Meranzin Hydrate Improves Depression-Like Behaviors and Hypomotility via Ghrelin and Neurocircuitry / 中国结合医学杂志

OBJECTIVE@#To investigate whether meranzin hydrate (MH) can alleviate depression-like behavior and hypomotility similar to Chaihu Shugan Powder (CSP), and further explore the potential common mechanisms.@*METHODS@#Totally 120 Spraque-Dawley rats were randomly divided into 5-8 groups including sham, vehicle, fluoxetine (20 mg/kg), mosapride (10 mg/kg), CSP (30 g/kg), MH (9.18 mg/kg), [D-Lys3]-GHRP-6 (Dlys, 0.5 mg/kg), and MH+Dlys groups by a random number table, 8 rats in each group. And 32 mice were randomly divided into wild-type, MH (18 mg/kg), growth hormone secretagogue receptor-knockout (GHSR-KO), and GHSR+MH groups, 8 mice in each group. The forced swimming test (FST), open field test (OFT), tail suspension test (TST), gastric emptying (GE) test, and intestinal transit (IT) test were used to assess antidepressant and prokinetic (AP) effects after drug single administration for 30 min with absorbable identification in rats and mice, respectively. The protein expression levels of brain-derived neurotrophic factor (BDNF) and phosphorylated mammalian target of rapamycin (p-mTOR) in the hippocampus of rats were evaluated by Western blot. The differences in functional brain changes were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD).@*RESULTS@#MH treatment improved depression-like behavior (FST, OFT) and hypomotility (GE, IT) in the acute forced swimming (FS) rats (all P<0.05), and the effects are similar to the parent formula CSP. The ghrelin antagonist [D-Lys3]-GHRP-6 inhibited the effect of MH on FST and GE (P<0.05). Similarly, MH treatment also alleviated depression-like behavior (FST, TST) in the wild-type mice, however, no effects were found in the GHSR KO mice. Additionally, administration of MH significantly stimulated BDNF and p-mTOR protein expressions in the hippocampus (both P<0.01), which were also prevented by [D-Lys3]-GHRP-6 (P<0.01). Besides, 3 main BOLD foci following acute FS rats implicated activity in hippocampus-thalamus-basal ganglia (HTB) circuits. The [D-Lys3]-GHRP-6 synchronously inhibited BOLD HTB foci. As expected, prokinetic mosapride only had effects on the thalamus and basal ganglia, but not on the hippocampus. Within the HTB, the hippocampus is implicated in depression and FD.@*CONCLUSIONS@#MH accounts for part of AP effects of parent formula CSP in acute FS rats, mainly via ghrelin-related shared regulation coupled to BOLD signals in brain areas. This novel functionally connection of HTB following acute stress, treatment, and regulation highlights anti-depression unified theory.

Proliferation of MicroRNA-365 and E74-like Factor 4 in Cervical Cancer Cells and Its Clinical Significance / 中国医学科学院学报

Objective To investigate the expressions,roles,and clinical significance of microRNA-365(miR-365)and E74-like factor 4(ELF4)in cervical cancer. Methods The expressions of miR-365 in normal cervical tissues(n=34),cervical intraepithelial neoplasia 1(CIN 1)(n=31),cervical intraepithelial neoplasia2-3(CIN 2-3)(n=37),squamous cell carcinoma of the cervix(SCC)(n=33),and three cervical cancer cell lines(C33A cells,Hela cells,and SiHa cells)were detected by real-time quantitative polymerase chain reaction(qPCR).Bioinformatic prediction and luciferase reporter gene assay were performed to verify whether ELF4 was a direct target of miR-365.Western blot and immunohistochemistry were used to detect ELF4 expression in cervical cancer cells and in different pathological cervix tissues.CCK8 assay was used to detect the effect of overexpression or inhibition of miR-365 on the proliferation of cervical cancer cells at different time points.The relationships among the miR-365 expression,ELF4 expression,and clinicopathological parameters of cervical cancer were analyzed by correlation analysis. Results qPCR results showed that compared with the normal cervical cell HcerEpic,the expressions of miR-365 in CIN1,CIN2-3,and cervical cancer tissues gradually decreased with the increased pathologic grade,and its expressions also decreased in different cervical cancer cell lines.The luciferase reporter gene assay confirmed that ELF4 was the direct target of miR-365.Western blot showed that the expression of ELF4 increased in all three cervical cancer cell lines compared with normal cervical epidermal cell(P=0.013,P=0.002,P=0.004).Immunohistochemistry showed that ELF4 expression was up-regulated in CIN and cervical cancer tissues.CCK8 assay showed that overexpression of miR-365 inhibited cell proliferation,while inhibition of miR-365 promoted the proliferation of three cervical cancer cells(PConclusion The decreased expression of miR-365 in human cervical cancer cells relieves its inhibitory effect on ELF4,which promotes the proliferation of cervical cancer cells and the formation of tumor.

Simultaneous Determination of 6 Residual Organic Solvents in Aprepitant Raw Material by Headspace Capillary GC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of 6 residual organic solvents in aprepitant raw material as methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether and tetrahydrofuran.METHODS:Headspace capillary gas chromatography was adopted.The determination was performed on DB-624 capillary column using temperature programming.The temperature of injector port was 180 ℃,and flame ionization detector was used with temperature of 260 ℃.Nitrogen was used as carrier gas with flow rate 3.0 mL/min.The spilt ratio was 5 ∶ 1,and head-space injection volume was 1.0 mL.The head-space equilibrium temperature was set at 80 ℃,and equilibrium time was 40 min.RESULTS:The linear ranges of methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether,tetrahydrofuran were 6.052-605.232 μ g/mL (r=0.999 9),9.987-998.718 μg/mL(r=0.999 9),9.998-999.768 μg/mL(r=0.999 8),9.986-998.634 μg/mL(r=0.999 9),9.991-999.090 μg/mL (r=0.999 7),1.461-146.133 μg/mL(r=0.999 5),respectively.The limits of quantitation were 1.782 1,2.079 0,0.749 8,1.777 8,0.223 1,0.607 0 μg/mL;the limits of detection were 0.594 0,0.693 0,0.249 9,0.592 6,0.074 4,0.202 3 μg/mL,respectively.RSD of precision test was lower than 2.0％.Only acetone and isopropyl alcohol were detected in stability test and reproducibility tests,RSD＜2.0％.Their recoveries were 99.34-100.75％ (RSD=0.52％,n=9),98.20％-100.24％ (RSD=0.69％,n=9),98.07％-100.07％ (RSD=0.84％,n=9),99.86％-101.32％ (RSD=0.58％,n=9),97.87％-104.02％ (RSD=2.13％,n=9),98.26 ％-100.58 ％ (RSD =0.75 ％,n =9),respectively.CONCLUSIONS:The established method is simple,accurate and reproducible,and can be used for simultaneous determination of 6 residual organic solvents in aprepitant raw material.

Risk factors for concurrent sepsis in neonates with necrotizing enterocolitis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors for concurrent sepsis in neonates with necrotizing enterocolitis (NEC).</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of 273 neonates with NEC. The risk factors for concurrent sepsis were analyzed from the aspects of perinatal factors and treatment regimen before the diagnosis of NEC.</p><p><b>RESULTS</b>The incidence rate of concurrent sepsis in NEC was 32.2% (88/273). The neonates with stage III NEC had a significantly higher incidence rate of concurrent sepsis than those with stage II NEC (69.0% vs 15.9%; P<0.05). Of all neonates with sepsis, 62.5% experienced sepsis within 3 days after the diagnosis of NEC, and 37.5% experienced sepsis more than 3 days after the diagnosis. Compared with those without concurrent sepsis, the neonates with concurrent sepsis had significantly lower gestational age and birth weight (P<0.05). The neonates who had scleredema, had stage III NEC, needed gastrointestinal decompression after the diagnosis of NEC, and experienced a long time of gastrointestinal decompression tended to develop sepsis more easily (P<0.05). Scleredema (OR=9.75, 95%CI: 2.84-33.52, P<0.001), stage III NEC (OR=12.94, 95%CI : 6.82-24.55, P<0.001), and gastrointestinal decompression (OR=2.27, 95%CI: 1.14-4.5, P=0.02) were independent risk factors for concurrent sepsis in NEC.</p><p><b>CONCLUSIONS</b>Scleredema, stage III NEC, and gastrointestinal decompression are independent risk factors for concurrent sepsis in neonates with NEC.</p>

Chemical constituents from stems of Cipadessa cinerascens / 中草药

To study the chemical constituents from the stems of Cipadessa cinerascens. The constituents were separated by column chromatography and their structures were elucidated by spectral data analyses. Seventeen chemical constituents were isolated from the EtOAc extract in the stems of C. cinerascens and their structures were identified as lanost-7-en-3-one-22, 25-epoxy-23, 24-acetone acetal (1), chisopanin M (2), 3β-hydroxy-5-en-stigmast (3), 7α-hydroxy-4-en-3-one-stigmast (4), 3β-hydroxy-5-en-7-one-stigmast (5), 7α-hydroxysitosterol (6), 22E-7α-methoxy-5α, 6α-epoxy-8 (14), 22-dien-3β-hydroxy-ergosta (7), 7β-hydroxy-4-en-3-one-cholest (8), 3β-acetyloxy-2β, 4β-dihydroxy-16-one-pregnan (9), 17α, 20R-dihydroxy-3, 16-dione-pregnan (10), 2β, 3β-dihydroxy-16-one-pregnan (11), 3β, 7α-dihydroxy-20-one-pregnan (12), 2α, 3β-dihydroxy-5-en-20-one-pregnan (13), 1, 4-dien-3, 16-dione-2-hydroxyandrosta (14), 5-en-17-one-3β, 16β-dihydroxyandrost (15), apegenin (16), and annuionone D (17). Conclusion All the compounds except 14 and 17 are obtained from this plant for the first time.

Effects of herbal medicine extraction on bone destruction and pain behaviors in rats of bone cancer pain / 国际中医中药杂志

Objective To evaluate therapeutic effects of Bushen-Zhuanggu medicine extraction on bone destruction in rats bone cancer pain.Methods Rat models of cancer-induced bone pain were established by inoculating MRMT-1 cells into tibia of rats.Behavioral signs indicative of pain including 50%paw withdrawal threshold(von Frey tactile sensitivity test)and thermal withdrawal latency were observed.Pathomorphological changes of tibia were monitored with HE staining.Results In the behavioral tests,herbal medicine treatment attenuated mechanical allodynia and thermal hyperalgesia.Histological examination showed that this treatment inhibited tumor proliferation and preserved the cortical and trabccular bone structure.Conclusion Bushen-Zhuanggu medicine extraction is an anti-nociceptive and bone-preserving agent in rats of bone cancer pain.