1.Network toxicology and its application in studying exogenous chemical toxicity
Yanli LIN ; Zehua TAO ; Zhao XIAO ; Chenxu HU ; Bobo YANG ; Ya WANG ; Rongzhu LU
Journal of Environmental and Occupational Medicine 2025;42(2):238-244
With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.
2.Interpretation of the Industry Standard Robotically-assisted Laparoscopic Surgical System
Chenxu YANG ; Shu LI ; Hao WANG ; Xiangfeng MENG
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1199-1206
With the widespread application of robotic technology in surgery, multiple robot-assisted laparoscopic endoscopic surgical systems are currently in the R&D phase, highlighting an urgent need for establishing a scientific and standardized quality evaluation framework. In 2024, the National Medical Products Administration issued the standard YY/T 1941-2024, entitled
3.Analysis of issues in quality control test results of linear accelerators in China
Hongbo WANG ; Xuexia LIU ; Songhui ZHANG ; Chenxu HUANG ; Yuexin GUO ; Quanfu SUN
Chinese Journal of Radiological Health 2024;33(6):675-680
Objective To study the unqualified items in the reported quality control tests of linear accelerators, analyze the issues in quality control tests, and propose the key points and development directions for accelerator quality control test in China. Methods A literature review was conducted using the CNKI database to analyze the qualified rates of test items and the issues in quality control tests. Results In the literature on the quality control tests of linear accelerators, except for a few provinces where the qualified rates of all test items were 100%, unqualified items were reported in most of the literature. There were unqualified items related to X-ray and electron beam in different reports. Error of dose indication was the unqualified item with the highest occurrence rate in X-ray test, and the item with the lowest qualified rates in X-ray and electron beam tests. The lowest qualified rate of X-ray dose indication error was 73.5% in 2016, and the lowest qualified rate of electron beam dose indication error was 46.2% in 2017. Conclusion Tests should be carried out strictly according to the items and intervals specified by the quality control test standards. Hospitals, radiation health technology service institutions, and health administrative departments should each fulfill their respective responsibilities, work together, and place emphasis on ensuring effective quality control tests of linear accelerators to further enhance the overall quality control standards for these devices.
4.Exogenous leptin improves cerebral ischemia-reperfusion-induced glutamate excitotoxic injury in mice by up-regulating GLT-1 and GLAST expression in astrocytes
Jie CHEN ; Chenxu LIU ; Chun WANG ; Li LI ; Weiting TAO ; Jingru XUN ; Honghui TANG ; Li HUANG
Journal of Southern Medical University 2024;44(6):1079-1087
Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.
5.Application value of intrathecal synthetic related markers in cognitive dysfunction and various dementia diseases
Yanan LIU ; Wencan JIANG ; Chenxu WANG ; Chunqing SHAO ; Menglue ZHANG ; Wenya JIA ; Yuxuan HUANG ; Jingchun ZHAI ; Jiayi LIAO ; Guojun ZHANG
International Journal of Laboratory Medicine 2024;45(17):2076-2080
Objective To evaluate the value of intrathecal synthetic related markers in patients with mild cognitive impairment(MCI),Alzheimer's disease(AD),and other types of dementia.Methods Retrospec-tively collect the clinical data of 577 patients diagnosed with MCI(MCI group,178 cases),AD(AD group,131 cases),and other types of dementia(other types group,268 cases)from June 2019 to July 2023 in Beijing Tiantan Hospital,Capital Medical University.Oligoclonal zone electrophoresis(OCB)and 24 h intrathecal pro-tein synthesis rate(ISR)of each group were investigated,and the difference of different indexes among the groups was compared to evaluate the value of related indexes in the differential diagnosis of different diseases.Results Compared with AD group and other groups,AD group had a higher proportion of females,more patients were>50-70 years old,and the incidence of abnormal lipid metabolism was higher,with statistical significance(P<0.05).There were significant differences in OB(S),cerebrospinal fluid albumin,serum albumin and cerebrospinal flu-id IgG in different disease groups(P<0.05).IgG index and ISR in patients with positive SOB(CSF)were higher than those in negative and weakly positive patients,and the differences were statistically significant(P<0.001).IgG index was positively correlated with ISR(r=0.878,P<0.001).Conclusion Intrathecal synthetic mark-ers such as IgG index,SOB(CSF)and 24 h ISR have synergistic effects in the diagnosis of cognitive dysfunction and various dementias,which can be collectively utilized in the diagnosis of diseases.
6.Effects of 2 650 MHz radiofrequency radiation on the behavior and hippocampal neurotransmitter release of mice
Yujie LIU ; Jun WANG ; Keqin LI ; Chenxu CHANG ; Ying LIU ; Hongyan ZUO ; Yang LI ; Hong YANG ; Yanhui HAO ; Hua DENG
Chinese Journal of Radiological Medicine and Protection 2024;44(5):354-360
Objective:To investigate the effects of 2 650 MHz radiofrequency (RF) exposure on the behavior and neurotransmitter release of mice.Methods:Adult male C57BL/6N mice were divided into a normal control (CON) group and a radiofrequency radiation (RFR) group using the random number table method. The mice in the RFR group were subjected to single-dose whole-body exposure to a uniform 2 650 MHz RF electromagnetic field for 3 h. During the RF exposure, the field strength in the effective working area of the RF radiation platform was measured using an electromagnetic radiation analyzer, and the changes in the anal temperature of the mice were monitored using an optical fiber thermometer. Moreover, the changes in the cognition, social interaction, and emotion of the mice were determined through the new object recognition test, social preference test, and open field test. Finally, the changes in the hippocampal neurotransmitter release levels of the mice were detected using microdialysis sampling and mass spectrometry, and the changes in the hippocampal tissue structure and ultrastructure were observed via microscopy.Results:Under the test conditions, RF radiation improved the anal temperature of the mice, with a maximum increasing amplitude of 0.61℃, falling within the range of thermal safety. The mice in the RFR group experienced a significant decrease in the frequency and time for exploring new objects ( t=4.50, 2.53, P < 0.05) in the new object recognition test, a significant decrease in the frequency ( t=0.08, P<0.01) and time ( t=0.03, P<0.05) for exploring other mice in the social preference test, and no significant change in the frequency and time for exploring the central area ( P > 0.05) in the open field test. Compared to the CON group, the RFR group showed an increase in the release of 5-hydroxytryptamine (5-HT) ( t=-2.56, P < 0.05) and a decrease in the release of acetylcholine (ACh) ( t=2.21, P < 0.05), no significant difference in the release of glutamate (Glu) and γ-aminobutyric acid (GABA) ( P > 0.05), and no evident damage to the hippocampal tissue and structure and synaptic ultrastructure. Conclusions:2 650 MHz RF radiation may induce cognitive impairment and abnormal social preference in mice, which is attributed to neuronal dysfunctions and neurotransmitter release disorders under RF exposure.
7.Operative technique and efficacy of three-incision laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy
Chenxu TIAN ; Qing SANG ; Dexiao DU ; Guangzhong XU ; Liang WANG ; Zhehong LI ; Weijian CHEN ; Nengwei ZHANG
Chinese Journal of General Surgery 2024;39(6):465-469
Objective:To present the surgical details of manual double-layer suturing in patients with obesity combined type 2 diabetes mellitus by three-incision laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy .Methods:Clinical data and follow-up information of 52 obesity combined type 2 diabetes mellitus patients (BMI 27.59-43.71 kg/m2) who underwent three-incision laparoscopic single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy from Jan 2019 to Jul 2022 at Beijing Shijitan hospital were retrospectively analyzed.Results:The procedure was successful in all patients. The median operative time was 120 (90, 120) min, and the median intraoperative bleeding was 20.0 (10.0, 27.5) ml. No fistula or serious surgical complications were observed in the patients at 1 month postoperatively. Compared with the preoperative period, the patient's weight decreased [(93.22±15.21) kg vs. (69.97±11.06) kg, t=21.707, P<0.01], BMI decreased [(33.11±4.09) kg/m 2vs. (24.86±2.95) kg/m 2, t=23.224, P<0.01], and the patient's fasting glucose level decreased [9.52 (7.57, 12.96) mmol/L vs. 5.47 (4.66, 6.39) mmol/L, Z=6.11, P<0.01]. The remission rate of various obesity comorbidities was greatly improved. Conclusion:Under the condition of three-incision laparoscopy, the pure manual duodenal and jejunal double-layer suture method is safe, feasible, and effective for patients with obesity combined with type 2 diabetes mellitus.
8.The mechanism of N-acetylserotonin regulating microglial polarization via NOD1/Rip2 pathway in rats after retinal ischemia reperfusion
Ying XU ; Jianliang LIU ; Yuze ZHAO ; Chenxu WANG ; Xinhao FU ; Xiaoshuang LI ; Xiaoli WANG ; Yansong ZHAO
Chinese Journal of Ocular Fundus Diseases 2024;40(4):287-295
Objective:To investigate the effect of N-acetylserotonin (NAS) on the retinal microglia polarization in retinal ischemia-reperfusion injury (RIRI) rats and explore its mechanism via nucleotide-bound oligomeric domain 1 (NOD1)/receptor interacting protein 2 (Rip2) pathway.Methods:Healthy male Sprague Dawley rats were randomly divided into Sham ( n=21), RIRI ( n=21) and NAS (injected intraperitoneally 30 min before and after modeling with NAS, 10 mg/kg, n=18) groups, using random number table. And the right eye was used experimental eye. The RIRI model of rats in RIRI group and NAS group was established by anterior chamber high intraocular pressure method. Rats in NAS group were intraperitoneally injected with 10 mg/kg NAS before and 30 min after modeling, respectively. The retinal morphology and the number of retinal ganglion cell (RGC) in each group were detected by hematoxylin-eosin staining and immunohistochemical staining. The effect of NAS on polarization of retinal microglia was detected by immunofluorescence staining. Transcriptome sequencing technology was used to screen out the differentially expressed genes between Sham and RIRI groups. Western blot and real-time quantitative polymerase chain reaction (RT-PCR) were used to examine the differentially expressed genes. Immunohistochemical staining, Western blot and RT-PCR were used to investigate the effect of NAS on the expression of NOD1 and Rip2 protein and mRNA in retinal tissue and microglia of rats. General linear regression analysis was performed to determine the correlation between the number difference of NOD1 + cells and the number difference of M1 and M2 microglia in retinal tissues of rats in NAS group and RIRI group. Results:A large number of RGC were observed in the retina of rats in Sham group. 24 h after modeling, compared with Sham group, the inner retinal thickness of rats in RIRI group was significantly increased and the number of RGC was significantly decreased. The thickness of inner retina in NAS group was significantly thinner and the number of RGC was significantly increased. Compared with Sham group, the number of retinal microglia of M1 and M2 in RIRI group was significantly increased. Compared with RIRI group, the number of M1 microglia decreased significantly and the number of M2 microglia increased significantly in NAS group. There was statistical significance in the number of M1 and M2 microglia in the retina of the three groups ( P<0.05). Transcriptome sequencing results showed that retinal NOD1 and Rip2 were important differential genes 24 h after modeling. The mRNA and protein relative expressions of NOD1 and Rip2 in retina of RIRI group were significantly higher than those of Sham group, with statistical significance ( P<0.05). The number of NOD1 + and Rip2 + cells and the relative expression of mRNA and protein in retinal microglia in RIRI group were significantly higher than those in Sham group, and NAS group was also significantly higher than that in Sham group, but lower than that in RIRI group, with statistical significance ( P<0.05). The number of Iba-1 +/NOD1 + and Iba-1 +/Rip2 + cells in retinal microglia in RIRI group was significantly increased compared with that in Sham group, and the number of Iba-1 +/Rip2 + cells in NAS group was significantly decreased compared with that in RIRI group, but still significantly higher than that in Sham group, with statistical significance ( P<0.05). Correlation analysis results showed that the difference of retinal NOD1 + and Rip2 + cells in NAS group and RIRI group was positively correlated with that of M1 microglia ( r=0.851, 0.895), and negatively correlated with that of M2 microglia ( r=-0.797, -0.819). The differences were statistically significant ( P<0.05). Conclusion:NAS can regulate the microglial polarization from M1 to M2 phenotype, the mechanism is correlated with the NOD1/Rip2 pathway.
9.Exogenous leptin improves cerebral ischemia-reperfusion-induced glutamate excitotoxic injury in mice by up-regulating GLT-1 and GLAST expression in astrocytes
Jie CHEN ; Chenxu LIU ; Chun WANG ; Li LI ; Weiting TAO ; Jingru XUN ; Honghui TANG ; Li HUANG
Journal of Southern Medical University 2024;44(6):1079-1087
Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.
10.Comparison of various prediction models in the effect of laparoscopic sleeve gastrectomy on type 2 diabetes mellitus in the Chinese population 5 years after surgery
Chengyuan YU ; Liang WANG ; Guangzhong XU ; Guanyang CHEN ; Qing SANG ; Qiqige WUYUN ; Zheng WANG ; Chenxu TIAN ; Nengwei ZHANG
Chinese Medical Journal 2024;137(3):320-328
Background::The effect of bariatric surgery on type 2 diabetes mellitus (T2DM) control can be assessed based on predictive models of T2DM remission. Various models have been externally verified internationally. However, long-term validated results after laparoscopic sleeve gastrectomy (LSG) surgery are lacking. The best model for the Chinese population is also unknown.Methods::We retrospectively analyzed Chinese population data 5 years after LSG at Beijing Shijitan Hospital in China between March 2009 and December 2016. The independent t-test, Mann–Whitney U test, and chi-squared test were used to compare characteristics between T2DM remission and non-remission groups. We evaluated the predictive efficacy of each model for longterm T2DM remission after LSG by calculating the area under the curve (AUC), sensitivity, specificity, Youden index, positive predictive value (PPV), negative predictive value (NPV), and predicted-to-observed ratio, and performed calibration using Hosmer–Lemeshow test for 11 prediction models. Results::We enrolled 108 patients, including 44 (40.7%) men, with a mean age of 35.5 years. The mean body mass index was 40.3 ± 9.1 kg/m 2, the percentage of excess weight loss (%EWL) was (75.9 ± 30.4)%, and the percentage of total weight loss (% TWL) was (29.1 ± 10.6)%. The mean glycated hemoglobin A1c (HbA1c) level was (7.3 ± 1.8)% preoperatively and decreased to (5.9 ± 1.0)% 5 years after LSG. The 5-year postoperative complete and partial remission rates of T2DM were 50.9% [55/108] and 27.8% [30/108], respectively. Six models, i.e., "ABCD", individualized metabolic surgery (IMS), advanced-DiaRem, DiaBetter, Dixon et al’s regression model, and Panunzi et al’s regression model, showed a good discrimination ability (all AUC >0.8). The "ABCD" (sensitivity, 74%; specificity, 80%; AUC, 0.82 [95% confidence interval [CI]: 0.74–0.89]), IMS (sensitivity, 78%; specificity, 84%; AUC, 0.82 [95% CI: 0.73–0.89]), and Panunzi et al’s regression models (sensitivity, 78%; specificity, 91%; AUC, 0.86 [95% CI: 0.78–0.92]) showed good discernibility. In the Hosmer–Lemeshow goodness-of-fit test, except for DiaRem ( P <0.01), DiaBetter ( P <0.01), Hayes et al ( P = 0.03), Park et al ( P = 0.02), and Ramos-Levi et al’s ( P <0.01) models, all models had a satifactory fit results ( P >0.05). The P values of calibration results of the "ABCD" and IMS were 0.07 and 0.14, respectively. The predicted-to-observed ratios of the "ABCD" and IMS were 0.87 and 0.89, respectively. Conclusion::The prediction model IMS was recommended for clinical use because of excellent predictive performance, good statistical test results, and simple and practical design features.

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