Organ transplantation is the optimal treatment for patients with an end-stage organ disease.The induction of donor-specific tolerance is necessitatd because of severe side-effects of immunosuppression and chronic rejection of the transplanted organ that defy management.Bone marrow infusion and costimulatory blockade are considered to be the most effective strategies to induce immune tolerance.This review briefly discusses the mechanism and clinical application of immune tolerance induced by bone marrow infusion combined with costimulatory blockade.

Sepsis leads to inhibition of protein synthesis , known as leucine resistance .mTOR regulates protein synthesis by phosphorylation of S6K1 and 4E-BP1.AMPK is an important negative regulator of mTOR and its activity is in an abnormal state in sep-sis.This review briefly discusses the AMPK/mTOR pathway in Sepsis-induced leucine resistance .

Objective To explore the efficacy and the safety of clinical trials of pemetrexed combined with carboplatin and gemcitabine with carboplatin in treating advanced NSCLC of the elderly patients.Methods A total of one hundred and twenty-eight elderly patients with advanced NSCLC were randomly divided into two groups(n=64).The PC group in which patients were treated with pemetrexed combined with carboplatin,and the GC group in which patients were treated with gemcitabine combined with carboplatin.The effects and the safety were assessed by the following indexes, treatment efficiency,side effects,LCSS. Results The treatment efficiency of the PC group and the GC group were 34.38% and 31.25% after chemotherapy.The difference was no statistically significant between two groups.The difference of LCSS was no statistically significant between two groups.Except hair loss,the incidences of nausea and vomiting,leukopenia,thrombocytopenia and neurotoxicity (grade III-IV )in the PC group (6.25%,3.13%,4.67%,7.81%)were significant lower than those in the GC group(17.18%,20.31%,15.63%,18.75%)(P<0.05).The 1-year and 2-year survival rates of the PC and GC groups were 46.2% VS 46.8% and 13.3% VS 12.5%,respectively,with a median survival of 12.1 VS 1 1.3 months,without a statistically significant difference between two groups.Conclusion PC and GC show similar efficacy for elderly NSCLC patients,however,the toxicities in PC patients are lower than those in GC patients.Thus,pemetrexed combined with carboplatin is an effective therapeutic regimen for advanced NSCLC in elderly patients.

AIM To investigate the effects of several 5-hydroxytryptamine(5-HT) subtype receptor antagonists on late slow excitatory postsynaptic potential(LS-EPSP) of the neurons of guinea pig inferior mesenteric ganglion(IMG). METHODS Intracellular recordings were made from neurons of the isolated guinea pig IMG. RESULTS Cyproheptadine and BRL 24924 suppressed LS-EPSP of 5-HT sensitive neurons reversibly, while mianserin, MDL 72222 and spiperone showed no significant effect. Continuous superfusion of IMG with MCPP suppressed LS-EPSP of 5-HT sensitive neurons by 5-HT 1P receptor desensitizated. CONCLUSION LS-EPSP of 5-HT sensitive neuron is mediated by 5-HT 1P subtype receptor.

Objective To introduce an operative method of rhytidectomy with W-incision and fewer complications for facial rejuvenation.Methods A total of 84 patients were treated with rhytidectomy by multi-methods and followed up from January 2007 to December 2012.The rhytidectomy was done along the temporal hairline edge through the combined procedures,including sharp and blunt separation,liposuction and filling with autologous fat,tighting and fixing the fascial flap of superficial musculoaponeurotic system,as well as the suspension of the zygomatic cheek fiber fat pad.Results Follow-up for 3 moths to 2 years after surgery in 84 patients showed that the wound was healing with good concealment and without complications such as facial nerve injury or local uneven.All the cases achieved good results in facelift with high satisfaction rate after the combined operations.Conclusions This combined rhytidectomy is safe,effective,simple and easy.And it is a good and ideal approach of facial rejuvenation worthy of clinical application.

Objective To activate and amplify γδT cells with low molecular peptide antigen of Mycobacterium tuberculosis low molecular peptide antigen (Mtb-Ag),and to investigate the expression of CD69 molecules on γδT cellular surface.Methods Healthy human peripheral blood mononuclear cells (PBMC) were obtained and separated,then positive cells were isolated by immuno-magnetic beads selection,and the proportion of γδT cells in the PBMCs was detected by fluorescent monoclonal TCR γδT-PE staining and flow cytometry.Expression of CD69 molecules in γδT cells was detected by γδ-PE/CD69 FITC double staining.Results The proportion of γδT cells was (4.9±1.85)％ in freshly obtained PBMC,(69.2±6.57)％ after 10 d of Mtb-Ag activation,and (99.3±8.92)％ after immuno-magnetic beads selection.The expression of CD69 molecules in γδT cells reached the peak (75.2％) at 24 h after initial Mtb-Ag stimulation,and reached the peak (72.0％) at 6 h after second stimulation.Conclusions MtbAg can specifically stimulate the proliferation of γδT cells in the PBMC.Both its initial and the second stimulation can specifically activate γδT cells.

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.

[Abstract] Objective: To investigate the effect of metformin on the senescence-associated secretory phenotype (SASP) of doxorubicin-induced gastric cancer BGC823 cells. Methods: Human gastric cancer BGC823 cells were cultured in vitro and treated with doxorubicin at gradient concentrations (50, 100, 150 and 200 nmol/L). Cell senescence was detected by SA-β-gal staining, and SASP factor expression was detected by ELISA. The effects of metformin on cell senescence and SASP factor secretion induced by doxorubicin (100 nmol/L) were observed by adding gradient concentrations of metformin (0, 5, 10 and 20 mmol/L). Results: With the increase of doxorubicin concentration and treatment time, the senescence rate of gastric cancer BGC823 cells increased first and then decreased. At 96 h after 100 nmol/L doxorubicin treatment, the peak aging rate reached 68.7%, accompanied with significantly increased expressions of SASP factors IL-1a, IL-6, IL-8 and CXCL1. The proportion of senescent cells was (55.2±1.9)%, (48.7±2.2)% and (40.8±2.3)% respectively under the effects of 5, 10 and 20 mmol/L metformin, which was significantly lower than that in the non-metformin treatment group (P< 0.01). At the same time, with the increase of metformin concentration, the production of SASP factors IL-1α, IL-6, IL-8 and CXCL1 showed a gradient decline. Compared with the non-metformin treatment group, IL-6 and IL-8 decreased significantly under the effect of metformin above 10 mmol/L (P<0.05 or P<0.01), while IL-1α and CXCL1 decreased significantly under the effect of 20 mmol/L metformin (all P<0.05). Conclusion: Metformin can inhibit the senescence and SASP production of gastric cancer cells induced by doxorubicin.

ObjectiveTo explore the anti-gout effect and mechanism of Derris eriocarpa extract by network pharmacological analysis combined with in vivo and in vitro experimental verification. MethodThe chemical components and candidate targets of D. eriocarpa were obtained from the database. The key targets and potential active components of D. eriocarpa in the treatment of gout were screened by the protein-protein interaction analysis， and then the Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were performed for the key targets. A mouse model of hyperuricemia was established by intraperitoneal injection of hypoxanthine to observe the effect of D. eriocarpa alcohol extract on hyperuricemia. A rat model of gouty inflammation induced by the injection of microcrystalline sodium urate crystals into the foot and plantar was used to observe the effect of D. eriocarpa alcohol extract on gouty inflammation. A xylene-induced acute inflammation model was established to observe the anti-inflammatory effect of D. eriocarpa alcohol extract. The hot plate test and twisting test were performed to observe the pain-relieving effect of D. eriocarpa. The lipopolysaccharide （LPS）-induced RAW264.7 cells were used to study the anti-gout effect and mechanism of D. eriocarpa alcohol extract. ResultA total of 12 key targets and 15 potential active components were obtained from the D. eriocarpa-component-gout target network. The emodin， betulinic acid， and medicarpin endowed D. eriocarpa with anti-hyperuricemia， anti-inflammatory， and pain-relieving effects by acting on Toll-like receptor 4 （TLR4）， NOD-like reception protein 3 （NLRP3）， and nuclear factor （NF）-κB. Compared with the control group， the model groups showed elevated serum uric acid level in mice （P<0.01）， increased swelling degree of rats （P<0.05， P<0.01）， alleviated the auricular swelling of mice （P<0.05）， reduced the twisting times of mice （P<0.05， P<0.01）， and increased the hot plate pain threshold （P<0.05）. Moreover， the model group showed up-regulated mRNA level of TLR4 and protein levels of TLR4， NF-κB， and NLRP3 in cells （P<0.01）， and elevated levels of TLR4 and NF-κB in the cell supernatant （P<0.05， P<0.01）. Compared with the model group， the alcoholic extracts （20， 10， 5 g·kg^-1） of D. eriocarpa lowered the serum uric acid level in hyperuricemic mice （P<0.01）， inhibited foot and plantar swelling in rats （P<0.05， P<0.01）， down-regulated the mRNA level of TLR4 and the protein levels of TLR4， NF-κB， NLRP3 in cells， and lowered the levels of TLR4， TNF-α， NF-κB， and IL-6 in cell supernatants （P<0.05， P<0.01）. ConclusionD. eriocarpa alcohol extract may exert the anti-gout， anti-inflammatory， and pain-relieving effects by regulating the TLR4/NF-κB/NLRP3 signaling pathway.

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