Objective To investigate changes in the firing activities of nucleus accumbens (NAc)neurons and their response to 5-HT7 receptor stimulation in a rat model of Parkinson’s disease (PD).Methods The firing activities and response of NAc neurons to 5-HT7 receptor agonist in PD rats were recorded by in vivo electroneurophysiology and neuropharmacology and then were compared with those in the sham group.Results The mean firing rate of NAc neurons was (5.46 ±0.88)Hz in the sham rats and (3.77 ±0.48)Hz in the PD rats. The firing rate of NAc neurons increased significantly compared with that in the sham rats (P <0.05).In PD rats, 65% of NAc neurons fired in bursts and 35% fired irregularly.However,in the sham rats,57.5% of NAc neurons fired in bursts and 42.5% fired irregularly.There was no significant difference in the firing pattern of NAc neurons between the PD and sham rats (P >0.05 ).Systemic administration of 5-HT7 receptor agonist AS1 9 increased the firing rate of NAc neurons in the sham and PD rats.This excitation was significant at a high dose of 1 60 μg/kg for NAc neurons in the sham rats (P <0.05).However,the excitation produced by AS1 9 was significant at a high dose of 80 μg/kg in PD rats (P <0.05).The cumulative dose-produced excitation in the PD rats was lower than that in the sham rats.The effects induced by AS1 9 were reversed by the 5-HT7 receptor antagonist SB269970 in both groups.Conclusion The reinforced firing activity of NAc neurons might be mediated by 5-HT7 receptor in the neurons of PD rats.

Objective To explore the effect of postnatal infection on SOX10 expression in cerebral white matter in immature rats. Methods A total of 96 newborn SD rats were randomly divided into hypoxia group, lipopolysaccharide (LPS) group, and control group. At day 3 and 6 after birth, the rats in LPS group and hypoxia group were intraperitoneally injected with 0.25 mg/kg of LPS while the rats in control group were injected with normal saline. Meanwhile the rats in hypoxia group were maintained in a hypoxic tank under atmospheric pressure and thermostatic water bath at 37℃for 2 hours of ventilation with mixed gas con-taining 8%O2 and 92%N2 at a rate of 2 L/min starting 3 days after birth. At day 7, 10, 14, 21 after birth, eight rats in each groups were sacriifced and the cerebral white matter was extracted. HE staining was performed to observe the pathological changes of cerebral white matter by light microscopy. The expression of SOX10 in cerebral white matter was determined by immunohisto-chemical and Western blotting analysis. The expression of TLR-4 was determined by Western blotting. Results In LPS group and hypoxia group, the SOX10 positive cells and expressions of SOX 10 and TLR-4 were increased at day 7, reached the peak at day 10, and then gradually declined. There were signiifcant differences between any two time points (P<0.05). In control group, there were a few positive cells and limited expressions of SOX 10 and TLR-4 and there were no differences between any two time points (P>0.05). At each time point, the difference in the SOX10 positive cells and the expressions of SOX 10 and TLR-4 were statistically signiifcant among three groups (P<0.05) in the order of hypoxia group>LPS group>control group and there were signiifcantly differences between each groups (P<0.05). Conclusions Postnatal infections can lead to cerebral white mat-ter lesions in immature rats. The existence of both hypoxia and infection can aggravate the brain injury. The high expression of SOX 10 may have the protective effect.

Objective:By comparing the expression levels of retinoic acid-related orphan nuclear receptorγt( RORγt) and in-terleukin-17 ( IL-17 ) in newborn rats′spleen tissue with cytomegalovirus infection with normal newborn to provide experimental evidence for the pathogenesis of CMV infection.Methods:Forty-eight newborn BALB/c mice were randomly divided into control group and MCMV group.Mice in virus group was given intraperitoneal injection of MCMV virus suspension,while the control group were given the same dose of normal saline as controls.Eight mice in the two groups were killed at day 3,7 and 14.The animal were sacrificed at day 3,7 and 14( n=8 for each interval) and spleens were obtained from the two groups.MCMV DNA,RORγt mRNA,IL-17 mRNA and protein of RORγwere detected by using RT-PCR and Western blot between the two groups.Results:Expression of MCMV DNA was in-creased in the MCMV group but absent in the control group.RORγt mRNA, IL-17 mRNA and protein expression of RORγt were significantly higher than the normal control group,with the extension of the infection time gradually increased( P<0.05 ) .Conclusion:The IL-17 and RORγt in spleen tissue may take part in the inflammatory response induced by MCMV, and may be involved in the pathogeneses of MCMV injury.

Objective:To evaluate the effect of active cycle of breathing techniques (ACBT) on respiratory muscle training in patients undergoing coronary artery bypass grafting (CABG) surgery.Methods:A quasi-experimental trial was performed. Patients were allocated to the control group or intervention group according to their time of admission. Patients who were admitted to hospital from January 2019 to April 2019 were assigned to the control group and patients admitted from May 2019 to October 2019 were allocated to the intervention group. The control group ( n=84) received routine perioperative care, and the intervention group ( n=82) received ACBT in addition to routine perioperative care. Patients in both groups were trained 3 to 5 times a day throughout their stay in the hospital. The primary outcome measure was maximum inspiratory pressure (MIP), peak of expiratory flow (PEF), forced vital capacity (FVC). Other outcomes included the postoperative pulmonary complications (PPC), days of postoperative hospital stay. Results:The MIP, PEF, FVC value of the control group 3 days after extubation were (64.77±9.80) cmH 2O (1 cmH 2O=0.098 kPa), (139.52±23.74) L/min, (1.07±0.20) L, the intervention group were (69.89±10.92) cmH 2O, (150.37±28.65) L/min, (1.15±0.22)L, the differences between the two groups were statistically significant ( t values were -3.177,-2.657,-2.409, P <0.05). The MIP, PEF, FVC value of the control group 5 days after extubation were (71.13±8.64) cmH 2O, (270.48±44.36) L/min, (2.02±0.29) L, the intervention group were (74.72±12.48) cmH 2O, (287.07±58.61) L/min, (2.21±0.35) L, the differences between the two groups were statistically significant ( t values were -2.161,-2.060,-3.605, P <0.05). The days of postoperative hospital stay of control group and intervention group were (8.15±0.98) and (7.80±1.23) d, there were significant differences ( t value was 2.021, P <0.05). Conclusions:ACBT is an effective and economical pulmonary rehabilitation method, it has effect on Respiratory Muscle Training in Patients Undergoing CABG surgery.

Objective To study the time extended for getting emergency intervention in different modes of transportation and factors influencing the modes of transportation of patients with ST elevation myocardial infarction (STEMI).Methods A total of 564 consecutive patients with STEMI admitted from September 2013 to June 2016 were enrolled in the study.The clinical data about time consumed for getting emergency intervention and modes of transportation were collected.Results According to the mode of transportation,patients were divided into three groups:emergency care system (EMS) transportation group (n =96),self-transportation group (n =206) and referral group in which the patients were sent in from other hospitals (n =262).EMS transportation group had significantly shorter total ischemic time before emergency treatment than self-transportation group (229 rin vs.418 min,P ＜ 0.05) and referral group (229 min vs.512 rin,P ＜ 0.05),and significantly shorter length of pre-hospital time than self-arrival group (55 min vs.110 min;P＜0.05) and referral group (55 min vs.372 min;P＜0,05).The referral group had longer pre-hospital time and the self-transportation group had longer door-to-balloon time,but there was no difference in total ischemic time between the self-arrival and referral group (Z =-1.882,P =0.068).Multivariate logistic regression was used to analyze influence factors in mode of transportation:(1) patients characterized with high school or university education,profession of civil service,and their transportation distance more than 30 km were greater in number than referral group (P ＜ 0.05);(2) patients identified with senior middle school education,staff member of public sectors or company,their transportation distance less than 30 km,and with killip grade above Ⅱ were more likely to have EMS transport (P ＜ 0.05);(3) patients defined as businessmen without taking out new rural cooperative medical insurance,taking up transportation distance less than 80 km,and subjecting to killip grade Ⅰ had a higher proportion of individuals of this kind taking self-transportation (P ＜ 0.05).Conclusion Mode of transportation is an important factor that affects the time extended to get emergency intervention.Education level,occupation,medical insurance type,transportation distance,killip grade are associated with modes of transport.

Objective:To explore the mechanism of zoledronic acid (ZOL) affects osteogenic differentiation and bone formation through the regulation of sirtuin 3 (SIRT3) / P53 expression.Methods:Bone marrow mesenchymal stem cells (BMSCs) were induced to differentiate into osteogenic cells, the expression of SIRT3 in the cells was detected, and the targeting regulation relationship between SIRT3 and P53 was analyzed. The intracellular expressions of SIRT3 and P53 were intervened and ZOL was used to treat the cells. MTT method, Western blot method and kit were used to detect cell viability, osteogenesis-related genes Osteoprotegerin (OPG), runt-related transcription factor 2 (Runx2) expression, alkaline phosphatase (ALP) activity and alizarin red S (ARS) staining, respectively. Ovariectomy (OVX) was used to construct a rat model and explore the effect of ZOL on the progression of osteoporosis (OP) in vivo.Results:ZOL promoted osteogenic differentiation of BMSCs. The expression of SIRT3 was down-regulated in the serum of OP patients (0.78±0.23) compared with that of healthy subjects (1.00±0.26 vs. 0.78±0.23. t=3.85, P<0.001). During the osteogenic differentiation of BMSCs, the expression level of SIRT3 gradually increased with the prolonged induction of osteogenesis. Compared with the p53 protein expression and BMSCs activity in the control group, SIRT3 knockout could increase the expression level of p53 protein (0.59±0.05 vs. 1.01±0.11. t=6.02, P=0.004) but inhibited the activity of BMSCs (100.00±8.41 vs. 51.26±5.59. t=8.36, P=0.001). After ZOL treatment, the inhibitory effect of SIRT3 on cell viability (49.61±5.11 vs. 87.61±7.31. t=7.38, P=0.002) and osteogenesis was relieved, and the level of P53 was inhibited (1.10±0.10 vs. 0.69±0.04. t=6.59, P=0.003). P53 overexpression partially offseted the effects of ZOL on cell viability (84.61±6.52 vs. 66.54±5.47. t=3.68, P=0.021) and osteogenesis. Compared with the sham surgery group, the OVX group showed inhibition of osteogenesis in rats, and ZOL treatment significantly improved osteogenic inhibition. ZOL treatment increased the expression level of SIRT3 protein in bone tissue of OVX rats, but inhibited the expression level of P53. Conclusion:ZOL promoted osteogenic differentiation and bone formation of BMSCs by promoting the ubiquitination and degradation of P53 by SIRT3.

Objective To investigate the delay of door to signature time in primary percutaneous coronary intervention (PCI) and its influence in patients with ST segment elevation myocardial infarction (STEMI),therefore to provide a scientific basis for further effective shortening the time of primary PCI in patients with STEMI.Methods A total of 226 patients who diagnosed with STEMI and underwent primary PCI at Henan Provincial People's Hospital from June 2016 to December 2017 were enrolled in the study.Observation indicators include:(1) baseline data of patients;(2) time segments in primary PCI:total ischemic time (TIT),door to balloon time (DTBT),door-to-signature time (DTST),signature to balloon time (STBT);(3) the demographic characteristics of the family members who signed informed consent;and (4) the psychological factors and coping strategies of family members before signing informed consent.All data was analyzed using SPSS software (version 22.0).Multiple linear regression analysis was used to analyze the influencing factors of delay of DTST.A P＜0.05 was considered statistically significant.Results In this study,226 patients with STEMI who were first diagnosed in our hospital had a mean age of 55.23±10.80 years,and 181 (80.1％) were male.The median of TIT,DTBT,DTST,STBT were 312 min,166 min,82 min,and 80 min.The ratio of DTST in DTBT and TIT was 50％ and 28.5％,respectively.The multiple linear regression analysis showed that the number of direct family members (P＜0.001),the degree of educational in middle school and below (P=0.010),high school/technical secondary school (P=0.029),families worrying about the high cost of medical care (P=0.020),families consulted each other repeatedly (P=0.022),and consulted the other medical staff(P=0.022) are risk factors of DTST delay,and city residence (P=0.048) is the protection factor of DTST delay.Conclusions The long time of DTS is a reality of the practice of primary PCI in China.The factors that lead to longer DTST include demographic characteristics,psychological factors and coping strategies of family members.The STBT of primary PCI in China should be taken into the value while emphasizing the DTBT.

Objective:To investigate the relationship between the expression level of platelet microparticle (PMP) and the disease activity of inflammatory bowel disease (IBD) in IBD patients, and to explore the ability of PMP from different sources to induce the formation of neutrophil extracellular trap (NET) in vitro. Methods:From May 2018 to July 2019, 118 patients with IBD admitted to the Department of Gastroenterology at The First Affiliated Hospital of Anhui Medical University were selected, among whom 54 cases were ulcerative colitis (UC) patients (UC group) and mild, moderate and severe cases were 17, 25 and 12, respectively; and 64 cases were Crohn′s disease (CD) (CD group), 6 were in remission stage, and mild, moderate, severe cases were 27, 22 and 9, respectively. During the same period, 35 healthy individuals with normal checkups were selected as the healthy control group. Specimens were collected and the expression levels of PMP were measured by flow cytometry.And the correlation between the expression level of PMP and the disease activity index (DAI) score was analyzed.NET formation experiment groups were set up, including neutrophils of healthy control group (6 cases), neutrophils of IBD group (6 cases), neutrophils of healthy controls + PMP of IBD group (12 cases) and neutrophils of healthy controls+ PMP group (6 cases). After immunofluorescence staining, the proportion of NET formation of each group was observed under laser scanning confocal microscopy (LSCM). Mann-Whitney U test, Spearman correlation analysis and Independent-sample t test were used for statistical analysis. Results:The expression levels of PMP in peripheral blood of the UC group and the CD group were 2 184.5(2 817.0)/μL and 2 209.0(2 409.0)/μL, respectively, which were all higher than that of the healthy control group (776.0(407.0)/μL), and the differences were statistically significant ( U=-6.018 and -6.426, both P<0.01). The expression level of PMP of patients with severe UC was 3 873.0(4 611.3)/μL, which was higher than those of patients with mild or moderate UC (1 248.0(1 888.0)/μL and 1 432.0(1 783.0)/μL, respectively), and the differences were statistically significant ( U=-2.745 and -2.547, both P<0.05). The expression level of PMP of patients with severe CD was 5 658.0(5 067.5)/μL, which was higher than those of patients with mild or moderate CD or in remission (1 327.5(1 934.0)/μL, 1 405.0(2 965.0)/μL and 2 300.0(1 552.0)/μL, respectively), and the differences were statistically significant ( U=-1.650, -1.955 and -1.306, all P<0.05). There was no statistically significant difference in the expression level of PMP between the UC group and the CD group, between the mild and moderate UC patients, and between the CD in remission and the mild, moderate patients (all P>0.05). The results of correlation analysis showed that the expression levels of PMP in peripheral blood of patients with UC or CD were positively correlated with DAI score and CRP ( r=0.406, 0.358, 0.325, and 0.256; all P<0.05). The proportion of NET formation in the neutrophils of healthy control+ PMP of IBD group was (14.67±5.35) %, which was higher than those of the neutrophils of healthy control groap, neutrophils of IBD group and neutrophils of healthy control+ PMP group ((2.00±0.63)%, (1.67±0.82)% and (5.83±2.86)%), and the differences were statistically significant ( t=5.694, 8.230 and 3.748, all P<0.05). There was no statistically significant difference in the proportion of NET formation between the neutrophils of healthy control group and the neutrophils of IBD group ( P>0.05). Conclusions:The expression level of PMP in peripheral blood of IBD patients increases and is correlated with the disease activity degree in IBD patients. PMP has the ability to induce the NET formation in neutrophils. Moreover, PMP of IBD patients is more likely to induce NET formation than those of healthy individuals, which may be involved in the intestinal inflammatory process by activating neutrophils to produce NET.

Objective:To investigate the expression of Piezo1 in small intestinal mucosal epithelial cells of patients with Crohn′s disease (CD) and its clinical correlation with CD.Methods:From January 1st 2010 to November 30th 2020, the clinical data including age, gender, disease location and biological behavior, etc of 57 patients with CD (CD group) who underwent surgery at The First Affiliated Hospital of Anhui Medical University were retrospectively. And at same time the normal samll intestinal epithelial tissues of 10 healthy individuals who underwent colonoscopy were collected as the healthy control group. The expression of Piezo1 in small intestinal epithelial cells of CD patients with different disease sites, biological behavior and disease activity were detected by immunofluorescence staining and hematoxylin-eosin staining. The histological score system and intestinal fibrosis score were used to analyze the inflammation and fibrosis of the intestinal tissues of patients with CD. Semi-quantitative analysis of Piezo1 in small intestinal epithelial cells was analyzed by ImageJ software. And the correlation between Piezo1 expression and clinical characteristics and pathological features of small intestine was also analyzed. Independent sample t test and analysis of variance were used for statistical analysis. Results:In CD group, there were 37 males (64.9%) and 20 females (35.1%). The age was (39.1±14.2) years old, ranged from 18 to 71 years old, and the average duration of the disease was (26.5±24.1) months. There were 29 cases (50.9%)of ileal type, 26 cases (45.6%) of ileocolonin type and 2 cases (3.5%) of colonic type. There were 12 cases (21.1%) of non-penetrating non-stenotic type, 31 cases (54.4%) of stenotic type and 14 cases (24.6%) of penetrating type. There were 47 cases (82.5%) with moderate activity and 10 cases (17.5%) with severe activity. There were 17 cases (29.8%) of moderate intestinal inflammation, 40 cases (70.2%) of severe intestinal inflammation. The score of intestinal fibrosis in six cases (10.5%) was 1, 28 cases (49.1%) was 2, 18 cases (31.6%) was 3, five cases was 4. The relative expression level of Piezo1 in intestinal mucosal epithelial cells of CD group was higher than that of healthy control group (12.9±4.6 vs. 8.5±1.1), the relative expression of Piezo1 in intestinal mucosal epithelia cells of stenotic type and penetrating type CD patients were both higher than that of non-penetrating and non-stenotic CD patients (12.6±3.8 and 9.8±2.4 vs. 6.0±1.3), and the differences were all statistically significant ( t=3.00, -3.66 and -3.32, all P<0.01). The relative expression of Piezo1 in small intestinal epithelial cells of CD patients with severe intestinal inflammation was higher than that of CD patients with moderate intestinal inflammation (13.1±4.0 vs. 9.7±3.1), and the difference was statistically significant ( t=-2.65, P<0.05). The relative expression levels of Piezo1 in small intestinal epithelial cells of patients with intestinal fibrosis score of 4, 3, 2 and 1 were 17.6±5.2, 12.6±1.7, 9.1±2.1 and 5.8±1.1, respectively; the relative expression levels of Piezo1 in intestinal epithelial cells of patients scored 4 were higher than that of patients scored 3, 2 and 1, and that of patients scored 3 was higher than patients scored 2 and 1, and that of patients scored 2 was higher than that of patients scored 1, and the differences were all statistically significant ( t=-2.98, -5.10, -3.84, 4.60, 6.55 and 2.56, all P<0.05). The relative expression of Piezo1 in intestinal mucosal epithelial cells was related to the severity of intestinal inflammation and fibrosis. The more severe the intestinal inflammation and fibrosis, the higher the relative expression of Piezo1 in intestinal mucosal epithelial cells. Conclusions:The relative expression of Piezo1 in small intestinal epithelial cells is related to the biological behavior and the severity of intestinal inflammation and fibrosis of CD. It is speculated that the expression of Piezo1 in small intestinal epithelial cells may be clinically related to the process of intestinal wall fibrosis in CD to some extent, however whether it plays an important role in the process of intestinal wall fibrosis in CD and its specific mechanism need to be further studied.

OBJECTIVETo correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations.

METHODSSomatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients.

RESULTSThe mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons).

CONCLUSIONGenetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Leukemia, Myeloid, Acute ; genetics ; mortality ; Male ; Middle Aged ; Mutation ; Prognosis ; Young Adult