Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. △9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

Objective To study the mechanism of marcosomia by investigating insulin-like growth factor 2(IGF_2)imprinting status,expression level and the promoter usage in the placenta of macrosomia. Methods We selected heterozygous cases for Apa Ⅰ polymorphism in exon 9 of IGF_2 gene and then analyzed its imprinting status in 168 placentas of macrosomia and normal pregnancies.IGF_2 transcription levels and promoter usages in macrosomic and normal placenta were evaluated by using semi-quantitative RT- PCR assay.Results Thirty specimens of macrosomic placenta and 30 of normal placenta were identified as heterozygous for IGF_2.All of the heterozygous specimens showed maintenance of imprinting.The expression of placental IGF_2 mRNA(2.2?1.2)was significantly higher in macrosomia than that of normal weight group (1.6?0.6,P 0.05).Conclusion It is possible that over expression of IGF_2 in placenta contributes to macrosomia while the promoter usage and imprinting status are not associated with macrosomia.

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

Purpose To describe the clinicopathologic features, diagnosis and differential diagnosis, and prognosis of secretory breast carcinoma (SBC). Methods Clinicopathological and follow-up data of six SBC patients were collected. Histopathologic analysis was performed on hematoxylin and eosinstained (HE) section. Immunohistochemical staining was performed by En Vision two-step method and ETV6 gene detected by fluorescence in situ hybridization (FISH), then relevant literatures were reviewed. Results The ages of the patients ranged from 6 to 76 years with a mean age of 38.7 years, including one male and five female patients. The right breast was involved in 4 cases, and the left, in 2 cases. Five cases showed painless breast mass while one presented with a nipple discharge. The tumor size ranged from 1.0 to 3.1 cm with a mean size of 2.0 cm. Most of the tumors were circumscribed, solid gray white to light brown. Histologically, tumor showed solid nested microcystic, glandular or papillary pattern separating by hyaline fibrous tissue and growed in multiple nodular from. The cytoplasm contains abundant eosinophilic secretions or secretory vesicles. Immunhistochemistry, all cases were positive for CK7, S-100 and CEA, but negative for estrogen and progesterone receptors (ER and PR) and HER-2, and the proliferation index Ki-67 ranged from 10％ to 40％. Molecular testing confirmed the presence of the EVT6 gene translocation in one case. Lumpectomy was performed in 2 cases and modified radical mastectomy in 4 cases, two of them had lymph node metastasis (3/15, 1/16). Five cases were followed up for 6 months to 20 years, 1 case had lung metastasis. Conclusion SBC is a rare breast tumor with relatively indolent clinical and good prognosis. It can be diagnosed according to typical pathological morphology and immunohistochemical characteristics. The characteristic EVT6 gene translocation also has important differential diagnostic value.

OBJECTIVETo investigate the effect of miRNA silencing HIF-1α gene on the proliferation of HepG2 cells.

METHODSThe eukaryotic expression plasmids of HIF-1α miRNA and report gene containing hypoxia-reponse element were constructed and transfected into HepG2 cells. The expressions of HIF-1α gene and protein were determined by real time-PCR and Western blotting. The expressions of HIF-1α, vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were quantitatively detected by ELISA. The alterations of cell cycles and apoptosis rate were quantitatively measured by flow cytometry and Annexin V-FITC/PI double dyeing assay.

RESULTS72 h after transfection the down regulations of HIF-1α mRNA and protein were 87% and 56% respectively, and the decrease of target gene was 46% in the report gene, 54% in VEGF and 36% in Ang-2, respectively. The apoptotic ratio of HepG2 cells was 22.46+/-0.61% (P < 0.01). The cell cycle changed greatly at the ratio of G1 (61.49+/-1.12%) and S (22.40+/-0.58%, P < 0.01). After being combined with doxorubicin, the apoptotic ratio increased to 36.99+/-0.88% and the ratios of G1 and S phases were upregulated to 65.68+/-0.91% and 19.47+/-1.34% respectively.

CONCLUSIONSHIF-1α miRNA or / and doxorubicin can regulate the growth cycles of HepG2 cells, promote the cell apoptosis and inhibit the cell proliferation.

Apoptosis ; Cell Cycle ; Cell Proliferation ; Gene Silencing ; Hep G2 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; MicroRNAs ; genetics ; RNA, Messenger ; genetics ; Transfection

OBJECTIVETo explore the molecular mechanism via which the chemotherapeutic drug hydroxyurea (HU) enhances K562 cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

METHODSChronic myelogenous leukemia-derived K562 and SVT-35 cells were treated with recombinant soluble TRAIL (rsTRAIL) alone or combined with HU for a time course, and the cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl-2H-tetrazolium-phenazine methosulphate assay. Western blot was performed to analyze the activation of apoptosis-related protein kinases and the expression of apoptosis inhibitor molecules.

RESULTSThe survival rates of SVT-35 and K562 cells treated with 1 μg/ml rsTRAIL for 24 hours were 32% and 93%, respectively. HU significantly increased the sensitivity of K562 cells to rsTRAIL cytotoxicity. Combination of rsTRAIL and HU resulted in the phosphorylation of rat sarcoma (RAS), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase and in the significant reduction of apoptosis-inhibited molecule Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 in K562 cells.

CONCLUSIONSHU enhanced K562 cell sensitivity to rsTRAIL is mediated by Ras-MEK-ERK signaling pathway. Expression of antiapoptotic proteins cellular Fas associated death domain protein-like interleukin-1 beta-convening enzyme inhibitory protein and cellular inhibitor of apoptosis protein-1 is also down-regulated during this process. These results may through light on the therapeutic study of human chronic myelogenous leukemia.

Apoptosis ; drug effects ; physiology ; CASP8 and FADD-Like Apoptosis Regulating Protein ; metabolism ; Humans ; Hydroxyurea ; pharmacology ; Inhibitor of Apoptosis Proteins ; metabolism ; K562 Cells ; MAP Kinase Signaling System ; TNF-Related Apoptosis-Inducing Ligand ; pharmacology

The renin/prorenin receptor (RnR) has recently been cloned and demonstrated to exist in different cells in the cardiovascular and renal systems, playing an important role in physiological and pathophysiological situations. In the present study, we used immunofluorescence method to identify whether and where the RnR expressed in cultured rat renal mesangial cells (MCs) and rat kidney. By using the prorenin handle region peptide (HRP) as a decoy peptide of the RnR, we observed the distribution of the HRP-RnR complex in the MCs. Our results showed that the RnR was localized in the perinuclear zone and plasma membrane of the MCs. At the organ level, the RnR was observed in the mesangium of cortical glomeruli in rat kidney. The FITC-labeled HRP (FITC-HRP) translocated from cell culture medium into the cytoplasm within 30 s. Colocalization of the HRP and RnR was observed mainly on the cell membrane and in the perinuclear zone of cytoplasm by using immunofluorescence and confocal microscopy. At 30 min the FITC-HRP was mainly observed in the nucleus while the RnR remained in the perinuclear zone of cytoplasm. Taken together, our results confirm the expression of RnR in the renal MCs. It is suggested that internalization of the RnR after binding with its ligand is at least one of the pathways through which the RnR exerts its biological actions.
Animals ; Kidney ; metabolism ; Mesangial Cells ; metabolism ; Rats ; Receptors, Cell Surface ; metabolism

OBJECTIVETo measure the diameter of T4 pedicle-rib compomers in normal human spines and discuss the importance of related dates.

METHODST4 computerized tomography (CT) images,including two-dimensional,three-dimensional reconstruction, of 12 random adult patients were harvested. There were 7 males and 5 females with a mean age of 23 years (ranged, 19 to 28 years). The patients were divided into groups by self control,which means the diameter of pedicle compared with that of pedicle-rib unit in the same side of each T4. The facility was GE light speed 16. Measurement of the body specimens from T3 to T5 . The parameter included the width of pedicle-rib unit compared with pedicle,the longitudinal diameter of pedicle-rib unit compared with pedicle, especially for the pedicle-rib overlap.

RESULTSThe relationship of T4 pedicle and rib were not on the same level but overlapping. The width of pedicle-rib unit was significantly larger than that of pedicle (P<0.05). The longitudinal diameters of pedicle-rib unit or pedicle were significantly larger than those of pedicle-rib overlap (P<0.05); while there was no significantly difference between the pedicle-rib unit and pedicle (P>0.05).

CONCLUSIONThe overlapping relationship of T4 pedicle and rib is partly but not whole, which means the longitudinal diameter of T4 pedicle-rib overlap should not be considered as the same of unit or pedicle.

Adult ; Female ; Humans ; Male ; Ribs ; anatomy & histology ; Thoracic Vertebrae ; anatomy & histology ; Tomography, X-Ray Computed ; Young Adult

Identifying a target molecule that is crucially involved in pancreatic tumor growth and metastasis is necessary in developing an effective treatment. The study aimed to investigate the role of the eukaryotic translation initiation factor 3a (eIF3a) in the cell proliferation and motility in pancreatic cancer. Our data showed that the expression of eIF3a was upregulated in pancreatic ductal adenocarcinoma as compared with its expression in normal pancreatic tissues. Knockdown of eIF3a by a specific shRNA caused significant decreases in cell proliferation and clonogenic abilities in pancreatic cancer SW1990 and Capan-1 cells. Consistently, the pancreatic cancer cell growth rates were also impaired in xenotransplanted mice. Moreover, wound-healing assay showed that depletion of eIF3a significantly slowed down the wound recovery processes in SW1990 and Capan-1 cells. Transwell migration and invasion assays further showed that cell migration and invasion abilities were significantly inhibited by knockdown of eIF3a in SW1990 and Capan-1 cells. Statistical analysis of eIF3a expression in 140 cases of pancreatic ductal adenocarcinoma samples revealed that eIF3a expression was significantly associated with tumor metastasis and TNM staging. These analyses suggest that eIF3a contributes to cell proliferation and motility in pancreatic ductal adenocarcinoma.
Adenocarcinoma ; Animals ; Cell Movement ; Cell Proliferation* ; Mice ; Neoplasm Metastasis ; Neoplasm Staging ; Pancreatic Ducts ; Pancreatic Neoplasms* ; Peptide Initiation Factors* ; RNA, Small Interfering ; Wounds and Injuries

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of lopinavir and ritonavir in human plasma. Analytes were separated from plasma by a combination of alkalinized protein precipitation and liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Agilent ZORBAX Eclipse XDB-C18 column with the mobile phase consisted of methanol-0.1% formic acid in water (80:20). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 629.6 --> 155.2, m/z 721.4 --> 268.2, and m/z 515.2 --> 276.2 for lopinavir, ritonavir and telmisartan (internal standard), respectively. The method showed a good linearity in a concentration range of 62.5 - 10000 ng mL(-1) for lopinavir, and 12.5 - 2000 ng mL(-1) for ritonavir. The lower limits of quantification were 15 pg mL(-1) and 8 pg mL(-1) for lopinavir and ritonavir, respectively. The intra- and inter-day precision was less than 15% and the absolute recovery was above 75%. This method was selective and rapid, sensitive for investigating blood drug concentrations in clinics.
Chromatography, Liquid ; methods ; HIV Infections ; blood ; Humans ; Lopinavir ; blood ; Ritonavir ; blood ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; methods