Objective To investigate the awareness,willingness,motivation,and influencing factors of outpatients for participating drug clinical trials,and provide references for decision-making of drug clinical trials.Methods An amnonymous survey was conducted in the departments of internal medicine,surgery,gynecology,and obstetrics of a randomly selected tertiary referral center,and the results were statistically analyzed.Results A total of 1 067 available questionnaires were received.The total awareness rate of clinical trials was 31.02％,which was closely correlated with age and the degree of education.40.86％ of respondents were willing to participate in drug clinical trials.And 55.28％ of them chose yes because of the willingness to contribute to the development of medical science.People having cognition on clinical trials had more willingness to participate in drug(OR:1.361,95 ％ CI:1.042-1.777).59.14％ of the respondents refused to participate in drug clinical trials,68.62％ of whom refusing to participate mainly worried about the safety of drugs.57.37％ of the respondents comfirmed that they might change their idea if experts were involved.41.33％ were willing to accept training about clinical trials.Conclusion Investigators'overall cognition on clinical trials is closely correlated with the willingness to participate in drug clinical trials.There should propagandize drug clinical trials to make sure the improvement of drug clinical trial progress.

In this paper, fourteen new L-proline derivatives were designed and synthesized, and their acetlcholinesterase (AChE) inhibitory activities were also investigated in vitro. New L-proline derivatives were prepared from substituted 2-bromo-1-acetophenones through four-step reaction; and their bioactivities as AChE inhibitors were measured by Ellman spectrophotometry. The results showed that the target compounds had a certain AChE inhibitory activity to in vitro. The bioactivity of compound 8b was the best of them, and its IC50 value was 5.45 µmol.L-1, which was better than that of rivastigmine. So the acetylcholinesterase inhibitory activities of new L-proline derivatives were worth to be further studied.
Acetylcholinesterase ; Cholinesterase Inhibitors ; chemical synthesis ; chemistry ; Drug Design ; Proline ; analogs & derivatives ; Rivastigmine ; chemistry ; Structure-Activity Relationship

Objective To investigate the value of three-dimensional speckle tracking imaging (3D-STI) in assessment of left ventricular (LV) strains. Methods Thirty healthy young adults examined by two-dimensional speckle tracking imaging (2D-STI) and 3D-STI. And the results of LV measurements were compared, which included mean peak systolic longitudinal strains, radial strains and circumferential strains. Also, the time consumption of these two methods was compared. Results The time needed for 3D-STI in acquisition and analysis of the images were (309.3±23.4)s, (305.5±11.2)s, while the time for 2D-STI were (490.6±14.4)s, (1261.4±39.9)s. The differences were signiifcant(t=-21.81, 69.94, both P<0.01). The global mean peak systolic radial strains was (48.59±7.68)%by 3D-STI and (33.25±7.27)%by 2D-STI. The difference was signiifcant(t=9.16, P<0.01). The global mean peak systolic longitudinal and circumferential strains were (-17.66±3.14)%, (-17.13±2.29)% by 3D-STI and (-21.35±2.46)%, (-21.97±3.84)% by 2D-STI. The differences were signiifcant(t=5.33, 5.99, both P < 0.01). The 3D-STI strains were different at different levels of LV. The longitudinal, circumferential and radial 3D-STI strains were largest at middle levels. However, 2D-STI strains didn′ t show such trend. Peak strains measured by 3D-STI and 2D-STI showed high inter-observer and intra-observer agreement in Bland-Altman chart. Conclusion 3D-STI is a novel, convenient and reproducible method to evaluate the strains of LV.

The Wnt signaling exists in every kinds of species and regulates a variety of biological processes including cell fate, proliferation and function, immunity, stress, apoptosis and so on. During the researching, Wnt signaling also plays an important role in chondrocyte differentiation and maturation. So it has been the new spot in pathogenesis of osteoarthritis study.
Animals ; Chondrocytes ; metabolism ; pathology ; Humans ; Osteoarthritis ; metabolism ; pathology ; Signal Transduction ; Wnt Proteins ; metabolism

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
Antifungal Agents ; pharmacology ; Berberine ; pharmacology ; Candida albicans ; drug effects ; Drug Resistance, Fungal ; Drug Synergism ; Fluconazole ; pharmacology ; Isoquinolines ; pharmacology ; Microbial Sensitivity Tests

Objective To explore the feasibility of open visiting among mothers' of very-low-birth-weight(VLBW) infants and observe effects.Methods Totally 74 eligible VLBW infants were recruited,those who were visited and cared daily by mothers were assigned into the experimental group(n=36) and those who were not visited by mothers were assigned into the control group(n=38).The experimental group received open visiting as well as individualized developmental nursing care,and the control group only received individualized developmental nursing care.Relevant regulations and procedures were designed,and clinical pathways of mothers' involvement in nursing care were developed and implemented.Incidence of infection,time to reach full oral feeding,weight gaining during hospitalization,rate of breast-feeding during hospitalization and 30 days after discharge,hospitalization time and rate of readmission 30 days after discharge were recorded and compared.Results There was no significant difference in incidence of infection between two groups (P＞0.05).Time to reach full oral feeding in the experimental group was earlier than that of the control group,weight gaining during hospitalization in the experimental group was faster than that of the control group,rate of breast-feeding 30 days after discharge was higher in the experimental group,and the differences were significant (P＜0.05).Hospitalization time in the experimental group was shorter than that of the control group,rate of readmission 30 days after discharge in the experimental group was lower,and the differences were significant (P＜0.05).Conclusion Mother's open visiting for VLBW infants in NICU does not increase the incidence of infection,but can shorten time to reach full oral feeding,promote weight gaining,increase rate of breast-feeding 30 days after discharge,reduce hospitalization time,and decrease rate of readmission 30 days after discharge.

Objective To study the correlation between preoperative frailty and short-term prognosis after abdominal surgery, and to explore its predictive value. Methods A total of 156 elderly patients undergoing abdominal surgery from July 2017 to December 2017 in Tianjin Third Center Hospital were prospectively observed and classified into non-frail group, pre-frail group and frail group according to the Fried's frailty phenotype before surgery. The postoperative hospital stay and incidence of adverse outcomes were compared among the three groups, and the effect of frailty on the risk prediction model of the American Society of Anesthesiology (ASA) was analyzed. Results The postoperative hospital stay and the incidence of adverse outcomes in the three groups were statistically significant (P<0.05). Negative binomial regression analysis found that preoperative frailty was associated with prolonged postoperative hospital stay (pre-frail incidence rate ratio was 1.428 (95% CI : 1.250-1.974);frail incidence rate ratio was 3.692 (95% CI : 1.282-4.230) .Logistic regression analysis found that preoperative frailty was associated with an increased risk of postoperative adverse outcomes (pre-frail: OR=2.303(95% CI : 1.810-4.127); frail: OR=3.512 (95% CI : 2.054-5.689)). Frailty increased the diagnostic value of the ASA risk prediction model (Z=3.718, P<0.01). Conclusions Frailty of elderly patients is an important predictor of short-term prognosis of abdominal surgery, and it increases the diagnostic value of ASA risk model. The preoperative frailty assessment of elderly patients undergoing abdominal surgery is helpful for preoperative clinical decision-making and prognosis evaluation.

Objective:To evaluate the role of P2X 7 receptor in microglia in the medial prefrontal cortex (mPFC) in neuropathic pain (NP) and the relationship with autophagy in rats. Methods:Sixty-four healthy SPF male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-250 g, were divided into 4 groups ( n=16 each) using a random number table method: sham operation group (S group), NP group, sham operation+ P2X 7 receptor blocking group (SP group), and NP+ P2X 7 receptor blocking group (NP+ P group). The NP model was established by ligation of the sciatic nerve.Fourteen days later a cannula was placed in the mPFC with a brain stereotactic instrument, P2X 7 receptor blocker A-740003 0.5 μg/0.5 μl was injected into bilateral mPFC for 3 consecutive days starting from the 14th day in SP and NP+ P groups, and DMSO 0.5 μl was injected instead of A-740003 in S and NP groups.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 3, 7 and 10 days after establishing the model and 14, 15 and 16 days after administration.Then the rats were sacrificed, and the mPFC was removed for determination of the expression of P2X 7 receptor and mRNA and autophagy-related proteins Beclin1 and LC3Ⅱ/Ⅰ (by quantitative real-time polymerase chain reaction or by Western blot) and co-expression of P2X 7R and microglia (by immunofluorescence) and the number of autophagosomes in mPFC (with a transmission electron microscope). Results:Compared with group S, MWT was significantly decreased, and TWL was shortened at 3, 7 and 10 days after establishing the model, the expression of P2X 7 receptor and mRNA, Beclin1 and LC3Ⅱ/Ⅰ was up-regulated at 30 min after administration on 16 days after establishing the model, and the number of cells co-expressing P2X 7 receptor and IBA-1 and the number of autophagosomes were increased in NP and NP+ P groups ( P<0.05), and no significant change was found in the indexes mentioned above in group SP ( P>0.05). Compared with group NP, MWT was significantly increased, and TWL was prolonged at 30 min after administration on 14, 15 and 16 days after establishing the model, the expression of P2X 7 receptor and mRNA, Beclin1 and LC3Ⅱ/Ⅰ was down-regulated, and the number of cells co-expressing P2X 7 receptor and Iba-1 and the number of autophagosome were decreased in group NP+ P ( P<0.05). Conclusion:Up-regulation of P2X 7 receptor expression in microglia in mPFC is involved in the process of NP in rats, which is associated with the promotion of autophagy.

Objective:To evaluate the relationship between thalamocortical glutamate and neuronal activity in mice with neuropathic pain-induced sleep disorders.Methods:SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 15-25 g, were divided into 2 groups ( n=14 each) using a random number table method: sham operation group (Sham group) and neuropathic pain group (CCI group). Neuropathic pain was induced by chronic constrictive injury (CCI). The animals were anesthetized with intraperitoneal 10% chloral hydrate 3 ml/kg.The right sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.The mechanical paw withdrawal threshold and thermal paw withdrawal latency on the operated side were measured at 1 day before CCI (T 0) and 3, 5, 7, 14 and 21 days after CCI (T 1-5). Electroencephalogram recording electrodes were stereotaxically implanted in visual cortex at T 3, and electroencephalogram were monitored for 6 h, the percentages of non-rapid eye movement, rapid eye movement and wakefulness in the total time were calculated.Microwire electrodes were implanted epidurally over the ventral posterior (VP) nucleus of the thalamus and primary somatosensory cortex (S1) using a brain stereotaxic apparatus at T 3, and the data acquisition system was used to record field potentials at T 4, the percentage of power of each wave was calculated, and the coherence of the field potentials of VP and S1 was simultaneously evaluated.The mice were sacrificed at T 4, brain tissues were collected, and proton nuclear magnetic resonance spectroscopy was used to determine the level of neurotransmitter in the thalamus and cortex. Results:Compared with group Sham, the mechanical paw withdrawal threshold was significantly decreased and thermal paw withdrawal latency was shortened at T 1-5, the percentage of non-rapid eye movement time was decreased, the percentage of wakefulness time was increased, the percentage of δ wave power in the VP area was decreased, the percentage of δ wave power in the VP and S1 areas was increased, and the coherence of the field potentials of VP-S1 was increased in the frequency range of δ wave (1-4 Hz) and α wave (8-14 Hz), and the levels of glutamate, glutamine and glutamate-glutamine in the thalamus and cortex were increased in group CCI ( P<0.05). Conclusions:Neuropathic pain-induced sleep disturbance is related to increased thalamocortical glutamate levels, resulting in changes in the electrical activity of thalamocortical neurons of mice.

This study was aimed to investigate the clinical value of multiplex nested reverse transcription PCR (RT-PCR) in detecting MLL-related fusion genes in myelodysplastic syndrome (MDS). Ten MLL-related genes (dupMLL, MLL-ELL, MLL-ENL, MLL-AF6, MLL-AF9, MLL-AF10, MLL-AF17, MLL-CBP, MLL-AF1P, MLL-AF1Q) in 221 MDS cases were detected by multiplex nested RT-PCR. The results indicated that 20 patients were detected with positive result among 221 patients and the positive rate was 9.05%. The number of the positive cases and positive rates of the above mentioned 10 fusion genes were in order: 7 (3.16%), 2 (0.9%), 1 (0.45%), 1 (0.45%), 2 (0.9%), 2 (0.9%), 1 (0.45%), 2 (0.9%), 1 (0.45%), 1 (10.45%). It is concluded that the multiplex nested RT-PCR has been confirmed to be able to detect 10 fusion genes in MDS patients, which can provide important evidences for assessing diagnosis and treatment, and give related necessary information about minimal residual disease and its prognosis.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Karyotyping ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Oncogene Proteins, Fusion ; genetics ; Polymerase Chain Reaction ; methods ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Young Adult