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

OBJECTIVETo observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice.

METHODSThirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR.

RESULTSBody weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05).

CONCLUSIONCZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.

Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Diet, High-Fat ; Drugs, Chinese Herbal ; pharmacology ; Fructose ; administration & dosage ; adverse effects ; Inflammation ; Lipid Metabolism ; Male ; Mice ; Mice, Inbred C3H ; Myeloid Differentiation Factor 88 ; metabolism ; Non-alcoholic Fatty Liver Disease ; drug therapy ; Signal Transduction ; drug effects ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the chemical constituents in the medicative part of Sorbaria sorbifolia.

METHODBy means of silica gel re-chromatography and thin layer chromatography, chemical constituents from the CHCl3 and EtOAc extract of the medicative part of S. sorbifolia were studied and their structures were identified by their physical-chemical constants, spectral analysis and comparison with the authorized samples.

RESULTSEight compounds were obtained and identified as follows: noreugenin (I), wogonin (II), 5,7,3',4'-tetrahydroxy-3-methoxyflavone (III), protocatechuic acid (IV), benzoic acid (V), p-hydroxy benzoic acid (VI), emodin (VII) and daucosterol (VIII).

CONCLUSIONAll of the compounds were isolated from this genus for the first time.

Flavanones ; Flavonoids ; chemistry ; isolation & purification ; Flavonols ; Hydroxybenzoates ; chemistry ; isolation & purification ; Plant Components, Aerial ; chemistry ; Plants, Medicinal ; chemistry ; Quercetin ; analogs & derivatives ; chemistry ; isolation & purification ; Rosaceae ; chemistry

In order to understand the alcohol's toxicity to the quantitative alternations of synapses in mouse visual cortex, the expression of synaptophysin after prenatal alcohol exposure was investigated. In present study, the experimental mice at P0, P7, P14 and P30 were grouped, as control, 2 g x kg(-1) alcohol treatment and 4 g x kg(-1) alcohol treatment. The pre-synaptic elements which were used to represent synapses were marked with synaptophysin (a synaptic vesicle associated protein) by immunocytochemistry technique. The synaptophysin positive boutons in layer VI of visual cortex were imaged under laser confocal microscope. With stereological methods, the number cal density of synapse in visual cortex was calculated in different groups at various ages. Moreover, Western blotting was carried out to detect the expression of synaptophysin in visual cortex. The results showed that prenatal alcohol exposure could cause synaptic loss with long-term effect and in a dose dependent manner. For instance, there were significant difference among the different treatment groups of P0, P14 and P30 as well (P < 0.05). Western blotting supported the results of immunofluorescent labeling. In conclusion, prenatal alcohol exposure can induce the synaptic loss dose dependently and with long-term effect. Our findings implicate that the synaptic loss with long-term effect in CNS probably contributes to the lifelong mental retardation and memorial lowliness associated with childhood FAS.
Animals ; Dose-Response Relationship, Drug ; Ethanol ; administration & dosage ; toxicity ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Pregnancy ; Prenatal Exposure Delayed Effects ; physiopathology ; Random Allocation ; Synapses ; drug effects ; Synaptophysin ; metabolism ; Visual Cortex ; drug effects ; physiopathology

Objective To evaluate the clinical application of laparoscopic local resection for gastric tumors.Methods Twenty-three patients with gastric tumors who were performed laparoscopic gastric local resection were retrospectively analyzed with the size of tumor,location of tumor,operative time,blood loss during the operation,time for passage of flatus,post-operative hospital stay,operative complications,post-operative pathological findings and result of follow-up.Results Twenty-three patients were successfully performed laparoscopic local resection,including 8 laparoscopic wedge resection(LWR)and 15 intragastric mucosal resections(IGMR),with no conversion to open surgery.The mean size of gastric tumor was(2.8?1.3)cm,the mean operative time was(82.2?35.5)min,the mean blood loss was(26.5?15.3)mL,the length of incision was(3.1?1.1)cm,the time for passage of flatus was(2.1?0.9)d,and the mean post-operative hospital stay was(7.8?2.0)d.Two patients(8.7%)were found with postoperative gastric mucosal blee-ding and were recovered well through non-operative treatment.The median time of follow-up was 12 months(2-45 months),and no recurrent tumor was observed.Conclusion Laparoscopic local resection is a feasible,safe,effective and less invasive procedure for gastric tumors.

OBJECTIVETo investigate JAK2 exon 12 mutations in patients with Philadelphia (Ph) chromosome-negative myeloproliferative neoplasms (MPN) and the clinical characteristics of patients with JAK2 exon 12 mutants.

METHODSAllele-specific PCR (AS-PCR) was applied to identify JAK2 V617F mutation. Genomic DNA corresponding to exon 12 of JAK2 gene and epigenetic regulator gene (TET2, ASXL1, EZH2) were amplified by polymerase chain reaction (PCR). Identification of mutants was by direct sequencing and classification of mutation types by sequencing followed by plasmid cloning. SNP genotyping of two 46/1 tag SNPs, rs12340895 and rs10974944, was analyzed using commercially available Taqman assays on the 7500HT real-time PCR instrument according to standard protocols.

RESULTSNo JAK2 exon 12 mutation was detected in patients with ET, PMF or JAK2 V617F positive PV. Among 13 JAK2 V617F negative PV patients, JAK2 exon 12 mutation was detected as N542-E543del in 2(15.4%) patients who presented with a phenotype of predominant erythrocytosis and erythroid colonic grown from their bone marrow samples in the absence of exogenous EPO, reduced serum erythropoietin (EPO) level, and no mutations in TET2, ASXL1 or EZH2 genes. One of the affected patients was heterozygous for 46/1 but the second was negative for this haplotype.

CONCLUSIONThere was no need to detect JAK2 exon 12 mutation in ET, PMF or MPN-U patients without JAK2 V67F mutation. Ph negative MPN patients with JAK2 exon 12 mutations had somewhat unique clinical and laboratory features.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow Neoplasms ; genetics ; DNA Mutational Analysis ; Exons ; Female ; Genotype ; Humans ; Janus Kinase 2 ; genetics ; Male ; Middle Aged ; Myeloproliferative Disorders ; genetics ; Philadelphia Chromosome ; Young Adult

OBJECTIVETo evaluate laparoscopic surgery for gastric and small intestinal stromal tumors.

METHODSThe clinical data of patients with laparoscopic resection of gastric and small intestinal tumors, admitted to our center from Dec. 2003 to Jul. 2006, were retrospectively analyzed. The data included the surgical procedure, operative time, blood loss, length of incision, time for passage of flatus, postoperative length of stay, operative complications, pathology and the results of follow-up.

RESULTSAll the 33 patients with gastric and small intestinal stromal tumors were treated by laparoscopic procedures successfully, including 8 laparoscopic gastric wedge resections, 8 laparoscopic transgastric tumor-everting resections, and 17 laparoscopic segmental resections of small intestine. The mean operative time was (73.1+/-27.0) min, the mean blood loss was (19.8+/-14.0) ml, the mean length of incision was (3.3+/-1.1) cm, the mean time for passage of flatus was (2.2+/-1.0) d and the postoperative length of stay was (8.1+/-2.0) d. The bleeding of intestinal anastomosis and gastric mucosa occurred on 3 patients (9.1%), who were healed with conservative therapy. No recurrence was found during 2-33 months follow-up.

CONCLUSIONLaparoscopic surgery is an effective, safe, less invasive procedure for treatment of gastric and small intestinal stromal tumors.

Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors ; surgery ; Humans ; Intestine, Small ; Laparoscopy ; methods ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Objective To evaluate the safety,efficacy and advantages of laparoscopic colorectal surgery for elderly patients with colorectal cancer.Methods Operation safety,complications,and postoperative recovery of 35 patients aged 70 years and over who underwent laparoscopic colorectal surgery(LAPA group) were analyzed retrospectively and compared with those of 78 elderly patients performed with conventional open surgery(OPEN group) and 35 patients younger than 65 years performed with laparoscopic colorectal surgery(LAPB group) between December 2002 and December 2003.Results No surgery-related death occurred in LAPA group and LAPB group,but 2 deaths were found in OPEN group because of severe pulmonary infection and anastomotic leakage respectively.There were 33 (42.3%) cases of complications in the OPEN group which were significantly more than those in LAPA and LAPB group (P0.05).Local recurrence rate,metachronous metastases rate and cumulative survival probability at 30 months were similar in the LAPA and OPEN groups.Conclusions Laparoscopic colorectal surgery is safe and beneficial to the patients aged 70 years and over and it could be adopted widely.

OBJECTIVETo evaluate the clinical use of laparoscopy in diagnosis and surgical treatment in small intestinal tumors.

METHODSClinical data of 42 patients with small intestinal tumor undergoing laparoscopic diagnosis and surgical procedure from Sep. 2003 to Dec. 2005 were analyzed retrospectively. The operative time, blood loss,length of incision, time for passage of flatus, post-operative hospital stay and operative complications were evaluated.

RESULTSAll the patients were diagnosed and treated by laparoscopic procedure successfully, including 4 laparoscopic local resection of the tumors, 36 laparoscopy-assisted partial intestinal resections, 1 right hemicolectomy, and 1 laparoscopic exploration. The mean operative time was (73.1+/-32.9) min, the mean blood loss was (20.7+/-31.2) ml, the mean length of incision was (3.7+/-1.2) cm, the mean time for passage of flatus was (2.2+/-0.8) d, and the post-operative hospital stay was (8.0+/-3.1) d. Postoperative complications occurred in 2 patients (4.8% ) including anastomosis bleeding and adhesive intestinal obstruction in one case respectively. After follow-up from 3 to 30 months, no recurrent tumor was found except one patient with advanced intestinal carcinoma.

CONCLUSIONLaparoscopic exploration can diagnose small intestinal tumors accurately, and laparoscopy-assisted surgical treatment is safe with less trauma and fast recovery.

Adult ; Aged ; Female ; Humans ; Intestinal Neoplasms ; diagnosis ; surgery ; Intestine, Small ; Laparoscopy ; Middle Aged ; Retrospective Studies

Objective To evaluate the laparoscopic management in diagnosing and treating small intestinal stromal tumors.MethodsSeventeen patients with small intestinal stromal tumors,who underwent laparoscopic diagnosis and surgical procedures,were retrospectively analyzed with the size of tumor,operative time,blood loss,length of incision,time for passage of flatus,post-operative hospital stay,operative complications and result of follow-up.Results All the 17 patients were diagnosed and treated by laparoscopic partial intestinal resections.The mean diameter of tumors was(3.6?1.3)cm,operative time(62.1?25.7)min,blood loss(17.1?15.2)mL,length of incision(3.4?1.1)cm,time for passage of flatus(2.2?1.2)d and post-operative hospital stay(7.8?2.0)d.As for the complications,one(5.9%)anastomosis bleeding was found and was treated by non-surgical procedure.After follow-up for 2-34 months,no recurrent tumor was found.Conclusion Laparoscopic exploration is useful to diagnose small intestinal stromal tumor accurately,and laparoscopic partial intestinal resection is a safe,effective and less invasive procedure for small intestinal stromal tumors.