Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

Non-alcoholic fatty liver disease(NAFLD)is a series of diseases characterized by hepatic steatosis and is also a metabolism-associated disease and an important factor for liver fibrosis,liver cirrhosis,and hepatocellular carcinoma.Endoplasmic reticulum is a core organelle for the regulation of lipid metabolism,and unfolded protein response is an important process of endoplasmic reticulum stress(ERS).Based on the important stress role of endoplasmic reticulum in metabolism-associated diseases,this article explores the influencing mechanism between ERS and NAFLD and reviews the research advances in lipid metabolism,inflammatory response,hepatocyte death,fibrosis,and ERS-targeted therapies in the pathological development of NAFLD.

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Objective: To investigate the mechanism of VPS26 effect on osteogenesis and adipogenesis differentiation of rat bone marrow mesenchymal stem cells (BMSC) in high fat environment, and to explore the effect of VPS26 on implants osseointegration of high fat rats and ectopic osteogenesis in nude mice. Methods: BMSC were cultured under normal osteogenic induction (osteogenic group) and high-fat osteogenic induction (high-fat group).High-fat group was transfected with VPS26 enhancer and inhibitor, and the expression levels of osteogenesis related genes and adipogenesis related genes were examined. Osteogenesis and adipogenesis of BMSC were detected by alkaline phosphatase (ALP) staining and oil red O staining after 7 and 14 days of induction.In osteogenic group,the binding of VPS26 to β-catenin was detected by immunofluorescence staining and immunoprecipitation, and dual luciferase reporter assay (TOP Flash) was used to analyze the TOP/FOP ratio. Eighteen male 12-week hyperlipidemic Wista rats (160-200 g) were implanted with implants, and six in each group were injected with VPS26 overexpression lentivirus (LV-VPS26 group), negative control lentivirus (LV-nc group) and saline (blank control group).Micro-CT analysis , HE and oil red O staining were used to evaluate the osseointegration of the implants and lipid droplets formation of the femur samples. Twenty female 6-week nude mice (30-40 g) were divided into five groups and subcutaneously implanted with osteogenic BMSC non-transfected and transfected LV-VPS26, LV-nc, shVPS26, and shscr lentivirus on the back. Samples were used to observe ectopic osteogenesis. Results: The mRNA expression levels of ALP in the high-fat group BMSC after overexpression of VPS26 (1.56±0.09) were significantly higher than those of the negative control (1.01±0.03) (t=10.09, P<0.001), while those of peroxisome proliferator-activated receptor-γ (PPAR-γ) (t=6.44, P<0.001) and fatty acid-binding protein4 (FABP4) (t=10.01, P<0.001) were lower than those of the negative control. Western blotting results showed that compared with the negative control, protein expression of ALP and Runt-related transcription gene 2 was enhanced in the high-fat group BMSC after overexpression of VPS26 while PPAR-γ and FABP4 were inhibited. ALP activity of BMSC in the high-fat group was stronger after overexpression of VPS26, and the formation of lipid droplets was weaker than that in negative control. The results of immunofluorescence, immunoprecipitation and dual luciferase reporter assays showed co-localization and interaction of VPS26 with β-catenin and a significant 43.10% increase in the TOP/FOP ratio (t=-3.17, P=0.034). VPS26 overexpression enhanced osseointegration and decreased the number of lipid droplets in high-fat rat and enhanced ectopic osteogenesis of nude mice. Conclusions: VPS26 activated osteogenesis differentiation and inhibited adipogenic differentiation of BMSCs through Wnt/β-catenin pathway, promoting osseointegration of high-fat rat implants and ectopic osteogenesis of nude mice.

Objective:To investigate the risk factors of post-stroke depression (PSD) in patients with first acute stroke 6 months after onset.Methods:Three hundred and sixty-seven patients with acute stroke who were treated for the first time in the Affiliated Hospital of Xuzhou Medical University were selected retrospectively. After onset for 6 months, the patients were followed up and divided into PSD group and non-PSD group. The clinical data, blood index, imaging data, degree of nerve damage and the patient's stigma level were compared between the two groups.Results:Totally 182 and 185 cases were included in the PSD and non-PSD groups, respectively. The incidence of PSD at 6 months post-stroke was 49.6% (182/367). The results of univariate analysis showed that diseased region, drinking history, monthly income, standard of culture, serum cortisol, total cholesterol (TC), high sensitivity C-reactive protein (hs-CRP), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), Stigma Scale for Chronic Illness-8 Chronic Disease Stigma Scale-8(SSCI-8) scores, National Institute of Health Stroke Scale (NIHSS) scores and subtype of stroke were risk factors for PSD ( P<0.05). Binary Logistic regression analysis showed that diseased region at frontal lobe ( OR = 3.245, P = 0.011), basal ganglia region ( OR = 2.820, P = 0.007), cerebellar hemisphere ( OR = 4.594, P = 0.010) and serum cortisol ( OR = 1.174, P<0.001), hs-CRP ( OR = 1.057, P<0.001), SSCI-8 scores ( OR = 1.674, P<0.001), NIHSS scores ( OR = 1.283, P<0.001) were independent risk factors for PSD. Conclusions:PSD is a common complication in patients with stroke. Diseased region (at frontal lobe, basal ganglia region, cerebellar hemispheres), hs-CRP, serum cortisol, level of morbidity stigma and degree of neurological impairment are development risk factors for the PSD at 6 months of acute stroke.

Bronchiectasis is a complex and heterogeneous group of diseases with their own characteristics in terms of etiology, symptoms, infections and inflammation, among which infections are both the most common cause of bronchiectasis and the most important factor contributing to the progression of the disease and affecting the prognosis. The current paper will focus on the characterization, diagnosis and treatment of pathogenic bacteria in bronchiectasis.

【Objective】 To systematically evaluate the therapeutic efficacy of autologous platelet-rich plasma combined with negative pressure wound therapy on chronic refractory wounds, and to provide reference for clinical treatment. 【Methods】 Randomized controlled trials of autologous platelet-rich plasma combined with negative pressure wound therapy for the treatment of chronic refractory wounds were included in the databases of CNKI, Wan fang, VIP, PubMed, Embase and Cochrane Library from the time of database construction to November 2022. After literature screening, data extraction and quality evaluation, Meta analysis was performed using Stata 15.1 software. 【Results】 After screening, a total of 11 Chinese literatures that met the criteria of this paper were retrieved, involving a total of 359 patients with chronic refractory wounds. The observation group was treated with autologous platelet-rich plasma combined with negative pressure wound therapy, and the control group was treated with negative pressure wound therapy alone. Meta-analysis suggested that compared with negative pressure wound therapy alone, autologous platelet-rich plasma combined with negative pressure wound therapy shortened wound healing time [WMD=-6.08, 95%CI (-7.77, -4.40), P<0.05]. The hospitalization was shortened [WMD=-8.24, 95%CI (-11.55, -4.94), P<0.05], the pain score was decreased [WMD=-1.73, 95%CI (-2.06, -1.40), P<0.05], and the positive rate of bacterial culture on the wound was decreased [RR=0.28, 95%CI(0.16, 0.49), P<0.05], the wound treatment effect was good [RR=1.28, 95%CI(1.17, 1.41), P<0.05]. 【Conclusion】 Based on current studies, compared with the negative pressure wound therapy alone, autologous platelet-rich plasma combined with negative pressure wound therapy can effectively promote the healing of chronic refractory wounds, shorten the hospital stay, reduce pain and infection, and the clinical treatment effect is better.

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) &mu;g/L, which reached a peak of 0.85(0.12, 3.01) &mu;g/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) &mu;g/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Objective:To investigate the changes of intestinal mucosal barrier function related indexes [diamine oxidase and secretory immunoglobulin A (sIgA)] in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with peripheral immune function.Methods:A total of 40 patients with RA who admitted to the Rheumatology and Immunology department of the Second Hospital of the Shanxi Medical University were enrolled. We collected their clinical and laboratory data, and selected 20 age and gender matched people as the control group. Enzyme-linked immunosorbnent assay (ELISA) was used to detect the level of DAO and sIgA in the peripheral blood, the lymphocytes and CD4 + T subsets were detected by flow cytometry. Then t-test, rank sum test and correlation analysis were conducted for statistical analysis. Results:① The level of DAO in patients with RA was higher than that of healthy controls [205(164, 251) ng/ml vs 364 (276, 483) ng/ml, Z=-4.48, P<0.001], while the level of sIgA was decreased [3.64 (2.76, 4.83)×10 5 ng/ml vs 6.83 (4.80, 9.44)×10 5, Z=-3.84, P<0.001]. ② The absolute number of B and CD4 + T cells were increased in RA, the difference were statistically significant, but the absolute number of T, natural killer cells (NK) and CD8 + T cells were not significantly different between the two groups. For CD4 + T subsets, the absolute number of T helper cells (Th)1 and Treg cells in RA group were significantly decreased than healthy controls, but there were no statistical significant difference in the number of Th2 and Th17 cells. ③ The level of DAO was positively correlated with absolute number of Th17 cells in patients with RA ( r=0.36 P=0.038), and positively correlated with age and white blood cell count ( r=0.40, P=0.021; r=0.40, P=0.020), but no significant correlation among other indicators were found. ④ The serum sIgA level of RA patients in antimutated citrullinated vimentin antibody (MCV), antiperinuclear factor (APF) and antikeratin antibody (AKA) positive group were higher than those in the negative group [3.99(2.99, 5.58)×10 5 ng/ml vs 2.73(2.29, 3.05)×10 5 ng/ml, Z=-2.55, P=0.011; 5.49 (3.26, 5.70)×10 5 ng/ml vs 3.12 (2.29, 4.04)×10 5 ng/ml, Z=-2.28, P=0.023; 4.07 (3.19, 5.65)×10 5 ng/ml vs 2.88 (2.24, 3.86)×10 5 ng/ml, Z=-2.42, P=0.016], while there was no significant difference in DAO level between groups. ⑤ The DAO level of RA patients with pulmonary interstitial fibrosis was significantly higher than that in the group without pulmonary interstitial fibrosis [421 (216, 528) ng/ml vs 191 (150, 223) ng/ml, Z=-2.81, P=0.005], while there were no significant differences in DAO and sIgA levels among other groups. Conclusion:In RA patients with inte-stinal mucosal barrier impairment, the DAO level is increased, while the sIgA is decreased, and in addition, elevated peripheral blood Th17 may be involved in the process of intestinal mucosal barrier impairment.