Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Depression is a widespread psychiatric disorder with complex pathogenesis and unsatisfactory therapeutic effects. As a native flavonoid, Isorhamnetin (ISO) has been deemed to exert neuroprotective effects by antioxidation and regulation of immunity. However, no reports of anti-depressed effect of ISO have yet been found. The present study was conducted to clarify the mechanism basis of anti-depressed effect of ISO utilizing behavioral, biochemical, molecular approaches in vitro and in vivo and bio-informatics analysis. The effects of ISO on depressed mice was investigated through the SPT and FST, and the lesions were examined by H&E staining. Besides, the inflammatory factor and indicator in kynurenine pathway were assessed through detection kits, and the microbiota were checked by 16sRNA. Molecular docking study was performed to investigate the target of ISO. Additionally, Western blot was used to test the activation of PI3K/AKT signaling pathway. The results indicated that ISO could enhance the sugar water preference of mice in SPT and reduce immobility time in FST. Further more, ISO suppressed peripheral and central inflammation, regulated the changes in kynurenine pathway and gut microbiota, inhibited activation of PI3K/AKT pathway, and presented good binding patterns with target proteins on PI3K/AKT signaling pathway. Collectively, these findings demonstrate that ISO alleviated depression-like behaviour by normalizing inflammation-induced dysregulation of the crosstalk between KP and gut microbiota disorder through regulated PI3K/AKT/NF-κB pathway.

Objective To analyze the characteristics of imported malaria epidemic from overseas in Wuhan, to explore the management mechanism of on-site cases, and to accumulate experience for the treatment of imported malaria in large cities after malaria elimination. Methods The epidemiological data on imported malaria from abroad during the period of malaria elimination (2010-2019) in Wuhan were collected. The gender, age and severe illness-related factors of the cases were analyzed. Based on the characteristics of the epidemic and the current situation of prevention and control, the content and experience of the “Municipal-District 24-7” case mechanism were discussed. Results The medical resources in Wuhan were the best in the central region, resulting in a large number of imported malaria cases, with a total of 474 cases reported from 2010 to 2019 (40.79% of the total number of cases in Hubei Province), including 359 cases of falciparum malaria, 36 severe cases and one death (the death rate was 0.28%). The patients were mainly young and middle-aged men aged 20 to 49 years old (97.26%). There were many referral cases (40.30%), and there was no seasonal clustering of cases reported. The undiagnosed proportion at the first visit was 44.85%, and the time of attack-diagnosis was 4 days or more in 61.00% of cases. The occurrence of severe cases was related to unconfirmed diagnosis at the first visit (χ²=35.46, P<0.001) and attack-diagnosis time (Z=-6.49, P<0.001). Conclusion Imported malaria occurs frequently in Wuhan, mainly falciparum malaria. However, “Municipal-District 24-7” case mechanism has effectively curbed the occurrence of severe and death cases and provided valuable experience for case management in similar cities in China.

ObjectiveTo investigate the association between obesity phenotype and the occurrence of hypertension in middle-aged and elderly adults in China. MethodsData were obtained from the China Health and Retirement Longitudinal Study （CHARLS） in 2011 and 2015. Participants who completed two visits with ≥45 years old age at baseline were enrolled. Obesity phenotype was defined as the following four groups according to weight and metabolic status：metabolically healthy non-overweight/obesity （MHNO）， metabolically healthy overweight/obesity （MHO）， metabolically abnormal non-overweight/obesity （MANO）， and metabolically abnormal overweight/obesity （MAO）. Cox proportional risk regression model was used to analyze the relationship between obesity phenotype and the incidence of hypertension. ResultsA total of3 781 subjects with 1 775（46.95%） males and mean age of （57.76±8.57） years were included in this study. When the metabolically normal non-overweight/obese group （MHNO） was regarded as the reference group， the risk of developing hypertension was significantly increased （P<0.01） in MHO， MANO， and MAO with HRs of 1.35（1.11‒1.63）， 1.51（1.15‒1.97）， and 2.00（1.68‒2.38） respectively.ConclusionBoth MHO phenotype and MAO/MANO are significantly associated with the occurrence of hypertension in middle-aged and elderly adults.

Objective To explore frequency distribution of vitamin D receptor (VDR) genotype and the correlations between polymorphism of VDR gene Bsm Ⅰ sites and bone mineral density in the patients undergoing maintenance peritoneal dialysis.Methods A case-control study was conducted based on 82 patients with maintenance peritoneal dialysis and 80 healthy people.The frequency distribution of VDR genotype in two groups was detected and analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Serum biochemistry and bone mineral density of the patients undergoing maintenance peritoneal dialysis were detected by dual energy X-ray absorption (DEXA) and automatic biochemical analyzer,respectively.All data was analyzed with SPSS 19.0 software.Results The frequency distribution of VDR genotype between case group and control group had no significant difference (P ＞ 0.05).The serum biochemical index such as Ca,P,alkaline phosphatase (ALP) and parathyroid hormone (PTH)] of patients with maintenance peritoneal dialysis had no significant difference among three VDR genotypes(P ＞0.05).Compared to VDR bb genotype,the serum Ca was significantly higher in VDR BB genotype (P ＜0.05).The bone mineral density (BMD) and T-Score of patients with VDR BB genotype were the lowest,the BB genotype was the highest,and the difference was statistically significant among three genotypes (P ＜0.05).Conclusions The frequency distribution of VDR genotype between case group and control group had no significant difference.However,there is a correlation between VDR gene BsmⅠ sites and bone mineral density of maintenance peritoneal dialysis patients.

Objective To explore the characters of lower urinary tract symptoms (LUTS) in patients with Parkinson's Disease (PD).Methods From Oct 2013 to Jun 2016,after evaluating of movement disorder by modified Hoehn-Yahr(H-Y) scale and LUTS by international prostate symptom score (IPSS),urodynamic study was performed in PD patients with LUTS.The incidence of every symptom of LUTS,the relationships between the IPSS categories and urodynamic study were analyzed.Results 64 patients (containing 26 male and 38 female) with 40-80 (62.7 ± 10.2) years old were included.2,4,30,19,12 and 6 patients were belonged to modified H-Y scale 1-4,respectively.Frequency (50 patients,78.1％) was the most common LUTS,while frequency all day (20 patients,31.3％) was the most common symptom for the most severe LUTS.IPSS was 1 7.5 ± 7.8 (4-35) and quality of life was 5.1 ± 0.6 (4-6) for the patients.There was no significant correlation between modified H-Y scale and IPSS (P ＞ 0.05).According to the criteria of IPSS,28 patients (43.8％) only had irritative symptoms,3 patients (4.7％) only had obstructive symptoms,while 26 patients (40.6％) had mixed symptoms and 7 patients (10.9％) belonged to no one.Urodynamic study showed 11 patients (39.3％) with only irritative symptoms had detrusor overactivity(DO),6 patients (23.1％) with mixed symptoms had DO + bladder outlet obstruction (BOO) or DO + detrusor underactivity,however,there was no one with BOO in the three patients with only obstructive symptoms.Conclusion Frequency was the most common LUTS,while frequency all day was the most common symptom for the most severe LUTS in PD patients.Irritative and mixed symptoms were common in PD patients with LUTS,but the urodynamic results were not consistent with the category of LUTS in most of the patients.LUTS severity was not correlated with movement disorders in PD patients.

Objective To evaluate the role of the sodium removal and explore the relationship of sodium balance and blood pressure in patients with traditional hemodialysis.Methods Fourteen patients with maintenance hemodialysis were randomly enrolled in this study.Serum sodium concentration was measured at the pre-dialysis and post-dialysis.At the beginning of dialysis and every half hour,20 ml waste dialysates were collected,10 ml were drown from total 180 ml waste dialysates that had being mingled for measuring total NaCl removal and the removal caused by ultrafiltration.The Fisher's Exact Test was used to analyze the difference in incidence of hypertension(≥ 150/90 mmHg group or ＜ 150/90 mmHg) between the different NaCl removal groups.Results The total NaCl removal in single hemodialysis session was (29 ±14.9)g,A average of (18 ± 6.9)g sodium was removed by ultrafiltation (83 ± 58.6)％.The patients whose sodium removal in a hemodialysis session were less than 29 g,which were vulnerable to hypertension (≥ 150/90 mmHg group) (P =0.023).Conclusions The factors that effected sodium removal in hemodialysis session were complicated; most of sodium was removed by ultrafiltration of plasma water.These results demonstrated that adequate ultrafiltration volume in triple times a week rather than restriction of fluid intake was the principal factor that controls blood pressure in patients with traditional hemodialysis.

Objective To compare the impacts of subtotal nephrectomy and ischemiareperfusion injury on renal stem cells and progenitor cells of rats,and to explore the significance of renal stem cells and progenitor cells for renal repair and the possible mechanisms of prognosis in rats with acute renal failure (ARF) or chronic renal failure (CRF).Methods Rats of CRF or ARF model underwent 5/6 nephrectomy or renal artery ligation and repedusion respectively,and rars in control group underwent sham operation.Scr,BUN and 24 hour urine protein were regularly measured.Kidney specimens were obtained at the set time for HE staining and fluorescence staining.Expressions of CD24,CD133 and podocin were detected by immunofluorescence.RT-PCR was performed to quantify the expression of transforming growth factor β1 (TGF-β1),Notch2,hepatocyte growth factor (HGF),bone morphogenetic protein 7 (BMP7) and Pax-2 mRNA in renal tissue and the expression of podocin mRNA in renal cortex.Correlation among the expressions of Pax-2 mRNA,podocin mRNA and glomemlosclerosis index were analyzed.Results The rats of two models presented typical ARF or CRF in renal pathology and function.Glomerulosclerosis index in CRF group increased gradually with time,which were (2.34±0.28)％,(25.12±5.67)％,(89.42±12.28)％ and (171.23±32.28)％ at day 14,day 30,day 60 and day 90 respectively.Compared with sham group,the CD24+CD133+ cells of the ARF rats showed no significant change in quantity and distribution,while the CRF rats showed gradual reduction of CD24 +CD133+ cells.The expression of podocin in glomerulus decreased temporarily and recovered finally after ischemiareperfusion injury,but decreased gradually after 5/6 nephrectomy.Compared with sham group,expression of TGF-β1,Notch2 mRNA in renal tissue was increased in CRF group,while the expression of HGF,BMP7 mRNA in renal tissue of ARF group were increased.Between the expression of Pax-2 mRNA in renal tissue and the expression of podocin mRNA in renal cortex,there was positive correlation in CRF group,while they both were negatively correlated with glomerulosclerosis index.Conclusions Ischemia-reperfusion injury makes no obvious impairment to renal progenitor cells.Having progressively injured the living environment of renal progenitor cells,subtotal nephrectomy reduces renal progenitor cells,and causes podocytes to repairing incompetently,which may be the main pathogenesis of CRF with poor prognosis.

Objective To study the relationship between cardiovascular diseases (CVD)and 24-h peritoneal protein losses (PPL) in continuous ambulatory peritoneal dialysis (CAPD)patients. Methods One hundred and seventy-eight CAPD patients in our department were enrolled in this study. Their 24-h PPL was measured and other clinical data were recorded at the beginning. Meanwhile, Doppler ultrasound examination was performed. They were then followed-up prospectively for the development of CVD. Results The average of 24-h PPL was (5.0±1.8) g.Patients with diabetic status or preexisting CVD or carotid arteries arteriosclerosis had higher 24-h PPL than those without (t=2.082, P=0.039; t=2.601, P=0.010; t=2.217, P=0.029). 24-h PPL was positively correlated with left ventricular end-diastolic diameter (LVDd), interventricular septal thickness (IVSTd), posterior wall diameter of left ventricle at end-diastolic (LVPWd) and left ventricular mass index (LVMI) (r=0.222, P=0.040; r=0.217, P=0.043; r=0.339, P=0.002; r=0.305, P=0.007). It was negatively correlated with ejection fraction of left ventricle (r=0.221, P=0.040). One hundred and fourteen CAPD patients were prospectively followed-up for at least twelve months. Patients developing CVD were 40.4% and 19.3% for high and low PPL groups respectively (x2=6.035, P=0.014). In the multivariable logistic regression analysis, the 24-h PPL was one of the independent factors for developing CVD. Conclusions There is a significant and independent relationship between 24-h PPL and new cardiovascular events. 24-h PPL may be an important predictor of cardiovascular disease.