Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P＜0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P＜0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.

Objective To investigate the effect and mechanism of nodakenin(Nod)in neuropathic pain(NP).Methods Differential expression genes in the primary somatsensory cortex(S1)of NP data and overlapping genes between the dataset and mitochondrial data were screened and analyzed.Overlapping gene interaction networks were overlapped and core genes were screened.A total of 27 mice were randomly divided into the sham operation group,the model group and the drug administration group(9 mice/group).The chronic compression injury model of sciatic nerve was constructed in the model group and the drug administration group.Nod 10 mg/kg was intraperitoneally injected into the drug administration group for 1 week.Changes of pain behavior and motor ability in mice were detected.HE staining and Nissl staining were used to detect effects of nerve injury and inflammation on brain tissue of S1 region of mice.The expression levels of interleukin-1β,early gene(c-Fos),panthenol-cytochrome c reductase complex III subunit(Uqcrq)and ubiquinone oxidoreductase subunit(Nduf)b5 in S1 brain region were analyzed by Western blot assay.Molecular docking was used to study the target of Nod.PC12 cells were divided into the control group,the IL-1β group(1 μmol/L IL-1β treatment)and the IL-1β+Nod group(1 μmol/L IL-1β+1 μmol/L Nod treatment),and mitochondrial membrane potential was detected in each group.Results In the NP dataset GSE180627,S1 brain region contained 293 differentially expressed genes,and the mitochondrial data contained 1 082 genes.There were 34 overlapping genes,and genes related to oxidative phosphorylation and electron transport chain were enriched.The protein interaction network showed that core genes included electron transport chain related proteins Ndufb5,Uqcrq,Ndufs8,Ndufa7,Ndufa3,Cox6b1 and Mrps33.Compared with the model group,the mechanical foot shrinkage threshold,thermal foot shrinkage reflex latency and rod rotation residence time of mice were increased in the drug administration group,the number of inflammatory infiltrating cells in S1 tissue and the number of Nislet bodies in neurons,expression levels of c-Fos and IL-1β in neurons were decreased,and expression levels of Uqcrq and Ndufb5 were increased(P＜0.05).Molecular docking showed that Nod could bind Uqcrq and Ndufb5.Compared with the IL-1β group,the fluorescence signal of mitochondrial membrane potential was enhanced in the IL-1β+Nod group(P＜0.05).Conclusion Nodakenin can improve pain behavior in mice,and its mechanism involves ameliorating mitochondrial damage in S1.

Objective·To explore the effect of continuous nursing based on EMS[environment management(E),medicine direction(M)and self monitoring(S)]management mode on the preschool children with asthmatic diseases.Methods·A total of 67 children aged 0 to 6 years with asthmatic diseases admitted to the Department of Respiratory Medicine,Shanghai Children's Hospital,Shanghai Jiao Tong University School of Medicine from December 2019 to November 2020 were selected and divided into observation group(33 cases)and control group(34 cases)according to the random number table method,with 3 cases lost,and finally 32 cases in each group.The observation group received continuous nursing care based on EMS management mode,while the control group received routine care and discharge follow-up through the telephone.The children in the two groups were followed up at 1,3,and 6 months after discharge to evaluate the results of Test for Respiratory and Asthma Control in Kids(TRACK)and wheezing recurrence;Medication Adherence Report Scale for Asthma(MARS-A)and Nursing Job Satisfaction Questionnaire were used to evaluate medication adherence and nursing job satisfaction 6 months after discharge.Results·There was no significant difference in demographic characteristics and clinical baseline characteristics between the two groups.Repeated measures analysis of variance showed that effects of time,groups and the interaction of groups×time on the total score of TRACK were statistically significant.The total scores of TRACK in the observation group were significantly higher than those in the control group at 1,3,and 6 months after discharge(P=0.000).The total scores of TRACK in the two groups gradually increased with time(P=0.000).The recurrence rates of wheezing in the observation group were 25.0%,18.7%,and 9.4%at 1,3,and 6 months after discharge,which were significantly lower than those in the control group(50.0%,43.7%,and 31.3%,respectively,P<0.05).Generalized estimating equation analysis showed that there was a statistically significant difference between the two groups(P=0.013),and the intervention effect of the observation group was better than that of the control group(OR=0.292).The MARS-A score of the observation group was 4.519±0.395 at 6 months after discharge,which was significantly higher than that of the control group(3.994±0.739,P=0.001).The nursing job satisfaction of the observation group was significantly higher than that of the control group(P=0.000).There was a moderate positive correlation between the MARS-A score and the nursing job satisfaction(r=0.389,P=0.001).Conclusion·Continuous nursing based on EMS management mode can significantly improve the medication compliance and wheezing control level of the preschool children with asthmatic diseases,significantly reduce the recurrence rate of wheezing,and improve the nursing satisfaction.

Objective To investigate the mechanism of icariin regulating the NLRP3 inflammasome in the treatment of cerebral ischemia-reperfusion injury in rats.Methods A rat model of focal cerebral ischemia-reperfusion was induced using the thread embolism method.At 24 hours post-operation,the rats were randomly allocated into a sham operation group,model group,butylphthalide group(70 mg/kg),ICA-low dose(20 mg/kg),ICA-middle dose(40 mg/kg),and ICA-high dose(80 mg/kg)groups.The corresponding drugs were administered by gavage at 10 mL/kg once a day for 13 consecutive days.One hour after the last administration,neurological function was scored.The cerebral cortex was observed by hematoxylin-eosin(HE)staining.Expression of interleukin(IL)-1β and IL-18 in the cerebral cortex was determined by immunohistochemistry.Expression of NLRP3,ASC,and Caspase-1 in the cerebral cortex was determined by Western Blot.Results In contrast to the sham operation group,there was a notable increase in neural function scores within the model group.The ischemic area around the visible cerebral cortex showed neuron necrosis at various level or glial cell proliferation,and the number of intact neurons was significantly reduced.IL-1β and IL-18 positive cells were significantly increased.Expression of NLRP3,ASC,and Caspase-1 was significantly increased(P＜0.01,P＜0.05).After treatment with icariin,the neural function score was decreased significantly.The degree of neuronal necrosis in the peri-ischemic area was significantly reduced,and the number of intact neurons was significantly increased.IL-1 β and IL-18-positive cells were decreased significantly.Expressions of NLRP3,ASC,and Caspase-1 were significantly decreased(P＜0.01,P＜0.05).Conclusions Treatment of cerebral ischemia-reperfusion injury by icariin may be related to regulation of the NLRP3 inflammasome.

Objective:To evaluate the safety and efficacy of endovascular thrombectomy (EVT) in acute anterior circulation large vessel occlusive stroke (ALVOS) and explore the related influencing factors for prognoses in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECT).Methods:Patients with acute ALVOS who underwent EVT in Yijishan Hospital of Wannan Medical College from January 2019 to June 2022 were sequentially enrolled. (1) Patients were divided into a low ASPECT group (0-5) and a non-low ASPECT group (6-10), and the differences between the two groups were compared with respect to incidence of perioperative complications and good prognosis rate [modified Rankin scale (mRS) score≤2] 90 days after onset. (2) According to the prognoses 90 days after onset, the low ASPECT group was divided into the good prognosis (mRS score≤2) and poor prognosis (mRS score>2) subgroup. Univariate analysis and multivariate logistic regression analysis were used to investigate the independent risk factors for prognoses of the low ASPECT patients after EVT.Results:A total of 582 patients [age 26-94(69±11) years, 345 male patients (59.3%)] were enrolled for analysis. The baseline ASPECT score was 8 (7, 10), and the baseline NIHSS score was 14 (11, 18). Among them, 102 (17.5%) patients were in the low ASPECT score group and 480 (82.5%) patients were in the non-low ASPECT score group. In the total cohort, patients in the low ASPECT score group had a higher incidence of symptomatic intracranial hemorrhage, lower 90-day good prognosis rate, and higher 90-day mortality rate. Further, propensity score matching statistical analysis showed that patients in the low ASPECT score group had a significantly higher incidence of malignant brain edema after EVT treatment (40.0% vs. 17.6%, χ2=9.13, P=0.003), and a significantly lower 90-day good prognosis rate (24.7% vs. 41.6%, χ2=4.96, P=0.026), but there was no significant difference in the incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (40.3% vs. 26.0%, χ2=3.55, P=0.060). Among 102 patients with low ASPECT score, 22 (21.6%) patients had good prognosis and 80 (78.4%) had poor prognosis. Multivariate logistic regression analysis showed that history of atrial fibrillation ( OR=4.478, 95% CI 1.186-16.913, P=0.027) was an independent risk factor for poor prognosis of EVT in patients with low ASPECT score, while good collateral circulation (grade 2 vs. grade 0: OR=0.206, 95% CI 0.051-0.842, P=0.028) was a protective factor for good prognosis of EVT in patients with low ASPECT score. Conclusions:Although the 90-day good prognosis rate of EVT treatment for patients with low ASPECT score was lower than that of the non-low ASPECT group, 21.6% patients still benefitted from EVT treatment, especially patients with non-atrial fibrillation and good collateral circulation. Future studies involving more patients are needed to validate our observations.

Objective:To investigate the association between door-in-door-out time (DIDO) and clinical outcome of patients with acute large vessel occlusion stroke (AIS-LVO) of anterior circulation after early endovascular therapy (EVT).Methods:The patients with AIS-LVO of anterior circulation who received EVT in the advanced stroke center of the Yijishan Hospital of Wannan Medical College from February 2019 to December 2021 were retrospectively analyzed. The baseline characteristics, time metrics and clinical outcomes were collected. DIDO was defined as the duration of time from arrival to referral at the primary stroke center, and the primary outcome was favorable clinical outcome, as evaluated by a modified Rankin Scale score of 0 to 2 at 3 months after EVT. Univariate and multivariate regression analysis was used to explore the relationship between DIDO and early endovascular treatment clinical outcomes in patients with AIS-LVO.Results:A total of 320 patients [aged (69.6±10.2) years] were enrolled. The baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program early CT score were 14 (11, 18) and 8 (7, 9). The DIDO time was 76 (50, 120) minutes. DIDO was not an independent correlation factor for clinical outcomes in patients with EVT in the overall population. However, in patients receiving early EVT (onset-to-reperfusion≤300 minutes), DIDO ( OR=1.030, 95% CI 1.001-1.059, P=0.041) was an independent correlating factor of clinical outcome in patients with EVT. According to the receiver operating characteristic curve, the DIDO cutoff of 74.5 minutes can be used as an important indicator of prehospital delay in referral to EVT for large vascular occlusion stroke. Door to computed tomography time ( OR=1.393, 95% CI 1.212-1.601, P<0.001) and computed tomography to transfer time ( OR=1.386, 95% CI 1.220-1.575, P<0.001) were factors associated with DIDO≤74.5 minutes in a multivariate analysis in this time frame. Conclusions:In transferred patients undergoing EVT early, DIDO has a signifificant impact on clinical outcome. DIDO can be used as an important quality control indicator to evaluate the referral process for patients with AIS-LVO.

Objective:To evaluate the effect of oral acitretin on the height and bone development of children.Methods:Clinical and imaging data were collected from 106 children receiving oral acitretin for at least 1 month in Department of Dermatology, Beijing Children′s Hospital from March 2007 to January 2021, and retrospectively analyzed. The main outcome measures were height and near-adult height. Multivariate logistic regression analysis was carried out to investigate relevant factors for short stature in children, and non-inferiority test was used to analyze the proximity of the actual height to target height of children who had reached near-adult height. The secondary outcome measures were bone age and epiphyseal closure. Wilcoxon signed-rank test was used to analyze differences in the value of bone age minus chronological age between the baseline and last follow-up, and the premature closure of epiphysis was also evaluated.Results:Among the 106 children, 62 were males and 44 were females; 84 were diagnosed with pustular psoriasis, 10 with psoriasis vulgaris, 11 with pityriasis rubra pilaris, and 1 with lupus miliaris disseminatus faciei. These children received oral acitretin at doses of <1 mg·kg -1·d -1 for 1 - 90 months. Among the 96 children aged under 18 years, 91 (94.8%) were of normal stature, and 5 (5.2%) were short in stature; among the 83 children receiving acitretin monotherapy, 81 (97.6%) were of normal stature, and 2 (2.4%) of short stature. Binary logistic regression analysis showed that the risk of short stature caused by acitretin combined with glucocorticoid therapy was 76.57 times higher than that of acitretin monotherapy ( OR = 77.57, 95% CI: 2.20 - 2 738.82, P = 0.017) , while the type of disease, gender, age at onset, age at initial treatment with acitretin, course of treatment, and average daily dose of acitretin did not significantly affect the stature of children ( P = 0.988, 0.214, 0.087, 0.078, 0.066, 0.350, respectively) . At the last follow-up visit, 13 children who had reached near-adult height were of normal stature, and the non-inferiority test showed that their near-adult height was not inferior to the target height (Satterthwaite = 0.23, P = 0.030) . Bone age was evaluated in 45 children at baseline and last follow-up visit, there was no significant difference in the value of bone age minus chronological age between the baseline and last follow-up ( Z = -0.85, P = 0.250) , and no patients experienced premature closure of epiphysis before and after the treatment. Conclusion:This study preliminarily revealed that oral acitretin at doses of <1 mg·kg -1·d -1 for less than 90 months might not significantly affect the height and bone development of children.

Lung cancer is one of the malignant tumors with the highest morbidity and mortality rate, and effective screening and early diagnosis methods can significantly reduce the morbidity and mortality rate of lung cancer patients. Traditional lung cancer detection methods mainly include imaging tests, sputum cell tests, bronchoscopy, and needle biopsy, but these methods have disadvantages such as being highly invasive, complicated operation processes, prone to false positives, and low detection index. Tumor markers can reflect the occurrence and development of tumors and can monitor the effect of tumor treatment. Therefore, tumor marker detection is of great significance for early cancer diagnosis. Biosensor technology is a new rapid detection technology with promising applications. In recent years, research related to biosensors has been intensified in clinical testing and biomedicine. In this paper, the traditional detection methods for lung cancer were briefly introduced, and the technologies and detection methods related to optical or electrochemical lung cancer tumor marker biosensors based on immunology, nanomaterials, and aptamers were highlighted in recent years, and the future development trend of lung cancer tumor marker biosensors was prospected.

Clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats -associated protein (CRISPR/Cas) has been developed as a precise, efficient, affordable and sensitive nucleic acid detection tool due to its efficient targeted binding ability and programmability. At present, biosensors based on CRISPR-Cas system have shown excellent performance in the detection of nucleic acid of pathogens, which has attracted widespread attention, and is expected to replace the conventional detection methods. This review summarizes the latest research progress of biosensors based on CRISPR/Cas system for detecting nucleic acid of pathogens.
Biosensing Techniques ; CRISPR-Cas Systems/genetics* ; Nucleic Acids/genetics*

Chromatin conformation, localization, and dynamics are crucial regulators of cellular behaviors. Although fluorescence in situ hybridization-based techniques have been widely utilized for investigating chromatin architectures in healthy and diseased states, the requirement for cell fixation precludes the comprehensive dynamic analysis necessary to fully understand chromatin activities. This has spurred the development and application of a variety of imaging methodologies for visualizing single chromosomal loci in the native cellular context. In this review, we describe currently-available approaches for imaging single genomic loci in cells, with special focus on clustered regularly interspaced short palindromic repeats (CRISPR)-based imaging approaches. In addition, we discuss some of the challenges that limit the application of CRISPR-based genomic imaging approaches, and potential solutions to address these challenges. We anticipate that, with continued refinement of CRISPR-based imaging techniques, significant understanding can be gained to help decipher chromatin activities and their relevance to cellular physiology and pathogenesis.
CRISPR-Cas Systems ; genetics ; Clustered Regularly Interspaced Short Palindromic Repeats ; genetics ; Genetic Loci ; Genomics ; Molecular Imaging ; methods ; Nanoparticles ; chemistry