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1.
Protein & Cell ; (12): 203-219, 2022.
Article in English | WPRIM | ID: wpr-929177

ABSTRACT

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.


Subject(s)
Animals , Disease Models, Animal , Fragile X Mental Retardation Protein/metabolism , Fragile X Syndrome/metabolism , Humans , Mice , Mice, Knockout , Neurons/metabolism
2.
Article in English | WPRIM | ID: wpr-914751

ABSTRACT

Purpose@#To accelerate magnetic resonance fingerprinting (MRF) by developing a flexible deep learning reconstruction method. @*Materials and Methods@#Synthetic data were used to train a deep learning model. The trained model was then applied to MRF for different organs and diseases. Iterative reconstruction was performed outside the deep learning model, allowing a changeable encoding matrix, i.e., with flexibility of choice for image resolution, radiofrequency coil, k-space trajectory, and undersampling mask. In vivo experiments were performed on normal brain and prostate cancer volunteers to demonstrate the model performance and generalizability. @*Results@#In 400-dynamics brain MRF, direct nonuniform Fourier transform caused a slight increase of random fluctuations on the T2 map. These fluctuations were reduced with the proposed method. In prostate MRF, the proposed method suppressed fluctuations on both T1 and T2 maps. @*Conclusion@#The deep learning and iterative MRF reconstruction method described in this study was flexible with different acquisition settings such as radiofrequency coils. It is generalizable for different In vivo applications.

3.
Article in Chinese | WPRIM | ID: wpr-888115

ABSTRACT

As a common disease worldwide, alcoholic liver injury is caused by long-term or excessive intake of alcohol and triggers cell death due to alcohol metabolism and reactive oxygen species(ROS)-mediated cytotoxicity. Wangshi Baochi(WSBC) Pills have been widely adopted in clinical practice for evacuating stasis, resolving turbidity, clearing heat, tranquilizing mind, invigorating sto-mach, promoting digestion, purging fire and removing toxin. This study aimed to investigate the efficacy of WSBC Pills in dispelling the effect of alcohol and protecting against acute alcoholic liver/stomach injury in mice, and preliminarily investigate its possible mole-cular mechanism. The results found that the preventive treatment with WSBC Pills contributed to elevating the activity of alcohol dehydrogenase(ADH) and its expression in liver and shortening the time required for sobering up of mice with acute alcoholic liver injury. The staining of liver pathological sections as well as the detection of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and liver ROS levels revealed that WSBC Pills protected the liver by reducing serum AST and ALT. It suppressed oxidative stress-induced liver injury by lowering liver ROS and elevating superoxide dismutase(SOD), and the liver-protecting effect was superior to that of silibinin. Western blot assay confirmed that WSBC Pills inhibited the oxidative stress by up-regulating SOD1 and NAD(P)H: quinone oxidoreductase 1(NQO-1). In addition, WSBC Pills lowered the ROS level to protect against the acute alcoholic stomach injury in mice. The findings have suggested that WSBC Pills alleviated the acute alcoholic liver/stomach injury in mice by increasing ADH and resisting oxidative stress.


Subject(s)
Animals , Chemical and Drug Induced Liver Injury , Ethanol , Liver/metabolism , Liver Diseases, Alcoholic , Mice , Oxidative Stress , Stomach
4.
Article in English | WPRIM | ID: wpr-903921

ABSTRACT

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)uclear factor erythroid 2-related factor 2 (Nrf2) axis.Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSEmediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

5.
Acta Pharmaceutica Sinica ; (12): 60-66, 2020.
Article in Chinese | WPRIM | ID: wpr-780561

ABSTRACT

The p21-activated kinase 1 (PAK1) is a member of the P21-activated protein kinase family that plays an important role in the proliferation and on cogenesis of pancreatic cancer. PAK1 is an important target for the treatment of pancreatic cancer. At present, akinase inhibitor targeting PAK1 is still in the preclinical research stage. Therefore, screening for new PAK1 kinase inhibitors is of great significance. In this study the natural compound celastrol was found to have a significant inhibitory effect on PAK1, with an IC50 value of 3.614 μmol·L-1. Molecular docking results showed that celastrol had good binding to PAK1. An MTT assay indicated that celastrol inhibited the proliferation of pancreatic cancer cells BxPC-3 and PANC-1. Mechanistic studies revealed that the inhibition of pancreatic cancer cells by celastrol was reversed by PAK1 siRNA. Celastrol inhibited PAK1 and the subsequent activation of downstream signaling pathways, thereby activating apoptosis signaling pathways and triggering apoptosis in pancreatic cancer cells. These findings suggested that celastrol induced apoptosis in pancreatic cancer cells by suppressing the PAK1 kinase signaling pathway and has potential value for the treatment of pancreatic cancer.

6.
Article in English | WPRIM | ID: wpr-896217

ABSTRACT

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)uclear factor erythroid 2-related factor 2 (Nrf2) axis.Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSEmediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

7.
Article in Chinese | WPRIM | ID: wpr-828049

ABSTRACT

Polysaccharide from Ganoderma applanatum has the activities of anti-tumor and enhancing immune function. There were no reports on antitumor effect of its intratumoral injection. In this study, the polysaccharide was extracted from G. applanatum by water extraction and alcohol precipitation, and purified by ceramic membrane after removing protein by Sevage method. The total polysaccharide content from G. applanatum(PGA)was about 63%. The combination of PGA and paclitaxel showed synergistic effect on cytotoxicity of 4 T1 cells at lower concentrations in vitro. In addition, the growth curve of 4 T1 cells showed that PGA could retard the growth of 4 T1 cells gradually. The PGA thermosensitive gel(PGA-TG)was prepared by using poloxamer 188 and 407. The gel temperature was 36 ℃, and the PGA-TG could effectively slow down the release rate of PGA in vitro. 4 T1 breast cancer-bearing mice were used as a model to evaluate the therapeutic effect of intratumoral injection of PGA combined with tail vein injection of nanoparticle albumin-bound paclitaxel(nab-PTX). In high and low dose PGA groups, each mice was given with 2.25, 1.125 mg PGA respectively, twice in total, and the dosage of paclitaxel was 15 mg·kg~(-1), once every 3 days, for a total of five times. The tumor inhibition rate was 29.65% in the high dose PGA-TG group, 58.58% in the nab-PTX group, 63.37% in low dose PGA-TG combined with nab-PTX group, and 68.10% in high dose PGA-TG combined with nab-PTX group respectively. The inhibitory effect in high dose PGA-TG group combined with nab-PTX on tumors was significantly higher than that in nab-PTX group(P<0.05). The results showed that paclitaxel therapy combined with intratumoral injection of PGA-TG could improve the therapeutic effect for 4 T1 mice and reduce the side effects of chemotherapy.


Subject(s)
Animals , Breast Neoplasms , Cell Line, Tumor , Ganoderma , Mice , Neoplasms , Paclitaxel , Poloxamer , Polysaccharides
8.
Article in Chinese | WPRIM | ID: wpr-824944

ABSTRACT

Objective: To observe the effects of electroacupuncture (EA) on the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex of type 2 diabetic rats with cognitive impairment (CI), and to explore the mechanism of EA in improving the learning and memory abilities. Methods: A total of 100 Sprague-Dawley (SD) rats were divided into a normal group (n=10) and a model group (n=90) by random number table method. Rats in the model group were intraperitoneally injected with a small dose of streptozotocin (STZ) to establish the type 2 diabetic models, after being fed with high-fat and high-sugar diet for 1 month. Twenty CI rats were selected from the 50 successful model rats by the Morris water maze (MWM) test and randomly divided into a model group and an EA group according to the blood glucose level and MWM data (n=10). Rats in the EA group received acupuncture at Zusanli (ST 36), Neiting (ST 44) and Yishu (Extra), of which Zusanli (ST 36) and Neiting (ST 44) were stimulated by EA apparatus, 20 min/time, once a day for 6 d a week and 4 consecutive weeks. The rats in the model and the normal groups were fixed without treatment. After 4-week treatment, the random blood glucose level of the rats was measured; the learning and memory abilities of rats were measured by MWM; terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells; Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the protein and gene expressions of Bax, Caspase-3 and Bcl-2 in cerebral cortex. Results: After modeling, the random blood glucose level and the escape latency tested by MWM were significantly increased, and the number of crossing the platform tested by the MWM was decreased in the EA and model groups, and were significantly different from those in the normal group (P<0.05 or P<0.01), while the differences between the model group and the EA group were not statistically significant (all P>0.05). After 4-week treatment, the random glucose level and the escape latency tested by MWM were significantly increased (both P<0.05), and the number of crossing the original platform tested by the MWM was significantly reduced (P<0.01), the protein and gene expressions of Bax and Caspase-3 were significantly increased (all P<0.001), the protein and gene expressions of Bcl-2 were significantly reduced (both P<0.001), and the number of neuron apoptosis was significantly increased (P<0.001) in the model group than in the normal group; the random blood glucose level was significantly reduced (P<0.05), the escape latency tested by MWM was significantly shortened (P<0.05), and the number of crossing the original platform tested by MWM was significantly increased (P<0.05), the protein and gene expressions of Bax and Caspase-3 were significantly reduced (all P<0.001), the protein and gene expressions of Bcl-2 were significantly increased (both P<0.001), and the number of neuron apoptosis was significantly reduced (P<0.001) in the EA group than in the model group. Conclusion: EA can improve the learning and memory damages induced by type 2 diabetic model rats with CI; the action mechanism may be achieved via anti-apoptosis.

9.
Article in Chinese | WPRIM | ID: wpr-863837

ABSTRACT

Objective:To compare the therapeutic effects of nasal high-flow oxygen therapy (HFNC) and nasal canal oxygenation (NCO) during breaks off non-invasive ventilation (NIV) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore the feasibility of NIV combined with HFNC in the treatment of AECOPD.Methods:From August 2017 to July 2019, AECOPD patients with type Ⅱrespiratory failure (arterial blood gas pH <7.35, PaCO 2 > 50 mmHg) who were treated with NIV were randomly (random number) assigned to the HFNC group and NCO group at 1:1. The HFNC group received HFNC treatment during breaks from NIV and the NCO group received low-flow NCO during the NIV interval. The primary endpoint was the total respiratory support time. The secondary endpoints were endotracheal intubation, duration of NIV treatment and breaks from NIV, length of ICU stay, total length of hospital stay and so on. Results:Eighty-two patients were randomly assigned to the HFNC group and the NCO group. After secondary exclusion, 36 patients in the HFNC group and 37 patients in the NCO group were included in the analysis. The total respiratory support time in the HFNC group was significantly shorter than that in the NCO group [(74 ± 18) h vs. (93 ± 20) h, P = 0.042]. The total duration of NIV treatment in the HFNC group was significantly shorter than that in the NCO group [(36 ± 11) h vs. (51 ± 13) h, P=0.014]. There was no significant difference of the mean duration of single break from NIV between the two groups, but durations of break from NIV in the HFNC group were significantly longer than those in the NCO group since the third break from NIV ( P < 0.05). The intubation rates of the HFNC and NCO groups were 13.9% and 18.9%, respectively, with no significant difference ( P=0.562). The length of ICU stay in the HFNC group was (4.3 ± 1.7) days, which was shorter than that in the NCO group [(5.8 ± 2.1) days, P=0.045], but there was no significant difference in the total length of hospital stay between the two groups. Heart rate, respiratory rate, percutaneous carbon dioxide partial pressure and dyspnea score during the breaks from NIV in the NCO group were significantly higher than those in the HFNC group, and the comfort score was lower than that in the HFNC group ( P<0.05). Conclusion:For AECOPD patients receiving NIV, compared with NCO, HFNC during breaks from NIV can shorten respiratory support time and length of ICU stay, and improve carbon dioxide retention and dyspnea. HFNC is an ideal complement to NIV therapy in AECOPD patients.

10.
Article in Chinese | WPRIM | ID: wpr-863453

ABSTRACT

Objective:To investigate the expressions of sphingosine-1-phosphate transporter 2 (SPNS2) and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) in laryngeal squamous cell carcinoma and their correlations with clinicopathological features and prognosis.Methods:A total of 82 cases of squamous cell carcinoma were collected from the paraffin-embedded specimens of laryngeal cancer in Taixing People′s Hospital of Jiangsu Province from March 2012 to March 2016. The expressions of SPNS2 and Lgr5 were detected by immunohistochemistry in 82 cancerous tissues and 50 adjacent normal tissues. The relationships between the expressions of SPNS2 and Lgr5 in patients with laryngeal squamous cell carcinoma and clinicopathological features and prognosis were analyzed.Results:The high expression rate of SPNS2 in laryngeal squamous cell carcinoma tissues was 40.24% (33/82), which was higher than 8.00% (4/50) in normal tissues adjacent to cancer. The high expression rate of Lgr5 in cancerous tissues was 46.34% (38/82), which was higher than 12.00% (6/50) in normal tissues adjacent to cancer. The differences were statistically significant ( χ2=16.008, P<0.001; χ2=16.484, P<0.001). The expression status of SPNS2 was related to tumor size ( χ2=5.713, P=0.017), tumor stage ( χ2=7.071, P=0.008), tumor differentiation degree ( χ2=5.722, P=0.017) and lymph node metastasis ( χ2=6.595, P=0.010). There were significant differences in the expression status of Lgr5 in different tumor stage ( χ2=8.200, P=0.004), tumor differentiation ( χ2=9.435, P=0.002) and lymph node metastasis ( χ2=16.188, P<0.001). The 3-year overall survival rate of patients in SPNS2 low expression group was 90.91%, which was higher than that of patients in SPNS2 high expression group (71.43%, χ2=4.975, P=0.026). The 3-year progression-free survival rate of patients in SPNS2 low expression group was 78.79%, which was higher than that of patients in SPNS2 high expression group (55.10%, χ2=6.113, P=0.013). The 3-year overall survival rate of patients in Lgr5 low expression group was 86.84%, which was higher than that of patients in Lgr5 high expression group (65.91%, χ2=5.801, P=0.016). The 3-year progression-free survival rate of patients in Lgr5 low expression group was 78.95%, which was higher than that of patients in Lgr5 high expression group (56.82%, χ2=6.316, P=0.012). Multivariate Cox regression analysis showed that differentiation ( RR=0.199, 95% CI: 0.057-0.691, P=0.011), tumor staging ( RR=0.167, 95% CI: 0.053-0.531, P=0.002), SPNS2 ( RR=0.208, 95% CI: 0.072-0.604, P=0.004) and Lgr5 ( RR=0.198, 95% CI: 0.060-0.655, P=0.008) were risk factors for the prognosis of patients with laryngeal squamous cell carcinoma. Contingency correlation analysis showed a positive correlation between SPNS2 and Lgr5 expressions in laryngeal squamous cell carcinoma ( C=0.591, P<0.001). Conclusion:SPNS2 and Lgr5 are highly expressed in laryngeal squamous cell carcinoma and are closely related to clinicopathological features. And SPNS2 and Lgr5 are risk factors for the prognosis of patients with laryngeal squamous cell carcinoma.

11.
Acta Pharmaceutica Sinica ; (12): 1837-1844, 2019.
Article in Chinese | WPRIM | ID: wpr-780314

ABSTRACT

Calcium-binding protein S100A9 is closely related to inflammation and tumor invasion, and is one of the specific markers of myeloid-derived suppressor cells (MDSC). In this study, a recombinant polypeptide vaccine CTB-S100A9 targeting mouse calcium-binding protein S100A9 was constructed by fusion cholera toxin B subunit (CTB) with S100A9 gene. The CTB-S100A9 fusion protein was expressed in E coli. and purified by Ni+ affinity chromatography. Vaccinate the purified recombinant CTB-S100A9 protein supplemented with aluminum hydroxide adjuvant can break the autoimmune tolerance and produce high titer of S100A9 antibody in mice. Moreover, the S100A9 antibody produced by CTB-S100A9 vaccination is more specific and does not cross-react with S100A8. In the mouse 4T1 breast cancer model, CTB-S100A9 vaccination not only has significant tumor prevention effects, but also has significant tumor therapeutic effects. In addition, CTB-S100A9 significantly inhibited lung metastasis in 4T1 mice breast cancer model. Further analysis by flow cytometry showed that CTB-S100A9 vaccination can significantly reduce the tumor induced Treg cells and granulocyte-derived MDSC in 4T1 mice model, and reverse the tumor immunosuppressive environment, thereby promote the anti-tumor efficacy. The animal experiments in this study were carried out under the animal care guidelines approved by the Animal Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. This study shows that CTB-S100A9 is a good recombinant vaccine that targets the tumor immune-suppression environment and has great potential for the future clinical application.

12.
Article in Chinese | WPRIM | ID: wpr-791836

ABSTRACT

Objective To explore the relationship between positive rate of de novo donor specific antibody (dnDSA ) and human leukocyte antigen (HLA ) mismatch after kidney transplantation and explore the impact of dnDSA upon long-term graft survival and rejection .Methods Retrospective analysis was conducted for clinical data of 101 kidney transplant recipients .Based upon HLA antibody and dnDSA ,they were divided into three groups of HLA-(n=70) ,dnDSA- (n=23) and dnDSA+(n=8) .Rejection and graft survival were recorded for evaluating the impact of dnDSA on rejection and graft survival and observing the differences among all groups .Results The mismatchs of HLA-A/B and HLA-DR were more frequent than HLA-and dnDSA-groups(P=0 .047 , P=0 .010)and graft survival was lower in dnDSA+ group than HLA-and dnDSA-groups (P=0 .001) .The rejection rate was higher in dnDSA+ group (62 .5% ) than HLA- group (8 .57% ) and dnDSA-group (8 .69% ) . The difference was statistically significant (P=0 .013) . Pathological examination indicated microcirculatory inflammation (glomerulonephritis & trichodangiitis ) and damage (multilayer change of capillary basement membrane) occurred frequently in dnDSA + group and C4d remained positive . However ,scar ,arterial fibrosis or tubulointerstitial inflammation was not correlated with dnDSA . Conclusions HLA mismatch is correlated with dnDSA positivity . And dnDSA may reduce graft survival and enhance rejection rate . Rejection mediated by dnDSA is often accompanied by microcirculatory inflammation and C4d positivity .

13.
Article in Chinese | WPRIM | ID: wpr-755934

ABSTRACT

Objective To summarize the experience of one case of anastomotic leakage after simultaneous pancreas-kidney transplantation (SPK ) with enteric drainage .Methods One case of type 2 diabetes mellitus complicated with end-stage nephropathy undergoing SPK was retrospectively analyzed .Iliac venous systemic circulation was employed for pancreatic venous reflux ,transplanted pancreas exocrine via enteric drainage and side-to-side anastomosis between donor pancreaticoduodenum and recipient jejunum . Pancreatoduodenal anastomotic leakage occurred at 12 days post-operation .During re-operation ,Roux-en-Y anastomosis was established between donor pancreaticoduodenum and recipient jejunum .And the relevant domestic and foreign literatures were searched .Results The follow-up time was 3 month after a second operation .Recipient pancreas and kidney transplantation survived well . There was no onset of enteric leakage .The incidence of anastomotic leakage varies greatly between different transplantation centers both at home and abroad .The incidence ranged from 3 .6% to 11 .3% .And the risk of pancreatic loss was as high as 54 .6% .Conclusions As a severe postoperative complication ,anastomotic fistula after SPK may cuase abdominal infection . Even after reparing enteric fistula , the risk of leakage remains high . Roux-en-Y anastomosis is other therapeutic option .

14.
Chinese Critical Care Medicine ; (12): 539-544, 2019.
Article in Chinese | WPRIM | ID: wpr-754006

ABSTRACT

Objective To investigate the benefits and risks of stress ulcer prevention (SUP) using proton pump inhibitors (PPI) for critical patients. Methods The clinical data of adult critically ill patients admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients who were treated with PPI for SUP within the first 48 hours after ICU admission were enrolled in the SUP group. Those who not received PPI were enrolled in the control group. A one-to-one propensity score matching (PSM) was performed to control for potential biases. The gender, age, underlying diseases, main diagnosis of ICU, drug use before ICU admission, sequential organ failure score (SOFA) at ICU admission, risk factors of stress ulcer (SU) and PPI usage were recorded. The end point was the incidence of gastrointestinal bleeding, hospital acquired pneumonia, Clostridium difficile infection and 30-day mortality. Kaplan-Meier survival curves were plotted, and survival analysis was performed using the log-rank test. Results 1 972 critical patients (788 in the SUP group and 1 184 in the control group) were enrolled, and each group enrolled 358 patients after PSM. Prior to PSM, compared with the control group, the SUP group had older patients, more underlying diseases, higher proportion of acute coronary syndrome (ACS), acute cerebrovascular disease, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and poisoning in main diagnosis of ICU, more serious illness, and more risk factors of SU, indicating that ICU physicians were more likely to prescribe SUP for these patients. The incidence of gastrointestinal bleeding in the SUP group was significantly lower than that in the control group [1.8% (14/788) vs. 3.7% (44/1 184), P < 0.05], while the incidence of hospital acquired pneumonia and 30-day mortality were significantly higher than those in the control group [6.6% (52/788) vs. 3.5% (42/1 184), 17.9% (141/788) vs. 13.1% (155/1 184), both P < 0.01]. There was no significant difference in the incidence of Clostridium difficile infection between the SUP group and the control group [2.9% (23/788) vs. 1.8% (21/1 184), P >0.05]. After the propensity scores for age, underlying diseases, severity of illness and SU risk factors were matched, there was no significant difference in the incidence of gastrointestinal bleeding or 30-day mortality between the SUP group and the control group [2.2% (8/358) vs. 3.4% (12/358), 15.9% (57/358) vs. 13.7% (49/358), both P > 0.05], but the incidence of hospital acquired pneumonia in the SUP group was still significantly higher than that in the control group [6.7% (24/358) vs. 3.1% (11/358), P < 0.05]. Kaplan-Meier survival curve analysis showed that the 30-day cumulative survival rate of the SUP group was significantly lower than that of the control group before the PSM (log-rank test: χ2 = 9.224, P = 0.002). There was no significant difference in the 30-day cumulative survival rate between the two groups after PSM (log-rank test: χ2 = 0.773, P = 0.379). Conclusion For critical patients, the use of PPI for SUP could not significantly reduce the incidence of gastrointestinal bleeding and mortality, but increase the risk of hospital acquired pneumonia.

15.
Article in Chinese | WPRIM | ID: wpr-752723

ABSTRACT

Objective To understand the experience and needs of elderly specialist nurses during the period of specialist training, and to provide reference and basis for the establishment of a more perfect training plan for elderly specialist nurses. Methods A one-to-one in-depth interview was conducted among 5 students in the third training course of the Beijing Nursing Society with the method of phenomenological research. Colaizzi undefineds seven-step data method of phenomenology was used to analyze the results. Results Five topics were abstracted from the experience of training aged specialist nurses, including stress, safety awareness, harvest and growth, professional pride, teaching teachersundefined views and suggestions on scientific research. Conclusions The curriculum setup of elderly specialist nurses needs to be optimized. It is necessary to strengthen the training of scientific research, optimize the teachersundefined strength and perfect the training means, and the managers should formulate the specialty and standardization of the elderly nursing as soon as possible. To provide the necessary support for the training of elderly specialist nurses.

16.
Article in Chinese | WPRIM | ID: wpr-803293

ABSTRACT

Objective@#To understand the experience and needs of elderly specialist nurses during the period of specialist training, and to provide reference and basis for the establishment of a more perfect training plan for elderly specialist nurses.@*Methods@#A one-to-one in-depth interview was conducted among 5 students in the third training course of the Beijing Nursing Society with the method of phenomenological research. Colaizzi undefineds seven-step data method of phenomenology was used to analyze the results.@*Results@#Five topics were abstracted from the experience of training aged specialist nurses, including stress, safety awareness, harvest and growth, professional pride, teaching teachersundefined views and suggestions on scientific research.@*Conclusions@#The curriculum setup of elderly specialist nurses needs to be optimized. It is necessary to strengthen the training of scientific research, optimize the teachersundefined strength and perfect the training means, and the managers should formulate the specialty and standardization of the elderly nursing as soon as possible. To provide the necessary support for the training of elderly specialist nurses.

17.
Chinese Journal of Orthopaedics ; (12): 1239-1248, 2019.
Article in Chinese | WPRIM | ID: wpr-803101

ABSTRACT

Objective@#To evaluate the clinical and radiological outcomes,and the complications of staged minimally invasive surgery for adult degenerative scoliosis, comparing with that of the conventional open surgery.@*Methods@#From Jun 2013 to Jun 2017, a total of 42 cases of degenerative scoliosis underwent surgical treatment. Among which, 23 cases underwent staged minimally invasive surgery(MIS group) and 19 cases underwent posterior open surgery(open group). The intra-operative bleeding, and operation time were recorded.The clinical outcomes were assessed using the Oswestry Disability Index (ODI), Visual Analogue Scale (VAS) for low back pain and leg pain.The radiological outcome was evaluated with Cobb angles and sagittal balance parameters (Sagittal Vertical Axis (SVA), Pelvic Incidence (PI)-Lumbar Lordosis (LL), Pelvic Tilt (PT)). The occurrence of complications was recorded.@*Results@#The baseline demographic features of both groups (gender, age, medical comorbidity, etc.) were similar.The mean follow-up period for both groups was more than 2 years.The intraoperative bleeding in the MIS group 405.7±144.8 ml was significantly lower than that in the open group (2 005.3±728.4 ml, t=10.31, P<0.001); The total operation time 414.3±63.0 min of MIS group was significantly longer than that of the open group (304.2±51.8 min, t=6.10, P<0.001), but the operating time of each stage was shorter than the open group. The VAS score for back pain and leg pain,the ODI scores were significantly improved after surgery for both group, there was no significant difference between the two groups, but the low back pain and function in MIS group were better than the open group. The parameters of the coronal and sagittal deformity were significantly improved in both groups, correction of coronal deformity in MIS groupwassignificantly superior to the open group (F=12.02, P=0.001), there was no significant difference in sagittal balance correction between the two groups. The overall complication rate (63.2%) was slightly higher in the open group than in the MIS group (34.8%) without significant difference(χ2=3.36, P=0.07). The incidence of major complications in the open group was significantly higher than that in the MIS group (P=0.014).@*Conclusion@#Staged minimally invasive surgery can significantly relieve the patient's pain, improve functionand the coronal and sagittal balance of the patient, the early clinical and radiological outcomes were comparable to the open surgery; Minimally invasive surgery may significantly reduce the amount of bleeding and major complications. Minimally invasive surgery is safe and effective for carefully selected patients with degenerative scoliosis.However, the long-term outcomes of minimally invasive surgery remains to be followed up.

18.
Article in Chinese | WPRIM | ID: wpr-811731

ABSTRACT

@#PAK1 plays an important role in the development of tumors. It is of great significance to screen and develop new PAK1 inhibitors as targeted drugs for cancer treatment. The traditional PAK1 inhibitor screening method has the problems of high cost and low efficiency. Computer virtual screening can reduce the cost of finding active lead compounds and improve the screening efficiency. In this study, a kind of PAK1 candidate compound was screened by computer assisted virtual screening combined with Z′lyteTM high flux kinase screen. In vitro enzyme activity screening showed that compound 18(K788)had good PAK1 inhibitory activity(inhibition rate was 42. 7%). Furtherly by MTT detection, it was found that K788 had significant PAK1 positive tumor killing activity, which was even better than the positive drug IPA-3. Flow cytometry and Western Blot showed that K788 could activate caspase apoptosis pathway and induce apoptosis of colon cancer cell DLD-1 by inhibiting PAK1 expression and activation. K788 has great potential for clinical development and application, and can be used as a PAK1 target for further research.

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Article in Chinese | WPRIM | ID: wpr-712654

ABSTRACT

Objective:To observe the effect of acupuncture in regulating ubiquitin-proteasome pathway (UPP),and discuss the action of acupuncture in intervening heroin-induced brain damage.Methods:Thirty male Sprague-Dawley (SD) rats were divided into a control group,a model group and an acupuncture group by using the random number table.Rats in the model and acupuncture groups received intramuscular heroin injection for successive 8 d at a progressively increased dose.Afterwards,the injection was suspended for 5 d for withdrawal.The heroin relapse rat model was established by repeating the drug addiction and withdrawal process for 3 times.The control group followed the step of the model establishment,but was given intramuscular injection of normal saline at the stage of addiction and no intervention at the stage of withdrawal;the model group was given intramuscular heroin injection at a progressively increased dose at the addiction stage and no intervention at the withdrawal stage;the acupuncture group was dealt in the same way as the model group at the addiction stage,but received acupuncture at Baihui (GV 20) and Dazhui (GV 14) at the withdrawal stage,with the needles retained for 30 min each time,1 session a day,for successive 5 d.On the 39th day,brain tissues were extracted from the hippocampus and ventral tegmental area (VTA) of the three groups of rats.The apoptosis of brain nerve cells was detected by using terminal deoxynucleotidyl transferase-mediated nick and labeling (TUNEL).The mRNA and protein expressions of ubiquitin (Ub),ubiquitin protein ligase (E3) and 26S were examined by immunohistochemistry and quantitative real-time polymerase chain reaction (RT-qPCR).Results:Compared with the model group,rat's hippocampus and VTA in the acupuncture group showed significantly fewer cells positively stained by TUNEL staining (P<0.01),and its mRNA and protein expressions of Ub,E3,26S were significantly lower (P<0.01).Conclusion:Reducing nerve cell apoptosis and regulating the mRNA and protein expressions of Ub,E3 and 26S in rat's hippocampus and VTA are possibly one of the action mechanisms of acupuncture in intervening heroin-induced brain damage.

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Chinese Journal of Urology ; (12): 814-818, 2018.
Article in Chinese | WPRIM | ID: wpr-709602

ABSTRACT

Objective To approach the spine MRI features and its possibility of etiology for refractory lower urinary tract symptoms(LUTS) in female patients.Methods We conducted prospectively a cross sectional description study of female patients with refractory LUTS during January 16 through March 27 in 2017 based on a urologist's outpatient work.The including criteria were adult female patients with refractory LUTS which defined as having LUTS more than three months and having poor response to behavior therapy and medication treatment.The excluding criteria were patients having evidence of infection,tumor,stone in urinary tract,any central nerve system diseases,or any other diseases may potentially producing LUTS.Data collected included patients demographic information,main complains,present disease features,disease history,physical examination,urine routine,urodynamic study and spine MRI.The characteristics of clinical manifestation,urodynamic study and spine MRI were analyzed.Results During the time span of study,totally 70 cases had been diagnosed as having refractory LUTS and had qualified data of clinical recordings,urodynamic study and spine MRI.Among these 70 cases,63 (90.9%) had storage phase symptoms,11 (15.7%) had voiding phase symptoms,8 (11.4%) had postmicturition symptoms,12 (17.1%) also had disorders in defecating,45 (64.3%) had pain in lower abdomen or pelvic region.69 cases (98.6%) had urodynamic disorders,33 (47.1%) had oversensitivity of bladder,12 (17.1%) had smaller bladder volume,16(22.9%) had detrusor overactivity,15 (21.4%) had bladder outlet obstruction,39(55.7%) had detrusor underactivity.69 cases(98.6%)had spine MRI abnormalities,54(77.1%) had sacral nerve lesions,49 (70.0%) had cervical lesions,48 (68.6%) had lumbar lesions,4 had thorathic lesions.Conclusions The present study revealed extraordinary high prevalence of abnormality in urodynamic parameters and spine MRI in female patients with refractory LUTS,which implies possibility that the refractory LUTS are caused by lesions in spinal nerve system.

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