Jianqu,a traditional Chinese medicine,alleviates functional dyspepsia in high-calorie and high-protein diet mice

Background:Jianqu has been used to alleviate symptoms in patients with functional dyspepsia,but its specific anti-functional dyspepsia effect is still unclear.Therefore,our study aimed to investigate the impact of Jianqu on functional dyspepsia in mice.Methods:The phytochemical profile of Jianqu was analyzed by UPLC-Q-TOF-MS.Subsequently,Kunming mice were fed a high-calorie or high-protein diet(HCHP)for 7 days,and then orally treated with vehicle or Jianqu(1.62 g/kg body weight(b.w.)and 3.25 g/kg b.w.)for 10 days.A carbon powder solution was used to detect the gastric emptying and intestinal transit rate.The pathological changes in stomach and duodenum were evaluated by hematoxylin-eosin staining.The occludin,claudin-1,ZO-1 and CD45 expression was measured by immunocytochemical staining.Importantly,the serum gastrointestinal hormones were detected by ELISA.In addition,the gut microbiota composition was determined using 16S rRNA gene sequencing.The cecal short chain fatty acids were assessed by gas chromatography.Results:In general,17 phytochemical compounds were identified from Jianqu,which significantly improved the gastric emptying rate and intestinal transit rate(p<0.01),increased the body weight and food intake(p<0.0001)in HCHP mice as well.Though HCHP did not cause significant pathological lesions in the gastrointestinal tract,increased the expression of CD45 in the duodenum(p<0.05)was observed.Notably,Jianqu attenuated this abnormal expression of CD45(p<0.05).The levels of serum gastrointestinal hormones were significantly normalized by Jianqu intervention(p<0.05).Moreover,Jianqu increased the relative abundance of Roseburia as well as short chain fatty acids levels in cecum(p<0.05).Conclusion:The present results showed that Jianqu alleviated dyspeptic symptoms in HCHP mice possibly through reducing the duodenal leukocyte infiltration,and regulating the expression of gastrointestinal hormones.These effects may be partly related to the increasing cecal short chain fatty acids levels probably via gut microbial modulation.

Analysis of risk and protective factors associated with retinal nerve fiber layer defect in a Chinese adult population

AIM:To investigate the risk and protective factors associated with the retinal nerve fiber layer defect(RNFLD)in a Chinese adult population.METHODS:This study was a cross-sectional populationbased investigation including employees and retirees of a coal mining company in Kailuan City,Hebei Province.All the study participants underwent a comprehensive systemic and ophthalmic examination.RNFLD was diagnosed on fundus photographs.Binary logistic regression was used to investigate the risk and protective factors associated with the RNFLD.RESULTS:The community-based study included 14440 participants.There were 10473 participants in our study,including 7120 males(68.0%)and 3353 females(32.0%).The age range was 45-108y,averaging 59.56±8.66y.Totally 568 participants had RNFLD and the prevalence rate was 5.42%.A higher prevalence of RNFLD was associated with older age[P<0.001,odds ratio(OR):1.032;95%confidence interval(CI):1.018-1.046],longer axial length(P=0.010,OR:1.190;95%CI:1.042-1.359),hypertension(P=0.007,OR:0.639;95%CI:0.460-0.887),and diabetes mellitus(P=0.019,OR:0.684;95%CI:0.499-0.939).The protective factors of RNFLD were visual acuity(P=0.038,OR:0.617;95%CI:0.391-0.975),and central anterior chamber depth(P=0.046,OR:0.595;95%CI:0.358-0.990).CONCLUSION:In our cross-sectional community-based study,with an age range of 45-108y,RNFLD is associated with older age,longer axial length,hypertension,and diabetes mellitus.The protective factors of RNFLD are visual acuity and central anterior chamber depth.These can help to predict and evaluate RNFLD related diseases and identify high-risk populations early.

Retinal vessel oxygen saturation in healthy subjects and early branch retinal vein occlusion

AIM： To measure the retinal oxygen saturation in healthy subjects and early branch retinal vein occlusion（BRVO） in Chinese population.METHODS： The retinal vessel oxygen saturation of the healthy subjects and BRVO patients were measured by a noninvasive retinal oximeter（Oxymap ehf.,Reykjavik,Iceland）.RESULTS： The study included 22 patients with unilateral BRVO（mean age： 55.1±8.8y） in the study group and 91 healthy participants（mean age： 37.5±14.0y） in the control group.In the healthy individuals,mean arterial and venous oxygen saturation were significantly（P〈0.001）higher in the superior nasal quadrant（98.5%±10.1%and 57.3%±8.7%,respectively） than in the inferior nasal quadrant（94.2%±9.0% and 54.1%±9.6%,respectively）,followed by the superior temporal quadrant（89.1%±10.1%and 51.9%±8.9%,respectively） and the inferior temporal quadrant（86.4%±9.4% and 46.6%±9.6%,respectively）.In patients with ischemic BRVO,arterial oxymetric values were significantly higher and venous measurements significantly lower for the affected vessel（107.5%±9.7% and46.4%±14.2%,respectively） than the unaffected vessel in the same eye（99.2%±12.2% and 55.5%±7.9%,respectively）and as compared to the vessel in the unaffected fellow eye（93.1%±6.9% and 55.7%±6.8%）（P=0.005 and P=0.02,respectively）.In the patients with non-ischemic BRVO,mean venous oxygen saturation was lower in the affected vein（39.8%±12.2%） than in the unaffected vessels of the same eye（50.8%±10.5%） and in the fellow eye（58.21%±5.7%）（P=0.03）.Mean arterial oxygen saturation did not differ significantly（P=0.42） between all three groups.CONCLUSION： In patients with BRVO,the venous oxygen saturation in the affected vessels is decreased potentially due to decreased blood velocity and flow.Interestingly,thearterial oxygen saturation in eyes with ischemic BRVO is increased in the affected arteries.

Hypoxia preconditioning protects Ca^(2+)-ATPase activation of intestinal mucosal cells against R/I injury in a rat liver transplantation model

AIM To investigate the effect of ischaemia and reperfusion(I/R) injury on the Ca^(2+)-ATPase activation in the intestinal tissue of a rat autologous orthotopic liver transplantation model and to determine if hypoxia preconditioning(HP) therapy induces HIF-1α to protect rat intestinal tissue against I/R injury.METHODS Rats received non-lethal hypoxic preconditioning therapy to induce HIF-1α expression. We used an autologous orthotopic liver transplantation model to imitate the I/R injury in intestinal tissue. Then, we detected the microstructure changes in small intestinal tissues, Ca^(2+)-ATPase activity, apoptosis, and inflammation within 48 h postoperatively. RESULTS HIF-1α expression was significantly increased in intestinal tissue at 12 h postoperatively in rats that were exposed to a hypoxic environment for 90 min compared with a non-HP group(HP vs AT, P = 0.0177). Pathological analysis was performed on the intestinal mucosa cells, and the cells in the HP group appeared healthier than the cells in the AT group. The Ca^(2+)-ATPase activity in the small intestinal cells in the AT group was significantly lower after the operation, and the Ca^(2+)-ATPase activity in the HP group recovered faster than that in the AT group at 6 h postoperatively(HP vs AT, P = 0.0106). BCL-2 expression in the HP group was significantly higher than that in the AT group at 12 h postoperatively(HP vs AT P = 0.0010). The expression of the inflammatory factors NO, SOD, IL-6, and TNF-α was significantly lower in the HP group than in the AT group.CONCLUSION Hypoxia-induced HIF-1α could protect intestinal mucosal cells against mitochondrial damage after I/R injury. HP could improve hypoxia tolerance in small intestinal mucosal cells and increase Ca^(2+)-ATPase activity to reduce the apoptosis of and pathological damage to intestinal cells. HP could be a useful way to promote the earlier recovery of intestinal function after graft procedure.

10-year fundus tessellation progression and retinal vein occlusion

AIM： To access the 10-year fundus tessellation progression in patients with retinal vein occlusion. METHODS： The Beijing Eye Study 2001/2011 is a populationbased longitudinal study. The study participants underwent a detailed physical and ophthalmic examination. Degree of fundus tessellation was graded by using fundus photographs of the macula and optic disc. Progression of fundus tessellation was calculated by fundus tessellation degree of 2011 minus degree of 2001. Fundus photographs were used for assessment of retinal vein occlusion. RESULTS： The Beijing Eye Study included 4403 subjects in 2001, 3468 subjects was repeated in 2011. Assessment of retinal vein obstruction and fundus tessellation progression were available for 2462 subjects（71.0%）, with 66 subjects fulfilled the diagnosis of retinal vein occlusion. Of the 66 participants, 59 participants with unilateral branch retinal vein occlusion, 5 participants with unilateral central retinal vein occlusion, 1 participant with bilateral branch retinal vein occlusion, and 1 participant with branch retinal vein occlusion in one eye and central retinal vein occlusion in the other eye. Mean degree of peripapillary fundus tessellation progression were significantly higher in the whole retinal vein occlusion group（0.33±0.39, P〈0.001）, central retinal vein occlusion group（0.71±0.8, P=0.025） and branch retinal vein occlusion group（0.29±0.34, P=0.006） than the control group（0.20±0.26）. After adjustment for age, prevalence of tilted disc, change of best corrected visual acuity, axial length, progression of peripapillary fundus tessellation was associated with the presence of retinal vein occlusion（P=0.004; regression coefficient B, 0.094; 95%CI, 0.029, 0.158; standardized coefficient B, 0.056）. As a corollary, after adjusting for smoking duration, systolic blood pressure, anterior corneal curvature, prevalence of RVO was associated with more peripapillary fundus tessellation progression（P〈0.001; regression coefficient B： 1.257; OR： 3.517; 95%CI： 1.777, 6.958）. CONCLUSION： Peripapillary fundus tessellation progresses faster in individuals with retinal vein occlusion. This may reflect the thinning and hypoperfusion of choroid in patients with retinal vein occlusion.

Influencing factors for peripheral and posterior lesions in mild non-proliferative diabetic retinopathy--the Kailuan Eye Study

AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospective study,683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study.Based on the undilated ultrawide field(200°;UWF)images and partial dilated digital fundus images,the diabetic retinopathy(DR)of the surveyed population was graded.Interobserver agreement was estimated by using Cohen’s Kappa statistics.The main outcome indicators included gender,age,weight,height,body mass index,blood pressure,circumferences of neck,waist and hip,current smoking,levels of fasting plasma glucose(FPG),hypersensitive C-reactive protein,creatinine,and cholesterol,etc.According to different lesions’locations of patients with mild NPDR,logistic regression models were used to estimate the odds ratios(ORs)and their 95%Cls of each risk factor.RESULTS:The study group of 683 patients included 570 males and 113 females.The mean age of the patients was62.18±9.41 y.Compared with dilated fundus examinations,there was fair agreement with the level of DR identified on UWF images in 63.91%of eyes(k=0.369,95%CI,0.00-0.00).Detected by UWF images,there were 98 patients with mild NPDR having peripheral retinal lesions,35 patients with mild NPDR having posterior lesions,44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area,and 336 patients with non obvious DR.Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance(OR,1.124;95%CI,1.044-1.211),and with posterior lesions were FPG(OR,1.052;95%CI,1.007-1.099).CONCLUSION:UWF is an effectiveness means of DR screening.Moreover,it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR.The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found.And the influencing factors in mild NPDR are differing by different lesions’locations.

Retinal nerve fiber layer thickness and retinal vascular caliber alterations in coal miners in northern China:a community-based observational study

AIM:To evaluate retinal nerve fiber layer thickness and retinal vascular caliber alterations in coal mine workers.METHODS:The community-based observational crosssectional study included 4004 participants of a subpopulation of the Kailuan Study.All the study participants underwent structured interviews with a standardized questionnaire,fundus photography and spectral-domain optical coherence tomography(OCT)examinations performed by trained doctors.RESULTS:The retinal nerve fiber layer thickness was significantly higher(P=0.006)and the central macular thickness was lower in coal miners(n=659,51.0±7.8 y)as compared to the control(working above the ground;n=477,51.8±7.5 y;P=0.032).Additionally,the downhole workers showed a significantly thicker retinal artery(P=0.012)and vein diameters(P<0.001).In multivariable regression,a thicker retinal nerve fiber layer was associated with a higher cumulative silica dust exposure(P=0.005)after adjusting for younger age and larger spherical equivalent.In a reverse pattern,a higher cumulative silica dust exposure(P=0.004)was significantly associated with a thicker retinal nerve fiber layer after adjusting for age,high-density lipoproteins and uric acid.Wider retinal vein diameters were associated with higher cumulative silica dust exposure(P=0.036)after adjusting for younger age and larger spherical equivalent.CONCLUSION:The retinal vessels diameters and retinal nerve fiber layer thickness are significantly thicker in long term of coal mining.The results of our study indicate that underground working environment may lead to retinal vessel dilation and inflammation.Thus,ocular examination might be needed within coal miners in order to monitor the occupational eye health as well as the incidence and progression of eye diseases.

MicroRNA-145 suppresses uveal melanoma angiogenesis and growth by targeting neuroblastoma RAS viral oncogene homolog and vascular endothelial growth factor

Background:Uveal melanoma(UM)is the most common primary intraocular malignancy in adults.It has been demonstrated that microRNA-145(miR-145)is correlated with the progression of various cancers by regulating the expression of multiple target genes,especially a number of genes that regulate angiogenesis and proliferation.However,the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated.Thus,we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis.Methods:Totally,24 choroid samples were collected in our study,including 12 UM samples and 12 normal uveal tissues.The expression of neuroblastoma RAS viral oncogene homolog(N-RAS),phosphorylated protein kinase B(p-AKT),and vascular endothelial growth factor(VEGF)in UM tissues and normal uveal tissues was analyzed using Western blotting analysis.Lentivirus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145.Transwell and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in vitro.The downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase assay.BALB/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in vivo.Group data comparisons were performed using analysis of Student’s t test.A two-tailed P<0.05 was considered as statistically significant.Results:The results of Western blotting analysis indicated that the expressions of N-RAS(1.10±0.35 vs.0.41±0.36,t=3.997,P=0.012),p-AKT(1.16±0.22 vs.0.57±0.03,t=7.05,P=0.001),and VEGF(0.97±0.32 vs.0.45±0.21,t=3.314,P=0.008)inUMtumor tissues were significantly higher than those in normal uveal tissue.Luciferase assay demonstrated N-RAS and VEGF as downstream targets of miR-145.Moreover,tube formation assay revealed that miR-145-transfected human microvascular endothelial cell line formed shorter tube length(36.10±1.51mm vs.42.91±0.94 mm,t=6.603,P=0.003)and less branch points(350.00±19.97 vs.406.67±17.62,t=3.685,P=0.021)as compared with controls.In addition,the numbers of invaded MUM-2B and OCM-1 cells with miR-145 overexpression were significantly lower than the controls(35.7±3.3 vs.279.1±4.9,t=273.75,P<0.001 and 69.5±4.4 vs.95.6±4.7,t=21.27,P<0.001,respectively).In vivo,xenografts expressing miR-145 had smaller sizes(miR-145 vs.miR-scr,717.41±502.62mm3 vs.1694.80±904.33mm3,t=2.314,P=0.045)and lower weights(miR-145 vs.miR-scr,0.74±0.46 g vs.1.65±0.85 g,t=2.295,P=0.045).Conclusion:Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.