Objective To find potential biomarkers and analyzing metabolic pathways of the treatment by honey-processed Hedysari Radix,the cecal contents of rats with spleen-Qi deficiency were used as samples for analysis.Methods Sixty male SD rats were randomly divided into blank,model,experimental and control groups.The rats in other groups except the control group were carried out by using the three-factor compound modeling method of bitter-cold diarrhea,excessive exertion and hunger and satiety disorders.Experimental group was given 12.60 g·kg-1 honey-processed Hedysari Radix;control group was given 0.63 g·kg-1 lactobacillus bifidum triplex tabletsa;control and model groups received with equal volume of distilled water for a total of 15 days.Measure body weight,anal temperature,immune organ index of rats.Ultra-pressure liquid chromatography-quadrupole-exactive-mass spectrometry technology was used to measure the levels of endogenous metabolites in cecum contents.Orthogonal partial least squares discriminant analysis and database"Kyoto Encyclopedia of Genes and Genomes"were used to identify potential differential metabolites and possible metabolic pathways.Results After the intervention,the average body weight of the experimental,control,model and blank groups was(216.87±7.85),(210.96±9.03),(159.47±5.18)and(293.51±22.98)g;anal temperature was(36.14±0.48),(35.40±0.64),(34.50±0.78)and(36.61±0.34)℃;the thymus indexes were(1.19±0.20),(1.24±0.25),(0.47±0.15)and(1.31±0.21)mg·g-1;the spleen indexes were(1.95±0.33),(2.18±0.28),(1.61±0.27)and(2.29±0.24)mg·g-1.Compared with the model group,the above indexes of the experimental group and the control group were significantly increased(all P＜0.01).A total of 14 potential biomarkers of Honey-processed Hedysari Radix in treating spleen-Qi deficiency syndrome were screened out in this study,which mainly involved amino acid metabolism such as tryptophan and glutamate,riboflavin metabolism and adenosine 5'-monophosphate-activated protein kinase metabolism.Conclusion Honey-processed Hedysari Radix can further protect the intestinal mucosal barrier and reduce the intestinal inflammatory response by improving the metabolic level of cecum contents in rats with spleen-Qi deficiency in cecum contents,thus exerting the effect of strengthening the spleen and tonifying the Qi.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective To explore the effect and mechanism of hydroxysafflor yellow A(HSYA)on autophagy in bEnd.3 cells after oxygen-glucose deprivation(OGD).Methods The bEnd.3 cells were divided into normal group(conventional culture),model group(OGD model),HSYA group(OGD model+75 μmol·L-1 HSYA),3-methyladenine(3MA)group(5 mmol·L-1 3MA+OGD model)and 3 MA+HSYA group(5 mmol·L-1 3 MA+OGD model+75 μmol·L-1 HSYA).The level of apoptosis was determined by TUNEL fluorescence staining;Western blot was used to detect the expression of autophagy,blood brain barrier(BBB)related proteins;real time fluorescence quantitative polymerase chain reaction method for determining the expression of sirtuin-1(SIRT1)and forkhead box protein O3a(FOXO3A)mRNA.Results In the normal group,model group,HSYA group,3MA group and 3MA+HSYA group,the positive cells selected for TUNEL staining were 5.00±1.00,28.00±2.00,21.00±3.00,35.33±2.51 and 29.67±2.52;the expression levels of microtubule-associated protein 1 light chain 3-Ⅱ/-Ⅰ(LC3-Ⅱ/-Ⅰ)were 0.90±0.20,1.34±0.10,1.95±0.14,0.76±0.15 and 1.14±0.09;sequestosome 1(P62)were 0.99±0.02,0.60±0.02,0.38±0.01,0.67±0.04 and 0.54±0.01;occludin were 1.39±0.17,0.62±0.15,1.00±0.09,0.40±0.13 and 0.80±0.15;zonula occludens-1(ZO-1)were 1.63±0.20,0.64±0.06,0.98±0.14,0.37±0.14 and 0.87±0.04;SIRT1 mRNA were 1.00±0.00,0.75±0.07,1.69±0.09,0.31±0.02 and 0.56±0.01;FOXO3A mRNA were 1.00±0.00,0.80±0.05,1.47±0.09,0.40±0.01 and 0.62±0.09,respectively.Significant differences were found between model group and normal group,HSYA group and model group,3MA+HSYA group and 3MA group(P＜0.05,P＜0.01,P＜0.001).Conclusion HSYA may enhance autophagy levels in bEnd.3 cells after OGD through the SIRT1/FOXO3A pathway,inhibit cell apoptosis and alleviate BBB damage.

Objective We aimed to explore the mechanism of Ziyin Mingmu Formula in improving retinitis pigmentosa.Methods Twenty SD rats were randomly divided into the blank serum group and the Ziyin Mingmu Formula containing serum group using a random number table method,with 10 rats in each group.The rats in the Ziyin Mingmu Formula containing serum group were given Ziyin Mingmu Formula(46.875 g/kg),while the rats in the blank serum group were given distilled water.The Ziyin Mingmu Formula containing serum and blank serum were prepared.Analysis of chemical components in Ziyin Mingmu Formula containing serum using liquid chromatography-mass spectrometry technology.Adult retinal pigment epithelial cell line-19(ARPE-19)cells were treated with tunicamycin to induce endoplasmic reticulum stress injury model.The optimal volume fraction of Ziyin Mingmu Formula containing serum was screened by CCK-8.ARPE-19 cells were divided into the blank group,the model group,the blank serum group,the Ziyin Mingmu Formula containing serum group and the tauroursodeoxycholic acid group,each group is intervened separately.After 24 hours of intervention,the morphological observation of cells was performed using a multi-time dynamic cell function analysis system,cell survival rate was detected by CCK-8,cell apoptosis rate was detected by Annexin V-FITC/PI,and protein and mRNA expressions of 78 kDa glucose regulated protein(GRP78),inositol-requiring enzyme 1(IRE1)and activating transcription factor 6(ATF6)were detected by Western blotting and ddPCR.Results The main chemical components in Ziyin Mingmu Formula containing serum were obtained by liquid chromatography-mass spectrometry analysis,such as arbutin,salicylic acid,luteolin,Salvianolic acid A,erysovine,taurine,quercetin,maltol,baicalin,and danshensu.Compared with the model group,the number of cells in Ziyin Mingmu Formula containing serum group increased,the growth was more uniform,and the floating dead ARPE-19 cells and fragments decreased.The cell survival rate of Ziyin Mingmu Formula containing serum group and taursodeoxycholic acid group increased,and the cell apoptosis rate decreased(P<0.05).The protein expressions of GRP78,IRE1,and ATF6 in Ziyin Mingmu Formula containing serum group were decreased,and IRE1 and ATF6 in taursodeoxycholic acid group were decreased(P<0.05).The mRNA expressions of GRP78,IRE1,and ATF6 in Ziyin Mingmu Formula containing serum group and tauroursodeoxycholic acid group were decreased(P<0.05).Conclusion Ziyin Mingmu Formula can reduce the cell apoptosis of ARPE-19 cells induced by endoplasmic reticulum stress,and its molecular mechanism is related to down-regulating the expression of GRP78,IRE1,ATF6 and inhibiting the endoplasmic reticulum stress response.

Humans ; Osteoblastoma/surgery* ; Neck/surgery* ; Spinal Neoplasms ; Cervical Vertebrae

ObjectiveTo study the effect of Ziyin Mingmu Formula （滋阴明目方） on retinitis pigmentosa mice and its possible mechanism. MethodsSixty rd10 mice were randomly divided into model group， vitamin A group， and Ziyin Mingmu Formula low-， medium-， and high-dose groups， 12 mice in each group； twelve C57BL/6 mice as the blank group. The mice in Ziyin Mingmu Formula low-， medium-， and high-dose groups were given 13.5， 27.0 and 54.0 g/（kg·d） of Ziyin Mingmu Formula by gavage， respectively； mice in the Vitamin A group were given 750 IU/（kg·d） of vitamin A soft capsule by gavage； mice in the blank group and model group were given 13.5 ml/（kg·d） of physiological saline by gavage. Each group was gavaged once a day for 28 days. Fundus photography and optical coherence tomography were used to detect the morphology of the fundus and retina， TUNEL method was used to detect apoptosis， microtitre digital PCR and immunofluorescence double staining were used to detect glucose-regulated protein 78 （GRP78）， inositol-requiring enzyme 1 （IRE1）， activated transcription factor 6 （ATF6）， and C/EBP homologous protein （CHOP） mRNA and protein expression levels. ResultsIn the model group， optic discs were yellowish， fundus was atrophic with large pigmentation. The retinal blood vessels were thinned， a large number of vascular white sheaths were seen， the retinal cell nuclei disorganised， and a large number of apoptotic cells were seen； the fundus conditions of the mice in all dosages of Ziyin Mingmu Formula and the vitamin A group were improved to varying degrees compared with those of the model group， the apoptotic cells reduced， with Ziyin Mingmu Formula middle- and high-dose groups showing more significant improvement. Compared with the blank group， the retinal thickness of mice in the model group reduced， and the expression of GRP78， IRE1， ATF6， CHOP mRNA and protein elevated （P＜0.01）. Compared with the model group， retinal thickness increased and GRP78， IRE1， ATF6 mRNA and protein expression decreased in the vitamin A group and Ziyin Mingmu Formula medium- and high-dose groups； CHOP mRNA and protein expression decreased in low-， medium-， and high-dose groups of Ziyin Mingmu Formula （P＜0.05 or P＜0.01）. Compared with vitamin A group and the low-dose group of Ziyin Mingmu Formula， retinal thickness increased in the high-dose group of Ziyin Mingmu Formula （P＜0.01）. Compared with vitamin A group， GRP78， ATF6， IRE1， and CHOP mRNA expression decreased in the medium- and high-dose groups of Ziyin Mingmu Formula， and GRP78 and CHOP protein expression decreased （P＜0.05 or P＜0.01）. Compared with the low-dose group of Ziyin Mingmu Formula， CHOP protein expression reduced in the medium- and high-dose groups of Ziyin Mingmu Formula （P＜0.01）. ConclusionZiyin Mingmu Formula can reduce apoptosis of retinal tissues by inhibiting the endoplasmic reticulum stress response， thus slowing down the progression of retinopathy and protecting visual function in a dose-dependent manner.

After entering the body from the drug delivery site, antitumor nanomedicines need to cross a series of physiopathological barriers to reach the target site of action to effectively exert antitumor therapeutic effects. The ligand modification strategy is a classic method to enhance the efficiency of nanomedicine delivery in vivo, but the contradiction between the single ligand modification strategy, which is characterized by unity and stage, and the in vivo delivery process, which is characterized by versatility and whole-process characteristics, determines that nanomedicines modified by a single ligand alone cannot satisfy the target efficacy requirements. Therefore, the use of multiligand combinatorial modification strategies by virtue of nanomedicine surface area advantages is key to advancing the next generation of smart nanomedicines. In this paper, on the basis of summarizing and classifying the commonly used functional ligands for in vivo delivery, the advantages and research progress of multiligand combination modification of antitumor nanomedicines are discussed with special focus, and the multiligand combination modification is classified as synergistic and complementary according to the combination of the ligands, which is of great significance to ensure that antitumor nanomedicines can overcome the multiple physiopathological barriers to achieve precise delivery.