OBJECTIVE:To compare the anti-inflammation,analgesia effects of decoctions extracted from Aconiti lateralis with different leaf shapes(dahua leaf,xiaohua leaf)from different producing areas(Jiangyou,Butuo). METHODS:Animals were randomly divided into blank group(distilled water),positive group,groups of Aconiti lateralis with dahua,xiaohua leaf from Ji-angyou,groups of Aconiti lateralis with dahua,xiaohua leaf from Butuo(with dose of 5 g/kg,calculated by crude drug). The an-ti-inflammation effect of decoctions extracted from Aconiti lateralis with different variety sources and leaf shapes was investigated by xylene-induced ear swelling test (n=12) in mice and egg white-induced toe swelling test (n=10) in rats (positive drug was Dexamethasone acetate tablet,0.005 g/kg). And its analgesic effect was investigated by acetic acid-induced writhing body reaction test(n=12)and hot-plate-induced pain test(n=12)in mice(positive drug was Morphine hydrochloride tablet,0.0025 g/kg). RE-SULTS:The decoctions extracted from Aconiti lateralis with dahua,xiaohua leaf from Butuo and xiaohua leaf from Jiangyou can significantly reduce the ear swelling degree(P<0.01). The decoctions extracted from Aconiti lateralis with dahua leaf from Jiangy-ou and Butuo can significantly decrease the toe swelling degree after 6 h of medication(P<0.05). And decoctions extracted from Aconiti lateralis with xiaohua leaf from Butuo can significantly reduce the number of writhing body in mice with acetic acid-in-duced pain and prolong the pain threshold of mice with hot-plate-induced pain (P<0.05 or P<0.01). CONCLUSIONS:Aconiti lateralis with dahua and xiaohua leaf from Butuo and with xiaohua leaf from Jiangyou show better anti-inflammation effect,and Aconiti lateralis with xiaohua leaf from Butuo shows better analgesic effect.

Objective To investigate the effects of human leukocyte-associated antigen-G (HLA-G) expression in silencing trophoblast cell line JEG-3 under normal and hypoxic conditions on invasion and proliferation of JEG-3 cells. Methods Inhibition of HLA-G expression in JEG-3 cells by transfection of small interfering RNA (siRNA),the transfected JEG-3 cells were divided into 4 groups: normoxia control group, hypoxia control group, normoxia inhibition group and hypoxia inhibition group. The levels of HLA-G mRNA and protein in 4 groups of cells were detected by real-time quantitive PCR and western blot. The proliferation activity and invasion ability of 4 groups of cells were determined by methylthiazolyl tetrazolium (MTT) assay and invasion assay.Results (1) Real-time quantitive PCR technology showed: the level of HLA-G mRNA in the hypoxic inhibition group (0.220±0.050) was significantly different (P<0.05), when compared with that in the hypoxic control group (0.630±0.030) and normoxic inhibition group (0.400± 0.020). (2) Western blot analysis showed: the expression level of HLA-G protein in the hypoxic inhibition group was 0.260±0.010, statistically different from that in the hypoxic control group (0.850±0.100) and the normoxic inhibition group (0.560±0.020; P<0.05).(3) MTT showed: proliferative activity of JEG-3 cells in the normoxic inhibition group was 0.490 ± 0.070, the ability of cell proliferation was reduced. When compared with that in the normoxic control group (0.850±0.050), the differences was statistically significant (P<0.05). The proliferative activity of JEG-3 cells in the hypoxic inhibition group (0.330±0.070) was lower than that in the normoxic inhibition group (0.490±0.070), and there was a significant difference (P<0.05). (4) Invasion assay showed: compared with the normoxic control group (98±7), the invasive ability of JEG-3 cells in the normoxic inhibition group (73 ± 7) was weakened, and the difference was statistically significant (P<0.05). The number of transmembrane cells (52±11) of JEG-3 cells in the hypoxic inhibition group was lower than that in the hypoxic control group (72±7), and the difference was statistically significant (P<0.05). Compared with the normoxic inhibition group, the invasion ability of JEG-3 cells in the hypoxic inhibition group decreased, and the difference was statistically significant (P<0.05). Conclusion Under hypoxia, using siRNA technology to down-regulate the expression of HLA-G may affect the proliferation and invasion ability of trophoblast cells, which may be involved in the occurrence of hypertensive disorder of pregnancy.

Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.

BACKGROUND:Skeletal muscle insulin resistance is the key pathological link of type 2 diabetes.Static exercise can effectively improve skeletal muscle insulin resistance,but the mechanism remains unclear. OBJECTIVE:To explore the mechanism of static exercise on insulin resistance in the skeletal muscle of type 2 diabetic mice based on the phosphatidyl inositol 3-kinase(PI3K)/protein kinase B(AKT)/glucose transporter(GLUT4)signaling pathway. METHODS:After 1 week of adaptive feeding,7 out of 40 C57BL/6 mice were randomly selected as blank group and fed common diet,while the other mice were fed high-fat diet and taken to prepare type 2 diabetes models through the low-dose streptozotocin intraperitoneal injection.Twenty-four mice were successfully modeled and they were randomly divided into model group(n=8),metformin group(n=8)and static exercise group(n=8),which continued to be fed high-fat diet.The metformin group was given 200 mg/kg metformin dissolved in normal saline(2 ml/kg)by gavage,once a day,for 6 weeks.The static exercise group was given normal saline daily by gavage and carried out static exercise,30 minutes a day,6 days per week.The model group was given the same dose of normal saline daily by gavage without exercise intervention.After the intervention,the fasting blood glucose of each group was detected,the intraperitoneal glucose tolerance test was performed,and the area under the glycemic curve was calculated.Glycosylated hemoglobin,serum insulin,insulin resistance index were detected by ELISA.Total cholesterol,triglyceride,high-density lipoprotein,low-density lipoprotein were detected using biochemical methods.The mRNA expression levels of PI3K,AKT and GLUT4 in the gastrocnemius of mice were detected by real-time quantitative PCR.Morphological changes of the gastrocnemius were observed by hematoxylin-eosin staining,and the cross-sectional area of muscle fibers was calculated. RESULTS AND CONCLUSION:Compared with the blank group,fasting blood glucose,glycosylated hemoglobin,area under the glycemic curve,insulin resistance index,total cholesterol,triglyceride and low-density lipoprotein levels were significantly increased in the model group(P<0.01,P<0.05).Whereas,these indicators were significantly lower in the static exercise and metformin group than the model group(P<0.01,P<0.05).Compared with the blank group,serum insulin and high-density lipoprotein levels were significantly declined in the model group(P<0.01)and the mRNA expression of PI3K,AKT and GLUT4 in the gastrocnemius of mice were also significantly reduced(P<0.01).These indicators were significantly elevated in the metformin group and static exercise group compared with the blank group(P<0.01).Compared with the blank group,the muscle fibers in the model group were disordered,and the muscle cells atrophied and the muscle fiber gap widened.The cross-sectional area of muscle fibers was significantly decreased in the model group compared with the blank group(P<0.01).Compared with the model group,atrophy of the gastrocnemius fibers and muscle fiber space were improved in the static exercise group and the metformin group,and the cross-sectional area of muscle fiber was significantly increased in both groups(P<0.01).These findings indicate that static resistance training may promote glucose uptake and utilization by up-regulating the expression of PI3K,AKT and GLUT4 mRNA in skeletal muscle tissue,thereby improving the morphology and function of skeletal muscle tissue,alleviating insulin resistance and regulating glucose homeostasis.

Objective:To study the changes in serum small molecule metabolites after brucella infection in humans using untargeted metabolomics methods, and screening representative biomarkers. Methods:A total of 109 serum samples collected from January 2019 to December 2021 at the Brucellosis Clinic of the Baotou Center for Disease Control and Prevention were divided into acute phase group ( n = 40), chronic phase group ( n = 35) of brucellosis, and healthy group ( n = 34) based on clinical diagnosis. Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry technology was used to test serum samples and screen for differential metabolites. Receiver operating characteristic curve was used to evaluate the predictive ability of differential metabolites for brucellosis. Enriched pathways were screened using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway to identify metabolic pathways significantly affected. Results:A total of 17 differential metabolites were screened between the acute phase group and the healthy group, and 12 differential metabolites were screened between the chronic phase group and the healthy group. There were a total of 5 differential metabolites (oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid) statistically significant among the three groups ( F = 16.84, 17.52, 14.31, 13.01, 20.76, P < 0.05). KEGG pathway analysis showed that the differential metabolites in the acute phase group were enriched in metabolic pathways such as ether lipid metabolism, glycerophosphate metabolism, sphingolipid signal and sphingolipid metabolism. The differential metabolites in the chronic phase group were enriched in metabolic pathways such as glycerophosphate metabolism, ether lipid metabolism, protein digestion and absorption metabolism. Conclusion:Untargeted metabolomics methods can screen out serum small molecule metabolites that undergo changes after brucella infection in the human body, including oleamide, linoleamide, stearamide, palmitoleic acid, α-linolenic acid can serve as potential biomarkers to distinguish brucellosis patients from healthy people.

Objective:To explore the effect of remote blood glucose management led by specialist nurses on blood glucose, self-management ability and quality of life of type 2 diabetic patients during home rehabilitation.Methods:From January to December 2019, convenience sampling was used to select 218 patients with type 2 diabetes in the First Affiliated Hospital of Xinjiang Medical University. According to the random number table method, the patients were divided into the observation group and the control group, each with 109 cases. The control group conducted conventional blood glucose management, and the observation group implemented remote blood glucose management led by specialist nurses for a total of three months of observation. Both were observed for 3 months. The self-management behavior and quality of life of the two groups of patients before and after the intervention were evaluated with the Diabetes Self-Management Behavior Scale (SDSCA) and the Diabetes Quality of Life Specific Scale (DSQL), and the blood glucose indicators of the two groups before and after the intervention were compared.Results:All 218 cases cooperated to complete all the research contents, and there was no dropout case. After the intervention, the fasting blood glucose, two hours postprandial blood glucose, glycosylated hemoglobin and DSQL score of the observation group were lower than those of the control group, and the SDSCA score was higher than that of the control group. The differences were all statistically significant ( P<0.05) . Conclusions:Compared with conventional blood glucose management, the remote blood glucose management led by specialist nurses can more effectively control the blood glucose of patients with type 2 diabetes, improve the patients' self-management ability and quality of life, and overall increase the management efficiency of patients during home rehabilitation.

OBJECTIVE To assess the long-term cost-effectiveness of five glucagon-like peptide-1 receptor agonists （GLP- 1RAs） in the treatment of poorly controlled type 2 diabetes mellitus （T2DM） treated with metformin. METHODS Baseline data from patients in previously published meta-analysis and included randomized controlled trials （RCTs） were extracted to predict survival， long-term efficacy， and costs for each group using the United Kingdom prospective diabetes study outcome model 2.1. The cost-effectiveness of 5 GLP-1RAs （liraglutide， lixisenatide， exenatide， dulaglutide， and semaglutide） was analyzed by cost- utility analysis. Sensitivity analysis and scenario analysis were also performed to verify the uncertainty of basic analysis results. RESULTS A total of 21 RCTs with 6 796 patients were included. Survival analysis curves showed the superiority of semaglutide in reducing the risk of death from cardiovascular disease and dulaglutide in reducing the risk of all-cause mortality over other GLP- 1RAs. The cost-utility analysis showed that the five drugs were economically superior to inferior in the order of lixisenatide， semaglutide， exenatide， dulaglutide， and liraglutide； one-way and probabilistic sensitivity analyses indicated that the results were robust. The scenario analysis results indicated that the price of semaglutide should decrease by at least 54.64% to 369.21 yuan， which is cost-effectiveness compared to lixisenatide. CONCLUSIONS For T2DM patients in China with poor glycemic control after treatment with metformin， lixisenatide and semaglutide may be considered as the preferred regimen.

To detemine the expression pattern of mTOR complex subunits Raptor and Rictor in the hair follicles of mice at different hair follicle stages, and to explore its significance. 
 Methods: Immunostaining of Ki-67, a proliferative marker, was used to determine the precise hair follicle stages of mouse dorsal skin at different postnatal time points. Real-time PCR was used to detect the mRNA expression of Raptor and Rictor in mouse dorsal skin at 43 days after birth (P43, early telogen), 56 days after birth (P56, mid-telogen), 69 days after birth (P69, late telogen) and 74 days after birth (P74, early anagen). The expression intensity and localization of Raptor and Rictor at different stages of hair cycle were tested by co-immumostaining.
 Results: Ki-67 immunostaining showed that the time points (P43, P56, P69, P74) and hair follicle stages (early telogen, mid-telogen, late telogen, early anagen) of the dorsal skin were consistent with each other. The results of real-time PCR and immunostaining were consistent, showing that the expression of Raptor and Rictor did not changed in the early-, mid-, late telogen, and early anagen. However, Raptor was specifically expressed in the bulge where hair follicle stem cells (HFSCs) are residing in, and Rictor was mainly detected in inner root sheath (IRS) cells. 
 Conclusion: The expression of Raptor and Rictor does not altered in the hair follicles at different hair follicle stages, but Raptor and Rictor are specifically expressed in the HFSCs and IRS cells, respectively, indicating that Raptor might be a molecular marker for HFSCs, and Rictor might be involved in the maintenance of IRS and formation of hair shaft.
Animals ; Hair ; Hair Follicle ; Mice ; Rapamycin-Insensitive Companion of mTOR Protein ; Raptors ; Skin ; TOR Serine-Threonine Kinases

ObjectiveTo determine the syndrome of a rat model of follicular dysplasia induced by Tripterygium glycosides based on prescriptions and investigate the mechanism of traditional Chinese medicine intervention via the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/hypoxia-inducible factor-1 （HIF-1）/vascular endothelial growth factor （VEGF） pathway. MethodForty-eight rats with regular estrous cycles were randomly assigned into a normal group （n=8） and a modeling group （n=40）. The rats in the modeling group were administrated with Tripterygium glycoside suspension （75 mL·kg^-1） by gavage for 30 days. The modeled rats were assigned into model， Siwutang （3.69 g·kg^-1）， Youguiyin （3.11 g·kg^-1）， Zuoguiyin （7.29 g·kg^-1）， and Guishenwan （10.35 g·kg^-1） groups， with 8 rats in each group. The drug intervention lasted for 14 days. The changes of estrous cycle were detected by Pap staining， and a stereoscope was used to observe the morphology of the ovarian tissue. Hematoxylin-eosin staining was employed to observe the pathological changes and follicle count in the ovarian tissue. Enzyme-related immunosorbent assay （ELISA） was used to measure the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） in the serum. Real-time fluorescence quantitative polymerase chain reaction and Western blot were employed to determine the mRNA and protein levels， respectively， of AMPK， mTOR， HIF-1， and VEGF in the ovarian tissue. ResultCompared with the normal group， the model group had a disordered estrous cycle， reduced secondary and mature follicles， increased atretic follicles， elevated FSH and LH levels， lowered E₂ level， up-regulated mRNA and protein levels of AMPK， and down-regulated mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with the model group， Guishenwan increased secondary and mature follicles， decreased atretic follicles， lowered the FSH and LH levels， elevated the E₂ level， down-regulated the mRNA and protein levels of AMPK， and up-regulated the mRNA and protein levels of mTOR， HIF-1， and VEGF （P<0.01）. Compared with Guishenwan group， Siwutang， Youguiyin， and Zuoguiyin decreased mature follicles， increased atretic follicles （P<0.01）， elevated the LH （P<0.01） and FSH （P<0.05） levels， and lowered the E₂ level （P<0.05）. In addition， Youguiyin up-regulated the protein level of AMPK （P<0.05） and down-regulated the mRNA levels of mTOR and HIF-1 （P<0.01） as well as the mRNA and protein levels of VEGF （P<0.01）. Siwutang down-regulated the mRNA levels of mTOR and HIF-1 as well as the mRNA and protein levels of VEGF （P<0.05）. Zuoguiyin down-regulated the mRNA level of mTOR and the protein and mRNA levels of VEGF （P<0.05）. ConclusionGuishenwan may improve the ovarian function and promote follicle maturation in a rat model of follicular dysplasia by inhibiting the AMPK/mTOR/HIF-1/VEGF pathway， with the therapeutic effect superior to Zuoguiyin， Youguiyin， and Siwutang. It was hypothesized that this model presented the syndrome of kidney-essence deficiency.

OBJECTIVE：To provide reference for the identification and proces sing end-point determination of raw Morus alba and its processed products （honey-processed M. alba ）. METHODS ：UPLC method was adopted. The determination was performed on Waters BEH Shield RP C 18 column with mobile phase consisted of acetonitrile- 0.1％ phosphoric acid solution （gradient elution ） at the flow rate of 0.30 mL/min. The column temperature was set at 30 ℃. The program wavelengths were set at 280 nm（0-4 min） and 320 nm（4-35 min）. Similarity Evaluation System for Chromatogram Fingerprint of TCM （2012 edition）was used to establish UPLC fingerprint and carry out similarity evaluation of 13 batches of M. alba and honey-processed M. alba . The chromatographic peaks were identified with reference substance fingerprint. The colorimetric value （L，a，b） of 13 batches of M. alba and honey-processed M. alba powder were determined ，and average total colorimetric value （E）was calculated. OPLS-DA and cluster analysis were adopted to analyze the differences in fingerprints and colorimetric values of M. alba before and after processing. At the same time ，the dynamic change rule of fingerprint and colorimetric value of honey-processed M. alba at different processing time points were analyzed to determine the processing end-point. RESULTS ：There were obvious differences in fingerprints before and after processing ，and the similarity of 13 batches of M. alba and honey-processed M. alba were all higher than 0.9. Totally 21 common peaks were calibrated for M. alba ，and 23 common peaks for honey-processed M. alba ；peak 1 and peak 2 were newly produced compounds of honey-processed M. alba . Peak 2，peak 7，peak 14 and peak 19 were identified as 5-hydroxymethylfurfural， mulberry glucoside A ，oxidized resveratrol ，mulberry flavonoids G. Results of OPLS-DA showed that the peak area-sample quantity ratio of peak 1，peak 2，peak 18，peak 20 and the chromaticity values （L，a，b）were the most important factors affecting the difference of raw and processed products of M. alba . When the E ranged 75.84-80.88 as the processing end-point of honey-processed M. alba ，the processing time was determined as 22-34 min. CONCLUSIONS ： The established UPLC fingerprint and colorimetric value determination method can be used to identify the raw and processed products of M. alba as well as determine the processing end-point of honey-processed M. alba .