Two Hofmann-Martius-like rearrangement products generated in the production of duloxetine hydrochloride were studied. The structures and generation mechanism of the two Hofmann-Martius rearrangement products were analyzed by LC-MS and NMR. The results showed that under the acidic conditions, the naphthol ether bond of duloxetine would break down and the intermediates of naphthol and the alkyl thiophene cation was generated; the two Hofmann-Martius-like rearrangement products were proven to be a pair of isomers produced by nucleophilic substitution between the naphthol intermediate state and the alkyl thiophene cation intermediate state at the ortho or the para position, respectively. The production of two isomers was related to the strong acidic and protic solvent environment. Therefore, in the salting process of duloxetine hydrochloride, the pH value should be controlled in the range of 3-7 and temperature should be maintained below 50 °C, as well as the nonprotic solvent acetone is chosen to avoid generation of the two isomers.

Ultra-rapid cooling and rewarming rate is a critical technical approach to achieve ice-free cells during the freezing and melting process. A set of ultra-rapid solid surface freeze-thaw visualization system was developed based on a sapphire flim, and experiments on droplet freeze-thaw were carried out under different cryoprotectant components, volumes and laser energies. The results showed that the cooling rate of 1 μL mixed cryoprotectant [1.5 mol/L propylene glycol (PG) + 1.5 mol/L ethylene glycol (EG) + 0.5 mol/L trehalose (TRE)] could be 9.2×10 ³ °C/min. The volume range of 1-8 μL droplets could be vitrified. After comparing the proportions of multiple cryoprotectants, the combination of equal proportion mixed permeability protectant and trehalose had the best vitrification freezing effect and more uniform crystallization characteristics. During the rewarming operation, the heating curve of glassy droplets containing gold nanoparticles was measured for the first time under the action of 400-1 200 W laser power, and the rewarming rate was up to the order of 10 ⁶ °C/min. According to the droplet images of different power rewarming processes, the laser power range for ice-free rewarming with micron-level resolution was clarified to be 1 400-1 600 W. The work of this paper simultaneously realizes the ultra-high-speed temperature ramp-up, transient visual observation and temperature measurement of droplets, providing technical means for judging the ice free droplets during the freeze-thaw process. It is conducive to promoting the development of ultra-rapid freeze-thaw technology for biological cells and tissues.
Freezing ; Vitrification ; Cryopreservation/methods* ; Trehalose ; Gold ; Rewarming ; Metal Nanoparticles ; Cryoprotective Agents ; Lasers

Objective:To find clues potentially valuable for fighting against infection with human respiratory syncytial virus (HRSV), the differentially expressed genes in HEp-2 cells infected with HRSV were analyzed.Methods:Gene expression profiles of HEp-2 cells infected with HRSV were collected from the public gene expression omnibus (GEO) database. The differentially expressed genes following HRSV infection at each time point of 4, 8, 12, and 15 hours were found using R language. The differentially expressed genes were analyzed by gene ontology (GO), KEGG pathway and protein-protein interaction network (PPI). Genes with relatively high protein interaction in PPI were randomly selected for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) verification at the transcription level from HEp-2 cells after HRSV infection at 4 hours.Results:A total of 101 differentially expressed genes were determined, including 92 upregulated genes and 9 downregulated genes. Function enrichment analysis revealed that HRSV infection could cause significant changes in multiple signaling pathways such as immune response in HEp-2 cells. The results of qRT-PCR were consistent with the trend of transcriptome data.Conclusions:The differentially expressed genes and the change of signaling pathways in HRSV-infected HEp-2 cells is of great significance to the studies on pathogenic mechanism and prevention of HRSV infection.

Objective: To evaluate the effect of tumor shape and location on pulmonary dose-volume parameters by intensity-modulated radiation therapy (IMRT) in patients with non-small cell lung cancer (NSCLC), aiming to provide a reference basis for establishing limits of the pulmonary dose-volume parameters during IMRT. Methods: Clinical data of 208 NSCLC patients undergoing radical IMRT from June 2009 to June 2016 were retrospectively analyzed. According to the tumor shape and location, 208 cases were divided into the vertical bar group (n=127) and the horizontal bar group (n=81), the superior lung group (n=103) and the inferior lung group (n=105). Regression model curve was used to evaluate the effect of tumor shape and location upon the common pulmonary dose-volume parameters(V₅, V₂₀, MLD, AVS₅ and AVS₂₀). Results: In all groups, the fitting curves of V₅, V₂₀ and MLD were manifested in the quadratic equation pattern, and AVS₅ and AVS₂₀ in the logarithmic equation manner. In the vertical bar group, the V₅(P=0.015), V₂₀(P=0.047) and MLD (P=0.012) were significantly higher, whereas the AVS₅(P=0.044) was significantly lower compared with those in the horizontal bar group. No statistical significance was observed in AVS₂₀ between two groups (P=0.490). The tumor location exerted significant effect upon V₅ alone (P=0.009). Conclusions When the tumors presents in the vertical bar shape, the limits of the common lung dose-volume parameters are likely to exceed those of tumors in the vertical bar shape. Lung tumors located in the inferior lobe exerts a more significant effect upon the low-dose region volume compared with the tumors in the superior lobe.

Objective To study the difference of the constructed doses between electronic portal imaging device (EPID) and dynalogs files of linac for in vivo phantom dosimetry.Methods Twelve pelvic patients treated with volumetric modulated arc therapy (VMAT) plans were selected and the information of each plan was copied to theCheese phantom to recalculate the doses before delivered on Varian RapidArc Linac.TheCheese phantom was placed on the isocenter and the electronic portal image (EPI) formed by the EPID was sent to EPIgray software to reconstruct the actual delivered doses.Meanwhile,dynalogs files were respectively imported to the Mobius software to reconstruct the actual delivered doses too.The point dose in the center of each VMAT plan (the center of the effective sensitive volume of ionization chamber) was measured by the A1SL ionization chamber.At the same time,the dose of sensitive volume of ionization chamber from treatment planning systcm (TPS) was recorded.Results The relative deviation between the dose from TPS and the measurement results by the ionization chamber was 1.13％.The difference between the reconstructed doses of EPID-based or the dynalogs file-based with the measurement results by the ionization chamber was not statistically significant (P ＞ 0.05).Conclusions The two methods of dose reconstruction can provide reference for in vivo dosimetry of VMAT.

Objective: The purpose of the present study was to investigate the effects of noise competition on word perception in normal hearing (NH) children and children with cochlear implantation (CI). Methods: To estimate the contribution of noise competition on speech perception, word perception in speech-shaped noise(SSN)and 4-talker babble noise(BN) with Mandarin Lexical Neighborhood Test were performed in 80 NH children and 89 children with CI. Corrected perception percentages were acquired in each group. Results: Both signal to noise ratio (SNR) and noise type influenced the word perception. In NH group, corrected percentages of disyllabic word perception in SSN were 24.2%, 55.9%, 77.1%, 85.1% and 88.9% at -8, -4, 0, 4 and 8 dB SNR, corresponding corrected percentages of monosyllabic word were 13.9%, 39.5%, 60.1%, 68.8% and 80.1%, respectively. In BN noise, corrected percentages of disyllabic word were 2.4%, 24.3%, 55.6%, 74.3% and 86.2%, corresponding monosyllabic word were 2.3%, 20.8%, 47.2%, 61.1% and 74.8%, respectively. In CI group, corrected percentages of dissyllabic word in SSN and BN at 10 dB SNR were 65.5% and 58.1%, respectively. Corresponding monosyllabic word were 49.0% and 41.0%. For SNR=5 dB, corrected percentages of disyllabic word in SSN and BN were 50.0% and 38.1%, corresponding corrected percentages of monosyllabic word were 40.8% and 25.1%, respectively. Analysis indicated that the masking effect were significantly higher in BN compared with SSN. Conclusions Noise competition influence word perception performance significantly. In specific, the influence of noise on word perception is bigger in children with CI than in NH children. The masking effect is higher in BN noise when compared with SSN.

Objective To observe the effect of acupuncture on the expression of nitricoxide synthase (NOS) in gastrointestinal tissues after operation for incomplete intestinal obstruction in rats, and to explore the mechanism of acupuncture in promoting the recovery of gastrointestinal motility. Methods Forty Sprague-Dawley (SD) rats were randomized into treatment group 1, treatment group 2, model group 1, model group 2, and a normal control group, 8 rats in each group. The incomplete intestinal obstruction models were developed by using single ligation method in treatment groups and model groups. Afterwards, the treatment groups were intervened by acupuncture at Zusanli (ST 36) and Yanglingquan (GB 34), and rats in treatment group 1 and 2 were respectively dissected after 1-day and 2-day treatment. The rats in model group 1 and 2 were respectively dissected 1 d and 2 d after modeling. The morphological observation was performed on rat’s intestinal tissues, and the average diameter of the upper part of the obstructed intestine and the expression of NOS in gastrointestinal tissues were compared. Results The average ileocecal diameter after modeling was significantly different from that in the normal control group (P<0.05). There was a significant difference in comparing the ileocecal diameter between model group 1 and 2 (P<0.05). The ileocecal diameter in treatment group 1 was significantly different from that in treatment group 2 and model groups (P<0.05). The ileocecal diameter in treatment group 2 was insignificantly different from that in the normal control group (P>0.05). The NOS content in model groups was significantly different from that in the normal group (P<0.05). The NOS content in treatment group 1 was markedly different from that in model groups and treatment group 2 (P<0.05) after intervention. There were no significant inter-group differences in comparing NOS content (P>0.05). Conclusions Acupuncture can promote the recovery of gastrointestinal motility by regulating intestinal NOS content in rats after operation for incomplete intestinal obstruction.

ObjectiveTo explore the clinic symptom and the characteristics of video,tightly close,intracranial electroencephalogram (EEG) of patients with central region diastematia epilepsy. Methods Retrospective analysis of 9 patients with central region diastematia epilepsy admitted from June,2007 to August,2009.The characteristics of all patients' seizure symptom and EEG manifestation were analyzed using patients' medical history,video and EEG records.ResultsPatients with central region diastematia epilepsy had relatively long sezure history.The duration of seizure was commonly short,with frequent episode and no obvious intelligence impairment.The seizure was often accompanied with the hyperkinesia in the lower limbs.Scalp EEG showed discharges with low amplitude waves in the mean line area.The superhigh amplitude and regular rhythm slow sharp wave could be found in the diastematia cortex EEG.All patients had an Engel Class Ⅰ outcome after surgery.ConclusionThe seizure symptoms are characteristic in the patients with central region diastematia epilepsy,and some special manifestations can be found in different phase,wave amplitude,rhythm,lead array.

To explore how to create and optimize a promotion index system of medical quality evaluation, this article focuses on the hospital visiting process from patients, using analyzing collected those index system from couples of Grade Ⅲ hospitals in Beijing, and combining the results of literal study, field study and specialist consult, according to the different situation of general hospitals and specially hospitals, with the spirit of "maintaining the patients benefits, safeguarding the patients safety,and enhancing the medical quality", introduces the framework of the promotion index system, the rules to select the indicator, and so on, and discusses several problerns related to creating the index system.

ObjectiveUsing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to evaluate the hemodynamic perfusion characteristics of bone marrow infiltration in patients with acute leukemia (AL). MethodsForty-seven patients with AL received coronal pelvic T1WI DCE-MRI with fast low angle shot (FLASH) sequence. Among them, 25 were initial onset untreated (IOU) patients, 22 were treated AL patients, including 14 with complete remission (CR) and 8 with non-remission ( NR). The hemodynamic perfusion parameters including maximum percentage of enhancement ( Emax ) and slope were determined based on enhancement-time curves ( ETCs ) of iliac and lumbar vertebra. The proportion of marrow myeloblasts was recorded.For all patients, quantitative perfusion parameters of bone marrow infiltration in ilium were compared with those in lumbar. The values of Emax and ES were compared among IOU,CR and NR patients.Correlations between perfusion parameters and histopathological results were assessed. ResultsIn all the 47 patients, the Emax values of bilateral iliac bone marrow ( 15.70 ± 7.06)were slightly higher than that of lumbar bone marrow ( 11. 28 ± 5.52 ), and the difference was statistically significant (P ＜0. 01 ).There was no significant difference in the slop value between bilateral iliac bone marrow (0. 82 ± 0. 12 ) and lumbar bone marrow (0. 80 ± 0. 09 ) ( P ＞ 0. 05 ). In the 25 untreated patients,the Emax and slop values were 17. 15 ± 5.75 and 0. 98 ± 0. 13, respectively; in the 14 CR patients, they were 8. 76 ±3.93 and 0. 26 ± 0. 04, respectively, and in the 8 NR patients, they were 21.62 ± 6. 50 and 1. 38 ± 0. 02, respectively. There was significant difference in the Emax and slop values among the three groups (P＜0. 05).Compared with IOU and NR patients, both the Emax and slop values decreased significantly in iliac bone marrow of AL patients with CR (P ＜ 0. 05 ). There was no significant difference between IOU and NR patients ( P ＞ 0. 05 ). A significant positive correlation was found between Emax value of iliac bone marrow and the proportion of marrow myeloblasts ( r ＝0. 501 ,P ＜0. 05 ). There was a negative correlation between slop value of iliac bone marrow and the proportion of marrow myeloblasts ( r ＝0. 235 ,P ＞0.05).ConclusionsDCE-MRI can beused for evaluating the hemedynamic characteristics of microcirculation of bone marrow infiltration in patients with AL, which can provide useful information in evaluating prognosis and monitoring therapeutic effect.