)of the external oblique muscle was used to detect the colorectal pain sensitivity thresholds of the rats in two groups;multi-channel physiological signal recorder was used to monitor the slow wave frequency of the colon of the rats in two groups.Results:There were no death rats in both groups during the modeling period.After modeling,the rats in model group exhibited poor mental status,reduced spontaneous activity,hypoactivity,disordered and dull fur,irritability,and unclean anal areas;whereas,the rats in control group showed no significant changes in the mental state,spontaneous activity,fur,and perianal area.Compared with control group,the body weight of the rats in model group was significantly decreased(P<0.05).The EPM test results showed that compared with control group,the OE percentage and OT percentage of the rats in model group were significantly decreased(P<0.01).The AWR test results showed that 12 rats in model group scored≥3 points,indicating that the successful rate in creating the visceral pain models was 60%.Compared with control group,the low frequency(LF)signals and the ratio of LF/high frequency(HF)of the rats in model group were significantly increased(P<0.01),and the HF was significantly decreased(P<0.05).The EMG results showed that compared with control group,the coloretal pain sensitivity threshold of the colon of the rats in model group was significantly decreased(P<0.01),and the slow wave frequency of the colon was significantly increased(P<0.01).Conclusion:The WAS method for establishing the rat model of IBS effectively demonstrates the changes in behavior and mental state,increased the visceral sensitivity,accelerated colonic slow wave frequency,and autonomic nervous system imbalance;the WAS method can serve as an effective modeling approach for observing and evaluating the related drugs and interventions on treatment of IBS.
3.Explanation and Elaboration for the ARRIVE Guidelines 2.0—Reporting Animal Research and In Vivo Experiments (Ⅰ)
Jian WANG ; Jin LU ; Zhengwen MA ; Guoyuan CHEN ; Xiao LU ; Yu BAI ; Xiaoyu LIU ; Xuancheng LU ; Jing GAO ; Yao LI ; Wanyong PANG
Laboratory Animal and Comparative Medicine 2023;43(2):213-224
Improving the reproducibility of biomedical research results is a major challenge. Researchers reporting their research process transparently and accurately can help readers evaluate the reliability of the research results and further explore the experiment by repeating it or building upon its findings. The ARRIVE 2.0 guidelines, released in 2019 by the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), provide a checklist applicable to any in vivo animal research report. These guidelines aim to improve the standardization of experimental design, implementation, and reporting, as well as the reliability, repeatability, and clinical translatability of animal experimental results. The use of ARRIVE 2.0 guidelines not only enriches the details of animal experimental research reports, ensuring that information on animal experimental results is fully evaluated and utilized, but also enables readers to understand the content expressed by the author accurately and clearly, promoting the transparency and integrity of the fundamental research review process. At present, the ARRIVE 2.0 guidelines have been widely adopted by international biomedical journals. this article is a Chinese translation based on the best practices of international journals following the ARRIVE 2.0 guidelines in international journals, specifically for the complete interpretation of the ARRIVE 2.0 guidelines published in the PLoS Biology journal in 2020 (original text can be found at
4.Safety of tirofiban in patients with acute anterior circulation large vessel occlusive cerebral infarction during bridging endovascular treatment after intravenous thrombolysis
Zhengwen CHEN ; Peicheng LI ; Yizhi LIU ; Bo LI ; Chen YUAN ; Kaiwen HOU ; Long CHEN
Chinese Journal of Neuromedicine 2023;22(2):149-156
Objective:To investigate the safety of tirofiban in patients with anterior circulation acute large vessel occlusion cerebral infarction during bridging endovascular treatment (EVT) after intravenous thrombolysis (IVT).Methods:Two hundred and three patients received bridging EVT after IVT in Department of Intervention, First Affiliated Hospital of Soochow University from January 2017 to January 2022 were chosen. Patients were divided into tirofiban group ( n=80) and non-tirofiban group ( n=123) according to whether or not tirofiban was used during EVT, and then patients from tirofiban group were subdivided into stent implantation group ( n=52) and non-stent implantation group ( n=28) according to whether or not emergency stent implantation was performed. The clinical data, safety indexes (intracranial hemorrhage [ICH] rate 24 h, 2-3 d, and 90 d after EVT, new ICH incidence 3-90 d after EVT, fatal ICH rate, and mortality 90 d after EVT), and prognoses 90 d after EVT were compared. Results:(1) Compared with the non-tirofiban group, the tirofiban group had significantly higher proportions of males, and patients with tandem occlusion, balloon dilation or stent implantation, and statistically lower proportion of patients with atrial fibrillation, significantly longer surgical time, and significantly different distribution of stroke types ( P<0.05). No significant differences were noted in ICH incidences 24 h after EVT, 2-3 d after EVT and 90 d after EVT, fatal ICH incidence, mortality incidence 90 d after EVT, or good prognosis rate 90 d after surgery between tirofiban group and non-tirofiban group ( P>0.05). (2) Patients in the stent implantation group had significantly higher percentages of tandem occlusion and balloon dilation compared with those in the non-stent implantation group ( P<0.05). No significant difference was noted in good prognosis rate 90 d after EVT or new ICH incidence 3-90 d after EVT between the stent implantation group and the non-stent implantation group ( P>0.05). Compared with the non-stent implantation group, the stent implantation group had statistically higher ICH incidences 24 h after EVT, 2-3 d after EVT, and 90 d after EVT, significantly higher fatal ICH incidence and mortality 90 d after EVT ( P<0.05). Conclusion:Tirofiban is safe in patients with anterior circulation acute large vessel occlusion cerebral infarction during EVT after IVT; however, if emergency stent implantation is performed, it will lead to increased intracranial hemorrhage and mortality.
5.Silencing STAT6 with siRNA prevents development of eosinophilic chronic rhinosinusitis: an experimental study
Hongqi WEI ; Zhengwen ZHU ; Hongyu XING ; Zhiyong LIU ; Zhongsheng CAO ; Longjiang XU ; Jisheng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(11):1102-1111
Objective:To investigate whether silencing signal transducer and activator of transcription 6 (STAT6) with siRNA can inhibit eosinophilic inflammation of sinonasal mucosa in a mouse model of eosinophilic chronic rhinosinusitis (ECRS).Methods:The study was conducted from March to September in 2022. Forty-eight female BALB/c mice were randomly divided into four groups: the control group, the Vehicle (transfection reagent)-treated group, the Scramble siRNA (Control siRNA)-treated group, and the STAT6 siRNA-treated group, with twelve mice in each group. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS murine model was established. SiRNA prepared in Lipofectamine was locally administered to the nasal cavity. After administration, samples of the peripheral blood and sinonasal mucosa were collected. Eosinophils in peripheral blood were detected by hematology analyzer. Total and OVA-specific IgE (OVA-sIgE) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Mucosal levels of cytokines and chemokines, including interleukin (IL)-5, IL-17A, interferon-γ (IFN-γ) and eotaxin-1, were also measured using ELISA. Mucosal histological changes of eosinophil infiltration were examined using hematoxylin, and eosin staining, and tissue eosinophil count was performed using a microscope under a high-power field (HPF). Tissue expression of STAT6 and phosphorylated STAT6 (p-STAT6) was detected with the western blot method. Immunofluorescence staining was used to localize the expression of p-STAT6 in sinonasal mucosa. Statistical analysis was conducted using SPSS 18.0 software.Results:Peripheral blood eosinophil count, percentage of peripheral blood eosinophil, total serum IgE level, and serum OVA-sIgE level in the STAT6 siRNA-treated group [(0.318±0.045)×10 3/μl, (3.667±0.479)%, (102.070±13.205) ng/ml, and (38.870±7.352) ng/ml] were significantly different from those of the Vehicle-treated group [(0.532±0.049)×10 3/μl, (6.710±1.061)%, (203.102±29.653) ng/ml, and (74.575±6.432) ng/ml, Z value was -2.56, -2.24, -2.40, and -2.56, respectively, all P<0.05] and Scramble siRNA-treated group [(0.493±0.036)×10 3/μl, (5.858±0.872)%, (189.964±30.042) ng/ml, and (80.935±8.358) ng/ml, Z value was -2.17, -2.08, -2.24, and -2.72, respectively, all P<0.05]. Besides, IL-5 and eotaxin-1 levels in the STAT6 siRNA-treated group [(312.279±34.281) pg/ml and (25.297±4.323) pg/ml] were significantly lower than those in the Vehicle-treated group [(689.667±31.905) pg/ml and (68.278±6.485) pg/ml, Z value was -2.73 and -2.88, respectively, both P<0.01] and Scramble siRNA-treated group [(661.783±42.094) pg/ml and (63.015±7.416) pg/ml, Z value was -2.72 and -2.81, respectively, both P<0.01]. Tissue eosinophil count in sinonasal mucosa was (29.132±4.163)/HPF in the STAT6 siRNA-treated group, and were significantly less than those in the Vehicle-treated group [(78.050±7.912)/HPF, Z=-2.88, P<0.01] and Scramble siRNA-treated group [(73.864±8.671)/HPF, Z=-2.72, P<0.01]. The expression level of STAT6 protein (0.105±0.021) was significantly decreased in the mice treated with STAT6 siRNA compared with PBS, Vehicle, and Scramble siRNA (0.232±0.037, 0.243±0.039, and 0.228±0.032, Z value was -2.25, -2.49, and -2.56, respectively, all P<0.05). Corresponding, p-STAT6 protein level (0.292±0.038) was markedly decreased by the introduction of STAT6 siRNA, the difference was statistically significant as compared with the Vehicle-and Scramble siRNA-treated groups (0.613±0.046 and 0.641±0.050, Z value was -2.81 and -2.88, respectively, both P<0.01). Immunofluorescence staining showed that p-STAT6 was mainly located in the nucleus of nasal epithelial cells and inflammatory cells. The green fluorescence of p-STAT6 expression in sinonasal mucosa in the STAT6 siRNA-treated group was weaker than that in the Vehicle-and Scramble siRNA-treated groups. Conclusion:Intranasal administration of STAT6 siRNA can significantly downregulate STAT6 expression, decrease p-STAT6 level, and prohibit the development of Th2-skewed ECRS.
7.HCV infection in 219 heroin addicts with pulmonary tuberculosis in Xi’an
Ye WANG ; Xiaoyun WANG ; Xiaoge ZHANG ; Kun ZHANG ; Feiyu LI ; Zhengwen LIU
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(4):612-616
【Objective】 To explore the incidence rate and characteristics of hepatitis-C virus (HCV) infection in heroin addicts with pulmonary tuberculosis (TB) in Xi’an so as to provide a basis for pulmonary TB and HCV prevention and control measures. 【Methods】 We carried out behavior investigation and serological detection of 219 heroin addicts with pulmonary TB infection in Xi’an Eighth Hospital. We analyzed HCV infection risk factors by Chi-square test and multi-factor Logistic regression method. 【Results】 The prevalence of HCV infection in heroin addicts with pulmonary TB was 71.2% and 92.9% in injected drug users (IDUs). The HCV infection rate was higher than the infection rate of HBV (10.9%) and HIV (5.9%) in heroin addicts with pulmonary TB. The major infection risk factors were intravenous injection (OR=18.632, 95% CI: 8.146-41.284) and longer duration of drug use (OR=1.428, 95% CI: 1.086-1.876). 【Conclusion】 The study found high HCV infection rate in heroin addicts with pulmonary TB and that the independent risk factors are the drug injection and duration of drug use. In order to prevent further spread of HCV in heroin addicts with pulmonary TB, we should establish and perfect the management system of HCV infection.
8.Use of sofosbuvir-based regimens in the treatment of adolescents and children with chronic hepatitis C
Shan HE ; Xiaoyun WANG ; Qunying HAN ; Zhengwen LIU
Chinese Journal of Hepatology 2021;29(1):83-86
Sofosbuvir has ushered in a new era of hepatitis C treatment with its strong inhibition on the replication of hepatitis C virus, favorable safety profile and less interactions with other drugs. Sofosbuvir-based regimens have been included as the first-line therapies for the treatment of adults with chronic hepatitis C (CHC) in international guidelines. Available clinical trial data show that sofosbuvir with ribavirin and ledipasvir/sofosbuvir are highly efficacious and safe in CHC patients aged 3-17 years old; therefore, they can meet the unmet medical needs of adolescents and children with CHC in China. Furthermore, the pan-genotypic sofosbuvir/velpatasvir is being investigated in adolescents and children with CHC, which is expected to make the treatment in such patients more convenient upon approval.
9.Research progress on hyperthermia in the treatment of glioma
Peng LU ; Jia LIU ; Zhengwen HE ; Minghua WU
Chinese Journal of Radiation Oncology 2020;29(8):691-694
Glioma is a highly common malignant brain tumor. Current mainstream treatments include surgery, radiotherapy and chemotherapy, but the low survival rate and poor prognosis of patients have led scientists to explore new therapies. Hyperthermia is a method of local or whole body heating that utilizes high temperature to kill tumor cells to achieve a therapeutic effect, which has multiple advantages in the treatment of glioma, such as minimal invasiveness and high precision, etc. Studies have shown that hyperthermia combined with radiotherapy and chemotherapy can improve the clinical prognosis of patients. Currently, it serves as a therapeutic tool for glioma with huge potential advantages. In this review, the hyperthermia methods applied to treat glioma were introduced. The application prospects and current status of hyperthermia in treating glioma were summarized. In addition, the mature equipment and operation methods that have been applied in the hyperthermia treatment of glioma were illustrated.
10.Preliminary study of in vivo dose measurement of intensity-modulated radiotherapy for cervical cancer
Xia TAN ; Huanli LUO ; Ying WANG ; Mingsong ZHONG ; Xianfeng LIU ; Shi LI ; Xiumei TIAN ; Guang LI ; Bo LI ; Zhengwen SHEN ; Yingchao XU ; Fu JIN
Chinese Journal of Radiation Oncology 2020;29(9):784-789
Objective:To monitor and evaluate in vivo dose changes of intensity-modulated radiotherapy (IMRT) in patients with cervical cancer in a real-time manner. Methods:Twelve patients with cervical cancer admitted to our hospital were enrolled in this study. The in vivo doses were monitored by PerFRACTION?. Electronic portal imaging device (EPID) were collected in each treatment fraction for two-dimensional in vivo dose verification[γ index and dose difference (DD) index]. Log files were recorded for three-dimensional in vivo dose verification (γ index). The correlation between in vivo dose and treatment duration was analyzed by Pearson correlation analysis. Results:A total of 206 sets of EPID images and corresponding Log files were collected. The three-dimensional in vivo dose verification γ 1%/1mm of all patients was not correlated with treatment fraction ( P>0.05). Among them, the absolute difference of γ 1%/1mm of 94.66% fractions was< 1%. The mean DD 3% of two-dimensional in vivo dose verification of all patients was negatively correlated with treatment fraction ( P<0.05). Among which, the average γ 3%/3mm of 9 patients was>89% in the treatment fractions, and the average γ 3%/3mm of 98.57% fractions of these 9 patients was>93%. The other 3 patients had an average γ 3%/3mm ranged from 38% to 100%. CBCT images showed that the bladder volume of these 3 patients was significantly decreased with the relative changes by 82.08%, 84.41% and 73.59%, respectively, and the target area was retracted significantly with the relative changes by 38.12%, 59.79% and 24.46%, respectively. Conclusion:Combined with γ index and DD index, PerFRACTION? can monitor the mechanical stability of accelerator and MU delivery accuracy during treatment fractions, and monitor the changes of in vivo dose in patients with cervical cancer, which can improve the safety and quality assurance of IMRT for cervical cancer patients and provide guidance for patients with adaptive radiotherapy.

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