A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.
Antidepressive Agents ; chemical synthesis ; chemistry ; Biological Transport ; Drug Design ; Isoindoles ; chemical synthesis ; chemistry ; Serotonin Uptake Inhibitors ; chemical synthesis ; chemistry ; Structure-Activity Relationship

A series of isoindoline derivatives were designed, synthesized, and evaluated for their double inhibitory activities. All of them were new compounds, and their structures were confirmed by 1H NMR and HR-MS. Preliminary in vitro pharmacological tests showed that all compounds exhibited 5-HT or NE reuptake inhibition activity. Among the tested compounds, compound I-3 exhibited potent inhibitory activity against 5-HT and NE reuptake in vitro, and exhibited potent antidepressant activity in vivo. These compounds designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well.

Objective To discuss features of angiogenesis in degenerative intervertebral disc and related factors.Methods In this case-control study,52 patients undergoing single level posterior lumbar interbody fusion during October 2012 to December 2013 were selected as research objects.Annulus fibrosus,nucleus pulposus and cartilage end plate of responsible level were collected in surgery for frozen section and HE staining.Angiogenesis in the intervertebral disc was identified according to the morphological characteristics of vascular endothelial cells,i.e.typical lumen structure and blue stained nucleus.These intervertebral disc specimens were divided into two groups according to the angiogenesis phenomenon.All specimens with angiogenesis were evaluated by blood micro-vessel density (MVD) counting.Related factors of angiogenesis including gender,age,VAS score,JOA lumbar score,classification of lumbar intervertebral disc degeneration,intervertebral disc calcification rate and classification of intervertebral disc herniation were compared between the two groups.Logistic regression analysis was further conducted on indicators with differences of statistical significance.Results In our group of 52 patients,28 patients had obvious angiogenesis:12 patients in annulus fibrosus,7 patients in cartilage endplate and 9 patients in annulus fibrosus and nucleus pulposus.Angiogenesis rate was 53.8％ (28/52).The mean value of MVD was 12.5±3.1.24 patients did not have obvious angiogenesis.Intervertebral disc calcification rate (75.0％ vs.37.5％),VAS score (6.79±2.06 vs.5.25±2.23) and JOA lumbar score (16.32±3.89 vs.19.08±4.24) were significant differences between two groups (P=0.006,0.013,0.018).Multi-factor regression analysis showed that VAS score (OR=7.248,P=0.011) and intervertebral disc calcification (OR=8.881,P=0.006) were important factors associated with intervertebral disc angiogenesis.JOA lumbar score (OR=3.739,P=0.070) was not associated with intervertebral disc angiogenesis.Conclusion Degeneration of the intervertebral disc is accompanied by angiogenesis.Intervertebral disc calcification and VAS score are important factors associated with angiogenesis in intervertebral disc.

OBJECTIVETo study characteristic presentations of Brucellar spondylitis on MRI in order to improve the diagnostic level.

METHODSFrom October 2009 to December 2010,15 patients with Brucellar spondylitis were evaluated by MRI. They included 11 males and 4 females ranging in age from 31 to 64 (mean 49) years. The major clinical manifestations were different degrees of fatigue,fever and low back pain. All patients underwent MRI and treated with antibiotic drugs.

RESULTSBrucellar spondylitis was mostly localized at the lumbar spine with obvious bony hyperostosis in the vertebral periphery. Most foci were in the edge, anterior and middle parts of the vertebral body, with low signals on T1WI and mixed low signals on T2WI, and high signals on T2 fat suppression, mostly without significant changes in intervertebral space. Paraspinal abscess was observed in 5 cases. Thirteen cases involved the lumbar vertebrae, 1 case involved the thoracic and lumbar vertebrae, and 1 case involved the lumbar and sacral vertebrae. Two vertebrae were affected in 14 cases, and 3 vertebrae were affected in 1 case.

CONCLUSIONMRI can provide imaging clues for diagnosis and differential diagnosis of Brucellar spondylitis, and has a high clinical value.

Adult ; Brucellosis ; diagnosis ; Diagnosis, Differential ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Spondylitis ; diagnosis

AIM To establish a quantitative analysis of multi-components by single-marker (QAMS) method for the simultaneous content determination of five constituents in Roudoukou-8 Powder (Myristicae Semen,Auck landiae Radix,Lignum aquilariae Resinatum,etc.).METHODS The analysis of 75％ methanol extract of this drug was performed on a 30 ℃ thermostatic Apollo C18 column (4.6 mm × 250 mm,5 μm),with the mobile phase comprising of methanol-0.1％ phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 225,254,273,281 nm.With eugenol as an internal standard,the relative correction factors of the other four constituents were calculated,after which the content determination was made.RESULTS Ellagic acid,eugenol,costunolide,dehydroroma lactone,dehydrodiisoeugenol showed good linear relationships within the ranges of 0.227 0-1.135 2,5.272 2-26.361 0,0.540 8-2.704 0,0.530 4-2.652 0,0.059 0-0.299 5 μg (r ＞0.999 0),whose average recoveries (RSDs) were 96.37％ (2.07％),102.19％ (2.78％),101.66％ (1.66％),103.46％ (1.17％),98.25％ (1.98％),respectively.The results obtained by QAMS approximated those obtained by external standard method.CONCLUSION This stable and reliable method can be used for the quality control of Roudoukou-8 Powder.

OBJECTIVE: To study the molecular pathogenesis of SLC26A4 mutations associated with inner ear malformations including large vestibular aqueduct syndrome (LVAS), Mondini dysplasia and inner ear malformations but not accompanied with LVAS. METHOD: DNA sample and clinical material were obtained from 14 sporadic LVAS probands, six Mondini dysplasia probands and seven inner ear malformations excluding IVAS probands. SLC26A4 gene mutation was analyzed by direct sequencing for its 20 coding exons. GJB2 gene and also mt12SrRNA were analyzed by direct sequencing. RESULT: In 14 cases of LVAS, two mutations were detected in 12 patients (85.7%, either homozygous or compound heterozygous mutations), and one mutation was found in two patients (14.3%). In six cases of Mondini dysplasia, two mutations were detected in all of patients (100%). No mutation could be found in the seven cases of other inner ear abnormalities not accompanied with LVAS. No pathogenic mutation was detected in all of these 27 probands in GJB2 gene and mt12SrRNA 1555/1494T. CONCLUSION We have shown that LVAS and Mondini dysplasia closely correlate with SLC26A4 gene. No mutation was detected in seven probands of inner ear malformations not accompanied with LVAS. We should study the molecular pathogenesis of this disease in depth.
Adolescent ; Adult ; Child ; Child, Preschool ; Connexins ; Ear, Inner ; abnormalities ; Exons ; Female ; Genome ; Humans ; Infant ; Male ; Membrane Transport Proteins ; genetics ; Mutation ; Sulfate Transporters ; Syndrome ; Vestibular Aqueduct ; abnormalities ; Young Adult

OBJECTIVETo evaluate the diagnostic value and safety of percutaneous lung biopsy in hematologic patients with lung infection.

METHODS28 cases hematologic patients received CT-guided percutaneous lung biopsy when they developed a fever associated with pulmonary nodules or lumps in CT scan whose clinical diagnosis were unclear during or after chemotherapy. Sample of each lesion were drawn twice. The lung tissue was re-scanned after lung biopsy to check up in order to discover bleeding and pneumothorax. Biopsy tissue was examined by bacteria culture, acid-fast staining and pathology. Pathological examination contained HE staining, acid-fast stain, PAS stain, TB-DNA, methenamine silver and others.

RESULTS28 cases contain 24 males and 4 females. Median age was 40 15 - 77 years old. Blood tests were as follows: 3 cases with HGB > 110 g/L, 9 with HGB 90 - 110 g/L, 12 with HGB 60 - 89 g/L, 4 with HGB < 60 g/L. 8 with WBC > 10×10(9)/L, 6 with WBC (4 - 10)×10(9)/L, 13 with WBC < 4×10(9)/L, 1 with WBC < 2×10(9)/L; 14 with PLT > 100×10(9)/L, 5 with PLT (50 - 100)×10(9)/L, 5 with PLT < 50×10(9)/L, 4 with PLT < 30×10(9)/L. 4 cases had mild extended PT, 3 mild extended APTT, 3 FIB lower than normal. Lung CT scans were as follows: 4 cases with simply lesion in right lung, 4 with simply lesion in left lung, 20 with lesions in bilateral lung. 8 cases were diagnosed as fungal infection, 3 as tuberculosis infection, 1 as lung cancer, 1 as pulmonary infiltration of lymphoma, 1 as pulmonary infiltration of leukemia, and 14 as inflammatory changes with no specific diagnosis. 4 cases came with pneumothorax during lung biopsy, mild to moderate in 3 cases and severe in 1 case. Severe patient turned better after CT-guided suction. 3 cases with mild hemoptysis turned better after treatment.

CONCLUSIONWhen hematopathy patients are with pulmonary nodules or lumps in CT scan whose clinical diagnosis is unclear, CT-guided percutaneous lung biopsy is safe and conducive to early diagnosis and conducive to early rehabilitation of patients if the coagulation function is basically normal and platelet count is not too low.

Adolescent ; Adult ; Aged ; Biopsy ; Female ; Hematologic Diseases ; microbiology ; pathology ; Humans ; Lung ; pathology ; Male ; Middle Aged ; Pneumonia ; diagnosis ; Young Adult

Aged ; C-Reactive Protein ; analysis ; Coronary Angiography ; Coronary Artery Disease ; blood ; diagnostic imaging ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Regression Analysis ; Severity of Illness Index

Objective To investigate the relationship of iatrogenic anemia and diagnosis blood loss for patients in RICU,and the change of the anemia before and after the optimized phlebotomy.Methods A prospective study was performed including 69 patients in RICU who met the inclusion criteria during January 2011 to May 2012.The patients adopted from January 2011 to July 2011 were assigned into control group (n =37) and from August 2011 to May 2012 were assigned into observation group (n =32).The control group received the conventional phlebotomy,while the observation group received optimized blood collection method aimed at reducing the blood loss volume respectively.Results In the control group the number of patients with anemia at the 7th day was more than that of the 1st day (23 vs 6 ; x2 =16.388,P =0.000) ; there was difference in Hbd1,Hbd3,Hbd7 (P ＜ 0.05) ; the mean daily phlebotomy volume of the first three days was greater than that of the last four days (P ＝ 0.000) ; Hbc1-3 and Hbc1-7 wcre related with BLd1-3,Hbc4-7 was related with BLd4-7 (P ＜0.05) ; BLd1-3,BLd4-7,BLd1-7 were related with APACHE Ⅱ score positively (P ＜ 0.05).In observation group there was no difference in the proportion of patients with anemia between the 7th day and the 1st day (19 vs 14 ;x2 =1.564,P =0.211); Hbd1,Hbd3 and Hbd7 were no difference (P ＞0.05); the average daily blood loss volume of the first three days was greater than that of last four days (P ＜ 0.05) ; Hbc1-3,Hbc4-7,Hbc1-7 were not related with BLd1-3,BLd4-7 and BLd1-7 (P ＞ 0.05).BLd1-3,BLd4-7 and BLd1-7 were unrelated with APACHE Ⅱ scores (P ＞ 0.05).BLd1-3,BLd4-7,BLd1-7,Hbc1-3,Hbc1-7 in the control group were greater than those of the observation group (P ＜ 0.05) ; there was no difference in Hbc4-7 between the two groups (P ＞ 0.05).Conclusions Diagnostic blood loss can cause the iatrogenic anemia of patients in RICU,and optimizing the blood collection method and enhancing blood conservation can reduce the incidence of iatrogenic anemia.

OBJECTIVE: To study the effects of prenatal cold stress on the behavior and mood of offspring in pregnant rats. METHODS: Six SPF-class Wister pregnant rats were randomly divided into normal temperature control group and cold stress group with 3 rats in each group. The pregnant female rats in the normal temperature control group were kept in the environment of (22 ±2)℃, and the pregnant female rats in the cold stress group were placed in the artificial intelligence climate chamber at(4 ±0.1)℃ for 7 days before the birth, and the young rats were divided into normal temperature after the young rats were born. After the young rats were born, they were divided into normal temperature control group of male rats (MR, 22), normal temperature control group of mother rats (FR, 15), cold stress group of male rats (MC, 15), and cold stress group of female rats (FC, 15) .In the fourth generation of the offspring, the open field experiment and the elevated cross maze test were carried out. RESULTS: In the open field experiment, there was no significant difference in spontaneous activity and exploration behavior between the normal temperature control group and the cold stress group (P＞0.05). In the elevated plus maze experiment, the retention time of the open arms, the number of open arms and the distance of the male and female rats in the cold stress group were significantly higher than those in the normal temperature control group (P＜0.05). CONCLUSION Prenatal maternal cold stress has no significant effect on spontaneous activity, exploration behavior and activity level of offspring, but the offspring have obvious abnormal behaviors with reduced anxiety behavior.
Animals ; Anxiety ; Behavior, Animal ; Cold-Shock Response ; Exploratory Behavior ; Female ; Male ; Maze Learning ; Pregnancy ; Prenatal Exposure Delayed Effects ; Random Allocation ; Rats ; Stress, Psychological