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.

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.

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.

Objective:To assess the correlation between circulating chemerin and two indicators of renal function, estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR), in individuals with type 2 diabetes and to determine whether chemerin is an independent marker of early renal insufficiency.Methods:A total of 742 patients with type 2 diabetes were recruited into the cross-sectional community study. Basic information, anthropometric parameters, and biochemical parameters of these individuals were determined and collected, and serum chemerin level was measured using enzyme-linked immunosorbent assay.Results:Chemerin levels were significantly higher in the eGFR-impaired group compared with eGFR-normal group, and macroalbuminuria group compared to the normal or microalbuminuria groups. Spearman′ rank correlation analysis showed serum chemerin level was correlated with eGFR ( r=-0.25, P<0.001), UACR ( r=0.23, P<0.001) and some other biochemical indicators such as triglyceride. And univariate and multivariate logistic regression analyses revealed circulating chemerin was an independent risk factor for eGFR impairment or proteinuria after adjusting corresponding covariates. Receiver operating characteristic (ROC) curve analysis showed that the area under curve (AUC) of circulating chemerin for predicting early impaired eGFR in type 2 diabetes was 0.747, while the AUC of circulating chemerin for predicting macroalbuminuria in type 2 diabetes was 0.748. Conclusion:Circulating chemerin is associated with eGFR or UACR and may be a potential diagnostic marker for early renal insufficiency in type 2 diabetes.

Objective:To investigate the relationship between serum lipocalin-2 level and the risk of cardiovascular disease(CVD) in patients with type 2 diabetes.Methods:A total of 279 type 2 diabetic patients were enrolled in this study. Basic information and clinical data were collected. These patients were divided into CVD group and non-CVD group according to their cardiovascular disease status. Serum lipocalin-2 level was assessed by enzyme linked immunosorbent assay.Results:Compared to non-CVD group, serum lipocalin-2 level was significantly higher in CVD group( P<0.01). The Spearman correlation analysis showed that serum lipocalin-2 level was positively correlated with waist circumstance, diastolic blood pressure, uric acid, triglyceride, and HbA 1C( P<0.05), while negatively correlated with high density lipoprotein-cholesterol level( P<0.01). In addition, the univariate and multivariate logistic regression analysis revealed that serum lipocalin-2 was an independent risk factor for CVD( P<0.01)after adjustment for potential confounders. Moreover, receiver operating characteristic curve analysis demonstrated that the area under curve value of lipocalin-2 was 0.74, with the optimal cutoff value of lipocalin-2 66.84 ng/mL. Conclusion:Serum lipocalin-2 is closely associated with CVD in patients with type 2 diabetes, which might be considered as one of the predictors for CVD in type 2 diabetes mellitus.

Objective Metabolites produced by metabolic imbalance such as free fatty acids and lipopolysaccharides can result in a state of chronic low-grade inflammation, or metabolic inflammation, which plays an important role in the pathogenesis of atherosclerosis, type 2 diabetes, non-alcoholic fatty liver disease, and obesity. The above metabolic disorders are closely related with the metabolic inflammation, which always coexist. Therefore, we proposed the concept ofmetabolic inflammatory syndrome ( MIS). According to our study, patients with two or more metabolic disorders above could be diagnosed as MIS. The current research is aimed to investigate the prevalence of MIS and its components, and to compare the clinical values of MIS and metabolic syndrome ( MS) . Methods 2 001 in patients with type 2 diabetes from 6 hospitals in Shanghai were recruited in the current multi-center cross-sectional study. The diagnostic rates of MIS and MS and their components of both syndromes were compared. Results In the patients with type 2 diabetes, the detective rate of MIS was 96. 2%, which was higher than that of MS (71. 3%). Among 4 components of MIS, atherosclerosis showed the highest detective rate (75.6%). MIS[OR=2.252(95%CI1.026-4.942),P=0.043],atherosclerosis[OR=2.726(95% CI1.953-3. 804),P<0. 001], and MS[OR=1. 915 (95%CI 1. 444-2. 540),P<0. 01] were the risk factors of coronary heart disease. Conclusion With atherosclerosis, type 2 diabetes mellitus, non-alcoholic fatty liver disease, and obesity as its 4 components, MIS has a high detective rate in patients with metabolic disorders, and seems to be more sensitive than MS to distinguish inflammation-related metabolic diseases. The concept of MIS will promote the screening and prevention of atherosclerosis in its early stage.

OBJECTIVE:To compare the efficacy and safety of gio combined with oxaliplatin (SOX) versus 5-fluorouracil (5-FU)combined with calcium folinate and oxaliplatin(mFOLFOX6)in the treatment of diffuse advanced gastric cancer. METH-ODS:The data of 128 patients with diffuse advanced gastric cancer was retrospectively analyzed and patients were divided into SOX group(66 cases)and mFOLFOX6 group(62 cases)by different medication. SOX group received Gio capsule after breakfast and dinner,which was <1.25 m2,40 mg,1.25-1.5 m2,50 mg,>1.5 m2,60 mg,d1-14+130 mg/m2 Oxaliplatin for injection,intrave-nously,d1;3-week was regarded as a treatment course,the efficacy was evaluated every 2 courses,and it lasted a maximum of 8 courses but a minimum of 2 courses. mFOLFOX6 group received 85 mg/m2 Oxaliplatin for injection,intravenously,d1+200 mg/m2 calcium folinate,intravenously,d1+400 mg/m2 5-FU for injection by rapid intravenous injection,d1,then 2 400 mg/m2 5-FU,main-taining 46 h by continuous infusion. 2-week was regarded as a treatment course,the efficacy was evaluated every 3 courses,and chemotherapy was conducted in a maximum of 12 courses but a minimum of 3 courses. Clinical efficacy,time to progression,sur-vival time and incidence of toxicities in 2 groups were observed. RESULTS:The objective response rate,time to progression and median survival time in SOX group was significantly higher than mFOLFOX6 group,the difference was statistically significant (P<0.05 or P<0.01). There was no significant difference in the disease control rate and incidence of toxicities in 2 groups(P>0.05). CONCLUSIONS:The efficacy of SOX is superior to mFOLFOX6 in the treatment of diffuse advanced gastric cancer,it can prolong the survival time,with similar safety.

[Summary] Four patients with hyperthyroid-associated exophthalmos, myxedema, acropachy ( EMA ) syndrome, including three male patients and one female patient were diagnosed with Graves′diseases and treated by 131 I therapy. Complaints of thyrotoxicosis were presented at the onset. Tibia myxedema and acropathy appeared, and eye symptoms aggravated in two patients after anti-thyroid drug therapy and 131 I therapy. Four cases were all given clobetasol propionate, miconazole nitrate, neomycin sulfate and urea cream alone or in combination with compound betamethasone local injection treatment, and three cases were given low-dose oral prednisone treatment. Complaints of tibia myxedema and eye symptoms were significantly improved after the treatment. Therefore, we should be wary of the occurrence of hyperthyroid-associated EMA syndrome after 131 I therapy. Corticosteroid might be the effective therapy for myxedema and eye symptoms of EMA syndrome.

Objective To investigate the outcome of postoperative hypopituitarism and hormone replacement in patients with pituitary adenoma,and to analyze the potential factors related to postoperative hypopituitarism.Methods A total of 215 postoperative patients with pituitary adenoma were analyzed.Pituitary functions( including gonadal,thyroid,and adrenal axes ) were asessed by strict criteria.Data of surgery history and hormone replacement situation were collected for statistical analysis.Results The prevalence of hypopituitarism was 54.0％,including 36.7％ hypogonadism,32.6％ hypothyroidism,and 28.4％ hypoadrenalism.Replacements of gonadal steroid,glucocorticoid,and thyroxine were carried out in 25.6％,84.3％,and 80.6％ of the cases,respectively.Univariate analysis showed that male sex and large tumor were related to hypopituitarism. Conclusion After pituitary adenomectomy,approximately half of the patients present anterior pituitary dysfunction,while quite a number of them have not been treated appropriately.

Objective To evaluate desmopressin stimulated inferior petrosal sinus sampling in diagnosing Cushing′s disease.Methods Sixteen ACTH-dependent Cushing′s disease patients underwent bilateral desmopressin stimulated inferior petrosal sinus ( IPS ) sampling because of negative or equivocal magnetic resonance imaging.Cortisol response to high-dose dexamethasone suppression test was also evaluated.ACTH sampling was taken from a peripheral vein and bilateral IPS before and both 5 and 10 min after injection of desmopressin.Diagnosis was based on the ratio of ACTH level in between IPS to peripheral vein by desmopressin test.Diagnosis was confirmed after surgery.Results High-dose dexamethasone suppression test showed suppressible in 9 of 16 patients with Cushing′s disease.An IPS gradient ＞2 was found in 14 of the 16 cases (87.5％ )with Cushing′s disease after desmopressin injection,while before injection the respective figure was 12 of 16 (75.0％).No severe adverse effects were observed during or after the procedure.Conclusion Desmopressin test during bilateral IPS sampling is a safe and effective diagnostic procedure in Cushing′s disease.