Aim To explore the mechanism of oxiracetam promoting neurogenesis and migration in rats with cer-ebral infarction through stromal cell-derived factor-1α(SDF-1α)/C-X-C chemokine receptor 4(CXCR4)pathway.Methods 100 SD rats were randomly divided into control group,cerebral ischemia(CI)group,oxiracetam(200 mg/kg)group,and oxiracetam(200 mg/kg)+AMD3100(5 mg/kg)group,with 25 rats in each group.Electrocoagulation was used to create rat model of local permanent cerebral infarction.After 1,7 and 14 days of modeling,neurological deficits were scored,TTC staining was used to detect the volume of cerebral infarction,Nissl staining was used to detect cell surviv-al in the infarcted area,Western blot was used to detect SDF-1α and CXCR4 protein levels in ischemic zone.After 1～7 days of modeling,BrdU(50 mg/kg)was continuously injected intraperitoneally.After 14 days,immunofluorescence double staining was used to detect the number of BrdU+Nestin+and BrdU+DCX+cells in the SVZ region.5 days before modeling,retroviruses carrying GFP were injected into the SVZ region.After 14 days,immunofluorescence double stai-ning was used to detect the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in infarction area.C17.2 cells were divided into control group,oxygen-glucose deprivation(OGD)group,oxiracetam(final concentration:200 mg/L)group,and oxiracetam(final concentration:200 mg/L)+AMD3100(final concentration:100 μmol/L)group.OGD was used to create cell CI model.After 12 hours,immunofluorescence double staining was used to detect the number of Br-dU+/Nestin+and BrdU+/MAP-2+cells,Transwell experiment was used to detect cell migration,Western blot was used to detect SDF-1α and CXCR4 protein levels in cell culture supernatant.Results Animal experiment results showed:compared with control group,mNSS score in CI group was increased,cerebral infarction volume was increased,the number of surviving cells in infarcted area was decreased,SDF-1α and CXCR4 protein levels were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in SVZ region were increased(P＜0.05);compared with CI group,mNSS score in oxiracetam group was decreased,cerebral infarction volume was decreased,the number of surviving cells in infarc-ted area was increased,SDF-1α and CXCR4 protein levels were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in SVZ region were increased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in in-farcted area were increased(P＜0.05);compared with oxiracetam group,mNSS score in oxiracetam+AMD3100 group was increased,cerebral infarction volume was increased,the number of surviving cells in infarcted area was decreased,CXCR4 protein level was decreased,the number of GFP+DCX+,GFP+MAP-2+and GFP+GFAP+cells in the SVZ region were de-creased(P＜0.05).Cell experiment results showed:compared with control group,the number of BrdU+/Nestin+and Br-dU+/MAP-2+cells in OGD group were increased,the number of cell migration,SDF-1α and CXCR4 protein levels in cell culture supernatant were increased(P＜0.05);compared with OGD group,the number of BrdU+/Nestin+and BrdU+/MAP-2+cells in oxiracetam group were increased,the number of cell migration,SDF-1α and CXCR4 protein levels in cell culture supernatant were increased(P＜0.05);compared with oxiracetam group,the number of BrdU+/Nestin+and BrdU+/MAP-2+cells in oxiracetam+AMD3100 group were decreased,the number of cell migration,CXCR4 protein level in cell culture supernatant were decreased(P＜0.05).Conclusion Oxiracetam may promote the migration of neural stem cells from the SVZ region to the ischemic zone,promoting neurogenesis and functional recovery in rats with cerebral infarction by activating SDF-1α/CXCR4 pathway.

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest(RF),extreme gradient boosting(XGBoost),light gradient boosting machine(LightGBM),and categorical boosting(CatBoost).Methods We obtained the ex-pression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prog-nosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost mod-els were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation.Results A total of 151 differentially expressed protein-coding genes related to survival prog-nosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance.Conclusions Three protein-coding genes(UGP2,C3orf80,and SPC25)were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

Objective:To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI.Methods:This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People′s Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model.Results:A total of 367 patients were enrolled, divided into control group ( n=172) and STEMI group ( n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) μg/L vs. 85.00 (53.93, 117.10) μg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11( OR=0.98, 95% CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI ( P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score ( P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95% CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95% CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95% CI: 0.72-0.81), all P<0.01. Conclusions:Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.

Neuropathic pain is a chronic disease that severely afflicts the life and emotional status of patients, but currently available treatments are often ineffective. Novel therapeutic targets for the alleviation of neuropathic pain are urgently needed. Rhodojaponin VI, a grayanotoxin from Rhododendron molle, showed remarkable antinociceptive efficacy in models of neuropathic pain, but its biotargets and mechanisms are unknown. Given the reversible action of rhodojaponin VI and the narrow range over which its structure can be modified, we perforwmed thermal proteome profiling of the rat dorsal root ganglion to determine the protein target of rhodojaponin VI. N-Ethylmaleimide-sensitive fusion (NSF) was confirmed as the key target of rhodojaponin VI through biological and biophysical experiments. Functional validation showed for the first time that NSF facilitated trafficking of the Cav2.2 channel to induce an increase in Ca²⁺ current intensity, whereas rhodojaponin VI reversed the effects of NSF. In conclusion, rhodojaponin VI represents a unique class of analgesic natural products targeting Cav2.2 channels via NSF.

Objective:To evaluate the real-world short-term effectiveness of ixekizumab in the treatment of psoriasis, and to investigate factors influencing the effectiveness.Methods:Baseline data and short-term effectiveness evaluation results were retrospectively collected from patients with psoriasis, who received ixekizumab treatment in Department of Dermatology, Xiangya Hospital from November 2019 to September 2021. A descriptive analysis was performed on the baseline characteristics of patients, continuous data were described as median (lower quartile, upper quartile), and categorical data were described as percentages. Comparisons of disease severity scores before and after the treatment with ixekizumab were performed using Wilcoxon signed-rank test or paired McNemar test. Multivariable logistic regression analysis was conducted to explore factors influencing the effectiveness of 4-week ixekizumab treatment.Results:A total of 118 patients with psoriasis were included, including 94 males and 24 females, and their age [ M ( Q1, Q3) ] was 43.4 (32.5, 53.0) years; plaque psoriasis (99 cases, 83.9%) and severe psoriasis (72 cases, 68.6%) predominated among the 118 patients, and skin lesions were mainly located on the scalp (59/116, 50.9%). Among the 49 patients who had received 2-week ixekizumab treatment, 27 (55.1%) achieved a 50% improvement in the psoriasis area and severity index (PASI) score (PASI50) ; after 4-week treatment, 44 (89.8%), 30 (61.2%), 13 (26.5%) and 10 (20.4%) patients achieved PASI50/75/90/100 respectively, and their PASI scores (2.1 [1.1, 7.1]), involved body surface area (3.9% [0.5%, 14.5%]), dermatology life quality index scores (1.0 [0.0, 2.0]) and physician global assessment (PGA) scores (1.0 [1.0, 3.0]) were significantly lower than the corresponding scores at baseline (12.4 [8.8, 23.2], 22.0% [11.3%, 43.4%], 6.0 [3.0, 11.0], 4.0 [3.0, 5.0], respectively; all P < 0.001]. Multivariable logistic regression analysis showed that the baseline body mass index was significantly associated with the PASI75 response rate ( OR = 0.814, 95% CI: 0.659 - 0.958, P = 0.029) and the proportion of patients with PGA0/1 ( OR = 0.743, 95% CI: 0.562 - 0.917, P = 0.017) after 4-week ixekizumab treatment, and the baseline BSA score was significantly associated with the proportion of patients with PGA0/1 after 4-week ixekizumab treatment ( OR = 0.924, 95% CI: 0.870 - 0.968, P = 0.003) . Conclusion:The 4-week ixekizumab treatment significantly decreased the severity of psoriasis, and may be more effective in patients with lower disease severity and lower body mass index at baseline.

This review summarizes dietary characteristics of patients with psoriasis, discusses effects of gluten-free diet, Mediterranean diet and dietary intervention-induced weight loss on psoriasis, and analyzes the efficacy of dietary supplements in the treatment of psoriasis, such as fish oil, vitamin D, vitamin B12, selenium, and probiotics.

Glaucoma is an irreversible blinding eye disease caused by the structural and functional damage of optic nerve induced by pathological increase of intraocular pressure (IOP), characterized by multiple causes and strong heterogeneity.The control of IOP to reduce the risk of optic damage has been the main therapeutic strategy of glaucoma for many years.However, in clinical experience, some patients show progress of optic nerve damage despite the effectively controlled IOP, the mechanism of non-IOP-dependent secondary damage is still an urgent problem to be solved and a research hotspot in the pathogenesis of glaucoma.With the continuous innovation of molecular biological technology, breakthroughs have been made in the field of basic research.Partial visual recovery can be boosted by alleviating local immune and inflammatory responses.Due to a lack of symbolic clinical application results, it has become an immediate priority to attach importance to the combination of basic clinical research and facilitate the transformation of results.Starting from the theory of glaucoma-immune inflammation, understanding the importance of the immune homeostasis of eyes, paying close attention to the linkage of eyes and brain in physiopathological process and the progression of diseases in the whole visual pathway, and fully understanding and effectively making good use of the opportunities and implications brought by new techniques will have significant effect in formulating clinical diagnosis and treatment plans.

Objective:To explore the clinical diagnosis and treatment of invasive gastrointestinal fungal infection plus pulmonary infection after renal transplantation.Methods:Clinical data were analyzed retrospectively for one patient with invasive fungal infection plus pulmonary infection after renal transplantation. The middle-aged female recipient underwent allogeneic kidney transplantation due to end-stage uremia. After successful kidney transplantation, there was postprandial epigastric pain not relieved by proton pump inhibitor. Gastroscopy after admission suggested that the nature of gastric mucosal lesions was to be determined. Pathological examination and special staining confirmed mucor.Results:After clarifying her conditions, the doses of such immunosuppression as tacrolimus, mycophenolate mofetil and prednisone were tapered and discontinued when necessary and using amphotericin B liposome plus posaconazole alleviated the digestive tract symptoms. Chest tightness, fever, shortness of breath after activities hinted at pulmonary infection after renal transplantation. Treatment was guided by the results of sputum culture.Conclusions:Mucor infection is rare in digestive tract complicated with pulmonary infection after renal transplantation. Clinicians should actively search for etiological evidence, seek multidisciplinary consultations for a definite diagnosis and provide empirical anti-infection treatments. Due attention is to be paid for double infection caused by anti-infection treatments and anti-infection treatment strategy should be timely adjusted and the dosage of immunosuppressant based upon immune monitoring.