1.Improving the Certainty of Evidence in Animal Experiment Systematic Review/Meta-Analysis: An Empirical Study of the GRADE Method
Tengfei LI ; Qingyong ZHENG ; Jianguo XU ; Yiyi LI ; Yongjia ZHOU ; Caihua XU ; Mingyue ZHANG ; Jiexiang TIAN ; Gang WANG ; Jinhui TIAN
Laboratory Animal and Comparative Medicine 2025;45(1):101-111
Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.
2.Research progress on oxidative stress mechanism and traditional Chinese medicine intervention in varicocele-induced infertility
Shengnan LI ; Hongyan CHEN ; Tengfei CHEN ; Boxian GAO ; Chongfu ZHONG
China Pharmacy 2025;36(12):1536-1541
Varicocele-induced infertility (VCI) is a common andrological disease in clinical practice. Oxidative stress represents the primary mechanism through which varicocele causes male infertility. Traditional Chinese medicine (TCM) treatment, characterized by its multi-target, multi-component, multi-system, and multi-pathway actions, has achieved favorable outcomes in the field of VCI treatment. This paper summarizes the underlying oxidative stress mechanism of VCI and the relevant signaling pathways involved. By reviewing the current research status on how monomers, active fractions, compound formulas, and related preparations of TCM can intervene in oxidative stress through the regulation of these signaling pathways to improve VCI, it is found that the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and the hypoxia-inducible factor-1α (HIF-1α) signaling pathway are closely related to the development of VCI. TCM monomers and active fractions (flavonoids from Cuscutae Semen, polysaccharides from Astragali Radix, curcumin, ginsenoside Rg1, hyperin and echinacoside), as well as compound formulas and related preparations of TCM (modified Dahuang zhechong granules, Shengjing huoxue formula, modified Tianxiong san, Tongjingling, Bushen huoxue formula, Mailuoshutong pill, Zishen yutai pill, Danhong tongjing formula) can alleviate oxidative stress, reduce lipid peroxidation damage, improve mitochondrial dysfunction, decrease sperm DNA fragmentation, and inhibit apoptosis by activating the Nrf2 signaling pathways and inhibiting the MAPK and HIF-1α signaling pathways, thereby improving reproductive function.
3.Progress in the research on the influencing factors of futile recanalization after mechanical thrombectomy
Xiao LIU ; Tengfei ZHOU ; Tianxiao LI
Journal of Interventional Radiology 2024;33(3):321-324
Mechanical thrombectomy can improve the clinical outcome of patients with acute anterior circulation larger vessel occlusive stroke.However,a remarkable proportion of patients,even they have achieved a successful recanalization,still develop adverse outcomes,such as futile recanalization(FR).According to relevant literature reports,there are many factors that can affect futile recanalization.In this paper,a series of factors such as age,recanalization time,infarct volume,baseline severity,blood pressure that may affect futile recanalization of mechanical thrombectomy in patients with inanterior circulation large vessel occlusion will be comprehensively described and analyzed.(J Intervent Radiol,2024,33:321-324)
4.Development trajectories and influencing factors of self-neglect behavior in older adults
Chenyu SUN ; Yihan DING ; Tengfei LI ; Tai ZHOU ; Mengqing LIU ; Yeke HE ; Guoqing JIANG ; Jie LI
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(3):259-264
Objective:To identify the development trajectories of self-neglect behavior in older adults and explore the associated influencing factors.Methods:A fixed cohort was constructed based on the data from three surveys of Chinese longitudinal healthy longevity survey (CLHLS) from 2011 to 2018. A total of eight variables from 4 dimensions including living environment, lifestyle, social interaction, and health care were selected to evaluate self-neglect. Group-based trajectory model was used to identify the development trajectory of self-neglect behavior in the older adults, and polynomial Logistic regression model was used to explore its influencing factors by Stata 16.1.Results:Finally, 2 754 older adults aged 60 and above were included.The development trajectory of self-neglect behavior in older adults, based on the group-based trajectory model, can be classified into stable-low group ( n=268, 9.7%), descending-moderate group ( n=2 224, 80.8%), and decreasing-high group ( n=262, 9.5%). Polynomial Logistic regression showed that, compared with stable-low group, living in rural areas ( B=1.116, OR=3.053, 95% CI= 2.278-4.091) and higher activities of daily living scores( B=0.137, OR=1.147, 95% CI=1.046-1.258) were the risk factors of descending-moderate group. Education levels with 1-6 years( B=-0.398, OR=0.672, 95% CI=0.469-0.963), >6 years( B=-1.072, OR=0.342, 95% CI=0.229-0.513), being married( B=-0.476, OR=0.621, 95% CI=0.444-0.870), self-reported good health( B=-0.808, OR=0.446, 95% CI= 0.213-0.932), improved health status( B=-0.704, OR=0.495, 95% CI=0.320-0.766), self-reported average economic status( B=-1.065, OR=0.345, 95% CI=0.148-0.802), self-reported good economic status( B=-1.634, OR=0.195, 95% CI=0.082-0.467), and a higher cognition score( B=-0.142, OR=0.867, 95% CI=0.798-0.942) served as protective factors of descending-moderate group. In addition to the above factors, being in the age group of 75-89 years( B=0.481, OR=1.617, 95% CI=1.057-2.473) was a risk factor for decreasing-high group compared to stable-low group. Conclusions:Three types of self-neglect behavior trajectories among older adults were identified in this study, suggesting that physical health and economy are the influencing factors of the development trajectory of self-neglect of the elderly.
5.Vascular suture, closure and occlusion devices at femoral artery puncture hemostasis after neuro-intervention: a clinical comparative study
Shuailong SHI ; Shuhai LONG ; Sun YU ; Chengcheng SHI ; Ji MA ; Renying MIAO ; Yan SONG ; Xinwei HAN ; Tengfei LI
Chinese Journal of Radiology 2024;58(1):71-78
Methods:From February 2018 to January 2022, the clinical data of 1 123 patients who underwent Starclose vascular closure device, Angio-Seal and Exoseal vascular occlusion devices and Perclose ProGlide vascular suture device at femoral artery puncture hemostasis after neuro-intervention, in the Department of Interventional Radiology (Eastern District), The First Affiliated Hospital of Zhengzhou University, were retrospectively analyzed. The patients were divided into three groups based on the intervention method: the closure group (Starclose, n=271), the occlusion group (Angio-Seal, n=327 and Exoseal, n=352) and the suture group (ProGlide, n=173). Next, the hemostatic efficacy and complications associated with the three devices were analyzed and compared. Additionally, regression analysis was conducted to identify any relevant factors that may contribute to complications. Results:Three vascular hemostatic devices demonstrated effective hemostasis and the success rate were 92.6% in the closure group (Starclose), 93.4% in the occlusion group (Angio-Seal 93.0% and Exoseal 93.8%) and 89.6% in the suture group (ProGlide). There was no statistically significant difference( χ2=3.026, P=0.388). Single or multiple complications were observed in 102 patients (9.1%), including local oozing (16 cases in the closure group, 39 cases in the occlusion group, 13 cases in the suture group), local hematoma (14 cases in the closure group, 31 cases in the occlusion group, 11 cases in the suture group), pseudoaneurysm (13 cases in the closure group, 35 cases in the occlusion group, 10 cases in the suture group), local infection (2 cases in the closure group, 3 cases in the occlusion group, 1 case in the suture group). There were no statistically significant differences ( P>0.05). Moreover, serious complications such as femoral artery occlusion, embolus shedding and permanent nerve injury weren′t observed in the three groups. Multivariate logistic regression analysis revealed that overweight ( OR=1.562,95% CI 1.023—2.385, P=0.039), femoral artery with calcified plaque ( OR=1.934,95% CI 1.172-3.189, P=0.010), combined use of multiple antiplatelet drugs ( OR=1.769,95% CI 1.103—2.839, P=0.018), use of an 8F sheath( OR=2.824,95% CI 1.406—5.671, P=0.004) and the operator′s proficiency ( OR=0.508,95% CI 0.328—0.788, P=0.002) were the independent factors influencing complications, of which the first four were identified as risk-promoting factors for complications while the operator′s rich experience and high proficiency were the protective factors. Conclusions:Three hemostatic devices demonstrate effective hemostasis and comparable rates of complications at femoral artery puncture hemostasis after neuro-intervention. Overweight, femoral artery with calcified plaque, combined use of multiple antiplatelet drugs, use of an 8 F sheath and the operator′s proficiency were independent factors influencing complications.Ojective:To investigate the efficacy and complications associated with vascular suture, closure and occlusion devices at femoral artery puncture hemostasis after neuro-intervention.
6.The application of percutaneous puncture renal fascia suspension in laparoscopic partial nephrectomy
Qi LI ; Pei ZHENG ; Yusheng WANG ; Guangyuan JING ; Mingrui WANG ; Bo ZHAO ; Tengfei XU ; Xiaoli WANG ; Kaidong WANG ; Xiao PAN ; Fen YIN
Chinese Journal of Urology 2024;45(1):53-54
When partial nephrectomy is performed by posterior abdominal approach, the surgical field is poorly exposed, resulting in increased surgical difficulty and risk of injury.In this study, 28 patients with T 1a stage kidney tumors underwent retroperitoneal laparoscopic partial nephrectomy. Intraoperatively, exposure of the surgical field was achieved using the percutaneous puncture of the renal fascia suspension technique. There were no dissatisfactory exposures due to peritoneal damage during the surgery, no additional tubes were inserted, and no conversions to open surgery were needed. The operation time was (76.5±20.3) minutes, blood loss was (92.1±18.7) ml, renal artery clamping time was (19.5±4.3) minutes. Postoperatively, there were no complications such as bleeding, infection, or hematuria.
7.Biomechanical characteristics of thoracic T10 bone tumor metastasis at different locations:three-dimensional finite element analysis
Guoren XIA ; Hao YU ; Shifeng JIANG ; Xin PENG ; Xiao FU ; Qi CHEN ; Lizhuang YANG ; Tengfei WANG ; Hai LI
Chinese Journal of Tissue Engineering Research 2024;28(36):5759-5765
BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.
8.Mechanism of Nephrotoxicity Induced by Ecliptasaponin A Based on Computational Toxicology
Han LI ; Ling SONG ; Yunhang GAO ; Tengfei CHEN ; Suzhen MU ; Weiya CHEN ; Guangping ZHANG ; Wang HUO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):72-80
ObjectiveTo predict the potential nephrotoxic components in traditional Chinese medicine health food products based on the Traditional Chinese Medicine Toxicity Alert System and Basic Toxicology Database (TCMTAS-BTD), screen and validate the predicted components by cell and animal experiments, and decipher the mechanism of nephrotoxicity by network pharmacology. MethodTCMTAS-BTD was utilized to predict the toxicity of 3 540 compounds found in the catalogue of traditional Chinese health food ingredients. In the cell experiment, the top 5 compounds with high toxicity probability were screened by measurement of cell proliferation and viability (CCK-8) and high-content screening. ICR mice were randomized into a control group, a low-dose (2.91 mg·kg-1·d-1) ecliptasaponin A, and a high-dose (29.1 mg·kg-1·d-1) ecliptasaponin A group, with 10 mice in each group, and treated continuously for 28 days. During the experiment, the general conditions of the rats were observed, and the kidney index was calculated. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) in the serum as well as the content of malondialdehyde (MDA) and superoxide dismutase (SOD) in the renal tissue were measured. The pathological changes of the kidney were observed. Network pharmacology was employed to predict the potential pathways of nephrotoxicity. Finally, the pathway-associated proteins were validated by Western blot. ResultThe top 5 compounds with high probability of nephrotoxicity were ecliptasaponin A, chrysophanol, rutaecarpine, tanshinoneⅠ, and geniposidic acid. In the cell experiment, CCK-8 results showed that 10 μmol·L-1 ecliptasaponin A, 60 μmol·L-1 chrysophanol, 40 μmol·L-1 rutaecarpine, and 20 μmol·L-1 tanshinone I altered the viability of HK-2 cells. High-content analysis showed that 10 μmol·L-1 ecliptasaponin A, chrysophanol, rutaecarpine, and tanshinone Ⅰ reduced the cell number (P<0.05, P<0.01). The animal experiment showed that the mice in the high-dose ecliptasaponin A group presented slow movement, slow weight gain (P<0.01), increased kidney index (P<0.01), elevated SCr, BUN, and MDA levels (P<0.01), and lowered SOD level (P<0.01). Mild histopathological changes were observed in the high-dose ecliptasaponin A group. The network pharmacology results showed that the key targets of nephrotoxicity induced by ecliptasaponin A were mainly enriched in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, prostatic cancer and lipid and atherosclerosis pathways. Western blot results verified that high dose of ecliptasaponin A raised the phosphorylation levels of PI3K and Akt (P<0.01). ConclusionOn day 28 of administration, 29.1 mg·kg-1 ecliptasaponin A was found to induce renal injury in rats. The mechanism may be related with the PI3K/Akt signaling pathway, which implied that excessive and prolonged usage of Ecliptae Herba may increase the incidence of adverse drug reactions.
9.Construction and Experimental Validation of Chemically-induced Cough Model Based on Cough Waveforms
Yunhang GAO ; Ling JIA ; Han LI ; Ling SONG ; Cong GUO ; Tengfei CHEN ; Hongping HOU ; Weiya CHEN ; Guangping ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):230-236
ObjectiveTo construct a cough model induced by chemical stimuli by whole-body plethysmography (WBP) for counting coughs based on cough waveforms, and use this model to explore the antitussive effect of GK-A. MethodDifferent chemical stimuli were used to induce coughs in mice or guinea pigs. Respiratory waveforms were monitored by WBP, and the recognizable and typical cough waveforms were selected for cough counting. Guinea pigs were induced to cough with different concentrations of citric acid or capsaicin, and cough waveforms were used to optimize the stimulation conditions. The optimized guinea pig model of cough was validated with dextromethorphan, and the optimized guinea pig model of capsaicin-induced cough was used to evaluate the antitussive effect of GK-A. ResultWBP could count the coughs induced by capsaicin and citric acid in guinea pigs by recognizable and typical respiratory waveforms. The optimized stimulation conditions were capsaicin concentration of 100 µmol·L-1 and nebulization for 2 min. The validation results showed that compared with the model group, the dextromethorphan group of guinea pigs had reduced coughs (P<0.05) and prolonged cough latency (P<0.01). GK-A prolonged the cough latency (P<0.05) and reduced coughs (P<0.05) in the mouse model of ammonia-induced cough. In the guinea pig model of capsaicin-induced cough, GK-A prolonged cough latency (P<0.05), reduced coughs (P<0.05), and decreased substance P (SP) content in the guinea pig serum (P<0.05, P<0.01). ConclusionA guinea pig model of capsaicin-induced cough was successfully established based on cough waveform counting, which provided an objective and accurate cough counting method. GK-A has antitussive effects, possibly by inhibiting the neuropeptide SP.
10.Imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses and efficacy and safety of intravascular interventional therapy in them
Tengfei LI ; Qi TIAN ; Shuailong SHI ; Jie YANG ; Ye WANG ; Zhen CHEN ; Yuncai RAN ; Baohong WEN ; Dong GUO ; Shaofeng SHUI ; Xinwei HAN ; Xiao LI ; Ji MA
Chinese Journal of Neuromedicine 2024;23(1):42-47
Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.

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