Objective: The study was designed to evaluate the changes and significance of circulating CD4~+CD25~+ and CD8~+CD28~- regulatory T cells (Tregs) in patients with multiple myeloma (MM).Methods:CD4~+CD25~+ and CD8~+CD28~-Tregs in peripheral blood of 38 patients with MM and of 20 healthy doners were measured by flow cytometry.Serum albumin and β_2-MG in patients with MM were measured using bromocresol green method,transmission turbidimetry respectively.Results:Compared to those of the controls,the proportions of CD4~+CD25~(+/high),CD4~+CD25~(high) CD127~(low) and CD8~+CD28~-Treg cells in newly diagnosed MM patients were elevated.Furthermore,the proportions of CD4~+CD25~(high) and CD4~+CD25~(high)CD127~(low) Tregs in each clinical stage were elevated when compared to those of the controls.The number of the Tregs were increasing with clinical stages and were significantly higher in stage Ⅲ MM than in stageⅠ MM;In stageⅡand Ⅲ MM,there were also elevated proportions of CD8~+CD28~- Tregs,increasing with clinical stages.However,there were no differences when compared between stage Ⅰ MM and the controls;Both the proportions of CD4~+CD25~(+/high) and CD4~+CD25~(high)CD127~(low) Tregs in active MM were not different from stable MM,although all of them were higher than those of controls.The proportion of CD8~+CD28~- Tregs was higher in active MM than in stable MM and controls,but there were no differences when compared between active and stable MM.The proportions of both CD4~+CD25~(high) Tregs and CD4~+CD25~(high)CD127~(low)Tregs had negative correlation with the levels of serum albumin.Conclusion:MM patients have elevated levels of circulating CD4~+CD25~+ and CD8~+CD28~-Tregs,which may be an important mechanism of MM immune evasion,and may be associated with clinical stages,disease progression and prognosis of MM to some extent.

Objective:To preliminarily study the immune response mediated by inducible costimulation molecule in the role of essential hypertensive renal damage .Methods: The blood pressure of spontaneously hypertensive rats and the wild control group (Wistar-Kyoto rats)was dynamically monitored by noninvasive tail artery blood pressure measuring instrument .The urine protein of the rats in 24 hours was dynamically detected by ELISA .The levels of ICOS protein and its mRNA in the rat′s kidneys were dynamically detected by immunohistochemistry , RT-PCR, respectively.The levels of IL-17A and TGF-β1 in the rat′s plasma and kidneys were dynamically detected by ELISA ,immunohistochemistry ,respectively.The renal pathological changes of the rats were detected by HE and MASSON staining.Results:The blood pressure and urine protein in 24 h of SHRs were significantly higher than that of group WKY from 6 weeks.The expression of ICOS protein and its mRNA in SHRs were significantly higher than that of WKY rats from 6 weeks,and there are significantly positive correlations between the dynamic change of ICOS protein and its mRNA and renal fibrosis score of SHRs (rA=0.813,PA<0.05;rB=0.753,PB<0.05).The expression of IL-17A and TGF-β1 in SHR′s plasma and kidneys were significantly higher than that of WKY rats at the weeks 10 and 23.HE and Masson staining showed that the degree of renal fibrosis of SHRs was sig-nificantly higher than that of WKY rats at 23 weeks.Conclusion:The immune response mediated by ICOS plays an important role in hypertensive renal damage .

Objective:To observe the dynamic variation of serum ferritin (SF), folic acid, and vitamin B_(12) levels in patients with acute promyelocytic leukemia (APL) at different disease stages. Methods:Serum SF, folic acid and vitamin B_(12) levels were successively tested in thirty-six patients with primary APL every 1 to 3 months by using chemiluminescence analysis. Five different disease stages were selected as dynamic observation time points: first diagnosed, first complete remission (CR1), six months after CR1, relapsed stage,and CR1 for three years. Results:There were 75.0%(27/36)of patients with abnormal high levels of SF, 77.8% (28/36)of patients with abnormal low levels of folic acid, and 100%(36/36)of patients with increased vitamin B_(12) levels in first diagnosed stage. The number of patients with abnormal variations of SF, folic acid and vitamin B_(12) level was decreased in CR1 stage compared with those in first diagnosed stage (SF: P<0.05;folic acid and vitamin B_(12): P<0.01). The serum SF, folic acid and vitamin B_(12) levels tended to recover step by step with chemotherapy. At six months after CR1 the three parameters of most patients recovered to normal levels. APL was relapsed in 4 patients after 1-year CR. Both SF and vitamin B_(12) levels were increased and the folic acid level was decreased compared with those before replase, but the difference had no significance (P>0.05). The serum SF, folic acid and vitamin B_(12) levels were in normal ranges in the patients who had 3-year CR. Conclusion:The serum SF, folic acid and vitamin B_(12) levels had dynamic variation in APL course. Increase in serum SF and vitamin B_(12) as well as decrease in folic acid are related with the active degree of APL and its tumor load.

OBJECTIVE: To observe the short-term and long-term curative effect of the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer) application used in the 82 cases postoperative tissue shortage repair that after the head neck carcinoma resection. METHOD: To held the 82 cases head neck carcinoma postoperative mucosa shortage repaired after resection by the xenogenic acellular dermal matrix membrane (or joint muscle flap transfer), 65 cases mucosa shortage wound be directly covered by the repair membrane and the other 17 cases mucosa shortage wound be repaired by the tranfered muscle tissue flap with the repair membrane covered; 53 cases underwent additional postoperative radiotherapy between 2-4 weeks and follow-up in 1, 3, 6, 12, 18, 24, 30, 36, 48, 60 months and observed the operation site repair process through the electronic laryngoscope, observed the patients respiration, swallow, phonation function. RESULT: Seventy-seven cases patients operation incision reached I phase healing standard, another 5 cases patients operation incision reached II phase healing standard because of the wound infection and fully-recovered through the local wound drainage,dressing process. All the patients tracheal cannula,the stomach tube be extubated successfully and without the local cicatricial constriction occurred. Seventy-eight cases follow up period reached 1 year including 53 cases who underwent postoperative radiotherapy, 49 cases follow up period reached 3 years including 32 cases who underwent postoperative radiotherapy, 14 cases follow up period reached 5 years including 12 cases who underwent postoperative radiotherapy. The patients with static local lesions discovered no reaction such as exclusion, allergy. CONCLUSION The application of xenogenic acellular dermal matrix membrane (or joint muscle flap transfer used in in the postoperative tissue shortage repair that after the head neck carcinoma resection have several advantage such as comparatively easily implementation, operation safety edge enough,well preserved organ function, comparatively low incidence about the laryngeal stenosis, the short-term and long-term repair effect are all exact.
Acellular Dermis ; Carcinoma, Squamous Cell ; radiotherapy ; surgery ; Female ; Head and Neck Neoplasms ; radiotherapy ; surgery ; Humans ; Male ; Mucous Membrane ; surgery ; Postoperative Period ; Squamous Cell Carcinoma of Head and Neck ; Surgical Flaps ; transplantation ; Wound Healing

Objective To investigate the relationship between serum cholesterol levels and immunoglobin types and clinical stages in the patients with multiple myeloma (MM). Methods We retrospectively analyzed the blood lipid levels in 65 patients with MM at diagnosis, including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein Al (apo-Al) and apolipoprotein B (apo-B), and explored relationship between lipid parameters and immunoglobulin types or clinical stages in patients with MM. Thirty healthy persons were served as controls. Results Of the 65 MM patients, 53.85% were IgG type, 63.1 % were at stage Ⅲ. The levels of TC, HDL-C, LDL-C, apo Al and apo B in the patients with MM were significantly lower than that in the controls (P <0.05), and TG in MM patients was no difference with that in the controls (P >0.05). Except one case of IgD type, the levels of TC, HDL-C, LDL-C, apo Al and apo B in Ig G and Ig A types of patients were significantly lower than that in the light chain type among other 64 cases (P <0.05), and TG levels in different immunoglobulin types was found no statistical differences. The levels of TC, HDL-C, LDL-C and apo A1 in the patients with stage Ⅲ were lower than that of stage I and controls (P <0.05), furthermore, the level of LDL in stage Ⅱwas lower than that in stage Ⅰ. Conclusion Hypocholesterolemia are seen in the patients with MM and serum cholesterol levels are related to MM staging.

Lignocellulose is the most abundant renewable biomass resource. Enzymatic breakdown of lignocellulose into oligosaccharides or monosaccharides is the key to exploit lignocellulosic biomass. However, traditional glycoside hydrolases are insufficient to degrade lignocellulose. The emergence of lytic polysaccharide monooxygenase, a novel enzyme for lignocellulose degradation, has enriched the deconstruction schema and accelerated the enzymatic conversion of polysaccharides, by introducing new chain breaks that allow hydrolases to initiate further degradation. Here, we review the discovery, classification and catalytic mechanism of the enzyme, as well as the methods for assaying its activity. The prospect for its application in feed additive, functional food and biofuel development is further discussed.

Isopeptide bond-mediated molecular superglue is the irreversible covalent bond spontaneously formed by the side chains of lysine (Lys) and asparagine/aspartic acid (Asn/Asp) residues. The peptide-peptide interaction is specific, stable, and can be achieved quickly without any particular physicochemical factor. In the light of recent progress by domestic and foreign researchers, here we summarize the origin, assembly system and mechanism of isopeptide bond reaction, as well as the molecular cyclization and protein topological structure mediated by it. The prospect for its application in synthetic vaccine, hydrogel and bacterial nanobiological reactor is further discussed.
Cyclization ; Lysine ; Peptides ; chemistry ; Proteins

OBJECTIVE: To study the effect of dexmedetomidine (Dex) on cognitive dysfunction induced by tibial fracture in rats. METHODS: Sixteen male SD rats were randomized into control group and tibial fracture group, and the behavior indicators were measured on days 1, 3, 5 and 7 after tibial fracture and the expressions of CX3L1 protein and mRNA in the hippocampus were detected. Another 24 male SD rats were randomly divided into control group, tibial fracture group, and tibia fracture with CX3CL1 antibody group, and the behavior indicators and hippocampal CX3L1 protein expression were evaluated after corresponding treatments. In another experiment, we randomized 24 male SD rats into control group, tibial fracture group and tibial fracture with Dex treatment, and tested their hippocampal CX3L1 protein and mRNA expressions as well as the behavior indicators after the treatments. RESULTS: Compared with the control rats, the rats with tibial fracture spent significantly less time in the novel arm on days 1, 3, 5 and 7 after the fracture ( < 0.05) with obviously lowered expressions of CX3L1 protein and mRNA in the hippocampus ( < 0.05). In the rats with tibial fracture, treatment with CX3CL1 antibody further decreased the time spent in the novel arm ( < 0.05) and the expression level of CX3L1 protein in the hippocampus ( < 0.05); In contrast, treatment with Dex significantly increased the time spent time in the novel arm ( < 0.05) and enhanced the hippocampal expressions of CX3L1 protein and mRNA in rats with tibial fractures ( < 0.05). CONCLUSIONS Dex can alleviate cognitive dysfunction induced by tibial fracture in rats by increasing the expression of CX3CL1 in the hippocampus.
Animals ; Cognitive Dysfunction ; Dexmedetomidine ; Hippocampus ; Male ; Rats ; Rats, Sprague-Dawley ; Tibial Fractures

OBJECTIVE： To study the mechanism of couplet medicine of Tripterygium hypoglaucum-Spatholobus suberectus in the treatment of rheumatoid arthritis （RA）. METHODS： The RA targets were retrieved and obtained by therapeutic target database （TTD）， DrugBank and DisGeNET databases， and the protein protein interaction （PPI） network was constructed to screen its key targets. Using oral bioavailability（OB）≥30％， drug like（DL）≥0.18 and drug half-life （HL） ≥4 h as index， active components were obtained from couplet medicine of T. hypoglaucum-S. suberectus by using TCM systematic pharmacological analysis platform （TCMSP） and TCM integrated database （TCMID）， and the targets were predicted. The active component-target network of couplet medicine of T. hypoglaucum-S. suberectus was constructed. Systems Dock Web Site online platform and Genomics platform were used to screen the active component and common targets of RA of couplet medicine of T. hypoglaucum-S. suberectus； KEGG signaling pathways of common targets were analyzed by using Cluego plug-in unit of Cytoscape 3.2.1 software. RESULTS： Totally 1 956 RA targets were retrieved， involving 11 key targets [such as IL-6， TNF， VEGFA]. The couplet medicine contained 30 active components （including luteolin， erythroxanthin， β-sitosterol and triptolide） and 229 targets. There were 37 common targets for couplet medicine of T. hypoglaucum-S. suberectus and RA （including MMP2， TNF， VEGFA）. KEGG signaling way involved cell apoptosis， IL-17 signaling pathway， Th17 cell differentiation pathway and TNF signaling pathway. CONCLUSIONS： The couplet medicine of T. hypoglaucum-S. suberectus may play a role in the treatment of RA by acting on cell apoptosis， IL-17 signaling pathway and other signaling pathways through MMP2， TNF， and VEGFA target. The results of this study can provide a reference for further study on the mechanism of the effects of couplet medicine of T. hypoglaucum-S. suberectus on RA.

The capacity for thermal tolerance is critical for industrial enzyme. In the past decade, great efforts have been made to endow wild-type enzymes with higher catalytic activity or thermostability using gene engineering and protein engineering strategies. In this study, a recently developed SpyTag/SpyCatcher system, mediated by isopeptide bond-ligation, was used to modify a rumen microbiota-derived xylanase XYN11-6 as cyclized and stable enzyme C-XYN11-6. After incubation at 60, 70 or 80 ℃ for 10 min, the residual activities of C-XYN11-6 were 81.53%, 73.98% or 64.41%, which were 1.48, 2.92 or 3.98-fold of linear enzyme L-XYN11-6, respectively. After exposure to 60-90°C for 10 min, the C-XYN11-6 remained as soluble in suspension, while L-XYN11-6 showed severely aggregation. Intrinsic and 8-anilino-1-naphthalenesulfonic acid (ANS)-binding fluorescence analysis revealed that C-XYN11-6 was more capable of maintaining its conformation during heat challenge, compared with L-XYN11-6. Interestingly, molecular cyclization also conferred C-XYN11-6 with improved resilience to 0.1-50 mmol/L Ca²⁺ or 0.1 mmol/L Cu²⁺ treatment. In summary, we generated a thermal- and ion-stable cyclized enzyme using SpyTag/SpyCatcher system, which will be of particular interest in engineering of enzymes for industrial application.
Animals ; Cyclization ; Endo-1,4-beta Xylanases ; chemistry ; metabolism ; Enzyme Stability ; Industrial Microbiology ; methods ; Microbiota ; Protein Engineering ; Rumen ; enzymology ; microbiology ; Temperature