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Objective:To validate and compare the value of the Status Epilepticus in Pediatric Severity Score (STEPSS) versus PEDSS in assessing the short-term prognosis of children with status epilepticus (SE).Methods:Clinical data of 152 children with SE hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were retrospectively analyzed.According to the STEPSS and PEDSS scores, children with SE were scored and their prognosis was predicted.Receiver operating characteristic (ROC) curves of the 2 scales in assessing the short-term prognosis of SE in children were plotted, and the area under the curve (AUC), optimal cut-off, sensitivity and specificity were calculated, thus validating and comparing the value of the STEPSS versus PEDSS in assessing the short-term prognosis of children with SE.Results:Of the 152 children with SE, 90 were male and 62 were female, with the age of (5.8±3.9) years (1 month to 15 years). There were 112 cases with good prognosis and 40 cases with poor prognosis, involving 13 deaths.The AUC of STEPSS and PEDSS scores in predicting the death in children with SE were 0.908(95% CI: 0.848-0.967) and 0.887(95% CI: 0.831-0.942), respectively, both with the optimal cut-off value of 4.The sensitivity of STEPSS and PEDSS scores in predicting the death in children with SE were 0.740 and 0.846, respectively, and the specificity were 0.745 and 0.835, respectively.There was no significant difference in predicting the death in children with SE between the 2 scales ( P>0.05). In predicting adverse outcomes, the AUC of the STEPSS and PEDSS scores were 0.869(95% CI: 0.800-0.937) and 0.926(95% CI: 0.873-0.979), respectively, both with the optimal cut-off value of 3.The sensitivity of STEPSS and PEDSS scores in predicting adverse outcomes in children with SE were 0.827 and 0.900, respectively, and the specificity were 0.732 and 0.866, respectively.There was significant difference in predicting the adverse outcomes in children with SE between the 2 scales ( P<0.05). Conclusions:Compared with the STEPSS, the PEDSS has a higher application in predicting the short-term treatment outcome of children with SE, which can be used as a routine method to assess the prognosis of children with SE.
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Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout (Tbc1d15CKO) or Tbc1d15 knockin (Tbc1d15CKI) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity.
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Objective:To construct an artificial intelligence-assisted diagnosis system to recognize the characteristics of Helicobacter pylori ( HP) infection under endoscopy, and evaluate its performance in real clinical cases. Methods:A total of 1 033 cases who underwent 13C-urea breath test and gastroscopy in the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from January 2020 to March 2021 were collected retrospectively. Patients with positive results of 13C-urea breath test (which were defined as HP infertion) were assigned to the case group ( n=485), and those with negative results to the control group ( n=548). Gastroscopic images of various mucosal features indicating HP positive and negative, as well as the gastroscopic images of HP positive and negative cases were randomly assigned to the training set, validation set and test set with at 8∶1∶1. An artificial intelligence-assisted diagnosis system for identifying HP infection was developed based on convolutional neural network (CNN) and long short-term memory network (LSTM). In the system, CNN can identify and extract mucosal features of endoscopic images of each patient, generate feature vectors, and then LSTM receives feature vectors to comprehensively judge HP infection status. The diagnostic performance of the system was evaluated by sensitivity, specificity, accuracy and area under receiver operating characteristic curve (AUC). Results:The diagnostic accuracy of this system for nodularity, atrophy, intestinal metaplasia, xanthoma, diffuse redness + spotty redness, mucosal swelling + enlarged fold + sticky mucus and HP negative features was 87.5% (14/16), 74.1% (83/112), 90.0% (45/50), 88.0% (22/25), 63.3% (38/60), 80.1% (238/297) and 85.7% (36 /42), respectively. The sensitivity, specificity, accuracy and AUC of the system for predicting HP infection was 89.6% (43/48), 61.8% (34/55), 74.8% (77/103), and 0.757, respectively. The diagnostic accuracy of the system was equivalent to that of endoscopist in diagnosing HP infection under white light (74.8% VS 72.1%, χ2=0.246, P=0.620). Conclusion:The system developed in this study shows noteworthy ability in evaluating HP status, and can be used to assist endoscopists to diagnose HP infection.
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Objective:To assess the diagnostic efficacy of upper gastrointestinal endoscopic image assisted diagnosis system (ENDOANGEL-LD) based on artificial intelligence (AI) for detecting gastric lesions and neoplastic lesions under white light endoscopy.Methods:The diagnostic efficacy of ENDOANGEL-LD was tested using image testing dataset and video testing dataset, respectively. The image testing dataset included 300 images of gastric neoplastic lesions, 505 images of non-neoplastic lesions and 990 images of normal stomach of 191 patients in Renmin Hospital of Wuhan University from June 2019 to September 2019. Video testing dataset was from 83 videos (38 gastric neoplastic lesions and 45 non-neoplastic lesions) of 78 patients in Renmin Hospital of Wuhan University from November 2020 to April 2021. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD for image testing dataset were calculated. The accuracy, the sensitivity and the specificity of ENDOANGEL-LD in video testing dataset for gastric neoplastic lesions were compared with those of four senior endoscopists.Results:In the image testing dataset, the accuracy, the sensitivity, the specificity of ENDOANGEL-LD for gastric lesions were 93.9% (1 685/1 795), 98.0% (789/805) and 90.5% (896/990) respectively; while the accuracy, the sensitivity and the specificity of ENDOANGEL-LD for gastric neoplastic lesions were 88.7% (714/805), 91.0% (273/300) and 87.3% (441/505) respectively. In the video testing dataset, the sensitivity [100.0% (38/38) VS 85.5% (130/152), χ2=6.220, P=0.013] of ENDOANGEL-LD was higher than that of four senior endoscopists. The accuracy [81.9% (68/83) VS 72.0% (239/332), χ2=3.408, P=0.065] and the specificity [ 66.7% (30/45) VS 60.6% (109/180), χ2=0.569, P=0.451] of ENDOANGEL-LD were comparable with those of four senior endoscopists. Conclusion:The ENDOANGEL-LD can accurately detect gastric lesions and further diagnose neoplastic lesions to help endoscopists in clinical work.
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Objective:To construct a real-time artificial intelligence (AI)-assisted endoscepic diagnosis system based on YOLO v3 algorithm, and to evaluate its ability of detecting focal gastric lesions in gastroscopy.Methods:A total of 5 488 white light gastroscopic images (2 733 images with gastric focal lesions and 2 755 images without gastric focal lesions) from June to November 2019 and videos of 92 cases (288 168 clear stomach frames) from May to June 2020 at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University were retrospectively collected for AI System test. A total of 3 997 prospective consecutive patients undergoing gastroscopy at the Digestive Endoscopy Center of Renmin Hospital of Wuhan University from July 6, 2020 to November 27, 2020 and May 6, 2021 to August 2, 2021 were enrolled to assess the clinical applicability of AI System. When AI System recognized an abnormal lesion, it marked the lesion with a blue box as a warning. The ability to identify focal gastric lesions and the frequency and causes of false positives and false negatives of AI System were statistically analyzed.Results:In the image test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 92.3% (5 064/5 488), 95.0% (2 597/2 733), 89.5% (2 467/ 2 755), 90.0% (2 597/2 885) and 94.8% (2 467/2 603), respectively. In the video test set, the accuracy, the sensitivity, the specificity, the positive predictive value and the negative predictive value of AI System were 95.4% (274 792/288 168), 95.2% (109 727/115 287), 95.5% (165 065/172 881), 93.4% (109 727/117 543) and 96.7% (165 065/170 625), respectively. In clinical application, the detection rate of local gastric lesions by AI System was 93.0% (6 830/7 344). A total of 514 focal gastric lesions were missed by AI System. The main reasons were punctate erosions (48.8%, 251/514), diminutive xanthomas (22.8%, 117/514) and diminutive polyps (21.4%, 110/514). The mean number of false positives per gastroscopy was 2 (1, 4), most of which were due to normal mucosa folds (50.2%, 5 635/11 225), bubbles and mucus (35.0%, 3 928/11 225), and liquid deposited in the fundus (9.1%, 1 021/11 225).Conclusion:The application of AI System can increase the detection rate of focal gastric lesions.
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ObjectiveUltra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) was used to identify the metabolites of limonin in rats, and to explore the gender differences in the distribution of prototype components and metabolites in rats after single dose intragastric administration of limonin, as well as to speculate the metabolic pathways. MethodThe separation was performed on a Thermo Scientific Accucore™ C18 column(3 mm×100 mm, 2.6 μm) with 0.1% formic acid aqueous solution(A)-0.1% formic acid acetonitrile solution(B) as mobile phase in a gradient elution mode(0-1 min, 5%B; 1-6 min, 5%-20%B; 6-18 min, 20%-50%B; 18-23 min, 50%-80%B; 23-25 min, 80%-95%B; 25-30 min, 95%B) at a flow rate of 0.3 mL·min-1 and a column temperature of 30 ℃. MS data of biological samples were collected under the positive ion mode of electrospray ionization(ESI) and in the scanning range of m/z 100-1 500. Plasma, tissues(heart, liver, spleen, lung, kidney, stomach and small intestine), urine and fecal samples were collected and prepared after intragastric administration, and the prototype component and metabolites of limonin were identified. ResultThe prototype component of limonin were detected in the feces, stomach, small intestine of female and male rats, and in the heart, liver, spleen, lung and kidney tissues of female rats. A total of 23 metabolites related to limonin were detected in rats, of which 2, 1, 5, 4, 23 metabolites were detected in liver, stomach, small intestine, urine and feces, respectively, and the main metabolic pathways were hydrolysis, reduction, hydroxylation and methylation, etc. The distribution of some metabolites differed between male and female rats. ConclusionThe prototype component of limonin are mainly distributed in the stomach and small intestine in rats, and the distribution of prototype component and some metabolites are different by gender. Limonin is mainly excreted through feces with phase Ⅰ metabolites as the main ones. The results of this study can provide a reference for further elucidation of the effect of gender differences on the metabolism of limonin in vivo and its mechanism of action.
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Objective:To evaluate the Kyoto gastritis score for diagnosing Helicobacter pylori ( HP) infection in Chinese people. Methods:A total of 902 cases who underwent 13C-urea breath test and gastroscopy at the same time at the Digestive Endoscopy center of Renmin Hospital of Wuhan University from January 2020 to December 2020 were studied retrospectively, including 345 cases of HP-positive and 557 of HP-negative. The differences of mucosal features and Kyoto gastritis score between HP-positive and HP-negative patients were analyzed. A receiver operating characteristic curve was plotted to predict HP infection by Kyoto gastritis score. Results:Compared with HP-negative patients, nodules [8.1% (28/345) VS 0.2% (1/557), χ2=86.29, P<0.001], diffuse redness [47.8% (165/345) VS 6.6% (37/557), χ2=413.63, P<0.001], atrophy [27.8% (96/345) VS 13.8% (77/557), χ2=52.90, P<0.001] and fold enlargement [69.0% (238/345) VS 36.6% (204/557), χ2=175.38, P<0.001] occurred more frequently in HP-positive patients. For predicting HP infection, nodules showed the highest specificity [99.8% (556/557)] and positive predictive value [96.6% (28/29)], diffuse redness showed the largest area under the receiver operating characteristic curve (AUC) of 0.707, and fold enlargement showed the highest sensitivity [69.0% (238/345)] and negative predictive value [76.7% (353/460)]. The Kyoto gastritis score of HP-positive patients was higher than that of HP-negative patients [2 (1, 2) VS 0 (0, 1), Z=20.82, P<0.001]. Furthermore, at an optimal threshold of 2, the AUC of the Kyoto gastritis score for predicting HP infection was 0.779. Conclusion:Nodules, diffuse redness, atrophy and fold enlargement under gastroscopy can suggest positive of HP infection, and the Kyoto gastritis score≥2 is sufficient reference to diagnose HP positive.
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The aim of this study was designed to investigate the effects of rhynchophyllin (RH) on neuroinflammation in Tourette syndrome (TS) rats. TS model was established in rats by the injection of selective 5-HT2A/2C agonist 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Behavior in DOI-induced rats was tested. Inflammatory cytokines levels such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum and striatum were detected. The expression levels of janus kinase 2 (JAK2)/signal transducer and transcription activator 3 (STAT3) and nuclear factor (NF)-κB pathways in striatum were measured by Western blot. Data indicated that RH can significantly reduce the numbers of nodding experiment of TS rats. RH significantly decreased IL-6, IL-1ß, and TNF-α in serum and striatum of TS rats, with altered expression of P-JAK2, P-STAT3, P-NF-κBp65, and P-IκBα in TS rats, as evidenced by Western blot analysis and immunohistochemistry, suggesting that the regulation of JAK2/STAT3 and NF-κB pathways might be involved in the mechanism of RH on TS.
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Corpo Estriado/imunologia , Medicamentos de Ervas Chinesas/administração & dosagem , Janus Quinase 2/imunologia , Oxindóis/administração & dosagem , Síndrome de Tourette/tratamento farmacológico , Uncaria/química , Animais , Corpo Estriado/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Janus Quinase 2/genética , Masculino , NF-kappa B/genética , NF-kappa B/imunologia , Propano/efeitos adversos , Propano/análogos & derivados , Ratos , Ratos Wistar , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Tourette/induzido quimicamente , Síndrome de Tourette/genética , Síndrome de Tourette/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Tourette syndrome (TS) is a chronic neuropsychiatric disorder with clinical manifestations of involuntary and repeated muscle twitching and vocal twitching. The drugs used to treat TS are relatively limited. The aim of this study was to investigate the effects of rhynchophylline (RH) and the underlying mechanism in 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)-induced neurotoxicity in a TS rat model. A TS model was induced with DOI. The rats were divided into control, TS, TS + tiapride (25 mg/kg), and TS + RH (20 and 40 mg/kg) groups. Behavioral tests were performed 24 h after the last administration by nodding and stereotype experiments. Interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) levels in striatum and serum were detected with an enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the expression levels of Toll-like receptor (TLR)/nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3)/nuclear factor kappa B (NF-κB) signal proteins in the striatum. The expression of TLR2 and NF-κB p65 subunit was detected with immunohistochemical analysis. RH may significantly improve behavioral changes in rats with DOI-induced TS and reduce the levels of inflammatory factors in serum and striatum. RH inhibited the activation of TLR/NLRP3/NF-κB signaling proteins in the striatum of TS rats. In BV2 cells, DOI-induced inflammation mediated through TLR/NLRP3/NF-κB was significantly inhibited following RH administration. The therapeutic effect of RH in TS was studied and its mechanism of action mediated via the TLR/NLRP3/NF-κB pathway was clarified in vitro and in vivo.
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Anfetaminas/toxicidade , Corpo Estriado/efeitos dos fármacos , Oxindóis/administração & dosagem , Síndrome de Tourette/induzido quimicamente , Síndrome de Tourette/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Encefalite/induzido quimicamente , Encefalite/metabolismo , Masculino , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To study the effects and mechanism of couplet medicines of Scutellaria baicalensis-Paeonia lactiflora on improving ulcerative colitis (UC) in mice. METHODS: A total of 70 mice were randomly divided into blank group, model group, S. baicalensis group (1. 5 g/kg), P. lactiflora group (1. 5 g/kg), S. baicalensis-P. lactiflora (2:1, 1:1, 1:2, m/m) groups (total amount of 1. 5 g/kg), with 10 mice in each group. Except for blank group, UC model of mice was induced in each group. The next day after modeling, treatment groups were given relevant medicine liquid 0. 2 mL/10 g (75 mg/mL, calculated by crude drug mass concentration), while blank group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 7 d. After administration, disease activity indexes (DAI) of rats were scored, and the serum levels of TNF-α, IL-1β, IL-6, D-LA and myeloperoxidase (DAO) were determined. The length of the colon was measured and the intestinal mass index was calculated in mice. The activities of medullary peroxide (MPO) and SOD, the levels of NO and MDA were determined in colon tissue. RESULTS: Compared with blank group, DAI score, serum levels of TNF-α, IL-1β, IL-6, D-LA and DAO, the levels of MPO, NO and MDA in colon were increased significantly in model group, while the length of colon, intestinal mass index and SOD level of colon tissue were decreased significantly, with statistical significance (P<0. 05 or P<0. 01). Compared with model group, DAI score, serum levels of TNF-α, IL-1β and DAO, the level of MDA in colon were decreased significantly in S. baicalensis group (P<0. 05 or P<0. 01). The serum levels of TNF-α and IL-1β, the level of MDA in colon were decreased significantly in P. lactiflora group (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (2:1) group were improved significantly except for the length of colon (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (1:1) group were improved significantly except for serum level of IL-6 and the level of SOD in colon (P<0. 05 or P<0. 01). Above indexes of S. baicalensis-P. lactiflora (1:2) group were improved significantly except for serum level of NO (P<0. 05 or P<0. 01). CONCLUSIONS: The couplet medicines of S. baicalensis-P. lactiflora can reduce the expression of proinflammatory factors, enhancing antioxidant activity of the body and decrease intestinal mucosal permeability so as to improve UC symptom of mice; and the effect of S. baicalensis-P. lactiflora (2:1) group is the best.
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Objective To observe the effects of Crk-SH3 domain guanine exchange factor(C3G)overexpression on the pro-liferation and apoptosis of high glucose-induced H9C2 cardiomyocytes.Methods H9C2 cardiomyocytes were transiently transfected with pCXN2-Flag(empty plasmid)and pCXN2-Flag-hC3G(human C3G mRNA)plasmids,then conducted high glucose(HG)in-tervention.The experiment was divided into the blank group,empty vector group,C3G overexpression group,blank + HG group, empty vector + HG group and C3G overexpression+ HG group.The C3G protein expressions,apoptosis and proliferation rate were respectively detected in each H9C2 cardiomyocytes groups.Results The proliferation rate in the blank+ HG group and empty vec-tor+ HG group were significantly decreased compared with the blank group and empty vector group,while the apoptosis rate was significantly increased.Compared with blank group and empty vector group,blank + HG and empty vector + HG group,the C3G protein expression and proliferation rate in the C3G overexpression group and C3G overexpression+ HG group were increased sig-nificantly,while the apoptosis rate was decreased significantly.Conclusion High glucose inhibits H9C2 myocardial cell proliferation and promots its apoptosis;furthermore,C3G overexpression can reversed the decrease of high glucose-induced H9C2 cardiomyocyte prolifer-ation rate and apoptosis increase.C3G overexpression can promote the survivability of high glucose-induced H9C2 cardiomyocytes.