Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.展开更多
EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A g...EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments.Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves.The gene’s immune relevance was explored through analyses of the tumor microenvironment(TME),Tumor Immune Single-cell Hub(TISCH),immune checkpoints,and immunotherapy sensitivity.Our results indicate that EVI2A expression is upregulated in KIRC,showing correlations with tumor grade and T/N/M stage.EVI2A demonstrates high diagnostic accuracy(AUC=0.906)and predicts poor overall and progression-free survival in KIRC patients.Furthermore,EVI2A expression exhibits significant associations with immunity,including TME scores and specific immune cell types such as Tfh cells,CD4 memory T cells,and CD8+T cells.Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors.In vitro assays confirmed the impact of EVI2A on KIRC behavior,with its knockdown resulting in reduced cell proliferation and migration.In conclusion,our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC.These findings hold significant implications for further research and potential clinical applications.展开更多
Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a complex disorder cha-racterized by symptoms resulting from intermittent hypoxia and hypopnea,with research indicating a crucial role of immune system dysregulation ...Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a complex disorder cha-racterized by symptoms resulting from intermittent hypoxia and hypopnea,with research indicating a crucial role of immune system dysregulation and genetic variations in its pathogenesis.A recent Zhao et al study utilizes Mendelian ran-domization analysis to explore the causal relationship between immune cell characteristics and OSAHS.The study identifies specific lymphocyte subsets as-sociated with OSAHS,providing valuable insights into the disease's pathophy-siology and potential targets for therapeutic intervention.The findings underscore the significance of genetic and immunological factors in sleep disorders,offering a fresh perspective on OSAHS's complexities.Compared to existing literature,Zhao et al's study stands out for its focus on genetic markers and specific immune responses associated with OSAHS,expanding upon previous research primarily centered on systemic inflammation.In conclusion,the study represents a signi-ficant advancement in the field,shedding light on the causal role of immune cells in OSAHS and paving the way for future research and targeted treatments.展开更多
[Objective] The aim of this study was to realize efficient expression of the porcine reproductive and respiratory syndrome virus (PRRSV) ORF7 gene in genetic engineering bacteria and analYze the immunological activi...[Objective] The aim of this study was to realize efficient expression of the porcine reproductive and respiratory syndrome virus (PRRSV) ORF7 gene in genetic engineering bacteria and analYze the immunological activity of the recombinant protein after purification. [ Method] The constructed recombinant expression vector pET-ORF7 was transformed into Escherichia co1BL21 (DE3) and induced by IPTG under the optimal condition. After analysis of SDS-PAGE and Western Blot, the expression products were purified by Ni-NTA His · Bind Resin chrom- atographic column under denaturing condition and renatured by gradient dialysis. Subsequently, the immunological activity of the renatured recombinant protein was detected by Westem Blot and indirect ELISA. [ Result] The recombinant plasmid pET-ORF7 expressed in E. coli successfully, and the fusion protein was in the form of inclusion body. By SDS-PAGE detection, the molecular weight of the expression protein was approximate 33 kD, according with the expectation. Analysis by Bandscan software showed that the expressed fusion protein was about 50% of total bacterial protein of BL21 (DE3). Wastem Blot and indirect ELISA detection showed that the renatured protein could react with PRRSV positive serum specifically, indicating its good immunological activity. [ Conclusion] This study lays a foundation for the preparation of PRRSV monoclonal antibody and diagnostic kit.展开更多
In this paper, the effects of compound P. igniarius oral liquid’s crude polysaccharide on the immunologic function of mice were studied from four aspects, namely, carbon clearance test of mice, macrophage phagocytosi...In this paper, the effects of compound P. igniarius oral liquid’s crude polysaccharide on the immunologic function of mice were studied from four aspects, namely, carbon clearance test of mice, macrophage phagocytosis of chicken red blood cel s in the enterocoelia of mice (semi-in vivo method), the ratio of organ to body weight, natural kil er (NK) cel activity in mice (the determination of lactate de-hydrogenase assay). The results showed that high-dosage group(40 mL/kg) of com-pound P. igniarius oral liquid can obviously enhance the ability of carbon clearance of mice; middle-(20 mL/kg) and high-dosage groups can significantly enhance the phagocytic rate and phagocytic index of chicken erythrocyte of mouse macrophage;low-(10 mL/kg), middle- and high-dosage groups can significantly enhance NK cel activity of mice. These showed that compound P. igniarius oral liquid can enhance mononuclear-macrophage and NK cel activity. In conclusion, compound P. igniarius oral liquid’s polysaccharide can enhance immunologic function and significantly im-prove the specific and nonspecific immunologic function.展开更多
Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six a...Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.展开更多
[ Objective] The research aimed to explore effects of an immunological stress on immune response in different breeds of piglets ( Lulai pig, Laiwu pig and Yorkshire pig). [Method] All the 12 weaning pigs (Lulai pig...[ Objective] The research aimed to explore effects of an immunological stress on immune response in different breeds of piglets ( Lulai pig, Laiwu pig and Yorkshire pig). [Method] All the 12 weaning pigs (Lulai pig, Laiwu pig and Yorkshire pig) weighing (12.6 ±0.5) kg were used in a 2 x3 factorial design. The main factors consisted of immunological challenge ( LPS or saline) and breeds ( Lulai pig, Laiwu pig and Yorkshire pig). On Day 1, six piglets of each breed were injected with LPS at the usage of 200 μg/kg BW or an equivalent amount of sterile saline, and in jected classical swine fever vaccine at the same time. Blood sample were collected on Day 2, 7 and 14 post injection to analyze the blood lympho cyte proliferation. The levels of antibodies against classical swine fever were tested on Day 1 prior to injection and on Day 7 and 14 post injection. [ Result] On Day 2 after injection, the lymphocyte transformation rate of piglets injected with LPS were significantly (P〈O. 01 ) increased compared with piglets injected with saline. The lymphocyte transformation rate of Laiwu piglets was significant higher than that of Yorkshire piglets ( P 〈 0.05). Effects of immunological stress on the level of antibodies against classical swine fever were not significantly different among different breeds of pig lets. [ Conclusion] LPS can effectively stimulate cellular immunity response in different breeds of piglets, and the immune response ability is different among various breeds of piglets.展开更多
The desensitization degree of emulsion explosives (EE) was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression...The desensitization degree of emulsion explosives (EE) was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression resistance, so the compression resistance of an explosive can be compared and analyzed quantificationally with the desensitization degree. The influence of an emulsifier on the pressure desensitization of EE was studied, including the content and category of emulsifiers. Three kinds of emulsifiers (Span-80, compound emulsifier, and T-152) were used in the tests. The experimental results show that both the content and category of emulsifiers make a great effect on the pressure desensitization of EE. The desensitization degree of EE reduces with the emulsifier content being increased, but there is an optimal content of an emulsifier for the compression resistance of EE. While the content of Span-80 reaches 4wt%, the desensitization degree of EE becomes a minimal value, and augments somewhat if the emulsifier content is increased more. That is to say, the compression resistance of EE becomes the highest while the content of Span-80 is 4wt%, and the compression resistance will decline if the content of Span-80 is increased more. The compression resistance of the explosive emulsified by compound emulsifier is the highest among all the explosives, when the content of the whole components and manufacturing engineering are kept invariable.展开更多
The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effec...The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (h=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=O.O33) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.展开更多
Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using stan...Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10, 100μ mol·L -1Ado, the ratio of shortened APD was ( 9.58± 1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1 μ mol·L -1Ado had no desensitization ( P >0.05), but the time of desensitization of 10μ mol·L -1 Ado and 100μ mol·L -1 Ado was 1 minute( P <0.05) and 5 minutes( P < 0.05), respectively. The desensitization of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4± 16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100 μ mol·L -1 Ado was (12.38±7.50)%,(19.00± 8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.展开更多
Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through ...Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.展开更多
This study was aimed to evaluate the long-term effects of telbivudine(Ld T) in the treatment of chronic hepatitis B(CHB) and HBV-related liver cirrhosis(LC) and to observe the changes of immunological responses ...This study was aimed to evaluate the long-term effects of telbivudine(Ld T) in the treatment of chronic hepatitis B(CHB) and HBV-related liver cirrhosis(LC) and to observe the changes of immunological responses during Ld T treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with Ld T for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen(HBe Ag) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after Ld T treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid(HA), human laminin(LN), human type Ⅳ collagen(Ⅳ-C) and human N-terminal procollagen Ⅲ peptide(PC-Ⅲ), were detected before and after Ld T treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with Ld T for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, Ld T treatment led to the fluctuation of the circulating interferon-γ(IFN-γ) and interleukin-10(IL-10) levels at different time points in CHB group. It was concluded that Ld T could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during Ld T therapy.展开更多
BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric ...BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.展开更多
Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accident...Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accidents during its storage and usage in ammunition.In this work,two kinds of insensitive step ladderstructured nitrocellulose(LNC)with different nitrogen contents were synthesized.The products were characterized by FT-IR,Raman,XRD,SEM,elemental analysis,TGA,DSC,accelerating rate calorimeter analysis(ARC),and drop weight test to study their molecular structure,thermal characteristics and desensitization performance.Compared with raw nitrocellulose,LNC has a sharper exothermic peak in the DSC and ARC curves.The H50values of the two kinds of LNC increased from 25.76 to 30.01 cm for low nitrogen content and from 18.02 to 21.84 cm for high nitrogen content,respectively.The results show that the ladder-structure of LNC which provides regular molecular arrangement and a soft buffer made with polyethylene glycol could affect the energy releasing process of LNC and reduce the sensitivity of LNC.Insensitive LNC provides an alternative to be used as a binder in insensitive propellants formulation.展开更多
The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients w...The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.展开更多
Objective: To observe the effect of low-frequency electroacupuncture (EA) on the immunologic function in morphine dependence rats. Methods: Forty SD rats were used in this study. Morphine-dependence model was establis...Objective: To observe the effect of low-frequency electroacupuncture (EA) on the immunologic function in morphine dependence rats. Methods: Forty SD rats were used in this study. Morphine-dependence model was established by intraperitoneal injection of morphine hydrochloride continuously for 5 days and hastened by administration (i.p) of Naloxone. These rats were randomly divided into control, model, EA and auto-demorphinization groups with 10 cases being in each group. In EA group, "Guanyuan"(CV 4),"Mingmen"(GV 4), etc. were punctured and stimulated electrically. Positive T lymphocyte subgroups, CD + 4 and CD + 8 in the peripheral blood were detected with fluorescence immuno-assay. Results: In model group, serum percentage of CD + 4 and CD + 4/CD + 8 decreased considerably in comparison with those of control group (P<0.01); while in EA group, CD + 4 level and CD + 4/CD + 8 increased significantly compared with those of model group (P<0.01); and no significant differences were found between auto-demorphinization group and model group and between EA and control groups in these two indexes. Conclusion: Low-frequency EA can promote the restoration of the immune function of morphine dependence rats.展开更多
OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as e...OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.展开更多
Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and ...Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.展开更多
Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization ast...Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization asthma model group.Asthma model was established,and on this basis,the method of atom-izing inhalation and intraperitoneal injections of salbutamol was used to prepareβ_(2)-AR desensitization asthma model.After the last stimulation on the 21st day of modeling,the airway resistance of mice was measured.ELISA was used to detect the content of serum IgE;HE staining was used to observe the lung organization degree of infla-mmatory cell infiltration;Western blot method was used to detect theβ_(2)-AR content in lung tissue,RT-PCR was used to detect theβ_(2)-ARmRNA expressionin lung tissue.Results:Compared with the blank group,as acetyl choline(Mch)levels increased,groups of OVA induced airway resistance increases;but theβ_(2)-AR desensitization asthma model group increased airway resistance was more significant(P<0.05);compared with the blank group,IgE levels of common asthma group andβ_(2)-AR desensitization asthma model group elevated(P<0.01).The pathological histology observation found theβ_(2)-AR desensitization asthma airway inflammation infiltration in mice,the excessive mucus secretion and collagen deposition,and the pathological performance obviously increase compared with the common asthma group;β_(2)-AR content in the lung tissue ofβ_(2)-AR desensitization asthma model in mice,β_(2)-AR mRNA expression level in the blank group and common asthma model group were significantly decreased(P<0.05).Conclusion:Theβ_(2)-AR desensitization asthma mouse model was successfully established,and the buildingcycle was short.展开更多
The results of the Be-induced leukocyte migration inhibition test(Be-MIT),the lymphocyte transformation test(LI),the E-rosette formation test(E-RFC),the old tuberculin test(OT),and sero-immunoglobulin(IgG,IgA,IgM)meas...The results of the Be-induced leukocyte migration inhibition test(Be-MIT),the lymphocyte transformation test(LI),the E-rosette formation test(E-RFC),the old tuberculin test(OT),and sero-immunoglobulin(IgG,IgA,IgM)measurements on 13 cases of berylliosis,44 members of the observation group,and 51 members of the contact group are rèported.In the Be-MIT,2 of the berylliosis patients were new cases that had been diagnosed and treated for a long time,and both tested positive(18%).Fourteen patients from the observation group tested positive(32%), and 15 from the contact group tested positive(30%).The 8 cases in the control group tested negative;7 patients from the observation group and 3 of the berylliosis cases tested negative after being treated.The lymphocyte transformation rates of the observation group and the berylliosis group were significantly lower than that of the control group(P<0.01).Both Et-RFC and Ea- RFC contents in the group with berylliosis were much lower than those in the control group(P <0.01).OT tests were performed on 8 berylliosis patients and 10 healthy men.Seven patients showed negative reactions and one showed a positive reaction.All the healthy men showed positive reactions.The IgG and IgA levels of the observation group were significantly higher than those of the control group(P<0.01).The Be-MIT could detect active beryllium disease at an early stage as well as Be-sensitive individuals.This test could be used as a supplementary diagnostic index for the differential diagnosis of berylliosis and for the evaluation of a curative effect.1989 Academic Press,Inc.展开更多
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
基金the Ethics Committee of the First Affiliated Hospital of Nanchang University(Approval:(2023)CDYFYYLK(03-013)).
文摘EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments.Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves.The gene’s immune relevance was explored through analyses of the tumor microenvironment(TME),Tumor Immune Single-cell Hub(TISCH),immune checkpoints,and immunotherapy sensitivity.Our results indicate that EVI2A expression is upregulated in KIRC,showing correlations with tumor grade and T/N/M stage.EVI2A demonstrates high diagnostic accuracy(AUC=0.906)and predicts poor overall and progression-free survival in KIRC patients.Furthermore,EVI2A expression exhibits significant associations with immunity,including TME scores and specific immune cell types such as Tfh cells,CD4 memory T cells,and CD8+T cells.Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors.In vitro assays confirmed the impact of EVI2A on KIRC behavior,with its knockdown resulting in reduced cell proliferation and migration.In conclusion,our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC.These findings hold significant implications for further research and potential clinical applications.
文摘Obstructive sleep apnea-hypopnea syndrome(OSAHS)is a complex disorder cha-racterized by symptoms resulting from intermittent hypoxia and hypopnea,with research indicating a crucial role of immune system dysregulation and genetic variations in its pathogenesis.A recent Zhao et al study utilizes Mendelian ran-domization analysis to explore the causal relationship between immune cell characteristics and OSAHS.The study identifies specific lymphocyte subsets as-sociated with OSAHS,providing valuable insights into the disease's pathophy-siology and potential targets for therapeutic intervention.The findings underscore the significance of genetic and immunological factors in sleep disorders,offering a fresh perspective on OSAHS's complexities.Compared to existing literature,Zhao et al's study stands out for its focus on genetic markers and specific immune responses associated with OSAHS,expanding upon previous research primarily centered on systemic inflammation.In conclusion,the study represents a signi-ficant advancement in the field,shedding light on the causal role of immune cells in OSAHS and paving the way for future research and targeted treatments.
文摘[Objective] The aim of this study was to realize efficient expression of the porcine reproductive and respiratory syndrome virus (PRRSV) ORF7 gene in genetic engineering bacteria and analYze the immunological activity of the recombinant protein after purification. [ Method] The constructed recombinant expression vector pET-ORF7 was transformed into Escherichia co1BL21 (DE3) and induced by IPTG under the optimal condition. After analysis of SDS-PAGE and Western Blot, the expression products were purified by Ni-NTA His · Bind Resin chrom- atographic column under denaturing condition and renatured by gradient dialysis. Subsequently, the immunological activity of the renatured recombinant protein was detected by Westem Blot and indirect ELISA. [ Result] The recombinant plasmid pET-ORF7 expressed in E. coli successfully, and the fusion protein was in the form of inclusion body. By SDS-PAGE detection, the molecular weight of the expression protein was approximate 33 kD, according with the expectation. Analysis by Bandscan software showed that the expressed fusion protein was about 50% of total bacterial protein of BL21 (DE3). Wastem Blot and indirect ELISA detection showed that the renatured protein could react with PRRSV positive serum specifically, indicating its good immunological activity. [ Conclusion] This study lays a foundation for the preparation of PRRSV monoclonal antibody and diagnostic kit.
基金Supported by National-level Innovative Training Program for Undergraduate Students"On the Preparation of Immunity Enhancement Food Taking Phellinus igniarius Polysaccharide from Medicinal Fungus as Main Component"(201314046008)the Project of Unversity Teaching Reform:On Comprehensive Reform of Food Quality and Safety Specialty(0137Z5)~~
文摘In this paper, the effects of compound P. igniarius oral liquid’s crude polysaccharide on the immunologic function of mice were studied from four aspects, namely, carbon clearance test of mice, macrophage phagocytosis of chicken red blood cel s in the enterocoelia of mice (semi-in vivo method), the ratio of organ to body weight, natural kil er (NK) cel activity in mice (the determination of lactate de-hydrogenase assay). The results showed that high-dosage group(40 mL/kg) of com-pound P. igniarius oral liquid can obviously enhance the ability of carbon clearance of mice; middle-(20 mL/kg) and high-dosage groups can significantly enhance the phagocytic rate and phagocytic index of chicken erythrocyte of mouse macrophage;low-(10 mL/kg), middle- and high-dosage groups can significantly enhance NK cel activity of mice. These showed that compound P. igniarius oral liquid can enhance mononuclear-macrophage and NK cel activity. In conclusion, compound P. igniarius oral liquid’s polysaccharide can enhance immunologic function and significantly im-prove the specific and nonspecific immunologic function.
文摘Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are lacking.Methods: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.
文摘[ Objective] The research aimed to explore effects of an immunological stress on immune response in different breeds of piglets ( Lulai pig, Laiwu pig and Yorkshire pig). [Method] All the 12 weaning pigs (Lulai pig, Laiwu pig and Yorkshire pig) weighing (12.6 ±0.5) kg were used in a 2 x3 factorial design. The main factors consisted of immunological challenge ( LPS or saline) and breeds ( Lulai pig, Laiwu pig and Yorkshire pig). On Day 1, six piglets of each breed were injected with LPS at the usage of 200 μg/kg BW or an equivalent amount of sterile saline, and in jected classical swine fever vaccine at the same time. Blood sample were collected on Day 2, 7 and 14 post injection to analyze the blood lympho cyte proliferation. The levels of antibodies against classical swine fever were tested on Day 1 prior to injection and on Day 7 and 14 post injection. [ Result] On Day 2 after injection, the lymphocyte transformation rate of piglets injected with LPS were significantly (P〈O. 01 ) increased compared with piglets injected with saline. The lymphocyte transformation rate of Laiwu piglets was significant higher than that of Yorkshire piglets ( P 〈 0.05). Effects of immunological stress on the level of antibodies against classical swine fever were not significantly different among different breeds of pig lets. [ Conclusion] LPS can effectively stimulate cellular immunity response in different breeds of piglets, and the immune response ability is different among various breeds of piglets.
基金This work was financially supported by the National Natural Science Foundation of China (No.50574004).
文摘The desensitization degree of emulsion explosives (EE) was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression resistance, so the compression resistance of an explosive can be compared and analyzed quantificationally with the desensitization degree. The influence of an emulsifier on the pressure desensitization of EE was studied, including the content and category of emulsifiers. Three kinds of emulsifiers (Span-80, compound emulsifier, and T-152) were used in the tests. The experimental results show that both the content and category of emulsifiers make a great effect on the pressure desensitization of EE. The desensitization degree of EE reduces with the emulsifier content being increased, but there is an optimal content of an emulsifier for the compression resistance of EE. While the content of Span-80 reaches 4wt%, the desensitization degree of EE becomes a minimal value, and augments somewhat if the emulsifier content is increased more. That is to say, the compression resistance of EE becomes the highest while the content of Span-80 is 4wt%, and the compression resistance will decline if the content of Span-80 is increased more. The compression resistance of the explosive emulsified by compound emulsifier is the highest among all the explosives, when the content of the whole components and manufacturing engineering are kept invariable.
基金This study was funded by the National Natural Science Foundation of China (No.30872175,No.81573236).
文摘The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-Desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (h=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=O.O33) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.
基金ThisresearchwassupportedbytheNationalNaturalScienceFoundationofChina (No .30 2 70 5 5 4No .39970 2 73) +1 种基金Doctonialsubject (No .2 0 0 10 6 980 34)keyItemofScientificTechnologyforministryofEducation (No .0 116 1) .
文摘Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10, 100μ mol·L -1Ado, the ratio of shortened APD was ( 9.58± 1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1 μ mol·L -1Ado had no desensitization ( P >0.05), but the time of desensitization of 10μ mol·L -1 Ado and 100μ mol·L -1 Ado was 1 minute( P <0.05) and 5 minutes( P < 0.05), respectively. The desensitization of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4± 16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100 μ mol·L -1 Ado was (12.38±7.50)%,(19.00± 8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.
文摘Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.
文摘This study was aimed to evaluate the long-term effects of telbivudine(Ld T) in the treatment of chronic hepatitis B(CHB) and HBV-related liver cirrhosis(LC) and to observe the changes of immunological responses during Ld T treatment. Clinical data of 80 CHB and 28 HBV-related LC patients who were administered with Ld T for 108 weeks and followed up were retrospectively analyzed. The liver function indicators including ALT, AST and γ-GT, HBV DNA copy number in serum and the rates of hepatitis B e antigen(HBe Ag) seroconversion were analyzed before and 12, 24, 36, 48, 60, 72, 84, 96 and 108 weeks after Ld T treatment in CHB and LC groups. Four serum fibrosis-related markers, including hyaluronic acid(HA), human laminin(LN), human type Ⅳ collagen(Ⅳ-C) and human N-terminal procollagen Ⅲ peptide(PC-Ⅲ), were detected before and after Ld T treatment in LC group. The results showed favorable viral suppression and biochemical responses after treatment with Ld T for 12 weeks, and a high rate of virological and biochemical control was maintained during the course of 108-week treatment in both CHB and LC groups. The four fibrosis-related markers, especially HA and LN, were down-regulated to some degrees in LC group. Moreover, Ld T treatment led to the fluctuation of the circulating interferon-γ(IFN-γ) and interleukin-10(IL-10) levels at different time points in CHB group. It was concluded that Ld T could favorably lead to the virological suppression and biochemical remission. Besides, IFN-γ and IL-10 may represent a suitable and effective predictor of responsiveness during Ld T therapy.
基金supported by a grant from the National Natural Science Foundation of China (30972920)
文摘BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.
基金supported in part by the National Natural Science Foundation of China(No.22075146)。
文摘Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accidents during its storage and usage in ammunition.In this work,two kinds of insensitive step ladderstructured nitrocellulose(LNC)with different nitrogen contents were synthesized.The products were characterized by FT-IR,Raman,XRD,SEM,elemental analysis,TGA,DSC,accelerating rate calorimeter analysis(ARC),and drop weight test to study their molecular structure,thermal characteristics and desensitization performance.Compared with raw nitrocellulose,LNC has a sharper exothermic peak in the DSC and ARC curves.The H50values of the two kinds of LNC increased from 25.76 to 30.01 cm for low nitrogen content and from 18.02 to 21.84 cm for high nitrogen content,respectively.The results show that the ladder-structure of LNC which provides regular molecular arrangement and a soft buffer made with polyethylene glycol could affect the energy releasing process of LNC and reduce the sensitivity of LNC.Insensitive LNC provides an alternative to be used as a binder in insensitive propellants formulation.
文摘The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.
文摘Objective: To observe the effect of low-frequency electroacupuncture (EA) on the immunologic function in morphine dependence rats. Methods: Forty SD rats were used in this study. Morphine-dependence model was established by intraperitoneal injection of morphine hydrochloride continuously for 5 days and hastened by administration (i.p) of Naloxone. These rats were randomly divided into control, model, EA and auto-demorphinization groups with 10 cases being in each group. In EA group, "Guanyuan"(CV 4),"Mingmen"(GV 4), etc. were punctured and stimulated electrically. Positive T lymphocyte subgroups, CD + 4 and CD + 8 in the peripheral blood were detected with fluorescence immuno-assay. Results: In model group, serum percentage of CD + 4 and CD + 4/CD + 8 decreased considerably in comparison with those of control group (P<0.01); while in EA group, CD + 4 level and CD + 4/CD + 8 increased significantly compared with those of model group (P<0.01); and no significant differences were found between auto-demorphinization group and model group and between EA and control groups in these two indexes. Conclusion: Low-frequency EA can promote the restoration of the immune function of morphine dependence rats.
文摘OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and schizophrenia.Star⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.
文摘Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.
基金General Projects of National Natural Science Fund(81873338)Key Scientific and Technological Projects in Henan Province(202102310491)Training Subjects of Leading Talents in the Department of Traditional Chinese Medicine in Henan Province(Yuweizhongyihan[2021]No.8)。
文摘Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization asthma model group.Asthma model was established,and on this basis,the method of atom-izing inhalation and intraperitoneal injections of salbutamol was used to prepareβ_(2)-AR desensitization asthma model.After the last stimulation on the 21st day of modeling,the airway resistance of mice was measured.ELISA was used to detect the content of serum IgE;HE staining was used to observe the lung organization degree of infla-mmatory cell infiltration;Western blot method was used to detect theβ_(2)-AR content in lung tissue,RT-PCR was used to detect theβ_(2)-ARmRNA expressionin lung tissue.Results:Compared with the blank group,as acetyl choline(Mch)levels increased,groups of OVA induced airway resistance increases;but theβ_(2)-AR desensitization asthma model group increased airway resistance was more significant(P<0.05);compared with the blank group,IgE levels of common asthma group andβ_(2)-AR desensitization asthma model group elevated(P<0.01).The pathological histology observation found theβ_(2)-AR desensitization asthma airway inflammation infiltration in mice,the excessive mucus secretion and collagen deposition,and the pathological performance obviously increase compared with the common asthma group;β_(2)-AR content in the lung tissue ofβ_(2)-AR desensitization asthma model in mice,β_(2)-AR mRNA expression level in the blank group and common asthma model group were significantly decreased(P<0.05).Conclusion:Theβ_(2)-AR desensitization asthma mouse model was successfully established,and the buildingcycle was short.
文摘The results of the Be-induced leukocyte migration inhibition test(Be-MIT),the lymphocyte transformation test(LI),the E-rosette formation test(E-RFC),the old tuberculin test(OT),and sero-immunoglobulin(IgG,IgA,IgM)measurements on 13 cases of berylliosis,44 members of the observation group,and 51 members of the contact group are rèported.In the Be-MIT,2 of the berylliosis patients were new cases that had been diagnosed and treated for a long time,and both tested positive(18%).Fourteen patients from the observation group tested positive(32%), and 15 from the contact group tested positive(30%).The 8 cases in the control group tested negative;7 patients from the observation group and 3 of the berylliosis cases tested negative after being treated.The lymphocyte transformation rates of the observation group and the berylliosis group were significantly lower than that of the control group(P<0.01).Both Et-RFC and Ea- RFC contents in the group with berylliosis were much lower than those in the control group(P <0.01).OT tests were performed on 8 berylliosis patients and 10 healthy men.Seven patients showed negative reactions and one showed a positive reaction.All the healthy men showed positive reactions.The IgG and IgA levels of the observation group were significantly higher than those of the control group(P<0.01).The Be-MIT could detect active beryllium disease at an early stage as well as Be-sensitive individuals.This test could be used as a supplementary diagnostic index for the differential diagnosis of berylliosis and for the evaluation of a curative effect.1989 Academic Press,Inc.