Objective To investigate the role of circular RNAs(circRNA)in Alzheimer's disease(AD)and its potential mechanism.Methods Six-month-old APP/PS1 mouse model of AD and wild type(WT)mice were subjected and then randomly divided into WT group,WT+circ-Olfm1 knockout group,AD group(transgenic APP/PS1 mice),AD+circ-Olfm1 knockout group,AD+FOXO3a knockout group,with 3 mice in each group.① The total RNA of mouse brain was extracted,and the differential expression of circRNAs and mRNAs between the AD mice and WT mice was detected,and the obtained circRNAs and mRNAs were analyzed with gene ontology(GO)analysis.② RT-qPCR was used to detect the expression of the top 10 up-regulated and down-regulated circRNAs,as well as the expression of circ-Olfm1 and miR-330-5p.③ Lentiviral vectors were prepared and stereotaxically injected into the cortex or hippocampus of WT and AD mice to knock out circ-Olfm1 gene.Water maze test was used to evaluate the effect of circ-Olfm1 knockout on cognitive function,and immunofluorescence assay was employed to observe the deposition of amyloid β(Aβ)plaque in the brain.④ The interaction between circ-Olfm1 and miR-330-5p was verified by double luciferase reporter gene analysis.⑤ The protein levels of AMPK and FOXO3a were detected by Western blotting.⑥ Transmission electron microscopy was utilized to observe the mitochondria of the hippocampus.⑦ The levels of inflammatory factors IL-6,IL-1β and TNF-α were detected by ELISA.Results There were totally 52 differentially expressed circRNAs identified between the AD and WT mice,including 28 up-regulated and 24 down-regulated(fold change>1.5,P<0.05).These differentially expressed genes are mainly involved in signal transduction,learning and memory and other functions.circ-Olfm1 was identified as the most significantly differentially expressed circRNA,which is highly expressed in the neurons and up-regulated in the cerebral cortex and hippocampus of the AD mice.Knockout of circ-Olfm1 reduced the number of Aβ plaques in the cerebral cortex and hippocampus of AD mice(P<0.01).In starBase database,there are complementary sequences observed between circ-Olfm1 and miR-330-5p.Western blotting showed that the addition of Aβ42 significantly increased the expression of AMPK and FOXO3a in the neuronal cells(P<0.01).And silencing circ-Olfm1 led to decreased expression of AMPK and FOXO3a in neuronal cells+Aβ42(P<0.01).ELISA revealed that knockout of FOXO3a significantly increased the levels of inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).Transmission electron microscopy displayed that knocking FOXO3a out significantly aggravated mitochondrial damage(P<0.01).Conclusion circ-Olfm1 is up-regulated in the brain tissue and neurons+Aβ42 of AD rats,and the mechanism of cognitive impairment in AD rats may be through its regulating FOXO3a protein.

Objective To explore the relationship between postoperative defecation dysfunction and quality of life in children with anorectal malformation(ARM)complicated with spinal cord anomalies(SCA)and analyze the impact of different types of SCA on ARM patients in order to provide a reference for the early clinical identification of high-risk children with poor prognosis.Methods A retrospective analysis was conducted on 282 ARM neonates admitted to our department between June 2015 and April 2021.Radiological examinations were applied to evaluate the development of the spinal cord,and Rintala score and the PedsQL 4.0 scale were employed to assess postoperative defecation function and quality of life,respectively.According to their SCA types and other complications,the patients were grouped.The relationship between these factors and defecation function as well as quality of life was then analyzed.Results Among the 282 subjected children,104(36.9%)had SCA.The incidence of SCA varied significantly across different types of ARM(P=0.002),with the highest incidence observed in vaginal fistula patients(100.0%)and the lowest in children without fistula(13.6%).Radiological findings revealed that sacral bone anomalies were common,with absent coccyx(62.7%)and vertebral anomalies(69.8%)being the most prevalent.The SCA group had significantly lower Rintala bowel function score(12.70±3.24)and PedsQL 4.0 quality of life score(81.42±5.03)than the non-SCA group(P<0.001).As the increment of SCA types,both the Rintala score and PedsQL 4.0 score were in a significant downward trend(P<0.001).Among the children with different types of SCA,those with tethered cord syndrome had the statistically lowest Rintala score(8.05±2.35,P<0.05).Meanwhile,their PedsQL 4.0 score(75.90±3.35)was significantly lower than those of other types except syrinx(P<0.05).Multiple linear regression analysis indicated that both SCA and sacral bone anomalies exerted notably negative impacts on the Rintala score and PedsQL 4.0 score(P≤0.001),with SCA having the most pronounced effect.Conclusion SCA is closely associated with postoperative defecation dysfunction and diminished quality of life in ARM children.The greater the type and number of SCAs,the worse the postoperative defecation function and quality of life.Early identification of concomitant SCAs holds significant clinical value for predicting postoperative outcomes in ARM patients.

Objective To investigate the relationship between the development of terminal rectal ganglion and spinal cord/sacral abnormalities in boys with complex anorectal malformations(ARMs)in order to improve the understanding of rectal ganglion development abnormalities in ARMs patients.Methods A retrospective trial was conducted on the male patients with complex ARMs admitted to our hospital from 2015 to 2021.The terminal rectal specimens were taken from them during anoplasty.According to the findings on development of terminal rectal ganglion after HE staining,the patients were classified into G1 group(ganglion cells observed)and G2 group(no ganglion cells observed).Imaging techniques were used to evaluate whether there were abnormalities in the spinal cord and sacrum,and their correlation with the terminal rectal ganglion development was analyzed.Results A total of 139 patients were enrolled,and their median age at anoplasty was 5.77(4.57,6.97)months.There were no significant differences between the G1(n=80,57.6％)and G2(n=59,42.4％)groups in ARMs pathological type(P=0.706)and age at surgery(P=0.140).Radiological findings showed there were 48 cases(34.5％)of spinal cord anomalies(SCA),25 cases(18.0％)of sacral abnormalities and 18 cases(12.9％)of coccyx abnormalities.No significant differences were observed in the incidences of SCA and sacral abnormalities between the G1 and G2 groups(P＜0.05).Moreover,the differences of fatty filum terminale and syrinx were statistically significant(P＜0.05).In addition,the ratio of sacrum to coccyx between the G1 and G2 groups were 0.72±0.10 vs 0.67±0.12(P＜0.05)of the anteroposterior position and 0.77±0.09 vs 0.72±0.09(P＜0.05)of the lateral position.Multivariate logistic regression analysis showed that sacral abnormalities,fatty filum terminale and syrinx were independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.Conclusion The development of terminal rectal ganglia in male patients with ARMs is closely associated with the abnormalities of spinal cord and sacrum.Sacral abnormalities,fatty filum terminale and syrinx are independent predictors of rectal terminal ganglion absence in male patients with complex ARMs.

Objective:To understand the epidemic characteristics and influential factors of brucellosis patients in Laizhou, Shandong Province, and to provide scientific basis for prevention and control of brucellosis.Methods:Retrospective analysis was conducted to collect the surveillance data and epidemiological investigation results of confirmed cases of brucellosis in Laizhou from 2016 to 2019 through the "Infectious Disease Report Information Management System of the China Disease Prevention and Control Information System". The general situation, epidemiological characteristics, and clinical characteristics of brucellosis were analyzed by descriptive epidemiology. Using the case-control study method, 81 confirmed cases of brucellosis and 162 healthy people in the same area, same gender and same age as confirmed cases were selected to analyze the influential factors of brucellosis.Results:Totally 222 cases of brucellosis had been reported in Laizhou, with an average annual incidence of 6.57/100 000. The onset age of brucellosis was mainly from 45 to 59 years old, accounting for 46.40% (103/222); male-to-female ratio was 2.42 ∶ 1.00 (157 ∶ 65); the occupation distribution was mainly farmer, accounting for 95.95% (213/222). The onset time of brucellosis was mainly from March to July, accounting for 58.11% (129/222). Cases of brucellosis were reported in 17 townships (streets) of Laizhou, and the top five townships were Zhuqiao, Shahe, Tushan, Chengguo and Yidao towns in order of incidence. Among 222 cases of brucellosis, the shortest interval from onset to diagnosis was 5 d, the longest was 36 d, and the median was 11 d. The main clinical manifestations of the patients were fever (89.19%, 198/222), fatigue (80.63%, 179/222), joint muscle soreness (72.97%, 162/222), and a few accompanied by liver, spleen and testis enlargement. The logistic regression analysis showed that contact with urine, feces and other excrements of diseased animals [odds ratio ( OR) = 6.244, 95% confidence interval ( CI): 1.609 - 24.231] and family members suffering from brucellosis ( OR = 16.363, 95% CI: 2.250 - 119.023) were risk factors of brucellosis. Conclusions:The incidence of brucellosis is mainly among 45 - 59 middle-aged farmers in Laizhou and the incidence peaks in spring and summer. Direct contact with excrements of diseased animals and family members suffering from brucellosis are the risk factors of brucellosis. Health departments should carry out health education and behavioral intervention for farmers in the season and areas with high incidence of brucellosis, so as to improve personal awareness of protection.

OBJECTIVE: To explore the effect of mild hypothermia on inflammatory response and angiogenesis in brain tissues of rats with intracerebral hemorrhage (ICH) and its possible mechanism for improving behavioral deficits of the rats After ICH. METHODS: A total of 120 healthy male SD rats were randomly divided into sham operation group, ICH group and mild hypothermia group. Rat models of ICH were established in the latter two groups by stereotactic injection of autogenous blood in the brain, and the rats in the sham operation group received injection of normal saline in the same manner. At 15 min after modeling, the rats in hypothermia group were subjected to mild hypothermia (30-32 ℃) for 8 h followed by rewarming (37-38 ℃); the body temperature was maintained at 37-38 ℃ in the other two groups. At 2, 4, 7, 14 and 21 days after the treatment, Longa scoring, balance beam scoring and Berderson scoring were used to evaluate the behavioral deficits of the rats. Immunohistochemical staining was used to detect the protein expressions of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the brain tissue of the rats, and the mRNA expressions of α subunit of hypoxia-inducible factor 1 (HIF1-α) and vascular endothelial growth factor (VEGF) were detected using RT- PCR. RESULTS: At 2, 4, 7, 14 and 21 days after the treatment, the behavioral scores of the rats were significantly higher in ICH group and mild induced hypothermia group than in the sham operation group ( < 0.05 or 0.01). The protein expressions of TNF-α and NF-κB and mRNA expressions of HIF1-α and VEGF were significantly higher in ICH group and mild hypothermia group than in the sham operation group ( < 0.01). The behavioral scores were significantly lower in mild hypothermia group than in ICH group ( < 0.05), and the protein expressions of TNF-α and NF-κB were lower and the mRNA expressions of HIF1- α and VEGF were higher in mild hypothermia group than in ICH group ( < 0.05 or 0.01). CONCLUSIONS Mild hypothermia can improve behavioral deficits in rats with ICH possibly by antagonizing brain inflammation and promoting angiogenesis.

Androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of many severe diseases such as prostate cancer, muscle atrophy, and osteoporosis. Binding of ligands to AR triggers the conformational changes in AR that may affect the recruitment of coactivators and downstream response of AR signaling pathway. Therefore, AR ligands have great potential to treat these diseases. In this study, we searched for novel AR ligands by performing a docking-based virtual screening (VS) on the basis of the crystal structure of the AR ligand binding domain (LBD) in complex with its agonist. A total of 58 structurally diverse compounds were selected and subjected to LBD affinity assay, with five of them (HBP1-3, HBP1-17, HBP1-38, HBP1-51, and HBP1-58) exhibiting strong binding to AR-LBD. The IC values of HBP1-51 and HBP1-58 are 3.96 µM and 4.92 µM, respectively, which are even lower than that of enzalutamide (Enz, IC = 13.87 µM), a marketed second-generation AR antagonist. Further bioactivity assays suggest that HBP1-51 is an AR agonist, whereas HBP1-58 is an AR antagonist. In addition, molecular dynamics (MD) simulations and principal components analysis (PCA) were carried out to reveal the binding principle of the newly-identified AR ligands toward AR. Our modeling results indicate that the conformational changes of helix 12 induced by the bindings of antagonist and agonist are visibly different. In summary, the current study provides a highly efficient way to discover novel AR ligands, which could serve as the starting point for development of new therapeutics for AR-related diseases.
Androgen Receptor Antagonists ; pharmacology ; Androgens ; metabolism ; pharmacology ; Biological Assay ; Cell Line, Tumor ; Drug Discovery ; methods ; Humans ; Ligands ; Male ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Phenylthiohydantoin ; analogs & derivatives ; pharmacology ; Principal Component Analysis ; Prostatic Neoplasms ; drug therapy ; Protein Binding ; physiology ; Protein Conformation ; drug effects ; Receptors, Androgen ; metabolism

Objective To study the bowel-cleansing efficacy, patient security and mucosal injury of low-volume PEG plus ascorbic acid regimen. Methods Five hundred patients referred for colonoscopy were enrolled and randomly divided into two groups. Group A received low-volume PEG regimen, Group B received sodium phosphate (NaP) regimen for bowel preparation. Patients of the two groups drank solution 5 h before colonoscopies, serum creatinine and electrolyte were monitored at 5 h and 3 h before colonoscopies. The bowel-cleansing efficacy was rated during colonoscopy. All mucosal injuries observed during colonoscopy were biopsied and histopathologically reviewed. Results The patients of group A completed bowel preparation of 233 cases, completed colonoscopy 226 Cases, group B completed bowel preparation 238 cases, completed colonoscopy 210 cases. There was no significant difference in bowel cleansing between the groups (P > 0.05). Group A reported less incidence rate of the mucosal injuries than Group B. Group A reported better patient security than Group B at the same time. Conclusion Compared with sodium phosphate (NaP) regimen low-volume Polyethylene Glycol (PEG) plus ascorbic acid regimen exhibited equivalent bowel-cleansing efficacy and less incidence rate of the mucosal injuries and better patient security.

Objective To evaluate the relevance of MSCT pulmonary function parameters and pulmonary function test (PFT) parameters, and to define the reference value of MSCT pulmonary function parameters. Methods Thirty male volunteers received clinical PFT and MSCT scan. MSCT scan was perfomed at the end of the maximum inspiratory and maximum expiratory. All data were analyzed with the lung analysis software of computer-aided inspection system correlatedly with pulmonary function parameters. Results The lung volume at full inspiratory volume (Vin) and full expiratory volume (Vex) in MSCT scan had good correlation with total lung capacity (TLC) and residual volume (RV) (r=0.90, P<0.01; r=0.74, P<0.01). Vex/Vin was correlated with RV/TLC (r=0.74, P<0.01), and Vin-Vex was correlated with MVC (r=0.85, P<0.01). In inspiration, the average lung density was (-879.51±32.82) HU, the density per unit volume was (0.12±0.03) g/cm3, while in expiratory they were (-688.14±62.38) HU and (0.31±0.06) g/cm3. Conclusion MSCT pulmonary function tests with the analysis software of computer-aided inspection system have good correlation with PFT.

Objective To investigate the effects of clonidine on the visceral pain induced by acute myocardial ischemia. Methods Male SD rats weighing 250-280 g were operated upon under general anesthesia with intraperitoneal methane 1.2 g/kg and local infiltration of the skin incision. After tracheal intubation, the animals were mechanically ventilated (VT = 5-7 ml/kg, RR = 75 bpm). The anterior descending branch of left coronary artery was occluded with a snare through the left 4 th intercostal space. The animals were then fastened to a brain stereotaxic instrument and a burr hole was made in the skull. A glass micro-electrode was inserted into the brain. The discharges of noxious stimulation responding neuron (NSRN) in parafascicular nucleus were recorded. Twenty-four rats detected NSRN showed response to coronary artery occlusion (CAO) were randomly divided into 4 groups (n =6 each): group Ⅰ CAO + normal saline 0.1 ml; group Ⅱ CAO + elonidine 30 μg; group Ⅲ CAO + clanidine 100 μg; group Ⅳ CAO + clonidine 100 μg + yohimbine (an α2-adrenergic receptor antagonist) 200 μg. In group Ⅳ , clonidine was administered intravenously 15 min after CAO, and then yohimbine was injected intravenously 15 min later. The discharges of NSRN were recorded every 5 min for 60 min from the beginning of CAO. Results Clonidine 100 μg significantly inhibited the increased frequency of nociceptive discharge rate of NSRN after CAO. However, this effect could be blocked by the α2-adrenergic receptor antagonist yohimbine.Conclusion Clonidine 100 μg can reduce the visceral pain induced by acute myocardial ischemia through activiting α2-adrenergic receptor.

Objective.So far,it has not been established a satisfactory method for early diagnosis and studying on epidemiology for leprosy,we want to develop a molecular biological method for solving this point.Materials and methods.Based on the M.leprae gene coding groEL,65kD and 16S rRNA,three polymerase chain reactions were developed by using plikaytis',Woods' and Pattyn's procedures.It was optimized that the experimental parameters for each PCR,and a comparative study on practivity among three PCRs was also conducted for practical purpose.Results and conclusion.For detecting infection with M.leprae,all of PCRs established by us were highly sensitive and specific,but for practicl purpose,the woods'PCR optimized by us ought to be chosen firstly.