Objective:To investigate the inhibitory effect of ferulic acid on the retina of diabetic mice and high glucose-induced human retinal pigment epithelium (RPE) cell injury and the mechanism.Methods:Thirty 8-week-old SPF male type 2 diabetic db/db mice were selected and divided into a model group and a ferulic acid group by the random number table method, with 15 mice in each group.Another 15 db/m mice of the same age were selected as a control group.The model and control groups received normal saline (5 ml/kg) by gavage daily, and the ferulic acid group received ferulic acid solution (0.05 g/kg) by gavage daily.After two months of treatment, the mice were sacrificed and the eyeballs were removed.The morphological changes of mouse retinal tissues were observed by hematoxylin-eosin staining.The fluorescence intensity and expression levels of mitochondrial calcium uniporter (MCU), p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylated p38 MAPK (p-p38 MAPK) in mouse retinal tissues were detected by immunofluorescence staining and Western blot.Human RPE cells were divided into control group, dimethyl sulfoxide (DMSO) group, high glucose group and high glucose+ ferulic acid group.The control group received no treatment, and the other cell groups were cultured with the corresponding reagents for 24 hours.The reactive oxygen (ROS) level of RPE cells in each group was detected with the ROS detection kit.The mitochondrial membrane potential level of RPE cells was detected with the a mitochondrial membrane potential detection kit (JC-1).The MCU and microfilament fluorescence intensity of RPE cells were detected with the a microfilament green fluorescent probe.To explore the regulatory relationship between MCU, p38 MAPK and p-p38 MAPK, the MCU protein level was silenced and overexpressed by lentivirus transfection technology.The fluorescence intensity and expression levels of MCU, p38 MAPK and p-p38 MAPK proteins in RPE cells were detected by immunofluorescence staining and Western blot.The use and feeding of experimental animals followed the 3R principle and the Statement of the Association for Research in Vision and Ophthalmology on the Use of Animals in Ophthalmology and Vision Research.This study protocol was approved by the Ethics Committee of Ningxia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region (No.2019085).Results:The intercellular space of the outer nuclear layer, inner nuclear layer and ganglion cell layer of the retinal tissue in the model group was increased and the cell arrangement was disordered compared with the control group, and the retinal tissue in the ferulic acid group was significantly improved.Compared with the control group, the fluorescence intensity of MCU, p-p38 MAPK and MCU+ p-p38 MAPK protein of mouse retinal tissue in model group and ferulic acid group was significantly increased (all at P<0.05).Compared with the model group, the fluorescence intensity of MCU, p-p38 MAPK and MCU+ p-p38 MAPK protein of mice retinal tissue in ferulic acid group was significantly decreased (all at P<0.05).Compared with the control group, the relative expression levels of MCU, p38 MAPK and p-p38 MAPK proteins of mouse retinal tissue in model group were significantly increased (all at P<0.05).Compared with the model group, the relative expression levels of MCU, p38 MAPK and p-p38 MAPK proteins of mice retinal tissue in ferulic acid group were significantly decreased (all at P<0.05).The ROS fluorescence intensities in the control group, DMSO group, high glucose group and high glucose+ ferulic acid group were 0.22±0.02, 0.22±0.03, 0.30±0.02 and 0.24±0.02, respectively, and the overall difference was statistically significant ( F=7.845, P<0.01).The ROS fluorescence intensity was significantly higher in the high glucose group than in the control and DMSO groups, and it was significantly lower in the high glucose+ ferulic acid group than in the high glucose group (all at P<0.05).The mitochondrial membrane potential was significantly lower in high glucose group and high glucose+ ferulic acid group than in control and DMSO groups, and significantly higher in high glucose+ ferulic acid group than in high glucose group (all at P<0.05).Compared with the control group and DMSO group, the fluorescence intensity of MCU was higher in the high glucose group, accompanied by the decrease and thinning of cell microfilaments, and the fluorescence intensity of MCU protein was significantly decreased in high glucose+ ferulic acid group, with the number of microfilaments increased significantly.Compared with the control group and DMSO group, the fluorescence intensity and relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly increased in the high glucose group (all at P<0.05).Compared with the high glucose group, the fluorescence intensity and relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly decreased in the high glucose+ ferulic acid group (all at P<0.05).Compared with the control group and the empty vector group, the relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly increased in the MCU overexpression group and significantly decreased in the MCU shRNA group and the MCU overexpression+ ferulic acid group (all at P<0.05).Compared with MCU overexpression group, the relative expressions of MCU, p38 MAPK and p-p38 MAPK proteins were significantly decreased in MCU shRNA group and MCU overexpression+ ferulic acid group, and the differences were statistically significant (all at P<0.05). Conclusions:Ferulic acid can regulate oxidative stress and mitochondrial dysfunction, thereby ameliorating retinal damage and high glucose-induced RPE cell injury in diabetic mice, which may play a protective role through MCU and p38MAPK signaling pathways.

Objective:To investigate the effect and possible mechanism of circular RNA(circRNA)cerebellar degeneration-related protein 1 antisense transcript(CDR1-AS)on proliferation,apoptosis and immune factors expressions of lung cancer cells.Methods:Using BEAS-2B in adjacent tissues and bronchial epithelial cells as controls,qRT-PCR was used to detect expressions of CDR1-AS and miR-1277 in lung cancer tissues and lung cancer cell lines(NCI-H23,H1299,NCI-H446).Taking lung cancer H1299 cells as research object,after they were transfected with CDR1-AS small interfering RNA(si-CDR1-AS)or miR-1277 mimic,or co-transfected with si-CDR1-AS and miR-1277 inhibitor,CCK-8 experiment,clone formation experiment and flow cytometry were used to detect cell viability,clone formation number and apoptosis rate,respectively.ELISA was used to detect expressions of immune factors(TNF-α,IFN-γ)in cell culture supernatant.Dual-luciferase reporter gene experiment was used to verify the regulatory relation-ship between CDR1-AS and miR-1277.Results:Compared with adjacent tissues or BEAS-2B cells,expression of CDR1-AS in lung cancer tissues or cell lines(NCI-H23,H1299,NCI-H446)was increased(P<0.05),while expression of miR-1277 was decreased(P<0.05).After silencing CDR1-AS or overexpressing miR-1277,activity of H1299 cells,the number of clones and the secretion of TNF-α were decreased(P<0.05),while apoptosis rate and secretion of IFN-γ were increased(P<0.05).CDR1-AS targeted and bound to miR-1277,and expression of miR-1277 was increased in H1299 cells that silenced CDR1-AS(P<0.05).Down-regulation of miR-1277 reversed effects of silencing CDR1-AS on proliferation,apoptosis and expressions of immune factors in H1299 cells.Conclu-sion:Expression of CDR1-AS is up-regulated in lung cancer tissues and cell lines,silencing its expression can inhibit proliferation and tumor cell immune escape of lung cancer H1299 cells,and induce cell apoptosis by targeting up-regulation of miR-1277.

Objective To evaluate the diagnostic value of CEA, CA19-9, CA72-4, AFP, and CA125 in gastric stromal tumors. Methods 41 patients with gastric stromal tumors and 11 patients with gastric leiomyoma were recruited in this study from Qilu Hospital of Shandong University during May 2014 to December 2017. The tissue was collected by surgery, and HE staining was done. Immunohistochemistry was employed to detect the expression of CD34, CD117, and DOG-1. Serum of all cases and 41 healthy volunteers in the same hospital were collected. The levels of CEA, CA19-9, CA72-4, AFP and CA125 were examined by electrochemiluminescence assay, and the differences in each group were compared by M-W test or K-W test. Then the relationship between those biomarkers and the clinical parameters of gastric stromal tumors was analyzed. Moreover, AUC (Area Under the curve), cut-off value, sensitivity, specificity, positive predictive value, negative predictive value with drawing ROC curve (receiver operating characteristic curve) were also calculated. Results Spindle cells or epithelioid cells were observed in the tissue of gastric stromal tumors. The expression of CD34, CD117, DOG-1 were positive. The level of the serum CEA 1.53 (1.15, 2.22) ng/ml in patients with gastric stromal tumor patients was higher than that in healthy controls 1.06 (0.62, 1.48) ng/ml and that in patients with gastric leiomyoma 0.79 (0.39, 1.39) ng/ml (the U value was 446.5, and 113.0 respectively, P<0.05). The level of CA19-9 in gastric stromal tumors 9.30 (4.95, 12.70) U/ml was higher than that in healthy controls 6.62 (4.56, 8.82) U/ml (the U value was 615.5, P<0.05). There were no significant differences in AFP, CA125, and CA72-4 of three groups (the H value was 4.348, 1.073, and 3.897, P>0.05). Furthermore, the level of CEA was closely related to TNM stage (the U value was 129.0, P<0.05). The diagnostic value of CEA and CA19-9 was statistically not significant (P>0.05). However, the combination of two markers might increase diagnostic efficiency. The sensitivity, specificity, positive predictive value, negative predictive value and AUC was 92.7％, 48.8％, 64.4％, 87.0％ and 0.752 respectively. Conclusion The combination of CEA and CA19-9 has better sensitivity and negative predictive value in auxiliary diagnosis of gastric stromal tumors.

Objective To analyze the antibody titer value of indirect haemagglutination test(IHA)in 135 confirmed acute schistosomiasis patients,so as to provide the evidence for improving the diagnosis and treatment of acute schistosomiasis. Meth-ods A total of 135 acute schistosomiasis inpatients were selected from 2001 to 2006. They all received the IHA antibody titer de-tection,and the correlation among the age,incubation period,and hospitalization days was calculated. Results The antibody titers of IHA were higher than 1:320 in all the cases. The percentages of 1:640,1:1280,1:2560,1:5120 and 1:10240 were 1.48%,28.15%,35.56%,20.00%,and 14.81%respectively. The mean age was(47.70 ± 14.58)years,average incuba-tion period was(38.03 ± 4.59)days and mean hospital stay time was(15.08 ± 3.79)days. The antibody titer value had no corre-lation with the age distribution(r=0.109,P>0.05). There was a negatively correlation between the antibody titer value and in-cubation period,(r=-0.558,P<0.01),there was a positive correlation between the antibody titer value and hospitalization time(r=0.791,P<0.01),and there were significant differences among different groups(F=17.07,64.53,both P<0.01). Conclusions The antibody titer of acute schistosomiasis cases detected by IHA is 1:640 and above. There is no correlation be-tween the antibody titer value and age,but the antibody titer value is higher,the incubation period is shorter and hospitalization time is longer.

To implement the excellent doctor education training plan and construct the training model of practical ability in clinical education,the researchers analyzed the problems existing in the training of clinical practice ability and put forward a new train of thought,and constructed a training method system of personal experience,reading classics,teacher guidance,simulation training,clinical practice and reflection strengthening.In addition,we also established a safeguard mechanism with the characteristics of the organizational corporation of teaching,the expert-oriented teaching team,team-oriented mentoring,pro-ject-oriented ability training,the diversification of evaluation system,the modernization of teaching platform and the realistic training environment,to train the qualified clinical medical talents.

Objective To evaluate the molluscicidal effect of suspension concentrate of niclosamide ethanolamine salt(SC-NE)against Oncomelania hupensis snails in laboratory and field. Methods The experiment of SCNE against the snails by using the immersing and spraying methods was performed in laboratory and field,with control groups of wettable powder of ni-closamide ethanolamine salt(WPN). Results In the laboratory,LC50(s) of SCNE for 24,48 h and 72 h by using the immersion method were 0.0926,0.0629 mg/L and 0.0549 mg/L,respectively. The mortality rates of snails for 24,48 h and 72 h by using the immersion method were all 100％ with the concentrations of 0.25 mg/L. The mortality rates of snails were all 100％ while spraying SCNE for 3 d in the laboratory with the concentrations of 0.25 g/m2. In Jiangling County,except 0.5 g/m3 SCNE immers-ing the snails for 24 h,the mortality rates of snails by using SCNE with the immersing method were all 100％. While the concen-tration of SCNE was 0.5 g/m3 or above,the mortality rates were all 100％after the use of it with the immersion method for 2 d in Gong'an County. In Jiangling County,the mortality rates of snails by using SCNE 0.5 g/m3 for 1 d,3 d,and 7 d with the spray-ing method were 87.5％,92.82％and 97.40％respectively. While the concentration of SCNE was 0.5 g/m3,the mortality rates were 85.94％,86.78％and 94.21％respectively after the use of it with the spraying method for 1 d,3 d,7 d in Gong'an Coun-ty,and the molluscicidal effect of SCNE(1.0 g/m2)was higher than that of WPN. Conclusion SCNE has a high molluscicidal effect in the laboratory and field,and it is a novel and simple formulation of niclosamide.

Objective To identify and assess whether circumferential electrocautery is useful to improve outcomes after primary total knee replacement.Methods We searched MEDLINE,EMBASE,PubMed,SpringerLink,Web of Knowledge,OVID CINAHL,OVID EBM and Google Scholar,and included articles published through January 2014.This study used the methods of meta-analysis to assess whether circumferential electrocautery could improve anterior knee pain and knee function after total knee replacement,and identified the function of circumferential electrocautery in total knee replacement.Results A total of eight articles met the inclusion criteria.Among the 1 048 cases included in the analysis,526 cases had patellar denervation,and 522 cases were in the control group.The meta-analysis revealed no significant difference in the incidence of anterior knee pain (P =0.18) and visual analogue scale (VAS) (P =0.23) between two groups.However,patellar score (P =0.01),Western Ontario and McMaster Universities osteoarthritis index (WOMAC) score (P ＜ 0.01),and range of motion (ROM) (P ＜ 0.01) indicated that circumpatellar electrocautery improved clinical outcomes compared to non-electrocautery groups.Conclusions The results indicated that circumferential electrocautery of the patellar did not significantly improve anterior knee pain relative to non-electrocautery techniques.However,circumferential electrocautery significantly improved patients' knee function after surgery.Therefore,circumferential electrocautery might be beneficial to the outcome of primary total knee replacement surgery without patella replacement.

Objective To understand the schistosomiasis endemic situation at a national surveillance site in Gong an Coun-ty Hubei Province. Methods According to The Scheme of Schistosomiasis Surveillance in China the schistosome infection rates of residents and cattle and the Oncomelaniahupensissnail status were investigated yearly in Zhangjiahu Village a nation-al surveillance site in Gong an County from 2004 to 2013. Results From 2004 to 2013 the human schistosome infection rates decreased from 10.66%to 0.58% and the cattle schistosome infection rates from 12.75%to 0. Meanwhile the snail areas and densities reduced and the schistosome infected snails were eliminated. Conclusion The schistosomiasis endemic situa-tion declined dramatically at the surveillance site and schistosomiasis is well-controlled.

OBJECTlVE To investigate the antidepressant effect and reIated mechanism of the totaI fIavonoids extract parts( Iicorice fIavonoids,LF)from Glycyrrhiza uralensisFisch. cuItivated IocaIIy in Ningxia. METHODS Forced swimming test( FST)and taiI suspension test( TST)were adopted to study the antidepressant pharmacoIogicaI effect in the acute stress-induced depression modeI in mice. The Km mice were intragastricaIIy administered with LF(5,30 and 180 mg·kg-1 )once daiIy,for 21 con-secutive days. One hour after the first,seventh and Iast administrations,the mice were submitted to FST by recording the immobiIity period within the Iast 4 min of the totaI 6 min in both tests and the resuIts were expressed as decrease in immobiIity period with respect to vehicIe controI. In TST,the other group of Km mice was used to evaIuate the antidepressant effect in same protocoI. In the antagonism of reserpine-induced symptoms test( ART),ICR mice were administered intragastricaIIy with LF( 50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days. One hour after the Iast administration,the mice received reserpine(4 mg·kg-1 ,ip),and ptosis or akinesia was measured 1 h after reserpine injection whiIe rectaI temperature was measured 4 h after the reserpine injection respectiveIy. The same protocoI was adopted in yohimbine toxicity potentiation test(YTT)as in ART. Thirty minutes fter the Iast adminis-tration,the mice received the threshoId IethaI dosage of yohimbine(30 mg·kg-1 ,sc)respectiveIy,and the death number of the mice was caIcuIated in 24 h after the yohimbine administration. In the 5-hydroxy-L-tryptophan(5-HTP)induced head-twitches test(HTT)in mice,after being administered intragastricaIIy with LF(50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days,the mice received pargiIine (100 mg·kg-1 ,ip)the next day,and 30 min Iater,5-HTP(10 mg·kg-1 ,ip)was intraperitoneaIIy injec-ted to induced the head twitch respectiveIy,and the times of head twitch in a 30 min period after 5-HTP treatment were observed at 6 time points. After HTT,the mice were sacrificed quickIy,and the mono-amine oxidase(mAO)activity in the brain cortex,hippocampus and thaIamus was examined to evaIuate the antidepressant effect of fIavonoids with mAO inhibition. RESULTS Compared with the vehicIe controI,LF significantIy decreased the immobiIity period in both FST and TST(P﹤0.05). LF(50,150 and 400 mg·kg-1 )antagonized the ptosis and akinesia symptoms respectiveIy in 1 h after reserpine administration( P ﹤ 0. 05 ), but faiIed to antagonize hypothermia produced 4 h after reserpine administration. AIso,at the same dosage,LF did not synergeticaIIy produce the enhancement of death by subcutaneous injection of yohimbine at the threshoId IethaI dosage. LF(150 and 400 mg·kg-1 )couId significantIy and synergeticaIIy increase 5-HTP induced head-twitches response(P﹤0.05),but LF couId not promote mAO activity in the cortex,hippocampus and thaIamus at the same dosage. CONCLUSlON LF exerts antidepressant-Iike effect on the modeI of acute despair test. The mechanism might be reIated to direct enhancement of the serotonergic neuraI function in the brain.

Objective To evaluate the effect of schistosomiasis control in Gongan County,Hubei Province by longitudinal ob-servations so as to provide the evidence for formulating the schistosomiasis control strategy in lake and marshland regions. Meth-ods The schistosomiasis epidemic data in Gongan County from 2000-2013 were collected by the retrospective research method, and analyzed about the changing tendency of human and cattle infection rates,and Oncomelania hupensis snail situation. Re-sults The tendency of schistosomiasis epidemic situation was descended from 2000 to 2013. The human infection rate declined from 12.62%in 2000 to 0.69%in 2013. The decline scope of human infection rate was 24.1%in the first stage,64.4%in the sec-ond stage,and 73.0%in the third stage. Eight acute schistosomiasis cases were reported in the first stage,15 cases in the second stage,and none in the third stage. The cattle infection rate declined from 6.50%in 2000 to 0.30%in 2013. The rise scope of cattle infection rate was 74.2%in the first stage,but the decline scope was 75.0%in the second stage and 87.6%in the third stage. All the cattle were disposal at the end of 2013. The infection rate of snails,area with infected snails,and average density of living snails in the first stage increased by 18.1%,46.0%and 7.6%,respectively. The 3 indexes above-mentioned in the second stage de-creased by 76.8%,97.8%and 37.9%,respectively. In the third stage,the infection rate of snails and area with infected snails de-creased by both 100%,but the average density of living snails increased by 2.7%. The infected snails were found from 2000 to 2011,but none in 2012 and 2013. The infection rate of snails and area with infected snails dropped yearly,the infection rate of snails declined from 0.0007% in 2000 to 0.0002% in 2011,and the area with infected snails declined from 267.8 hm2 in 2000 to 6.37 hm2 in 2011. Conclusions After the implementation of the integrated schistosomiasis prevention and control strategy with the emphasis on infectious source control,the human and cattle schistosome infection rates decline significantly. Hereafter,it is necessary to prevent the schistosomiasis epidemic outbreak or rebound.